Science of Synthesis

Science of Synthesis
Guidebook
HoubenWeyl Methods of Molecular Transformations
Guidebook
Georg Thieme Verlag Stuttgart New York
Editorial Board D. Bellus E. N. Jacobsen S. V. Ley R. Noyori M. Regitz G. F. Herrmann M. F. Shortt de Hernandez P. J. Reider E. Schaumann I. Shinkai E. J. Thomas B. M. Trost
Managing Director Managing Editor
2004 Georg Thieme Verlag Stuttgart New York
6 This reference work mentions numerous commercial and proprietary trade names, registered trademarks and the like (not necessarily marked as such), patents, production and manufacturing procedures, registered designs, and designations. The editors and publishers wish to point out very clearly that the present legal situation in respect of these names or designations or trademarks must be carefully examined before making any commercial use of the same. Industrially produced apparatus and equipment are included to a necessarily restricted extent only and any exclusion of products not mentioned in this reference work does not imply that any such selection of exclusion has been based on quality criteria or quality considerations.
Warning! Read carefully the following: Although this reference work has been written by experts, the user must be advised that the handling of chemicals, microorganisms, and chemical apparatus carries potentially life-threatening risks. For example, serious dangers could occur through quantities being incorrectly given. The authors took the utmost care that the quantities and experimental details described herein reflected the current state of the art of science when the work was published. However, the authors, editors, and publishers take no responsibility as to the correctness of the content. Further, scientific knowledge is constantly changing. As new information becomes available, the user must consult it. Although the authors, publishers, and editors took great care in publishing this work, it is possible that typographical errors exist, including errors in the formulas given herein. Therefore, it is imperative that and the responsibility of every user to carefully check whether quantities, experimental details, or other information given herein are correct based on the users own understanding as a scientist. Scaleup of experimental procedures published in Science of Synthesis carries additional risks. In cases of doubt, the user is strongly advised to seek the opinion of an expert in the field, the publishers, the editors, or the authors. When using the information described herein, the user is ultimately responsible for his or her own actions, as well as the actions of subordinates and assistants, and the consequences arising therefrom. Date of publication: November 1, 2003 6th edition These versions of the Editorial Description, the Information for Authors, and of the Sample Contribution contained in this Science of Synthesis Guidebook are effective immediately and replace former versions.
Copyright and all related rights reserved, especially the right of copying and distribution, multiplication and reproduction, as well as of translation. No part of this publication may be reproduced by any process, whether by photostat or microfilm or any other procedure, without previous written consent by the publisher. This also includes the use of electronic media of data processing on reproduction of any kind. 2004 Georg Thieme Verlag Rdigerstrasse 14 D-70469 Stuttgart Printed in Germany Typesetting: Ziegler + Mller, Kirchentellinsfurt (3B2, V. 6.05c) Printing and Binding: Konrad Triltsch, Ochsenfurt-Hohestadt ISBN 1-58890-059-2 (TNY)
Preface
Facing dramatic developments in chemistry during the last few decades which have provided chemists with a wealth of new reagents and reactions, the need for a new, comprehensive, and critical treatment of synthetic chemistry has become apparent. To meet this challenge an entirely new edition of the esteemed reference work HoubenWeyl Methods of Organic Chemistry has been launched in the year 2000. This new edition is entitled Science of Synthesis, HoubenWeyl Methods of Molecular Transformations and is edited by D. Bellus (Basel, Switzerland), E. N. Jacobsen (Cambridge, USA), S. V. Ley (Cambridge, UK), R. Noyori (Nagoya, Japan), M. Regitz (Kaiserslautern, Germany), P. J. Reider (New Jersey, USA), E. Schaumann (Clausthal-Zellerfeld, Germany), I. Shinkai (Tokyo, Japan), E. J. Thomas (Manchester, UK), and B. M. Trost (Stanford, USA). Science of Synthesis is a balanced and critical reference work produced by the collaborative efforts of chemists, from both industry and academia, selected by the editorial board. All published results from journals, books, and patent literature from the early 1800s until the year of publication are considered by the authors, who are among the leading experts in their field, to provide chemists with the most reliable methods to solve their synthesis problems. Science of Synthesis will be updated periodically and will become a prime source of information for chemists in the 21st century. Science of Synthesis is organized in a logical hierarchical system based on the target molecule to be synthesized. The critical coverage of methods is supported by information intended to help the user choose the most suitable method for their application, thus providing a strong foundation from which to develop a successful synthetic route. Within each category of product, illuminating background information such as history, nomenclature, structure, stability, reactivity, properties, safety, and environmental aspects are discussed along with a detailed selection of reliable methods. Each method and variation is accompanied by reaction schemes, tables of examples, experimental procedures, and a background discussion of mechanistic rationale, stereochemistry, scope of the reaction described and its limitations, and functional group compatibility. In a format consisting of 48 volumes, Science of Synthesis is a unique reference work, selecting and evaluating all synthetic methodology and thus providing more than just a compound database or an indiscriminate review of the literature. To best meet the needs of the scientific community, Science of Synthesis is being published as an electronic version and also in print. The electronic version has been developed under the guidance of an advisory board comprising A. Barth (Fachinformationszentrum Karlsruhe, Germany), G. Baysinger (Stanford University, USA), A. Mullen (Bayer AG, Germany), H. Rzepa (Imperial College, UK), and E. Zass (ETH Zurich, Switzerland). It is equipped with a powerful and user-friendly information retrieval system to allow for keyword, text, substructure, structure, and reaction searches. Science of Synthesis provides a hypertext navigation system and thesaurus support. Crossovers to other databases and electronic journals are fully supported. Science of Synthesis is at the heart of the fully integrated laboratory of the future. The Publisher
Table of Contents
Editorial Description of Science of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Information for Authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sample Contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Category 1: Organometallics Contribution from Volume 2 published in 2002
2.6
11 37 61
Organometallic Complexes of Chromium, Molybdenum, and Tungsten without Carbonyl Ligands (R. Poli and K. M. Smith) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
63
Category 2: Hetarenes and Related Ring Systems Contribution from Volume 14 published in 2003
14.11
Selenopyranones and Benzoselenopyranones (P. J. Murphy) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
117
The People . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 Appendix List of All Volumes of HoubenWeyl Methods of Organic Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
11
Editorial Description
13
Table of Contents
1 1.1
Editorial Description of Science of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Why is there a Need for a New Edition of HoubenWeyl Methods of Organic Chemistry? . . . . . . . . . . . . . . . . . . . . . . . . . . . . HoubenWeyl Methods of Organic Chemistry Entering the New Millennium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Organizational Principles of Science of Synthesis, HoubenWeyl Methods of Molecular Transformations . . . . . . . . . . . . . . . . . . . . . . Classification Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
15 15 15 16 17
1.2
1.3
1.3.1 1.3.2
Complete Volume List of Science of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Editorial Description of Science of Synthesis
15

Why is there a Need for a New Edition of HoubenWeyl Methods of Organic Chemistry?
1.1
Synthesis is seen as the cornerstone of drug discovery; as John L. LaMattina, Vice President for Discovery Research at Pfizer stated, You need to get in the lab and make compounds and convert these compounds to drugs. That is a chemistry-intensive step. (Chemical and Engineering News, March 1998). Thus chemists today are facing ever-increasing demands on their time and synthetic excellence, whilst pharmaceutical and chemical companies are recognizing the need to move towards developing more efficient and productive R & D laboratories. Just to maintain current growth rates of 10% a year, the top ten pharmaceutical companies would each have to launch five new drugs a year. One of the key challenges facing these companies and scientists in academia is information management: the amount of chemical literature available from journals, and online and CD-ROM databases, has grown exponentially. Researchers today are facing information overload on reaction schemes and synthetic routes, even though a large number of products made in industry today are being produced with traditional synthetic methods developed 40 to 50 years ago. With this in mind, Thieme Publishers has seen the need to relaunch the HoubenWeyl series, a classical reference work in organic chemistry, in a new, very accessible, and focused format called Science of Synthesis, HoubenWeyl Methods of Molecular Transformations. By providing a clear and systematic synthesis series, Science of Synthesis is designed to be the first point of reference before embarking on further searches, providing a route through the mass of information available in the primary literature. Science of Synthesis contains synthetic methods selected by world-renowned chemists, giving full experimental procedures and background information. Science of Synthesis is designed to stimulate new discoveries and the development of new methodologies in both industry and academia by providing an understanding of the whole field of synthesis to date. Science of Synthesis is a flexible user-friendly system, allowing text, substructure, exact structure, and reaction searches with an easy-to-use interface. Science of Synthesis is an expert guidance tool giving high-quality, reliable, and selective solutions to scientists synthesis problems.
1.2
HoubenWeyl Methods of Organic Chemistry Entering the New Millennium
The series METHODEN DER ORGANISCHEN CHEMIE (HoubenWeyl Methods of Organic Chemistry) was established in 1909 by the German chemist Theodor Weyl and continued in 1913 by Heinrich J. Houben. The comprehensive description of preparative methods in a consistent style and their critical evaluation by leading experts is the philosophy on which HoubenWeyl was founded. The 4 volumes of the second edition were published between 1921 and 1924. The third edition, consisting of 4 volumes, was published between 1924 and 1941. The fourth edition (founded by O. Bayer, H. Meerwein, E. Mller, K. Ziegler) began in 1952, was continued from 1975 by H. Kropf and H.-G. Padeken, and ended in 1986 with a total of 67 volumes and 3 index volumes. The series was updated with 89 additional and supplementary volumes which placed emphasis on the treatment of important classes of compounds and significant preparative methods (edited by K. H. Bchel, J. Falbe, H. Hagemann, M. Hanack, D. Klamann, R. Kreher, H. Kropf, M. Regitz, E. Schaumann, and H.-G. Padeken). From 1990 onwards HoubenWeyl was published in English, thus making it accessible to chemists worldwide. The last volume of HoubenWeyl was published in the year 2003. The appendix contains a list of all HoubenWeyl volumes.
16
Houben-Weyl Methods of Molecular Transformations
The success of HoubenWeyl over the last 90 years was made possible by the collaborative work of world-renowned chemists in both industry and academia, who created a balanced work by considering published results from journals, books, and the patent literature. Thus, HoubenWeyl has become an important and celebrated standard reference work, serving the scientific community with a critical selection of synthetic methods. HoubenWeyl is an indispensable treatise for every synthetic chemist. At the turn of the century HoubenWeyl is now heading towards new directions. Facing dramatic developments in organic chemistry during the last decades, which have provided synthetic chemists with a wealth of new reagents and reactions, the board of editors has decided to carry on the long tradition of HoubenWeyl. An entirely new edition of HoubenWeyl has been launched in the year 2000. This new edition is entitled Science of Synthesis, HoubenWeyl Methods of Molecular Transformations and is edited by D. Bellus (Basel, Switzerland), E. N. Jacobsen (Cambridge, USA), S. V. Ley (Cambridge, UK), R. Noyori (Nagoya, Japan), M. Regitz (Kaiserslautern, Germany), P. J. Reider (New Jersey, USA), E. Schaumann (Clausthal-Zellerfeld, Germany), I. Shinkai (Tsukuba, Japan), E. J. Thomas (Manchester, UK), and B. M. Trost (Stanford, USA). Science of Synthesis will benefit from more than 90 years of experience and will continue the tradition of excellence in publishing organic chemistry reference works. It will offer a truly comprehensive, critical treatment of synthetic organic and organometallic chemistry. Science of Synthesis will cover the whole field of organic chemistry based on all published and readily available sources from the early 1800s until the year of publication. Widely acclaimed editors and authors will provide chemists with the most reliable methods to solve their synthesis problems. For each method a detailed experimental procedure will be included. Science of Synthesis will be updated periodically and will become a prime source of information for scientists in the 21st century. To best meet the needs of the scientific community, Science of Synthesis is published not only in a print version but also as an electronic version, which makes use of the latest developments in information technology and is equipped with a powerful and user-friendly information-retrieval system to allow for substructure, exact structure, and reaction searches. The electronic version is being developed under the guidance of an advisory board comprising A. Barth (Fachinformationszentrum Karlsruhe, Germany), G. Baysinger (Stanford University, USA), A. Mullen (Bayer AG, Germany), H. Rzepa (Imperial College, UK), and E. Zass (ETH Zrich, Switzerland). Science of Synthesis will support combined keyword, text and reaction searches. It will provide a hypertext navigation system and thesaurus support. Crossovers to databases and electronic journals are fully supported, thus allowing chemists to gather further information about their target compounds. Chemists are provided with customizable display and print formats. Science of Synthesis will be at the heart of the fully integrated laboratory of the future. The policy of the editorial board and the publishers is to ensure that Science of Synthesis is the ultimate tool for the synthetic chemist in the 21st century. This endeavor will be achieved by the combined efforts of the publishing house, the editors, and the authors, who are among the leading experts in their field.
1.3
Organizational Principles of Science of Synthesis, HoubenWeyl Methods of Molecular Transformations
The following organizational principles are designed to serve as guidelines for volume editors, authors, and users in deciding where in Science of Synthesis a given topic will be treated. These rules of classification will not, however, take precedence over chemical common sense in the organization of individual volumes, since it is the ultimate goal that the material be organized for the benefit of the user in a manner that is as simple and intuitive as possible.

1.3.1
17
Classification Principles
The organization of Science of Synthesis is based on the structural unit or functional group (for example, a heteroaromatic ring or an enone) that is to be constructed. That is to say the classification is based on the product (how do I make something?) as opposed to the reaction (what is the HornerEmmons reaction?), the reagent (what can I do with organocopper reagents?), or the starting material (what reactions do 1,2-diols undergo?). Thus, a given synthetic method, such as catalytic hydrogenation, that can be employed for a variety of product types, will be found throughout the work, depending on the structure of the compound produced. Likewise, the various reactions of a given compound class, such as alcohols, are located throughout the work on the basis of the product. The purpose of this classification system is to organize all synthetically useful reactions so that practicing chemists can readily find a solution to their synthetic problem, and ensure a minimum of overlap in the presentation throughout the entire work. Unfortunately, there is no universal organizational principle for all organic and organometallic chemistry that is simple and at the same time corresponds to generally accepted chemical common sense. Therefore, the following rules have not been rigorously derived from physical or chemical principles. A classification scheme is employed that corresponds to the general notion of oxidation state (carbonic acid derivatives, carboxylic acid derivatives, etc.). It is of interest to note that the number of heteroatom bonds to carbon, which is a rough indication of oxidation state, has been the underlying organizational principle of HoubenWeyl since the first edition. For organometallic and heteroaromatic compounds the editors have created two separate categories, in accordance with common chemical usage and the fact that these compound classes have unique chemical properties. Partially or fully saturated heterocyclics are, however, classified with the corresponding acyclic compounds (e.g., tetrahydrofuran with ethers). The result is a group of six categories given below in Section 1.3.1.2. When only one functionality is present in the target, the classification into one of the six categories is evident. This is also true with targets containing mutually remote functionalities in which only one functionality is formed by the method under consideration, since the classification is based solely on the functionality formed. However, with multifunctional targets, in which functionalities are directly bonded or in which more than one functionality is formed by the method under consideration, more elaborate classification rules are needed in order to determine in which category the target belongs and where within the category it will be treated (for an overview see Scheme 1). As with the CahnIngoldPrelog system, all functional groups and structural units must be given an order of priority for the purposes of classification. In each case where multiple functions are formed at the same time, the decision has to be made as to which functional group has the higher priority. For example, is the lithiation of pyridine covered under organometallics or hetarenes, i.e. which functionality has the higher priority, C-Li or pyridine? The following rules attempt to answer all such questions. Scheme 1 gives an overview of the classification principles of Science of Synthesis.
Scheme 1
18
Classification Principles of Science of Synthesis (Volume 9 Given as an Example)
CATEGORY
Organometallics (Vols 18)
2
VOLUME Vol. 9 PRODUCT CLASS 9.1 PRODUCT SUBCLASS 9.1.1 9.1.2 etc. 9.1.1.2 Rules 1113: etc. 9.1.1.1.2 etc. Rules 1417:* organization of methods and variations 9.1.1.1.1
Hetarenes (Vols 917)
Products of Organic Synthesis Vol. 10 etc. 9.2 etc. METHOD 9.1.1.1
4/3 C-X bonds (Vols 1824)
Rule 1: hierarchical organization
2 C-X bonds (Vols 2533)
1 C-X bond (Vols 3442)
VARIATION
All C bonds (Vols 4348)
Rule 2: six categories
organization of product classes/subclasses Also: Rules 110 apply
Selected Products and Reactions
Rules 310: classification of products within categories
* Rule 15 applies to Category 1 Rule 16 applies to Category 2 Rule 17 applies to Categories 3 6
Rule 18: organization of examples within methods or variations Also: Rules 113 apply
19
1.3.1.1 Rule 1
Modular Organization of the Text of Science of Synthesis Hierarchical Organization of the Content of Science of Synthesis
The content of Science of Synthesis will be organized hierarchically into: Categories, Volumes, Product Classes, Product Subclasses, Methods, Variations. Each product class can be divided into product subclasses if necessary. Methods will be ranked according to the organizational principles (e.g., in the case of allylstannanes, the synthesis of these products by formation of the C-Sn bond via a Grignard reaction has a higher priority than the synthesis by formation of the allylic C=C bond via a Wittig reaction, see Rule 14). Science of Synthesis will focus on selected and reliable methods, which have proved to be useful for the synthesis of a given product class. For each method a scheme and, if necessary, a table (with, in general, 5 to 10 examples) will be given. An experimental procedure, plus safety and environmental aspects, will further illustrate the method. Alterations to a method, e.g. changes in catalysts or reagents, the running of a reaction as a one-pot reaction, generation of reagents in situ, etc., which have a significant influence on the outcome of a reaction, will result in a variation. A variation will be described in the same way as a method. If there are several variations of a method, Method n as a heading (with introductory text only) is followed by Variation 1 (including introductory text, scheme, table of examples, experimental procedure), Variation 2, etc. According to these principles the text will be organized into the following sections:
Category 1 Volume 1 Introductory Text: Volume 1 Background Information: Products of Volume 1 (e.g., history, nomenclature, applications) Structure: Products of Volume 1 Stability: Products of Volume 1 Reactivity: Products of Volume 1 Physical Properties: Products of Volume 1 Spectroscopic Properties: Products of Volume 1 Safety and Environmental Aspects: Products of Volume 1 Product Class 1 (based on the organizational principles of Science of Synthesis) Introductory Text: Product Class 1 Background Information: Product Class 1 (e.g., history, nomenclature, applications) Location of Product Class 1 in HoubenWeyl, 4th Edition and E-Series Structure: Product Class 1 Stability: Product Class 1 Reactivity: Product Class 1 Physical Properties: Product Class 1 Spectroscopic Properties: Product Class 1 Safety and Environmental Aspects: Product Class 1
1.1
20
1.1.1
1.1.1.1
1.1.1.1.1
1.1.1.1.2 1.1.1.1.n 1.1.1.2 1.1.1.2.1 1.1.1.2.n 1.1.1.n 1.1.2 1.1.n 1.2 1.n 2 n n+1
Product Subclass 1 Introductory Text: Product Subclass 1 Background Information (e.g., history) Comparison of Methods Mechanistic Rationale Stereochemistry Scope Limitations and Problems Functional Group Compatibility Safety and Environmental Aspects Method 1 Introductory Text: Method 1 Background Information: Method 1 (e.g., history) Mechanistic Rationale Stereochemistry Scope Limitations and Problems Functional Group Compatibility Method 1: Scheme Method 1: Table of Examples Method 1: Experimental Procedure Method 1: Safety and Environmental Aspects Variation 1 Introductory Text: Variation Background Information: Variation 1 (e.g., history) Mechanistic Rationale Stereochemistry Scope Limitations and Problems Functional Group Compatibility Variation 1: Scheme Variation 1: Table of Examples Variation 1: Experimental Procedure Variation 1: Safety and Environmental Aspects Variation 2 Variation n Method 2 Variation 1 Variation n Method n Product Subclass 2 Product Subclass n Product Class 2 Product Class n Volume 2 Volume n Category 2 Volume n + 1 Category n Category 6
21
1.3.1.2 Rule 2
Classification of Products into Compound Categories Categories
All organic compounds are organized into six categories: Category 1: Category 2: Category 3: Category 4: Category 5: Category 6:
Organometallics, Hetarenes and Related Ring Systems, Four and Three Carbon-Heteroatom Bonds, Two Carbon-Heteroatom Bonds, One Carbon-Heteroatom Bond, All-Carbon Functions.
The priority among the categories corresponds to their order, with organometallics at the top. Category 1 focuses on organometallic and other metal-containing species which are important for synthetic transformations. The assignment of a functional group to Categories 35 is determined by the highest number of carbon-heteroatom (C-X) bonds to a single carbon atom, which can be either the carbon atom of attachment (e.g., C-OH, Category 5) or one in the functional group (e.g., CO2H, Category 3). This corresponds roughly to the standard classification by oxidation state into carbonic acid derivatives, carboxylic acid derivatives, ketone derivatives, etc. Example: Compounds with a carbon-metal bond formed are treated in Category 1. Organic compounds with a heteroatom-metal bond formed, however, are treated in Categories 25 with the corresponding heteroatom functional group; carboxylates, enolates and alcoholates, for example, are covered in Categories 3, 4 and 5, respectively.
1.3.1.3 Rule 3
General Rules for the Classification of Products within Categories Isolable Products
In general, only isolable products are included in the organizational scheme; intermediates are dealt with under mechanistic considerations for individual synthetic methods. Exceptions are key organometallic intermediates in reactions that form a metal-free product and important reactive intermediates that are formed in situ (e.g., some ylides and ketenes).
Rule 4
Heteroatoms
For the purposes of classification in Science of Synthesis, the following elements are considered to be heteroatoms: F, Cl, Br, I, O, S, Se, Te, N, P (Scheme 2). All other elements (except C and H) are classified as metals and their compounds with carbon are found in Category 1 (note that B, Si and As are classified with the metals).
22
Scheme 2 1
18 2 13 14 15 16 17
H Li Na
19 11 3
He Ne Ar Kr Xe Rn
86 54 36 18 10
Be Mg Ca Sr Ba Ra
88 56
#
B
3 4 5
23
C Si Ge Sn Pb
82 50 32 14
N
15
O
16
F Cl Br
53 35 17
12
10
11
12
Al Ga In Tl
81 49 31
13
20 38
Sc
39
21
Ti
22 40 72
Cr Mo W
106 74 42
24
Mn Tc Re
75 43
25
Fe Ru Os
76 44
26
Co Rh
77 45
27
Ni Pd Pt
78 46
28
Cu Ag Au
79 47
29
Zn Cd Hg
80 48
30
As Sb Bi
83 51
33
Se Te Po
84 52
34
Rb Cs Fr
#
37
Zr Hf
104
Nb Ta
105 73
41
55 87
57
La
Ir
At
85
89
Ac Unq Unp Unh

58 90 59 91 60 92 61 62 94 63 95 64 65 97 66 98 67 68 69 70 71
Lanthanide Series Actinide Series
Ce Th
Pr Pa
Nd U
Pm Np
93
Sm Pu
Eu Am
Gd Cm
96
Tb Bk
Dy Cf
Ho Es
99
Er Fm
100
Tm Md
101
Yb No
102
Lu
103
Lr
Rule 5
Multifunctional Compounds
In multifunctional compounds, the functional group produced by a given method determines the location of that compound in Science of Synthesis; other remote functional groups within this compound that remain unchanged are neglected in the classification, even if they have a higher priority. Exception: See Rule 10 below for the geminal attachment of two functional groups to one carbon.
Rule 6
Two or More Functional Groups
When two or more functional groups are produced at the same time, the assignment to one of the six categories is determined by the functional group with the highest priority.
Rule 7
C-X and C-C -Bonds
Functional groups containing C-X and C-C -bonds (e.g., C=C-X) are classified according to the highest number of both of these types of bonds to a single carbon atom, i.e. the C-C -bond is treated as an additional C-X bond. Example: Enol derivatives are found in the same category as ketones (Category 4). 1,2Dihaloalkenes (X-C=C-X) are also found in Category 4, while 1,1,2-trihaloalkenes (X-C=CX2) are found in Category 3. Within a category, the true C-X bond takes precedence over the C-C -bond, e.g. CX2 > C=C-X within Category 4 (see Rule 12).
Rule 8
Extended -Conjugation
Structural units with extended -conjugation are considered as a single functional group and are usually treated in a separate section (Scheme 3).
23
Example: Syntheses of ,-unsaturated ketones are found in Category 4, regardless of which part of the structural unit is produced by the method.
Scheme 3
OH O
,-unsaturated ketones from alcohols
O
,-unsaturated ketones from ketones
Cl
Rule 9
Conjugated Functional Group
When a conjugated functional group reacts, the classification is determined by the functional group in the product with the higher priority. Example: The reduction of the C=C bond of an ,-unsaturated ketone is covered under ketones from ,-unsaturated ketones and not under alkanes from alkenes.
Rule 10
The -Rule
For reactions at the carbon to a -functional group (FG1, e.g., arene, hetarene, CO2H, C=O, CN, C=C, Scheme 4) resulting in the formation of any second functional group (FG2, e.g., OH, SR)
Scheme 4
FG1C FG1CFG2
TMS
or transforming a second functional group (FG2, Scheme 5),

Scheme 5
FG1CFG2 FG1CFG3
O R CH2Br R
O CH2OAr
the choice of higher priority between FG1 and FG2 or between FG1 and FG3 in the product determines the classification. In Scheme 4, silicon has the higher priority, while in Scheme 5 the ketone has the higher priority. Example: All reactions to a heteroaromatic ring, except the formation of a C-M product, are found in Category 2 with the hetarene under consideration. Monohalogenation of ketones is covered under ketones (Category 4), not under halides (Category 5), while -alkoxycarbonylation of ketones is covered under esters (Category 3). Syntheses of allylic and benzylic alcohols are covered with alcohols in Category 5.
24
1.3.1.4
Product Classes within the Categories
The organization within the six categories is based on the following priority rules:
Rule 11
Priority Among Elements
All metals have a higher priority than all heteroatoms (see Rule 4). With this in mind, the groups of elements of the periodic table have decreasing priority from right to left and then within each group decreasing priority from top to bottom. Example: O > S > Se > N > P
Rule 12
Priority Among Functional Groups
Priority among functional groups is determined firstly by the highest number of true C-X (or C-M) bonds to a single carbon atom and secondly by the highest number of -bonds to a single carbon atom (i.e., sp > sp2 > sp3). If two functional groups are equal according to the above, further carbon atoms in the functional groups are compared until a difference is found. Example: C=X > C=C-X and CX > CC-X (more true C-X bonds to one carbon); CX > CX3 (hybridization); X-C=C-X > C=C-X (number of C-X bonds to further carbon atoms); C=C-C=C > C=C and CC > C=C=C (hybridization of further carbon atoms).
Rule 13
Priority for a Carbon-Bound Heteroatom
The priority for a carbon-bound heteroatom X is generally determined by the sequence -X-H > -X-M (metal priorities as above) > -X-C > -X-Y (priorities of heteroatoms Y as above) and the oxidation state of heteroatom X. The order in specific volumes, however, may deviate from this rule, based on the nature of the compound class under consideration. Therefore, the tables of contents of the individual volumes covering organosulfur, organonitrogen, and organophosphorus compounds should be referred to. Example: ROH > ROM > ROR > ROOH and R-SO3-H > R-SO2-H > RSOH.
1.3.1.5 Rule 14
Methods and Variations within the Product Classes Organization of Methods and Variations
Methods and variations within a given product class or product subclass are organized where applicable in the hierarchical fashion presented below (x: volume, y: product class, z: product subclass). The headings/subheadings are guidelines for the organization of the various methods, and need not be adopted verbatim in the text. For the purpose of prioritizing reactions involving more than one component (e.g., exchange and addition reactions), the component which is to be modified is defined as the one containing the functional group belonging to the product class y, irrespective of the priority of other groups involved (actively or passively) in the transformation. For methods which in most respects are similar (e.g., substitution reactions involving the transformation of identical highest priority components), chemical common sense should take precedence and further ordering is left to the discretion of the author and/or volume editor.
Synthesis by Substitution Of Hydrogen (includes oxidation C-H C-OH) Of Organometallic Groups
x.y.z.1 x.y.z.2

x.y.z.3 x.y.z.4
25
Of Carbon Functionalities (if two functionalities are involved, the one of highest rank decides) Of Heteroatoms Synthesis by Elimination Of Hydrogen Priority: (1) H2, (2) H-M, (3) H-R, (4) H-X Of Organometallic Groups (M-C or M-X) Of Carbon Functionalities Of Heteroatoms (includes Wittig reaction) Synthesis by Addition Reactions (includes C-C cleavage) Of Hydrogen Priority: (1) H2, (2) H-M, (3) H-R, (4) H-X Of Organometallic Groups (M-C or M-X) Of Carbon Functionalities Of Heteroatoms (includes carbonyl acetal) Synthesis by Rearrangement Synthesis with Retention of the Functional Group (e.g., introduction or elimination of a second group, chain elongation, transesterification) Organization of Methods and Variations within Category 1
x.y.z.5 x.y.z.6 x.y.z.7 x.y.z.8
x.y.z.9 x.y.z.10 x.y.z.11 x.y.z.12
x.y.z.13 x.y.z.14
Rule 15
The following points should be taken into consideration when preparing a manuscript for the organometallics category.
Product Class: For each metal there will be a separate product class. However, transition metals with closely related chemistry can be described in one product class to avoid redundancy of the methods described. The introductory texts for each product class should include problems of preparation, stability, and reactivity and be followed by a discussion on the scope of the reactions which employ the described product class, utility/versatility in organic synthesis, and whether the reaction is catalytic or stoichiometric. Product Subclass: Product classes will be divided into product subclasses depending on the ligands of the metal. Product subclasses should be ordered with descending hapticity of the ligands. Charged complexes should be ordered within product subclasses as follows: (1) neutral, (2) anionic, (3) radical anion, (4) radical, (5) radical cation, (6) cationic. It is recognized that the concept of charge of an organometallic species can in some cases only be applied to the extent possible, i.e. for defined conditions (e.g., for a defined polarity of the solvents). The oxidation state of the metal should be used for the description of the product subclasses. For each product subclass two aspects can be described: Synthesis of the Product Subclass and Applications of the Product Subclass in Organic Synthesis. For similar treatment within Categories 3 6, see Rule 17.
26
Synthesis of the Product Subclass: Methods should be organized according to the organizational principles described in Rule 14. Applications of the Product Subclass in Organic Synthesis: In this section typical methods for the use of the product subclass in organic synthesis can be described, if the product subclass in question is synthetically important. Reactions involving catalytic amounts of an organometallic complex or an uncharacterized intermediate should be given as methods. These methods usually give products that belong to other product classes within different categories of Science of Synthesis. These other product classes will also be discussed extensively in the appropriate category of Science of Synthesis, but in the organometallics category emphasis will be placed on the role of the organometallic complex. The organometallic volumes also contain inorganic compounds, metal compounds without a formal metalcarbon bond, that are significant for synthetic chemistry. The inorganic compound is conveniently covered together with true organometallics of similar structure (e.g., AlH3 with R2AlH). For those compounds that are readily available commercially, methods for their synthesis can be neglected such that only methods for their applications in organic synthesis are included. To the extent that an inorganic reagent is used mainly for metalation, then the principal treatment will come under the organometallic intermediate: its synthesis (using the inorganic reagent) and its further applications in organic synthesis. Ranking of applied methods should be carried out: 1. according to Rule 14 (preferred) 2. according to the product group being discussed (e.g., see Science of Synthesis, Volume 4, Section 4.4.12:
4.4.12 4.4.12.9 4.4.12.10 4.4.12.11 4.4.12.12
3.
according to the product produced (see Section 1.3.1.3 and Section 1.3.1.4)
Product Subclass 12: Haloorganosilanes Applications of Product Subclass 12 in Organic Synthesis Fluoroorganosilanes Chloroorganosilanes Bromoorganosilanes Iodoorganosilanes)
An example of this would be the synthesis of dialkylzinc compounds and the use of dialkylzinc compounds in the synthesis of secondary alcohols. In Science of Synthesis this would be dealt within the organometallics category as follows:
Category 1: Volume 3: Product Class: Product Subclass: Method x: Method x: Organometallics Compounds of Groups 12 and 11 (Zn, Cd, Hg, Cu, Ag, Au) Organometallic Complexes of Zinc Metal -Alkyl Homoleptic Complexes Synthesis of Product Subclass: Synthesis of Dialkylzinc Compounds Applications of Product Subclass in Organic Synthesis: Synthesis of Secondary Alcohols Using Dialkylzinc Compounds
There would also be a duplicate entry present in the one carbon-heteroatom bond category as follows:
Category 5: Volume 36: Product Class: Method x: Compounds with One Carbon-Heteroatom Bond Alcohols Secondary Alcohols Synthesis of Secondary Alcohols Using Transition Metals
27
The table of contents should take the following format:

Category 1: Organometallics Volume X Product Class Y: Organometallic Complexes of Metal X Product Subclass 1: MetalArene Complexes Synthesis of Product Subclass 1 Method 1 Applications of Product Subclass 1 in Organic Synthesis Method n Product Subclass 2: MetalTriene Complexes Synthesis of Product Subclass 2 Method 1 Applications of Product Subclass 2 in Organic Synthesis Method n Product Subclass 3: MetalDienyl Complexes Synthesis of Product Subclass 3 Method 1 Applications of Product Subclass 3 in Organic Synthesis Method n Product Subclass 4: MetalDiene Complexes Synthesis of Product Subclass 4 Method 1 Applications of Product Subclass 4 in Organic Synthesis Method n Product Subclass 5: MetalAllyl Complexes Synthesis of Product Subclass 5 Method 1 Applications of Product Subclass 5 in Organic Synthesis Method n Product Subclass 6: MetalAlkyne Complexes Synthesis of Product Subclass 6 Method 1 Applications of Product Subclass 6 in Organic Synthesis Method n Product Subclass 7: MetalAlkene Complexes Synthesis of Product Subclass 7 Method 1 Applications of Product Subclass 7 in Organic Synthesis Method n Product Subclass 8: MetalCarbene Complexes Synthesis of Product Subclass 8 Method 1 Applications of Product Subclass 8 in Organic Synthesis Method n Product Subclass 9: MetalCarbyne Complexes Synthesis of Product Subclass 9 Method 1 Applications of Product Subclass 9 in Organic Synthesis Method n Product Subclass 10: Metal -Alkyl Homoleptic Complexes Synthesis of Product Subclass 10
x x.y x.y.1 x.y.1.1 x.y.1.n x.y.2 x.y.2.1 x.y.2.n x.y.3 x.y.3.1 x.y.3.n x.y.4 x.y.4.1 x.y.4.n x.y.5 x.y.5.1 x.y.5.n x.y.6 x.y.6.1 x.y.6.n x.y.7 x.y.7.1 x.y.7.n x.y.8 x.y.8.1 x.y.8.n x.y.9 x.y.9.1 x.y.9.n x.y.10
28
x.y.10.1 x.y.10.n x.y.11 x.y.11.1 x.y.11.n x.y.12
x.y.12.1 x.y.12.n Rule 16
Method 1 Applications of Product Subclass 10 in Organic Synthesis Method n Product Subclass 11: Metal -Alkyl Non-Homoleptic Complexes Synthesis of Product Subclass 11 Method 1 Applications of Product Subclass 11 in Organic Synthesis Method n Product Subclass 12: Miscellaneous Complexes (i.e., carbonyl complexes, amine complexes, etc.) Synthesis of Product Subclass 12 Method 1 Applications of Product Subclass 12 in Organic Synthesis Method n Organization of Methods and Variations within Category 2
Category 2 includes fully unsaturated heterocycles with no sp3 carbon or heteroatoms not capable of conjugation, such as P5 or S6 in a five-membered ring. Compounds with a formal charge, such as pyrylium ion, are included. Compounds that satisfy the 4n + 2 rule via tautomeric forms and mesoionic compounds are also included. Systems that cannot be aromatic because of saturated carbon in the ring, such as 1,3-dioxine or oxete, as well as saturated or partially unsaturated heterocycles, are not covered in Category 2. Such systems are integrated into the coverage in Categories 35 where appropriate.
Science of Synthesis organizes hetarenes in the order of preference: 1. ring size, from smaller to larger, 2. number of heteroatoms, from less to more, 3. kind of heteroatoms in the order of preference: O, S, Se, Te, N, P, 4. valence of like heteroatoms, from higher to lower, such as P5 > P3 and S4 > S2, 5. annulated hetarenes directly after the corresponding monocyclic hetarene, e.g. oxazole, then benzoxazole, 6. (1) neutral, (2) anionic, (3) radical anion, (4) radical, (5) radical cation, (6) cationic.
Those fused hetarenes that are covered in Science of Synthesis as Product Classes or Subclasses are organized according to the ring size of the smallest hetarene component and the number and kind of heteroatoms in that ring, from less to more, as above for monocyclic hetarenes. When the number and kind of heteroatoms are the same, the order follows the lowest numbers in the name from left to right until a difference is found, i.e. 1,2,3 then 1,2,4 then 1,3,2 then 1,4,2 etc. When trivial names are used, which do not contain numbers in the name, the order follows the lowest numbers for the heteroatoms; e.g. isoxazole (1,2oxazole) then oxazole (1,3-oxazole). Coverage should concentrate on the synthesis of the heterocyclic system in question. The main subdivisions for a given Product Class or Subclass are Synthesis by Ring-Closure Reactions, Synthesis by Ring Transformation, Aromatization, and Synthesis by Substituent Modification, as shown below. The methods involving ring closure are organized according to the number and kinds of bonds formed; in cases of ambiguity arising from the presence of intermediates, it is at the discretion of the author to decide how many bonds are formed. The methods involving substituent modification are restricted to those relevant to the synthesis of specifically functionalized compounds. In the coverage of an annulated hetarene, the examples chosen to illustrate a given method could include not only the benzo derivative, but also other areno and hetareno
29
derivatives to the extent that this inclusion helps to show the scope and limitations of the method. This leads to the following general arrangement for a monocyclic hetarene:
x.y
x.y.1 x.y.1.1
x.y.1.2
x.y.1.3 x.y.1.4 x.y.1.5 x.y.1.6 x.y.1.7 x.y.1.8
x.y.2
x.y.3 x.y.4 x.y.4.1 x.y.4.1.1
x.y.4.1.2
x.y.4.1.3 x.y.4.1.4 x.y.4.2
x.y.4.2.1 x.y.4.2.2 x.y.4.2.3
Product Class Y Introductory Text Nomenclature, history, applications, reviews (including location in HoubenWeyl), structure (including tautomerism, ringchain equilibrium), stability (thermally, towards oxidation/reduction), reactivity (including acidity/basicity, ease of addition and substitution reactions), physical properties, spectroscopic characteristics, safety and environmental aspects Synthesis by Ring-Closure Reactions By Formation of Three Bonds [Priority: (1) Hetero-Hetero Bond, (2) Hetero-Carbon Bond, (3) Carbon-Carbon Bond; priority of heteroatoms follows Rule 4 and Rule 11] By Formation of Two Hetero-Hetero Bonds (includes cycloadditions; if more than one type of Hetero-Hetero Bond then further ranking according to Science of Synthesis priority rules; further subdivision according to starting material following Science of Synthesis priority rules, e.g. synthesis from CX4-, CX3-, CX2-, CX-hydrocarbon. Reactions involving a final aromatization step are also included here) By Formation of One Heteroatom-Heteroatom and One Heteroatom-Carbon Bond By Formation of Two Heteroatom-Carbon Bonds By Formation of Two C-C Bonds By Formation of One Heteroatom-Heteroatom Bond By Formation of One Heteroatom-Carbon Bond By Formation of One C-C Bond (order of subsections following the nomenclature of the heterocycle, i.e. C1C2 first, then C2C3, etc.) Synthesis by Ring Transformation [ring enlargement, formal exchange of ring members with retention of ring size, ring contraction; ranking of hetarenes according to the priorities given above] Aromatization (by Oxidation of Dehydro Compounds or Elimination Reactions) Synthesis by Substituent Modification Substitution of Existing Substituents Of Hydrogen [Priority: (1) H/D exchange, (2) metalation, (3) FriedelCrafts and the like, (4) halogenation, chalcogens, N, P. In tautomeric systems possible loss of the aromatic character.] Of Metals [Priority: (1) M H, (2) transmetalation (cross-reference to Category 1), (3) M C, (4) M heteroatom] Of Carbon Functionalities (e.g., decarboxylation dealkylation, following Science of Synthesis priority rules) Of Heteroatoms Addition Reactions (not involving ring modification since this should be included elsewhere, i.e. in the chapter on the ring system which is obtained) Protonation Addition of Organic Groups (e.g., N-alkylation) Addition of Heteroatoms (e.g., N-oxidation)
30
x.y.4.3 x.y.4.4
Rearrangement of Substituents Modification of Substituents [typically only at the -atom since modification at other sites would not be expected to be dependent on the heterocyclic ring system, e.g. oxidation at the -carbon; reactions converting an exocyclic double bond into an endocyclic double bond are also included here (Scheme 6), unless they are part of the ring-closure-reaction sequences covered in Section x.y.1]
Scheme 6
X XR
N H
N H
XR N H N
X = O, S, NR, CR2
Similarly, this leads to the following general arrangement for an annulated hetarene:
x.y
x.y.1 x.y.1.1 x.y.1.1.1
x.y.1.1.2
x.y.1.1.3 x.y.1.1.4 x.y.1.1.5 x.y.1.1.6 x.y.1.1.7 x.y.1.1.8
x.y.1.2 x.y.2
x.y.3 x.y.4 x.y.4.1
Product Class Y Introductory Text Nomenclature, history, applications, reviews (including location in HoubenWeyl), structure (including tautomerism, ring-chain equilibrium), stability (thermally, towards oxidation/reduction), reactivity (including acidity/basicity, ease of addition and substitution reactions), physical properties, spectroscopic characteristics, safety and environmental aspects Synthesis by Ring-Closure Reactions By Annulation to an Arene By Formation of Three Bonds [Priority: (1) Heteroatom-Heteroatom Bond, (2) Heteroatom-Carbon Bond, (3) C-C Bond; priority of heteroatoms follows Rule 4 and Rule 11] By Formation of Two Heteroatom-Heteroatom Bonds (includes cycloadditions; if more than one type of HeteroHetero Bond then further ranking according to Science of Synthesis priority rules; further subdivision according to starting material following Science of Synthesis priority rules, e.g. synthesis from CX4-, CX3-, CX2-, CX-hydrocarbon. Also reactions involving a final aromatization step are included here) By Formation of One Heteroatom-Heteroatom and One Heteroatom-Carbon Bond By Formation of Two Heteroatom-Carbon Bonds By Formation of Two C-C Bonds By Formation of One Heteroatom-Heteroatom Bond By Formation of One Heteroatom-Carbon Bond By Formation of One C-C Bond (order of subsections following nomenclature of the heterocycle, i.e. C1C2 first, then C2C3, etc.) By Annulation to the Heterocyclic Ring Synthesis by Ring Transformation [ring enlargement, formal exchange of ring members with retention of the ring size, ring contraction, ranking of hetarenes according to the priorities given above] Aromatization (by Oxidation of Dehydro Compounds or Elimination Reactions) Synthesis by Substituent Modification Substitution of Existing Substituents

x.y.4.1.1
31
x.y.4.1.2
x.y.4.1.3 x.y.4.1.4 x.y.4.2
x.y.4.2.1 x.y.4.2.2 x.y.4.2.3 x.y.4.3 x.y.4.4
Of Hydrogen [Priority: (1) H/D exchange, (2) metalation, (3) FriedelCrafts and the like, (4) halogenation, chalcogens, N, P. In tautomeric systems possible loss of the aromatic character.] Of Metals [Priority: (1) M H, (2) transmetalation (cross-reference to Category 1), (3) M C, (4) M heteroatom] Of Carbon Functionalities (e.g., decarboxylation dealkylation, following Science of Synthesis priority rules) Of Heteroatoms Addition Reactions (not involving ring modification since this should be included elsewhere, i.e. in the chapter on the ring system which is obtained) Protonation Addition of Organic Groups (e.g., N-alkylation) Addition of Heteroatoms (e.g., N-oxidation) Rearrangement of Substituents Modification of Substituents [typically only at the -atom since modification at other sites would not be expected to be dependent on the heterocyclic ring system, e.g. oxidation at the -carbon; reactions converting an exocyclic double bond into an endocyclic double bond are also included here (Scheme 7), unless they are part of the ring-closure-reaction sequences covered in Section x.y.1]
Scheme 7
X XR
N H
X = O, S, NR, CR2
N H
XR N H N
Rule 17
Organization of Methods and Variations within Categories 36
Categories 36 present the methods for the synthesis of organic compounds organized according to the functional group or groups prepared in the product. The underlying organizational principle is the oxidation state, i.e. all compounds are organized into product classes and product subclasses according to descending oxidation state (see Classification Principles, Section 1.3.1). Methods and variations within those product classes and subclasses are organized according to Rule 14 (Section 1.3.1.5). For some compounds, the principal interest to the synthetic chemist is their use as reagents, synthetic building blocks, catalysts, promoters, ligands or auxiliaries. Some reagents may also be highly reactive intermediates, which are not isolated (e.g., some ylides and ketenes). In such cases, synthesis of the product class (or product subclass) and applications of the product class (or product subclass) in organic synthesis should be described. The methods for their application will give products that belong to other product classes within other categories of Science of Synthesis, but in the section in question the emphasis will be placed on the role of the product class or product subclass covered.
32
Ranking of applied methods should be carried out: 1. according to the product produced (preferred; see Section 1.3.1.3 and Section 1.3.1.4) 2. according to Rule 14 3. according to the product being discussed (e.g., see Science of Synthesis, Volume 4, Section 4.4.12:
4.4.12 4.4.12.9 4.4.12.10 4.4.12.11 4.4.12.12
Product Subclass 12: Haloorganosilanes Applications of Product Subclass 12 in Organic Synthesis Fluoroorganosilanes Chloroorganosilanes Bromoorganosilanes Iodoorganosilanes)
The table of contents should take the following format:

x x.y x.y.1 x.y.1.1 x.y.1.1.1 x.y.1.1.n x.y.1.2 x.y.1.2.1 x.y.1.2.n x.y.2 x.y.n x.n
Volume x Product Class y Product Subclass 1 Synthesis of Product Subclass 1 Method 1 Method n Applications of Product Subclass 1 in Organic Synthesis Method 1 Method n Product Subclass 2 Product Subclass n Product Class n
1.3.1.6
Examples within Methods and Variations
The scope and limitations of a method or variation should be illustrated with several examples. The accompanying reaction scheme(s) should be made as general as possible by the use of X, R1, R2, etc. as substituents. If individual examples from a general scheme need to be discussed in the main text, then a table should be employed to present relevant data (e.g., R-groups, reaction conditions, solvents, chromatography conditions, chemical yield, optical purity, etc.) for the examples. If individual examples are not actively referred to in the main text, they should be presented in a scheme table if 8 or more examples are chosen, or they should simply be illustrated within the scheme itself if only a few examples are employed. Full details of the use, construction, and placement within the manuscript of tables, scheme tables, and schemes are given in the Information for Authors section.
Rule 18
Organization of Examples within Methods and Variations
Irrespective of the mode of presentation (vide supra), individual examples used to highlight methods and variations should be listed in an order which the author and/or volume editor believe best illustrates the scope and limitations of each method or variation (e.g., they may be listed in increasing order of substituent/reagent complexity, or in increasing order of chemical or optical yield).
Rule 19
Extent of Polymer Coverage
Polymers are considered to be an important class of compounds although they are not traditional target molecules for chemists working in the field of organic synthesis. However,
33
a thorough, synthetic and, comprehensive treatment of polymers is beyond the scope of the Science of Synthesis series. The focus of Science of Synthesis is on the synthesis of important monomeric molecular species. A compromise has been reached by covering the most important methods for polymer synthesis including introductory text together with leading references to more comprehensive reviews, handbooks and the original literature.
34
1.3.2
Complete Volume List of Science of Synthesis
Based on the classification principles outlined in Section 1.3.1, Science of Synthesis will be published as the following volumes:
Category Volume Category and Year Number Product Class Number of Number Responsible Volume Volumes of Pages Member of Editor(s) the Editorial Board 8 7052 1112 Trost Lautens
1 2001
18 1
Organometallics Compounds with Transition MetalCarbon -Bonds and Compounds of Groups 10 8 (Ni, Pd, Pt, Co, Rh, Ir, Fe, Ru, Os) Compounds of Groups 73 (Mn , Cr , V , Ti , Sc , La , Ac ) Compounds of Groups 12 and 11 (Zn, Cd, Hg, Cu, Ag, Au) Compounds of Group 15 (As, Sb, Bi) and Silicon Compounds Compounds of Group 14 (Ge, Sn, Pb) Boron Compounds Compounds of Groups 13 and 2 (Al, Ga, In, Tl, Be Ba) Compounds of Group 1 (Li Cs) Hetarenes and Related Ring Systems Fully Unsaturated Small-Ring Heterocycles and Monocyclic Five-Membered Hetarenes with One Heteroatom Fused Five-Membered Hetarenes with One Heteroatom Five-Membered Hetarenes with One Chalcogen and One Additional Heteroatom Five-Membered Hetarenes with Two Nitrogen or Phosphorus Atoms Five-Membered Hetarenes with Three or More Heteroatoms Six-Membered Hetarenes with One Chalcogen Six-Membered Hetarenes with One Nitrogen or Phosphorus Atom Six-Membered Hetarenes with Two Identical Heteroatoms Six-Membered Hetarenes with Two Unlike or More than Two Heteroatoms and Fully Unsaturated Larger-Ring Heterocycles
2002
1070
Noyori
Imamoto
2003 2001 2002 2004 2004 2004 2 2000
3 4 5 6 7 8 917 9
846 1060 864 840 660 600 9 9344 664
Ley Ley Thomas Regitz/ Schaumann Noyori Trost
ONeil Fleming Moloney Kaufmann/ Matteson H. Yamamoto Snieckus/ Majewski
Regitz
Maas
2000 2001
10 11
916 1160
Thomas Schaumann
Thomas Schaumann
2002 2003 2003 2004 2003 2003
12 13 14 15 16 17
796 1010 1010 720 1568 1500
Bellus Shinkai Thomas Regitz Shinkai Schaumann
Neier Storr/Gilchrist Thomas Black Y. Yamamoto Weinreb
35
Volume Editor(s)
Category Volume Category and Year Number Product Class
Number of Number Responsible Volumes of Pages Member of the Editorial Board 7 5220 1080 480 960 Ley Shinkai Jacobsen
3 2005 2004 2005
1824 18 19 20
Compounds with Four and Three Carbon-Heteroatom Bonds Four Carbon-Heteroatom Bonds: X-CX, X=C=X, X2C=X, CX4 Three Carbon-Heteroatom Bonds: Nitriles, Isocyanides, and Derivatives Three Carbon-Heteroatom Bonds: Acid Halides; Carboxylic Acids and Acid Salts; Esters, Polyesters, and Lactones; Peroxy Acids and R(CO)OX Compounds; R(CO)X, X = S, Se, Te Three Carbon-Heteroatom Bonds: Amides and Derivatives; Polyamides and Peptides; Lactams Three Carbon-Heteroatom Bonds: Thio-, Seleno-, and Tellurocarboxylic Acids and Derivatives; Imidic Acids and Derivatives; Ortho Acid Derivatives Three Carbon-Heteroatom Bonds: Ketenes and Derivatives Three Carbon-Heteroatom Bonds: Ketene Acetals and Yne-X Compounds Compounds with Two Carbon-Heteroatom Bonds Aldehydes Ketones Heteroatom Analogues of Aldehydes and Ketones Quinones and Heteroatom Analogues Acetals: Hal/X and O/O, S, Se, Te Acetals: O/N, S/S and S/N and Higher Heteroatom Analogues Arene-X Compounds X-Ene-X and Ene-O Compounds Ene-X Compounds (X O)
Knight Murahashi Panek
2005
21
720
Shinkai
Weinreb
2005
22
540
Thomas
Charette
2005 2005 4 2006 2004 2004 2006 2006 2006 2007 2007 2006
23 24 2533 25 26 27 28 29 30 31 32 33
720 720 9 6180 480 820 680 600 840 600 960 720 480
Bellus Schaumann
Danheiser de Meijere
Schaumann Thomas Bellus Bellus Ley Noyori Bellus Schaumann Trost
Brckner Cossy Padwa Griesbeck Warriner Otera
36
Category Volume Category and Year Number Product Class
Number of Number Responsible Volumes of Pages Member of the Editorial Board 9 7560 480 720 960 960 840 1080 960 Ley Schaumann Thomas Jacobsen Shinkai Noyori Schaumann
Volume Editor(s)
5 2006 2007 2007 2007 2007 2008 2008
3442 34 35 36 37 38 39 40
Compounds with One Carbon-Heteroatom Bond Fluorine Chlorine, Bromine, and Iodine Alcohols Ethers Peroxides, Inorganic Esters Sulfides, Selenides, and Tellurides Amines, Ammonium Salts, Haloamines, Hydroxylamines, Hydrazines, Triazanes, and Tetrazanes Nitro, Nitroso, Azo, Azoxy, and Diazonium Compounds, Azides, Triazenes, and Tetrazenes Organophosphorus Compounds Compounds with All-Carbon Functions Polyynes, Arynes, Enynes, and Alkynes Cumulenes and Allenes Arenes, Quasiarenes, Annulenes, and Polyenes 1,3-Dienes Alkenes Alkanes 6
Percy Kambe
2008
41
960
Shinkai
2007 6 2008 2008 2007 2008 2008 2008
42 4348 43 44 45 46 47 48
600 4200 720 480 840 600 960 600
Trost
Vedejs
Thomas Bellus Shinkai Trost Jacobsen Schaumann
Science of Synthesis will be published in a total number of 48 volumes, which will contain approximately 35 000 pages. It is estimated that Science of Synthesis will contain 5000 methods, 10 000 variations, 15 000 reaction schemes, and 15 000 tables. Science of Synthesis will cover ca. 150 000 reactions.
37
Information for Authors
39
Table of Contents
1 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9
Information for Authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
41 41
Disposition of the Manuscript . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Guidelines for Text . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Guidelines for References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Guidelines for Tables and Scheme Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Guidelines for Formulas and Schemes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 Guidelines for Figures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Delivery of the Manuscripts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Guidelines for the Preparation of the Manuscripts on Disks . . . . . . . . . . . . . . . . . . . 59
An updated version of Information for Authors can be found under: www.science-of-synthesis.com

1
41
The publication of Science of Synthesis as an electronic version demands absolute consistency of structure and style for the manuscripts. Authors are therefore requested to carefully read and follow the instructions for authors. Furthermore, manuscripts of the appropriate length and style will help to reduce costs and time-consuming editing. This will guarantee the economical and timely publication of Science of Synthesis, thus helping to cover the market worldwide. Only manuscripts perfect in style will be suitable for the production of the electronic version of Science of Synthesis. Manuscripts which are not written according to these guidelines will not be considered for publication and will be sent back to authors for redrafting. Electronic manuscripts conforming to these guidelines will result in minimum additional work for authors after submission. Authors are strongly encouraged to contact the editorial office (see Section The People) concerning all aspects of the manuscripts and to clarify any further questions. Science of Synthesis is scheduled to be completed in less than 10 years and will then be updated constantly. If a volume is delayed due to pending manuscripts its scientific impact will significantly decrease. We therefore must insist on the timely delivery of manuscripts.
1.1
General Criteria
question must be selected, their scope and limitations should be summarized and they should be illustrated by proven general or typical methods. Other methods or variations are to be covered in less detail. Further examples for the methods and variations should be summarized in tables. Each method and variation is to be highlighted by a corresponding scheme and an experimental procedure. New aspects of former methods should be extended. The authors should judge the relative merits of different synthetic methods. This should, if possible, result in a ranking of all methods for the product in question. Books, journals, and the patent literature must be considered equally. References to patents should be given whenever they contain relevant information. The authors should not hesitate to contact industrial chemists for procedures reported in patents. For free patent abstracts see www.qpat.com and www.uspto.gov. Care must be taken when evaluating the usefulness of such abstracts since they often give, by necessity, only very general information. Other useful addresses for patent information are www.european-patent-office.org (the European Patent Office), www.wipo.org (Patent Cooperation Treaty, the World Intellectual Property Organization, patent information and patent law), and www.questel.orbit.com (Questel and Orbit search databases and services). IBMs intellectual property resource page (www.patents.ibm.com/respage) provides a useful listing of many patent-related services available online. A useful reference on patent and Markush structure searching is Simmons, E. S., Drug Discovery Today, (1998) 3, 52. For all methods, references to the pertinent literature must be given. Excessive citation of semirelevant literature should be avoided. Articles written in the style of monographs or textbooks do not comply with the requirements of Science of Synthesis. The manuscript must be written according to the organizational principles as explained in the Editorial Description and Sample Chapter of Science of Synthesis. The sample chapter helps illustrate the editorial style points used and the application of the organizational principles of Science of Synthesis. It is requested, at the discretion of the volume editor, that part of the article should be prepared and submitted by the author to the volume editor and the editorial office for approval.
Science of Synthesis will critically evaluate all existing methods in organic and organometallic chemistry. The most important molecular transformations for the product class in
42
This process will ensure that the individual contribution fits into the general concept of Science of Synthesis. Since Science of Synthesis places emphasis on the synthetic methods of organic chemistry, mechanism should be discussed if mechanistic aspects are important to explain the occurrence of different products, solvent effects or the stereochemical outcome of a reaction. Authors are encouraged to specifically discuss if a described method has proven to be useful for solid-phase reactions.
1.2
Disposition of the Manuscript
number of pages for each volume. The authors are asked to contact the volume editor and the editorial office if their manuscripts differ from the agreed length of the manuscript. For estimating the final length of a contribution, the following general rules should be used (assuming that the author has used the document template): 1 typewritten page = 24 lines of 75 characters 3 typewritten pages = 1 printed page (without formulas and schemes) 2 typewritten pages = 1 printed page (with formulas and schemes)
1.2.1
For each volume the editor and the editorial office will specify a general outline which will serve as a guideline to all authors. Authors will be solicited by the volume editor. Authors will then submit for approval to the volume editor a table of contents according to the general outline. The volume editors and the authors are requested not to exceed the given
Organization of the Manuscripts for Science of Synthesis
The authors are requested to follow this general outline for their manuscripts: 1. Author (please give full name, postal address, phone number, fax number and e-mail address). 2. Table of Contents. 3. Text (including tables): Product Class, Product Subclass, Method, Variation. 4. References. 5. Notes to the volume editors or editorial office (comments or additions to the text). 6. Formulas and schemes. 7. Figures (graphs, drawings of apparatus). The author will write a contribution for a given category and product class and will then organize this manuscript in collaboration with the volume editor and the editorial office into product subclasses, methods, and variations. It is required that authors strictly adhere to the organizational scheme given in the Editorial Description of Science of Synthesis. Authors are encouraged to write the introductory texts to the different parts of their manuscripts in the style of a review. These parts should give a general introduction which will help readers to appreciate and understand details of the later-described methods and variations. However, all other parts of the manuscript have a strictly modular organization and should include only information of interest for the given section.
43
1.3 1.3.1
Guidelines for Text Format of Texts
Authors must produce their text with word processors. Authors are asked to use the document template (file: scisynth.dot) for their word processors which will be provided by the editorial office (see Section 1.9). Updated versions of the document template can be found under www.science-of-synthesis.com. Additional macros or word processor programming must not be used. The text should be typed with 1.5 times spacing (at least 5 mm between lines) in all parts of the manuscript (including references, notes, figure captions, and tables) and wide margins (ca. 2 cm at top, bottom, left- and right-hand side of each page). We recommend ca. 75 characters per line in a large proportional script (e.g., 12 point Times New Roman). High quality A4 size paper (21.0 29.7 cm, 8.3" 11.6") or US Letter size paper (21.7 27.9 cm, 8.5" 11") should be used. The pages should only be printed on one side. The highest quality for printing should be used. Underlining, indentations, and block capitals should be avoided. Boldface and italic fonts should be used according to the instructions [e.g., amine 6; J. Org. Chem., (1973) 38, 3438]. Handwritten additions and underlining, except for volume editors comments, etc., are to be avoided. References, notes, formulas, schemes, and figures (in this order) should be included at the end of the manuscript. Tables should be included in the appropriate position in the body of the text. All pages including authors address, contents, text, references, notes, and tables must be numbered consecutively. Tables, schemes, formulas, and figures should be numbered with Arabic numbers, not Roman numerals.
1.3.2
Style of the Manuscripts
All parts of Science of Synthesis will be written in English. American spelling according to Websters Dictionary [Merriam-Webster: Springfield MA, (1990)] will be used throughout Science of Synthesis. Authors not fluent in idiomatic English are strongly encouraged to ask fluent colleagues for assistance [see also: Schoenfeld, R. The Chemists English, VCH: Weinheim, (1990)]. For style of the manuscripts the ACS Style Guide [The ACS Style Guide, 2nd ed.; Dodd, J. S., Ed.; American Chemical Society: Washington D.C., (1997)] should be consulted. Authors for Science of Synthesis should produce their manuscripts in a style as concise as possible and yet deliver a complete work. Authors should indicate trademarks and registered trademarks by capitalization of the first letter. All parts of the manuscript should be written in the present or relevant tense, except for the experimental procedures which should be written in the past tense.
1.3.3
Nomenclature
In Science of Synthesis, systematic names will be given only to selected examples. Correct nomenclature should be used, based on the rules of IUPAC [see: A Guide to IUPAC Nomenclature of Organic Compounds: Recommendations 1993, Blackwell Scientific: Oxford, (1993)]. Whilst the IUPAC system is preferred whenever possible, names based on the systematic rules adopted by Chemical Abstracts (Appendix IV of the current Chemical Abstracts Index Guide) will be accepted if necessary, on the understanding that they will in most cases be converted by the editorial office into the appropriate IUPAC-approved form. Do not use a mixture of both systems, either within the same name or anywhere within the manuscript. An exception is the naming of ring systems, whose names and numberings may be taken or derived from the Ring Systems Handbook [American Chemical Society: Columbus OH, (1988) and supplements]. For biochemical nomenclature see: Compendium of Biochemical and Related Documents, Portland Press: London, (1992). Nomenclature
44
for inorganic compounds is provided by the corresponding IUPAC rules [Nomenclature of Inorganic Chemistry, 1970, Butterworths: London, (1971), and Recommendations, 1990, Blackwell Scientific: Oxford, (1990)]. In order to facilitate the construction of IUPAC- or CAS-approved names, authors are advised to use a dedicated software program such as ACD/Name (Advanced Chemistry Development Inc., Toronto; http://www.acdlabs.com/ products/name_lab/name/), which is utilized by our editorial office. Names of common reagents and solvents are to be retained, e.g. diethyl ether. Trivial names should be avoided unless they offer a distinct advantage over the corresponding systematic name or unless used by prior agreement with the volume editor and the editorial office. For classes of complex natural compounds, such as carbohydrates, peptides, or steroids, the most common name should be given. Compounds which are not named or have long names should be referred to unambiguously as amine 2 or thioester 14. In matters of style, i.e. which words or prefixes are hyphenated, italicized, capitalized, etc., consult the ACS Style Guide [The ACS Style Guide, 2nd ed.; Dodd, J. S., Ed.; American Chemical Society: Washington D.C., (1997)].
1.3.4
Units
Metric units (SI) should be used throughout the text. However, for pressure and for temperature, Torr/atm/Pa and 8C are to be used, respectively [note: 1013.25 mbar = 760 Torr = 101 325 Pa = 14.696 psi]. The unit kcal will also be accepted.
1.3.5
Abbreviations
The use of abbreviations is recommended in tables, formulas, schemes and experimental procedures, but not in titles or text. Common abbreviations used in Science of Synthesis are given in the following tables:
Chemical Name Used in Text Abbreviation Used in Tables and on Arrow in Schemes RAMP SAMP CAN AIBN BBA TEBAB TEBAC BSA 9-BBNH BMS NBS TBDMSCl TBPB CSA CSI Abbreviation Used in Experimental Procedures RAMP SAMP CAN AIBN BBA benzyltriethylammonium bromide benzyltriethylammonium chloride BSA 9-BBNH BMS NBS TBDMSCl tert-butyl peroxybenzoate CSA chlorosulfonyl isocyanate
(R)-1-amino-2-(methoxymethyl)pyrrolidine (S)-1-amino-2-(methoxymethyl)pyrrolidine ammonium cerium(IV) nitrate 2,2-azobisisobutyronitrile barbituric acid benzyltriethylammonium bromide benzyltriethylammonium chloride N,O-bis(trimethylsilyl)acetamide 9-borabicyclo[3.3.1]nonane boranemethyl sulfide complex N-bromosuccinimide tert-butyldimethylsilyl chloride tert-butyl peroxybenzoate 10-camphorsulfonic acid chlorosulfonyl isocyanate

Chemical (cont.) Abbreviation Used in Tables and on Arrow in Schemes MCPBA NCS TMSCl DABCO DBN DBU DBPO dba DBAD DDQ DCME DCC DAST DEAD DET BINAL-H DIBAL-H DIPT DME DMA DMAD Me2N(CH2)2OH DMAP DMF DMS DMSO DTBP DMPU EDA edta HMPA HMPT MeI NIS LDA LiHMDS LICA Abbreviation Used in Experimental Procedures MCPBA NCS TMSCl DABCO DBN DBU dibenzoyl peroxide dba di-tert-butyl azodicarboxylate DDQ DCME DCC DAST DEAD DET BINAL-H DIBAL-H DIPT DME DMA DMAD
45
Name Used in Text
3-chloroperoxybenzoic acid N-chlorosuccinimide chlorotrimethylsilane 1,4-diazabicyclo[2.2.2]octane 1,5-diazabicyclo[4.3.0]non-5-ene 1,8-diazabicyclo[5.4.0]undec-7-ene dibenzoyl peroxide dibenzylideneacetone di-tert-butyl azodicarboxylate 2,3-dichloro-5,6-dicyanobenzo1,4-quinone dichloromethyl methyl ether dicyclohexylcarbodiimide N,N-diethylaminosulfur trifluoride diethyl azodicarboxylate diethyl tartrate 2,2-dihydroxy-1,1-binaphthyllithium aluminum hydride diisobutylaluminum hydride diisopropyl tartrate 1,2-dimethoxyethane dimethylacetamide dimethyl acetylenedicarboxylate 2-(dimethylamino)ethanol 4-(dimethylamino)pyridine dimethylformamide dimethyl sulfide dimethyl sulfoxide di-tert-butyl peroxide 1,3-dimethyl-3,4,5,6-tetrahydropyrimidin-2(1H)-one ethyl diazoacetate ethylenediaminetetraacetic acid hexamethylphosphoric triamide hexamethylphosphorous triamide iodomethane N-iodosuccinimide lithium diisopropylamide lithium hexamethyldisilazanide lithium isopropylcyclohexylamide
2-(dimethylamino)ethanol DMAP DMF DMS DMSO DTBP DMPU EDA edta HMPA HMPT MeI NIS LDA LiHMDS LICA
46
Chemical
(cont.)
Name Used in Text
Abbreviation Used in Tables and on Arrow in Schemes LTMP lut MAD MEK NMM NMO NMP MVK PEa NPM PPA PPE KHMDS pyridineb PCC PDC PPTS Red-Al TBAB TBACl TBAF TBAI TCNE THF THP TMP TMANO TMEDA TosMIC TEBAB TEBAC TFA TFAA TMSCN
Abbreviation Used in Experimental Procedures LTMP lut MAD methyl ethyl ketone NMM NMO NMP methyl vinyl ketone petroleum ether NPM PPA polyphosphate ester KHMDS pyridine PCC PDC PPTS Red-Al TBAB TBACl TBAF TBAI tetracyanoethene THF THP TMP trimethylamine N-oxide TMEDA TosMIC TEBAB TEBAC TFA TFAA TMSCN
lithium 2,2,6,6-tetramethylpiperidide lutidine methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) methyl ethyl ketone methylmaleimide 4-methylmorpholine N-oxide 1-methylpyrrolidin-2-one methyl vinyl ketone petroleum ether N-phenylmaleimide polyphosphoric acid polyphosphate ester potassium hexamethyldisilazanide pyridine pyridinium chlorochromate pyridinium dichromate pyridinium 4-toluenesulfonate sodium bis(2-methoxyethoxy)aluminum hydride tetrabutylammonium bromide tetrabutylammonium chloride tetrabutylammonium fluoride tetrabutylammonium iodide tetracyanoethene tetrahydrofuran tetrahydropyran 2,2,6,6-tetramethylpiperidine trimethylamine N-oxide N,N,N,N-tetramethylethylenediamine tosylmethyl isocyanide triethylbenzylammonium bromide triethylbenzylammonium chloride trifluoroacetic acid trifluoroacetic anhydride trimethylsilyl cyanide
a b
Used to save space; abbreviation must be defined in a footnote. py used on arrow in schemes.
47
Ligands acetylacetonato 2,2-bipyridyl 1,2-bis(dimethylphosphino)ethane 2,3-bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene 2,2-bis(diphenylphosphino)-1,1-binaphthyl 1,2-bis(diphenylphosphino)ethane 1,1-bis(diphenylphosphino)ferrocene bis(diphenylphosphino)methane 1,3-bis(diphenylphosphino)propane 1,4-bis(diphenylphosphino)butane 2,3-bis(diphenylphosphino)butane bis(salicylidene)ethylenediamine cyclooctadiene cyclooctatetraene cyclooctatriene 5-cyclopentadienyl dibenzylideneacetone 6,6-dimethylcyclohexadienyl 2,4-dimethylpentadienyl ethylenediaminetetraacetic acid isopinocamphenyl 2,3-O-isopropylidene-2,3-hydroxy-1,4bis(diphenylphosphino)butane norbornadiene (bicyclo[2.2.1]hepta-2,5-diene) 5-pentamethylcyclopentadienyl Radicals acetyl aryl benzotriazol-1-yl benzoyl benzyl benzyloxycarbonyl benzyloxymethyl 9-borabicyclo[3.3.1]nonyl tert-butoxycarbonyl butyl sec-butyl tert-butyl tert-butyldimethylsilyl tert-butyldiphenylsilyl cyclohexyl 3,4-dimethoxybenzyl ethyl ferrocenyl 9-fluorenylmethoxycarbonyl isobutyl mesityl mesyl 4-methoxybenzyl (2-methoxyethoxy)methyl Ac Ar Bt Bz Bn Cbz BOM 9-BBN Boc Bu s-Bu t-Bu TBDMS TBDPS Cy DMB Et Fc Fmoc iBu Mes Ms PMB MEM acac bipy DMPE NORPHOS BINAP dppe (not diphos) dppf dppm dppp dppb Chiraphos salen cod cot cte Cp dba dmch dmpd edta Ipc Diop nbd Cp
48
Radicals
(cont.) MOM Me PNB Ph Phth NPhth Pr iPr THP Tol Ts TES Tf TIPS TMS SEM Tr
methoxymethyl methyl 4-nitrobenzyl phenyl phthaloyl phthalimido propyl isopropyl tetrahydropyranyl tolyl tosyl triethylsilyl triflyl, trifluoromethanesulfonyl triisopropylsilyl trimethylsilyl 2-(trimethylsilyl)ethoxymethyl trityl [triphenylmethyl] General absolute anhydrous aqueous boiling point catalyst catalytic chemical shift circular dichroism column chromatography concentrated configuration (in tables) coupling constant day density decomposed degrees Celsius diastereomeric ratio dilute electron-donating group electron-withdrawing group electrophile enantiomeric excess enantiomeric ratio equation equivalent(s) flash-vacuum pyrolysis gas chromatography gas chromatography-mass spectrometry gasliquid chromatography gram highest occupied molecular orbital high-performance liquid chromatography hour(s)
CD no abbreviation concd Config J d d dec 8C dr dil EDG EWG E ee er eq equiv FVP GC GC/MS GLC g HOMO HPLC h
abs anhyd aq bp no abbreviation cat.
49
General (cont.) infrared in situ in vacuo lethal dosage, e.g. to 50% of animals tested liquid liter lowest unoccupied molecular orbital mass spectrometry medium-pressure liquid chromatography melting point milliliter millimole(s) millimoles per liter minute(s) mole(s) nuclear magnetic resonance nucleophile optical purity phase-transfer catalysis proton NMR quantitative reference (in tables) retention factor (for TLC) retention time (chromatography) room temperature saturated solution temperature (in tables) thin layer chromatography ultraviolet volume (literature) via vide infra vide supra yield (in tables) IR in situ in vacuo LD50 liq L LUMO MS MPLC mp mL mmol mM min mol NMR Nu op PTC 1 H NMR quant Ref Rf tR rt sat. soln Temp (8C) TLC UV Vol. via vide infra vide supra Yield (%)
1.3.6
Experimental Procedures
Experimental procedures should follow the style of the Thieme journal SYNTHESIS. The experimental procedure itself is entitled with the product, or general classification of the product name (see example below), and must contain all the information necessary to guarantee reproducibility. This should be followed, where applicable, by the specification of: (1) General Procedure: A generalized version of a widely applicable experimental procedure. (2) Typical Procedure: A specific example of a widely applicable experimental procedure. (3) Single Procedure: Single procedures are not to be labeled but are defined as follows: A specific experimental procedure for a single compound which is not applicable to similar compounds or for which the scope has not been studied.
50
As the criteria used to assess experimental procedures include range of applicability, the majority of procedures will be Typical or General Procedures; non-typical procedures for individual examples are restricted to unique methods that are particularly useful for the synthesis of one synthetically important compound or intermediate. The author should indicate aspects of the procedure which are particularly critical to success, including any new observations on or adaptations of older literature methods. Available details of workup should be included. Authors are encouraged to specifically discuss if a described method has proven to be useful for solid-phase reactions. Physical or spectroscopic data should be given only to a very limited extent. Authors should choose significant spectroscopic data (e.g., shifts of important NMR signals) of the products. These data should help chemists to repeat the procedures and identify the products. The slash symbol is to be used for: (1) surfaces, e.g. Pd/C; (2) alloys and amalgams, e.g. 5% Na/Hg, Na/K (1:1); (3) solvent mixtures, e.g. EtOH/MeOH (95:5); (4) reagent concentrations, e.g. 2% HCl/H2O; (5) single reagents, e.g. Li/NH3. Each procedure title should take the format shown in Section 1.3.6.1 below. This includes the compound number, written in parentheses after the compound name, followed by a colon and then the reference number in superscript square brackets (see Section 1.4). For electronic processing reasons, compound numbers in procedure titles only should not be emboldened. Write procedures in the past tense and include the weight, number of moles, volume, etc., in brackets after the name of the substances or solvents. Avoid starting sentences with numbers, wherever possible.
1.3.6.1
Example of an Experimental Procedure
A soln of crude 3b (7.3 g, from 15 mmol of 2b) in THF (40 mL) was cooled in an ice bath and NaOH (1.5 g, 37 mmol) in H2O (8 mL) was added, followed by dropwise addition of H2O2 (30%, 5 mL, 50 mmol). The mixture was kept at 0 8C for 1 h, then at 25 8C for 6 h, during which time a pasty, colorless precipitate formed. The mixture was treated with Et2O (50 mL) and filtered. The aqueous phase was separated and extracted with Et2O (3 30 mL) and the combined organic phase was dried (MgSO4) and concentrated. The gel-like residue was flash chromatographed [silica gel, petroleum ether (bp 3040 8C)/ Et2O 9:1] to give the labile intermediate; yield: 3.98 g (76%); this was reacted further without characterization. To a soln of the intermediate (3.6 g, 10 mmol) in CH2Cl2 (10 mL) was added iPr2NEt (1.2 g, 10 mmol), followed by chloromethoxymethane (0.89 g, 11 mmol). The mixture was stirred for 1 h at 0 8C and 15 h at 25 8C, then concentrated. The resultant residue was treated with ice-cold 2 M HCl (10 mL) and extracted with petroleum ether (bp 3040 8C, 2 20 mL). Concentration of the organic phase (102 mbar) gave the product as a colorless solid; yield: 3.7 g (92%); mp 130 8C.
1.3.7
Tributyl[(R)-1-methoxymethoxy-2-methylpropyl]stannane (4b):[25]
Safety
Chemicals are associated with two types of hazard: hazards that are a direct result of the physical or reactive properties of a chemical; and hazards posed by the effect of a chemical on biological systems. Flammability and the stability of a chemical in air or towards water may be included in the first group, while the carcinogenic potential of a chemical or its effect on the reproductive system are health hazards due to the biological properties of a chemical. The different hazardous properties that authors should take into consideration when evaluating experimental procedures are as follows: Physical and reactive chemical hazards: Flammability Explosive properties
51
Stability in air or in contact with water (pyrophoric and water-reactive compounds) Incompatibility with commonly-available chemicals and reagents Potential for peroxidation Oxidizing or reducing properties Storage properties
Health effects of chemicals: Known human carcinogens and probable human carcinogens according to the International Agency for Research on Cancer (IARC) classifications Known human teratogens Chemicals known to have an effect on human reproduction Chemicals that are irritants to the skin, eyes and respiratory system (data from human exposure or animal tests) Chemicals that are corrosive to the skin, eyes and respiratory system (data from human exposure or animal tests) Skin sensitizers Chemicals that are highly toxic as a result of some specific pharmacological mechanism (e.g., the potent neurotoxin tetrodotoxin) Hazard information may be found in:
Rhodes, P. H., The Organic Chemists Desk Reference, Chapman & Hall: London, (1995); pp 112126. Urben, P. G. (Ed.), Brethericks Handbook of Reactive Chemical Hazards, 6th Edition, Butterworth-Heinemann: Oxford, (1999). Luxon, S. G. (Ed.), Hazards in the Chemical Laboratory, 5th Edition, Royal Society of Chemistry: Cambridge, (1992).
It is important that authors discuss potential hazards of the described compounds. Furthermore, the methods described in Science of Synthesis should be discussed in terms of atom economy, as well as their possible impact on the environment. If toxic solvents (e.g., chloroform), toxic catalysts [e.g., mercury(II) chloride], toxic reagents (e.g., phosgene) or any other hazardous compounds are used or recommended in certain experimental procedures, alternatives should be discussed. Safety guidelines should be given for dangerous compounds or procedures. Warnings should be given using the following format:
CAUTION: Hexamethyltungsten(VI) is known to decompose explosively. Proper safety precau-
tions should be taken during its synthesis, storage, and handling.

Copyright
1.3.8
It is the responsibility of the author to obtain copyright permission for any figures (see Section 1.7), tables, schemes, or textual information from another source that is to be reproduced in his/her Science of Synthesis contribution. Copyright infringement is usually the case when text or figures are taken from books [e.g., Brandsma, L.; Verkruijsse, H. D., Synthesis of Allenes and Cumulenes, Elsevier: Amsterdam, (1981)] or serial publications [e.g., Organic Synthesis, Coll. Vol. VI, Noland, W. E., Ed; Wiley: New York, (1988)] without significant adaptation of the original version. In the case of reproduction of experimental procedures and schemes from journal publications a full citation in the references section is sufficient acknowledgement of copyright ownership. The copy editor assigned to each manuscript will ask the author to apply for copyright if they have not already done so, and will add the appropriate credit line. If there is an appropriate and adequate alternative to a reference requiring copyright then this reference should be substituted, or if a similar procedure is available then this procedure should be used instead of that under
52
copyright. If the author cannot obtain permission then the text will be deleted. Permission request forms are in the authors information package or can be obtained from the editorial office. The editorial office will help authors to direct their applications to the appropriate departments.
1.4
Guidelines for References
References should be placed collectively at the end of the text (in Part 4 of your manuscript, entitled References) and numbered consecutively within chapters, with no subdivisions such as [3 a], [3 b], [3 c], etc. Each reference number should contain only one citation. Use one reference number for each reference only, do not repeat a reference citation with a new number every time it appears. References to literature appear in the text, tables, and scheme headings as superscript 10 pt Arabic numerals in square brackets following the punctuation, e.g. This is a sample sentence.[1] Authors should include reference numbers for schemes and figures in the scheme/figure caption; reference numbers for tables should be included in the tables as the final column. To facilitate the production of the electronic version of Science of Synthesis, the references do not follow the rules as given in the ACS Style Guide [The ACS Style Guide, 2nd ed.; Dodd, J. S., Ed.; American Chemical Society: Washington D.C., (1997)]. Authors are requested to ensure the accuracy of the references. Journals: provide the names of all authors. Do not use et al.. A comma should be used to separate the name of the last author and the title of the journal. Use the journal abbreviation in accordance with Chemical Abstracts [Chemical Abstracts Service Source Index (CASSI) 19071994 Cumulative and its supplements]. Science of Synthesis will support the citation of electronic journals. As soon as general document identifiers for journal articles are available, the editorial office will include them to allow users direct access to these references. Books: see sample references for books with and without editors. Patents: see sample reference. Important patents should be read in the original versions as Chemical Abstracts reports often do not contain all important details. Databases: reference can also be given to records in databases (e.g., spectra from databases like Specinfo). If reference is made to a patent or less readily available journal, the Chemical Abstracts reference or the English translation [e.g., J. Gen. Chem. USSR (Engl. Transl.)] should also be cited. The use of a reference-managing program (e.g., EndNote) is strongly recommended.
1.4.1
[1] [2]
Sample References
[3] [4]
[5]
[6]
[7]
[8] [9]
Trost, B. M.; Biddlecom, W. G., J. Org. Chem., (1973) 38, 3438. Hoppe, D.; Gonschorrek, C.; Egert, E.; Schmidt, D., Angew. Chem., (1985) 97, 706; Angew. Chem., Int. Ed. Engl., (1985) 24, 700; footnote 12. Pratt, A. J.; Thomas, E. J., J. Chem. Soc., Perkin Trans. 1, (1989), 1521. Abdrakhmanov, I. B.; Mustafin, A. G.; Tolstikov, G. A., Izv. Akad. Nauk SSSR, Ser. Khim., (1988) 8, 1852; Chem. Abstr., (1989) 110, 192619. Ingold, C. K., Structure and Mechanism in Organic Chemistry, Cornell University: New York, (1953); pp 598, 619. Ziegler, F. E., In Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I.; Paquette, L. A., Eds.; Pergamon: New York, (1993); Vol. 5, p 875. Iseki, K.; Kobayashi, Y., In Biomedical Frontiers of Fluorine Chemistry, Ojima, I.; McCarthy, J. R.; Welch, J. T., Eds.; ACS Symposium Series 639; American Chemical Society: Washington, DC, (1996); p 214. Simchen, G., In HoubenWeyl, (1986); Vol. E 5, p 3. Bellus, D.; Sauter, H.; Weis, C. D., Org. Synth., Coll. Vol. VI, (1988), 427.

[10] [11] [12]
53
[13]
Alper, H., EP 305 089, (1989); Chem. Abstr., (1989) 112, 76610. Studer, A., Ph.D. Dissertation ETH Zrich, (1995), pp 3, 116; cf. ref 14. Kajimoto, T.; Liu, K. K.-C.; Pederson, R. L.; Zhong, Z.; Ichikawa, Y.; Porco, J. A., Jr.; Wong, C.-H., J. Am. Chem. Soc., (1991) 113, 6187. Smith, A. B., III; Fukui, M.; Vaccaro, H. A.; Empfield, J. R., J. Am. Chem. Soc., (1991) 113, 2071.
1.5
Guidelines for Tables and Scheme Tables
Tables should be used to display examples of similar products prepared by a given method or variation in order that they may be critically discussed in the text. Do not list every example known; only selected examples should be given. Tables should contain 5 to 10 examples and should be placed in the appropriate position in the body of the text. Tables should be numbered with Arabic numerals and have captions with initial letters of major words capitalized. When referring for the first time to information given in a table, please quote the table number in brackets. The position of a table should be indicated in the text in the following way: < Table 1 > This is a Sample Caption In tables, collect comparable examples and quote, in the following order: (1) The starting material represented pictorially, e.g. either present a generalized equation above and then give only substituents R1, R2, X, etc. (vide infra) or, in the case of structurally diverse substrates, give the entire formula. An entry number is also acceptable for identifying the starting material. In all cases, arrange the examples in a manner which best illustrates the scope and limitations of the method (e.g., they may be listed in increasing order of substituent/reagent complexity, or in increasing order of chemical or optical yield, etc.). (2) Reagents, solvents, temperature, times, as applicable. (3) Product (formula or entry number). (4) ee, er (preferred), dr when applicable. (5) Yield data. (6) Physical data, if relevant (e.g., mp). (7) Citation of the relevant literature.
< Table 1 >
Starting Material (formula or entry number)
Caption
Reaction Conditions I (reagents, catalysts, solvents) Reaction Conditions II [Temp (8C), pressure (mbar)] Product (formula or entry number) er or dr Yield (%) Ref
Scheme tables should be employed in conjunction with schemes if the latter are likely to become over-cluttered with textual notes. They should be used to illustrate methods (or variations) when: (1) there are 8 or more examples for the method but they are not actively and individually discussed in the main text, and thus presented in a normal table (vide supra); (2) there are fewer examples but they contain several varying R-substituents on the reagent(s) in the scheme; (3) there are different conditions (e.g., solvent, temperature, ratio of reactants) employed for the same reaction which have a significant influence on the yield, purity, or optical purity, etc. of the product. All other cases should simply include the examples within the scheme itself (vide infra).
54
The content and layout of a scheme table should be similar to that employed for a table, and in all cases kept as simple as possible. An example of a scheme table is given below:
O R2 R1 + NMe2 9 COR3 10
toluene
NH Cl3C NH2 +
Cl3C MeO R
1
NH N
R2 N
OMe NMe2
R3 R1 N 11
CCl3
R1 H H H H Me Me Ph Ph Ph Ph
R2 CO2Me H Ph H CO2Me H CO2Me H Ph H
R3 OMe OEt OMe H OMe OEt OMe OEt OMe H
Ratio (9/10) 1:4 1:4 1:2 1:1 1:4 1:4 1:4 1:4 1:2.7 1:1.3
Conditions rt, 30 min 70 8C, 24 h 101 8C, 30 h rt, 30 min rt, 30 min 80 8C, 1 h rt, 30 min 80 8C, 3 h 101 8C, 4 h rt, 1 h
Chromatography Eluent, Ratio (hexane/EtOAc) 4:1 4:1 9:1 85:15 9:1 9:1 85:15 9:1 9:1 9:1
Yield (%) 98 75 51 66 76 65 73 56 40 43
Ref
[21] [21] [21] [2123] [2123] [21, 22, 36] [36] [36] [36] [23, 36, 45]
Scheme tables should be placed below the relevant scheme heading in the body of the text. Scheme tables will not have a caption but < Schemetable n > should be used as a pointer in the main text.
1.6
Guidelines for Formulas and Schemes
The formulas and schemes should be visual abstracts of the reactions performed, hence flow diagrams are preferred to individual structures. Formulas and schemes should be numbered with Arabic numerals and have captions with initial letters of major words capitalized. When referring for the first time to information given in a scheme, please quote the scheme number in brackets. Captions will not be listed at the end of the manuscript and will instead stay in the manuscript. A formula or scheme should be indicated in the text in the following way: < Formula 1 > This is a Sample Formula < Scheme 1 > This is a Sample Scheme Formulas and schemes should be placed separately in Part 6 of your manuscript. Formulas, schemes and figures must be submitted on a separate sheet. They should not be electronically embedded in the text. Formulas and schemes should not exceed a width of 16 cm; schemes wider than this will not be accepted. Bonds and reaction arrows should be placed vertically, horizontally or at 458 angles. Authors should try to make economic use of the space. Products (and substrates and intermediates that are referred to in the text) should be numbered with bold,
55
Arabic numbers from left to right in sequence as they appear in the schemes. Begin from 1 at the start of each product class. Every compound in a scheme does not have to have a number. If a compound is mentioned in the text it must have a number and the title compound in an experimental procedure should also have a number. For compounds with different substituents, the labels R1, R2, X, etc. must be used and explained below the reaction scheme or in a table. Do not use R without a superscript. Use + and (i.e., plus and minus symbols as superscripts) for electric charges (do not circle them). Two dots should be used to indicate a lone pair. Do not summarize several reaction steps by using only one reaction arrow. Each reaction arrow should symbolize only one single reaction. Reagents, conditions, etc., should appear above the arrow. Unstable intermediates should be drawn in square brackets (see below). Each individual reagent, condition, etc., should be separated from the next by a comma and one character space, not a semicolon or slash; no comma should appear at the end of a line. Reagents, conditions, etc., appear in the following order: (1) Reagents, including catalysts, e.g. H2(g), Pd/C, (Ph3P)4Pd. (2) No. of equivalents. (3) Solvents. (4) Special apparatus, e.g. sealed tube, autoclave. (5) Temperature, e.g. rt, 50 8C, reflux. (6) Pressure, e.g. 20 mbar, 100 Pa. (7) Time, e.g. 5 min, 12 d, 6 h. Eliminated products (preceded by a minus sign) and the reaction yield appear below the arrow. References will not appear in schemes but in the scheme headings. 1. 2. For intermediates in schemes the following rules apply: Isolable intermediates are to be included in schemes and will get put into a separate reaction database for reaction searching. Elusive intermediates and transition states can also be put into schemes but they will not be included in the reaction database. They should be placed within square brackets.
Scheme 1 shows an illustrative example of a reaction scheme.

Scheme 1 By Oxidative Addition of Alkanes and Arenes[108, 110]
H Cp2WH2
h, benzene H2 benzene
up to 80%
Cp2W Ph 63
Me4Si (neat) 70 oC, 2.5 d
Me4Si
ON
CH2But CH2But
ON
90%
CHBut
ON
CH2TMS CH2But
64
For drawings prepared by CSC ChemDraw, use the following settings, printed at 100% (page setup = 100%). Authors using different drawing programs are requested to use settings which are consistent with those below. Please do not use wedged bonds (bold or hashed) to represent chiral centers; use normal bold or hashed bonds instead (see Sample Chapter).
56
Choose settings type: Font for atoms, reaction conditions, yield and captions: Chain angle: Bond spacing: Fixed length: Bond width: Line width: Margin width: Hash spacing:
1.7
Science of Synthesis, except for the margin width 10 point Helvetica or Arial 120 degrees 18% of length 17 point (0.600 cm, 0.236") 2.0 point (0.071 cm, 0.027") 0.8 point (0.028 cm, 0.011") 2.2 point (0.079 cm, 0.031") 2.5 point (0.088 cm, 0.035")
Guidelines for Figures
Figures should be numbered with Arabic numerals. When referring for the first time to information given in a figure, please quote the figure number in brackets. Figure captions will not be listed at the end of the manuscript and will instead stay in the manuscript. A figure should be indicated in the text in the following way: < Figure 1 > This is a Sample Figure Figures should be placed separately in Part 7 of your manuscript. Figures must be submitted on a separate sheet. They must not be electronically embedded in the text. If necessary, figures will be redrawn by the publishers. For checking and correction, the redrawn figures will be sent back to the author. In the case of figures taken from existing publications, it is the legal responsibility of the author to obtain permission for reproduction from the copyright holder; this should be done at a very early stage of the book production. For figures of apparatus, please directly contact the apparatus producer company. If figures are not produced by the author, the copyright of the figure must be included in the caption. Submit only original figures or high quality photographic prints of originals. For the preparation of graphs, authors are requested to follow the suggestions of H. G. Hers [Nature, (1984) 307, 205]. The highest resolution of the printer available should be used for the printouts.
1.8
Delivery of the Manuscripts
Authors are requested to send one copy of their table of contents to the editorial office and one copy to the appropriate volume editor. Authors will then receive a revised table of contents with comments and suggestions from both the volume editor and the editorial office. Authors are requested, after approval of their table of contents, to submit a four-page sample of their work. This document should be a short example of the type of format the author envisages their final manuscript being submitted in. Sample pages should contain, where appropriate, examples of: Introductory text, Experimental procedures, Tables, Schemes, Figures, References. The sample pages should also have the document template styles applied to them wherever possible. Sample pages should be submitted on disk as detailed under Section 1.9 with a printout corresponding exactly to what appears on the disk. Submission of these sample pages enables the in-house copy editors to give feedback on editorial issues. It also
57
enables the author to identify potentially problematic issues regarding their manuscript. Sample chapter evaluations will be provided to authors after final approval from the appropriate volume editor. It is possible to see an example of how we would like a final manuscript to be presented by downloading the document template files from the Science of Synthesis website and looking at the file elecsamp.doc. If there are any questions regarding sample pages do not hesitate to contact the editorial office. Please send two copies of your completed manuscript to the volume editor, who will advise on revision if necessary (do not send a disk to your volume editor). The final version of the revised manuscript has to be sent to the editorial office on disk and as a hard copy by the agreed deadline. One hardcopy of the final version also needs to be sent to the volume editor. The manuscript submitted to the editorial office will then be assigned to a copy editor who will copyedit the manuscript and apply the necessary styles for Science of Synthesis, e.g. check nomenclature, grammar, syntax, punctuation, phrasing, redundancy of text, and the like. Copy editors will correspond directly with authors regarding any queries and try to resolve them before proceeding to the galley proof stage. It is inevitable that corrections will still need to be made to the galley proofs, but each copy editor will aim to eliminate as many errors as possible prior to this stage by editing the manuscript thoroughly. The editorial office will then use the manuscripts for the production of the electronic version and prepare them for typesetting. At this stage galley proofs will be sent to the author for correction. The correction of galley proofs should be limited to the correction of printing errors or other mistakes and should not involve major changes to the text. If more extensive corrections are necessary as a result of significant new developments, the volume editor should be consulted. The author may be required to provide additional information at the galley proof stage, in order to comply with the above instructions. Please note that the symbols nnn indicate that something was missing or unclear in the manuscript and the pertinent information should be added during correction. The galley proofs should be returned to the editorial office by the deadline given. The authors responsibilities end with the correction of the galley proofs. The author then signs the galley proofs as a permission to publish the manuscript (Imprimatur). By accepting a manuscript the publisher acquires all rights, in particular copyright and the right of translation. The page layout of the contribution follows the proof correction, i.e. the text is laid out to the exact page length, the pages are numbered, tables, formulas, schemes and figures are placed as near as possible to the positions indicated by the author in the galley proofs. Page proofs will subsequently be sent to the volume editor and the author. It is requested that corrections in the page proofs be limited to the elimination of printing errors. The proof sheets are not indicative of the quality of the final print.
Workflow Chart for Science of Synthesis

Editorial Office
Establish detailed table of contents Recruit authors Starts writing Submits table of contents/ Sample pages
58
Stage
1
Volume Editor Author
Overall plan Planning meeting/ Science of Synthesis guidebook
Typesetter
Commentary on substantive and technical points, e.g. revised table of contents, sample pages evaluation Commentary on scientific contents Completes manuscript Scientific assessment 1 2 months Copyediting (manuscript + schemes)
The author submits a table of contents and set of sample pages (ca. 4 pages of text) to the editorial office for review. The editorial office works together with the volume editor to provide the author with relevant feedback regarding the style, structure, and scientific content of the contribution. About 6 months later, the author sends his draft manuscript to the volume editor for review. Any further amendments requested by the volume editor are made by the author, who then submits the final manuscript to the editorial office. The manuscript is then assigned to a copy editor, who contacts the author directly with regard to any queries they might have.
Duration of stage 1: ~ 2.5 years
Stage Production: Electronic structuring of manuscript Receive/send out 1 2 weeks 5 7 days Galley proofs proofread 1 2 weeks Page proofs sent to indexer 5 7 days Page proofs proofread 3 4 days Last checks to manuscript + index made Page proofs checked/corrected permission to publish signed Galley proof corrections overseen
1 2 days
Galley proofs made
1 2 weeks Galley proofs checked/corrected Permission to publish signed
1 2 days
Page proofs made
1 2 weeks Page proofs checked/corrected
1 2 days
After copyediting is complete, the manuscript and schemes are sent to production for electronic structuring. The resulting SGML data is sent to the typesetter and from it the galley proofs are made. The galley proofs are first sent to the author for checking, returned to the editorial office, and then sent out to the volume editor for checking. Once the galleys are returned from the volume editor, they are assigned for proofreading before being sent to the typesetters and made into page proofs. The page proofs are sent simultaneously to the author and volume editor for a final check. Once returned in-house, the page proofs are again proofread and any final corrections are made to them before being sent to the typesetter. Last checks to all the manuscripts and the 2 indexes author and keyword are carried out until the finished films are finally produced.
Corrected page proofs made
Duration of stage 2: 23 months
Finished film made
SGML data
Printers + Binders
InfoChem
Publication
Electronic Product

1.9
59
Guidelines for the Preparation of the Manuscripts on Disks
In general, the editorial office can process disks in either DOS or Macintosh format. The following word-processing programs are preferred: MS Word 5.0, Word for Windows 2.0 and 6.0, MS Word 97, MS Word 2000, Word Perfect 8 (for PCs) and MS Word 5.1a, 6.0.1, 98, Word Perfect 3.5 (for Mac). The authors will be provided with style templates for these programs. The use of LATEX and DTP programs should be avoided. The Science of Synthesis template document contains a list of formatting styles that have to be applied to the chapter captions of your manuscript. The file is called scisynth.dot. However, the manuscript will not have the same print format as shown in the sample chapter. The sample chapter as it appears by using the template can also be found on the same disk elecsamp.doc. This file is intended to illustrate how the template should be used. It also shows that at this stage manuscripts do not have the same format as in print. Label the disk with the product class, the name of the author(s), the date, the platform, and the version of software used. Check disks with a virus-checking program before submission. Disks containing viruses will not be processed at the editorial office. The electronic version must exactly match the hardcopy version. Authors are strongly encouraged to check vigorously the final version for correct spelling and consistency of structure and style. Authors address, contents, text including tables, references, and notes should be, in this order, in one file. Schemes, formulas, and figures have to be supplied in separate files on disk. Use the formula, scheme or figure number as the file name, e.g. FIGURE1.TIF. The filename of the corresponding formula, figure, or scheme on the accompanying disk should be included (handwritten) at the place where it appears in the text (below the caption): < Figure 1 > This is a Sample Caption handwritten addition: figure1.tif Authors should use only predefined formats and linefeeds to mark paragraphs and document sections. Additional formatting information like separating lines should be omitted. End-of-line hyphenation should be turned off and the text should be left-justified. Do not insert spaces before punctuation. Carriage return should only be used to mark the end of a paragraph, title or heading. Only one font type should be used (e.g., 12 point Times New Roman) throughout the text. Special characters such as Greek symbols must not be presented as graphical objects. Use the Symbol font set and present them as normal characters. Files should be saved in the normal document format of the word-processing program, instead of as plain ASCII text files. RTF files are also acceptable. Tables should be prepared in the word-processing programs by using tabulators or the automatic table setup instead of space bars. Tables generated in the Microsoft Excel worksheet format are also acceptable. Formulas and schemes are most preferably generated by ChemDraw (latest version, both for Microsoft Windows or Macintosh) or by ISIS/Draw (MDL Information Systems, Inc., San Leandro, CA; latest version available at: www.mdli.com). They should be saved both in the usual ChemDraw or ISIS format and MDL Molfile format (this format is supported by nearly all structure-drawing programs). Reaction centers (the atoms of the molecule which actually participate in the reaction) should be marked in the hardcopy (see Section 1.6). Figures should be stored in one of the following formats: TIFF (preferred bitmap format), CDR (CorelDraw), HPGL (preferred vectorgraphic format), PostScript (PS), or Encapsulated PostScript (EPS).
61
Sample Contributions
Category Volume Product Class
1 2 2.6
Organometallics Compounds of Groups 73 Organometallic Complexes of Chromium, Molybdenum, and Tungsten without Carbonyl Ligands
R. Poli and K. M. Smith
Written by
Category Volume Product Class Written by
2 14 14.11
Hetarenes and Related Ring Systems Six-Membered Hetarenes with One Chalcogen Selenopyranones and Benzoselenopyranones
P. J. Murphy
63
Table of Contents
2.6
Product Class 6: Organometallic Complexes of Chromium, Molybdenum, and Tungsten without Carbonyl Ligands R. Poli and K. M. Smith Product Class 6: Organometallic Complexes of Chromium, Molybdenum, and Tungsten without Carbonyl Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Product Subclass 1: MetalCarbene Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . Method 1: Variation 1: Variation 2: Variation 3: Variation 4: Method 2: Method 3: Method 4: Method 5: Variation 1: Variation 2: Variation 3: Variation 4: Method 6: By -Hydrogen Elimination from Alkyl Complexes . . . . . . . . . . . Alkylation of Chloride Precursors . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ligand Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Replacement of an Oxo or Imido Ligand . . . . . . . . . . . . . . . . . . . . . Deprotonation with an External Base . . . . . . . . . . . . . . . . . . . . . . . . By Stoichiometric Alkene Metathesis . . . . . . . . . . . . . . . . . . . . . . . . By Carbene Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . From Carbyne Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Alkene Metathesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ring-Opening Metathesis Polymerization (ROMP) . . . . . . . . . . . . Alkyne Polymerization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ring-Closing Metathesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Other Selective Metathesis Processes . . . . . . . . . . . . . . . . . . . . . . . Carbonylmethylenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6
67 67 68 68 69 70 71 71 72 73 74 74 75 75 76 78 79 81 81 82 83 84 85 86 87 87 87
2.6.1
Synthesis of Product Subclass 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

2.6.1.1 2.6.1.1.1 2.6.1.1.2 2.6.1.1.3 2.6.1.1.4 2.6.1.2 2.6.1.3 2.6.1.4
Applications of Product Subclass 1 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . .

2.6.1.5 2.6.1.5.1 2.6.1.5.2 2.6.1.5.3 2.6.1.5.4 2.6.1.6 2.6.2
Product Subclass 2: MetalCarbyne Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Synthesis of Product Subclass 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Method 1: Method 2: Method 3: Method 4: Method 5: Method 6: Method 7: By ,-Hydrogen Elimination from Alkyl Complexes . . . . . . . . . By Addition of Alkynes to Compounds with Metal-Metal Triple Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . By Stoichiometric Alkyne Metathesis . . . . . . . . . . . . . . . . . . . . . . . . By Oxidation of Fischer-Type Carbyne Complexes . . . . . . . . . . . . By Rearrangement of Vinyl Complexes . . . . . . . . . . . . . . . . . . . . . . By Other Rearrangement Processes . . . . . . . . . . . . . . . . . . . . . . . . . Alkyne Metathesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6.2.1 2.6.2.2 2.6.2.3 2.6.2.4 2.6.2.5 2.6.2.6
Applications of Product Subclass 2 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . .

2.6.2.7 2.6.3
Product Subclass 3: Metal-Alkyl and -Aryl Homoleptic Complexes . . . Method 1:
Synthesis of Product Subclass 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

2.6.3.1 2.6.4
By Transmetalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Product Subclass 4: Metal-Alkyl and -Aryl Non-homoleptic Complexes 89 Synthesis of Product Subclass 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
64
2.6.4.1 2.6.4.2 2.6.4.2.1 2.6.4.2.2 2.6.4.3 2.6.4.4
Method 1: Method 2: Variation 1: Variation 2: Method 3: Method 4: Method 5: Variation 1: Variation 2:
By Transmetalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . By Oxidative Addition of Alkyl Halides . . . . . . . . . . . . . . . . . . . . . . One-Electron Oxidative Additions . . . . . . . . . . . . . . . . . . . . . . . . . . Two-Electron Oxidative Additions . . . . . . . . . . . . . . . . . . . . . . . . . . By Oxidative Addition of Alkanes and Arenes . . . . . . . . . . . . . . . By Protonation of Carbene and Carbyne Ligands . . . . . . . . . . . . Addition of Organochromium(III) Compounds to Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reaction of Organochromium(III) Compounds Prepared from Organochromium(III) Chloride by Transmetalation . . . . . Reaction of Organochromium(III) Compounds Prepared from Chromium(II) Chloride by Oxidative Addition (The NozakiHiyamaKishi Procedure) . . . . . . . . . . . . . . . . . . . . . Catalytic NozakiHiyamaKishi Reaction (The Frstner Procedure) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AdditiveReductive Carbonyl Dimerization . . . . . . . . . . . . . . . . .
90 91 91 91 92 93 93 94 94
Applications of Product Subclass 4 in Organic Synthesis . . . . . . . . . . . . . . . . . . . .

2.6.4.5 2.6.4.5.1 2.6.4.5.2
95 96 96 97 98
2.6.4.5.3 2.6.4.6 2.6.5
Variation 3: Method 6:
Product Subclass 5: Metallacyclic Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . Synthesis of Product Subclass 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Method 1: Method 2: Method 3:
2.6.5.1 2.6.5.2 2.6.5.3 2.6.6
By Transmetalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 By Reductive Coupling of Alkenes . . . . . . . . . . . . . . . . . . . . . . . . . . 99 By Addition of Alkenes to Carbene Complexes . . . . . . . . . . . . . . 100
Product Subclass 6: Complexes with Triply Bonded Heteroelement Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 Product Subclass 7: Complexes with Doubly Bonded Heteroelement Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 Synthesis of Product Subclass 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 Method 1: Method 2: Method 3: Method 4: Method 5: From Complexes Containing Singly Bonded Heteroelement Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . From Other Complexes Containing Doubly Bonded Heteroelement Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . From Complexes Containing Triply Bonded Heteroelement Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . By Oxidative Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6.7
2.6.7.1 2.6.7.2 2.6.7.3 2.6.7.4
102 103 104 105
Applications of Product Subclass 7 in Organic Synthesis . . . . . . . . . . . . . . . . . . . . 106

2.6.7.5 2.6.8
Catalytic Epoxidation of Alkenes . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Product Subclass 8: Complexes with Singly Bonded Heteroelement Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 Synthesis of Product Subclass 8 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 Method 1: Method 2: By Oxidative Addition of Compounds with Single Bonds between Heteroelements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 By Transmetalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
2.6.8.1 2.6.8.2
65
2.6.8.3 2.6.8.4 2.6.8.5
Method 3: Method 4: Method 5:
From -Alkyl Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 From Carbene or Carbyne Complexes . . . . . . . . . . . . . . . . . . . . . . 109 From Complexes Containing Doubly Bonded Heteroelement Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 110 110 110
2.6.9
Product Subclass 9: Miscellaneous Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . Synthesis of Product Subclass 9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Method 1: Allylidene Complexes from Cyclopropenes . . . . . . . . . . . . . . . . .
2.6.9.1
67
2.6
Product Class 6: Organometallic Complexes of Chromium, Molybdenum, and Tungsten without Carbonyl Ligands
R. Poli and K. M. Smith
General Introduction
Almost all of the complexes described in this product class are air- and/or moisture-sensitive, both as solids and in solution. Prior to use all solvents should be dried and distilled under nitrogen or argon, and the compounds should be synthesized, handled, and stored under an inert atmosphere using Schlenk or glovebox techniques. The bonds between group 6 metals and carbon are often readily hydrolyzed, with the notable exception of several alkylchromium(III) species. In general, these compounds are less sensitive to oxygen when the metals are formally in the +6 oxidation state, and are thus incapable of being oxidized further, although the extreme atmospheric sensitivity of molybdenum(VI) ring-closing metathesis catalysts (Section 2.6.1.5.3) provides a striking exception to this trend.[1] Due in part to their hydrolytic instability, the toxicity of the organometallic complexes described in this product class have generally not been investigated. A prominent exception is dichlorobis(cyclopentadienyl)molybdenum(IV), which has been studied as an antitumor agent.[2,3] Purely inorganic compounds of chromium(VI) are well-established carcinogens, in contrast to the relatively low toxicity characteristic of chromium(III) species. While chromium(III) compounds are not readily transported through cell walls, the negative charge and tetrahedral structure of the chromate dianion makes it analogous to the phosphate and sulfate ions, and so chromium(VI) is brought into the cell via nonspecific anion transport channels. Chromium(VI) is then reduced to chromium(III) inside the cell, leading to the DNA lesions responsible for the carcinogenic activity.[4] In the absence of more detailed toxicity studies for organometallic group 6 complexes, care should be taken when handling all the compounds in this product class.
2.6.1
Product Subclass 1: MetalCarbene Complexes
While group 6 complexes containing carbonyl ligands (Fischer-type) are most common for chromium, those without carbonyl ligands (Schrock-type, also called alkylidene complexes) are more typical of molybdenum and tungsten. Although a few chromium examples are known,[5] our attention will be almost completely devoted to molybdenum and tungsten systems. These complexes are generally found in high oxidation states (4) and supported by electronegative, -donor ligands (alkoxo, amido, imido). These ligands have the possibility of stabilizing low-coordination environments by -donation in excess of the valence requirement (e.g., + 2 MO or MNR for oxo and imido derivatives), resulting in tetrahedral species. Often, however, these complexes allow expansion of the coordination sphere by formation of dimers (e.g., halide bridged) or by addition of a two-electron donor with formation of five-coordinate and occasionally six-coordinate species, the formation of which is more likely for tungsten than for molybdenum and when the metal bears electron-withdrawing ligands.[6] Group 6 metalcarbene complexes are most stable when devoid of -hydrogen atoms on the carbene ligand, the latter leading to decomposition by 1,2-H migration and formation of alkene derivatives.[7] The carbene ligand usually bears hydrogen or alkyl substitufor references see p 112
68
Science of Synthesis 2.6 Complexes of Cr, Mo, and W without CO Ligands
ents, and is normally considered as a dinegative (=CR1R2)2 ligand for the purpose of formal oxidation state assignment. Like all other Schrock-type carbene complexes, those of group 6 metals present marked nucleophilic reactivity and undergo Wittig chemistry with X=Y molecules, the thermodynamics favoring the M=X and R2C=Y combination where X is harder than Y.[8] This reaction, however, does not represent particular advantages over classical Wittig reagents for organic synthesis, a major use being the metal removal at the end of organic transformations carried out on carbene complexes (e.g., alkene metathesis, see Section 2.6.1.5).
Synthesis of Product Subclass 1
2.6.1.1
Method 1: By -Hydrogen Elimination from Alkyl Complexes
High oxidation state dialkyl complexes may undergo transfer of an -hydrogen atom from one alkyl ligand to the second one under suitable conditions, with formation of a carbene product and elimination of alkane. The reaction is favored by an increase of steric bulk in the metal coordination sphere. This has been achieved in a number of ways, as outlined in the following variations.
2.6.1.1.1
Variation 1: Alkylation of Chloride Precursors
The replacement of a halide with a bulky alkyl group is often sufficient to induce the alkane elimination process. Thus, while the complex tert-butylimidochlorotris(2,2-dimethylpropyl)molybdenum(VI) (1) does not spontaneously undergo the -hydrogen elimination process, substitution of the chloride ligand with a fourth 2,2-dimethylpropyl ligand directly affords the carbene product 2 (Scheme 1).[9] For the analogous tungsten system, tetraalkylimido intermediates, e.g. phenylimidotetrakis[(trimethylsilyl)methyl]tungsten(VI), have been isolated, and their slow first-order elimination to the alkylidene product has been investigated.[10] Other alkane eliminations from stable dialkyl derivatives may be induced by simple irradiation,[11,12] e.g. the transformation of 3 into 4.[13]
Scheme 1 -Hydrogen Elimination Induced by Alkylation[9,13]
ButH2C ButH2C Cl Mo NBut CH2But 1 H W Pr
t-BuCH2Li, benzene rt, 10 min 75%
ButH2C Mo ButH2C 2
NBut CHBut
toluene, h (Xe, 340 nm) 26 h 64%
3
= 4-t-Bu-calix[4]-(O)4
A soln of W(cyclo-C4H8){4-t-Bu-calix[4]-(O)4} (8.45 g, 8.77 mmol) in toluene (200 mL) was irradiated with a Xe lamp (540 W m2 at 340 nm) for 26 h. Volatiles were removed in vacuo, pentane (60 mL) was added to the residue, and pale brown 4 was collected and dried in vacuo; yield: 5.62 g (64%); 1H NMR (benzene-d6, ): 10.0 [t, 3J = 7.5 Hz, 1H, WC(Pr)H], 5.47 [m, 2H, WC(H)CH2CH2CH3], 1.69 [m, 2H, WC(H)CH2CH2CH3], 1.15 [t, 3J = 7.2 Hz, 3H, WC(H)-
{4-tert-Butylcalix[4]-(O)4}butylidenetungsten(VI) (4):[13]
2.6.1
MetalCarbene Complexes
69
CH2CH2CH3]; 13C NMR (benzene-d6, ): 272 [d, WC(Pr)H, 1JCW = 180 Hz, 1JCH = 142 Hz], 41.6 (WCCH2CH2CH3), 29.5 (WCCH2CH2CH3), 14.5 (WCCH2CH2CH3).
2.6.1.1.2
Variation 2: Ligand Addition
When di- or polyalkyl complexes do not spontaneously give rise to -hydrogen elimination, this process may often be accomplished by addition of two-electron ligands (e.g., phosphines).[14,15] Thus, the tris(2,2-dimethylpropyl)(2,2-dimethylpropylidyne)tungsten complex 5 transforms into the (2,2-dimethylpropyl)(2,2-dimethylpropylidene)(2,2-dimethylpropylidyne) product 6 upon addition of trimethylphosphine (Scheme 2). The conditions required to induce this process depend on the system, from 78 8C for dibromotetrakis[(trimethylsilyl)methyl]dimolybdenum(III)(MoMo)[15] to room temperature for cyclopentadienylbis(2,2-dimethylpropyl)nitrosylmolybdenum(II).[16] In the synthesis of compound 7, substitution of two alkoxide ligands with the less sterically encumbering (and also poorer -donor) chlorides opens up the coordination sphere to the coordination of a bidentate 1,2-dimethoxyethane molecule, inducing carbene formation. The dialkoxo precursor, albeit five coordinate, does not spontaneously undergo the alkane elimination process.[17] The increase of the coordination sphere can also be achieved by replacement of a monodentate ligand (e.g., chloride) with a polyfunctional ligand, e.g. hydrotris(pyrazolyl)borate[18] or 2-[(dimethylamino)methyl]phenyl (see synthesis of 8) (Scheme 2).[19] This strategy has also been utilized in other cases via replacement of a bulky alkyl with chloride by protonation with LH+ Cl in the presence of excess ligand L.[10]
Scheme 2 -Hydrogen Elimination Induced by Ligand Addition[14,17,19]
ButH2C ButH
2C ButH
W
2C
CBut
Me3P (neat) 100 oC, 5 min quant
Me3P CBut ButH2C W Me3P 6 Pri CHBut
Pri ButH2C ButH2C OBut W N OBut Pri

PCl5, DME 35 oC 90%
Me O Cl N W t Pri O Cl CHBu Me 7 NMe2 NPh W CHTMS CH2TMS 8
Cl
CH2TMS NPh W CH2TMS CH2TMS
2-Me2NCH2C6H4Li Et2O, 78 oC 70%
Finely ground PCl5 (2.25 g, 10.8 mmol) was added to a chilled (35 8C) soln of [W(CH2tBu)2(Ot-Bu2)2(=NC6H3-2,6-iPr2) (7.0 g, 10.8 mmol) in DME (120 mL). The mixture was warmed to rt and stirred for an additional 1 h after all the solids had disappeared. The mixture was then concentrated in vacuo until an orange powder formed. This material was washed with cold pentane to give the product as a yellow-orange powder. This synthesis can fail virtually completely if the DME is not scrupulously dried and the PCl5 not
for references see p 112
Dichloro[(2,6-diisopropylphenyl)imido](1,2-dimethoxyethane-O,O)(2,2-dimethylpropylidene)tungsten(VI) (7); Typical Procedure:[17]
70
rigorously purified; yield: 5.75 g (90%); 1H NMR (benzene-d6, ): 9.97 (s, JHW = 7.3 Hz, CHtBu); 13C NMR (benzene-d6, ): 283.8 (d, W=C, 1JCH = 114 Hz, 1JCW = 163 Hz).
2.6.1.1.3
Variation 3: Replacement of an Oxo or Imido Ligand
Replacement of an oxo[2022] or imido[23] ligand with two singly bonded heteroelement ligands has often proven to be an efficient method for inducing the -elimination process from dialkyl compounds. Examples of syntheses of these types are shown in Scheme 3. The interaction between a dialkoxodialkyloxo complex of tungsten(VI) and a Lewis acid (AXn, viz. aluminum trichloride, tin(IV) chloride, magnesium bromide, etc.) proceeds via an isolable adduct containing the W=O-AXn moiety when conducted in hexane, which then yields the dialkoxodihalocarbene product.[24] Although this procedure is not general, subsequent ligand exchange or stoichiometric alkene metathesis (see Section 2.6.1.2) allows the preparation of a much broader series of derivatives.[21,22] Lewis base adducts such as compound 9 easily undergo exchange of the Lewis base, or can be converted into the base-free material. The reaction yielding 10 is the most convenient entry into the catalytically active dialkoxo(alkylidene)imido complexes of molybdenum and tungsten, since the trifluoromethanesulfonate ligands can be easily replaced with a variety of alkoxide groups, and the dialkyldiimido precursor complex is readily available in two high-yield steps from commercially available dichlorodioxotungsten(VI) or ammonium dimolybdate.[17,25]
Scheme 3 -Hydrogen Elimination Induced by Substitution of Oxo or Imido Ligands[8,17,23,29]
ButN Mo ButN CH2But CH2But
(CF3)2CHOH (2 equiv) pentane, rt 80%
ButN ButHC
OCH(CF3)2 Mo NH2But OCH(CF3)2 9
Pri Pri Pri N M N CH2R1 Pri

M = Mo, W R1 = t-Bu, CMe2Ph
CH2R1
TfOH (3 equiv) DME, 30 oC 6578%
Pri
Pri OTf Me N O M 1HC R O Me OTf 10
A prechilled soln of TfOH (3.15 mL, 35.5 mmol, 3 equiv) in DME (20 mL) was added in a dropwise manner to an orange soln of Mo(CH2t-Bu)2(=NC6H3-2,6-iPr2)2 (7.00 g, 11.8 mmol) in DME (200 mL) at 30 8C over a period of 10 min. [It is important in this step that the soln be homogeneous and cold. It is best to grind the crystals of the molybdenum starting complex to a fine powder to aid dissolution; the addition of some pentane (1530 mL) may facilitate this step.] The soln was allowed to warm up to rt and stirred for 3 h. During this period the color changed from orange to dark yellow. The solvent was evaporated in vacuo to yield a yellow solid, which was then extracted with cold toluene (100150 mL). The
[(2,6-Diisopropylphenyl)imido](1,2-dimethoxyethane-O,O)(2,2-dimethylpropylidene)bis(trifluoromethanesulfonato-O)molybdenum(VI) (10, M = Mo; R1 = t-Bu); Typical Procedure:[8]
2.6.1
71
extract was filtered through a bed of Celite and the toluene removed from the filtrate in vacuo to give the product as yellow flakes. The product should be checked by NMR for contamination by anilinium trifluoromethanesulfonate, which is slightly soluble in toluene; yield: 5.9 g (65%); 1H NMR (benzene-d6, ): 14.29 (s, CHt-Bu); 13C NMR (benzene-d6, ): 331.9 (d, Mo=C, 1JCH = 121 Hz).
2.6.1.1.4
Variation 4: Deprotonation with an External Base
Deprotonation of alkyl ligands at the -position is another potentially general method for forming carbene complexes from alkyl compounds that are either electronically unsaturated or possess labile ligands. However, this method is little documented for group 6 metals as well as for metals of other groups. The neutral dialkyl compound 11 reacts with a range of lithium reagents to yield the dimeric, anionic alkylalkylidene complex 12, as shown in Scheme 4.[26] Methylidene product 13 is only stable at low temperature, decomposing upon warming in a nonselective manner to yield alkylidene-bridged dinuclear products.[27]
Scheme 4 Deprotonation of Alkyl Complexes[26,27]
THF Mo ON CH2TMS CH2TMS 11

CH2Cl2 < 40 oC
+ LiHMDS
THF 100 oC to rt 62%
Mo TMS
ON Mo Li TMSH C CH2TMS 2 THF THF 12 NO
Li
TMS
[W(Me)4Cp]+ PF6
Et3N
W(Me)3Cp( 13
CH2)
[Mo(CH2TMS)2Cp*(NO)] (200 mg, 0.46 mmol) and LiHMDS (90 mg, 0.46 mmol) were intimately mixed and cooled to 100 8C in a small flask. THF was slowly poured down the sides of the flask and allowed to freeze onto the solid mixture. Over the course of 4 h, a color change from purple to red occurred; the final mixture was taken to dryness in vacuo. The remaining red solid was extracted into pentane (2 mL), and the extracts were filtered through Celite. Slow evaporation of the pentane filtrate resulted in the deposition of pale red crystals, which were recrystallized (pentane) to obtain pale yellow crystals of 12; yield: 143 mg (62%).
2.6.1.2
Bis{nitrosyl(5-pentamethylcyclopentadienyl)[(trimethylsilyl)methyl][(trimethylsilyl)methylidene]molybdenum(II)} (Dilithium)tris(tetrahydrofuran) (12):[26]
Method 2: By Stoichiometric Alkene Metathesis
The addition of an alkene to a carbene complex may lead to a metathesis reaction with exchange of the carbene ligand with one of the two halves of the alkene. The reaction proceeds via formation of an alkenecarbene complex, which rearranges via a metallacyclobutane intermediate.[28] This reaction is synthetically useful when a terminal alkene is used and vacuum evaporation of the more volatile alkene product (typically 3,3-dimethylbut-1-ene) is possible to displace the equilibrium.[22] An excess of the alkene reagent is also used to ensure a favorable equilibrium position (see Scheme 5). The properties of the anfor references see p 112
72
cillary alkoxide ligands can influence whether this reaction results in metathesis or the formation of stable tungstacyclobutane derivatives (see Section 2.6.5).[17,29]
Scheme 5 Stoichiometric Alkene Metathesis[8,17,22]
M( CHBut)(L)n + H2C CR1R2 M( CR1R2)(L)n + H2C CHBut
M(L)n [WBr2(OCH2t-Bu)2] [Mo(=NC6H3-2,6-iPr2){OCMe(CF3)2}2] [W(OR3)2(=NC6H3-2,6-iPr2)] a

a
R1 (CH2)4 H H
R2
Conditions CH2Cl2, rt, 4 h
Yield (%) of Ref [M(=CR1R2)(L)n] 87 74 5078

[22] [8]
TMS Si(OMe)3
pentane, 30 8C, 2.5 h pentane, rt, 30 min to 2.5 h
[17]
R3 = 2,6-iPr2C6H3, CMe2(CF3), CMe(CF3)2.
Methylenecyclopentane (0.36 mL, 3.42 mmol) was added to an orange soln of [WBr2(=CHtBu)(OCH2t-Bu)2] (0.127 g, 0.215 mmol) in CH2Cl2 (10 mL). After 4 h, the volatiles of the red mixture were removed in vacuo, and the orange residue was washed twice with pentane to give the product as an orange powder; yield: 110 mg (87%); 13C NMR (CD2Cl2, , gated decoupled): 47.1 (t, 1JCH = 134 Hz, W=CCH2), 28.2 (t, 1JCH = 131 Hz, W=CCH2CH2); the W=C signal could not be observed.
2.6.1.3
Dibromo(cyclopentylidene)bis(2,2-dimethylpropan-1-olato)tungsten(VI); Typical Procedure:[30]
Method 3: By Carbene Transfer
The carbene ligand may be either directly added to the metal center or exchanged for two X groups. The first strategy requires preparation of the metal in a reactive, reduced form. For the preparation of compound 14 (Scheme 6), this is achieved by sodium reduction of the dichloro precursor complex.[31] The phosphorane carbene transfer agent is readily accessible with a variety of carbene functionalities and the triphenylphosphine byproduct does not coordinate with the metal center, allowing its easy removal by scavenging with copper(I) chloride. For the tungsten(II) system 15 (L = tertiary phosphine), even ketones and imines are sufficiently good carbene transfer reagents, providing alkylideneoxo and alkylideneimido tungsten(VI) products 16, respectively, in remarkable four-electron oxidative addition reactions.[32] For ketones different than cyclopentanone, stable and unreactive bis(2-ketone) adducts are obtained by use of an excess of the ketone, but the use of one equivalent still leads to the alkylideneoxo product. The exchange strategy involves the use of reactive tantalum alkylidene complexes, resulting in the replacement of alkoxo ligands. This method, which is also accompanied by the scrambling of other ligands, applies equally well to the synthesis of the oxo and imido tungsten products 17,[33] but is limited by the availability of the tantalum alkylidene reagent and has not been reported for molybdenum.
2.6.1
73
Scheme 6 Carbene Transfer[3133]

OMe
R1 Cl N W Cl R1 OCMe(CF3)2 OCMe(CF3)2
Na/Hg, PPh3 benzene, THF, rt, 8 h 71%
MeO (F3C)2MeCO THF W N R1 OCMe(CF3)2 R1
R1 = H, Me, iPr
14
Cl L L W L Cl L 15
R1
R2
, benzene
4588%
Cl
L E W CR1R2 Cl L 16
L = PMe2Ph E = O, N-4-Tol R1,R2 = (CH2)4, Me2
E ButO W OBut ButO OBut

E = O, NPh
TaCl3(
CHBut)(PMe3)2 7983%
Et2O, rt, 12 h
PMe3 E W Cl CHBut PMe3 17 Cl
The compounds [WCl2{OCMe(CF3)2}2(=NC6H3-2,6-Me2)(THF)] (16.0 g, 19.8 mmol) and Ph3P=CH(C6H4-2-OMe) (7.78 g, 20.3 mmol) were dissolved in a mixture of benzene and THF (160 mL and 2.5 mL, respectively) and the resulting soln was added to 1% Na/Hg (3.59 g of Na, 7.90 equiv). After being stirred for 8 h at rt, the mixture was allowed to settle, and the orange-brown supernatant was added via a cannula to CuCl (2.07 g, 20.9 mmol). The residual Na/Hg was washed with Et2O (120 mL), and the combined benzene/Et2O soln was stirred with CuCl for 12 h before removal of the solvent in vacuo. The brown solid was then extracted with Et2O (260 mL). After addition of THF (2 mL) to the extract and filtering, the soln was slowly cooled to 50 8C to yield the product as an olive-yellow powder; yield: 12.0 g (71%); 1H NMR (benzene-d6, ): 10.81 (s, W=CHAr).
2.6.1.4
(2,6-Dimethylphenylimido)bis(1,1,1,3,3,3-hexafluoro-2-methylpropan-2-olato)(2-methoxybenzylidene-k C)(tetrahydrofuran)tungsten(VI) (14, R1 = Me); Typical Procedure:[31]
Method 4: From Carbyne Complexes
Addition of a proton to a carbyne ligand may transform it into a carbene. The proton can be provided by an external source or by transfer from another ligand. Examples of the first kind are provided by the addition of acids to complex 18 (see Scheme 7).[7] The use of pyridinium salts yields more stable pyridine adducts. This reaction can be reversed by the addition of a strong base (see Section 2.6.2). When an acid containing a noncoordinating anion is used, e.g. trifluoromethanesulfonic acid, cationic derivatives may be obtained.[34] Depending on the nature of the coligands, the proton may preferentially add to another position in the molecule (see Section 2.6.2). Internal proton transfer is observed for amido ligands. The reaction between the 1,2dimethoxyethane adduct of trichloro(carbyne)molybdenum or -tungsten complexes and (trimethylsilyl)arylamines produces the stable intermediates 20. The latter, however, refor references see p 112
74
arrange by a base-catalyzed proton transfer to the final carbeneimido products 21.[8,17,29] These proton-transfer processes occur much more slowly or not at all for the dialkoxo analogues, although the anticipated proton-transfer products are stable systems. A mechanism of reversible amine-assisted dehydrohalogenation has been proposed for this transformation. This synthetic route is inconvenient for the molybdenum system, mainly because of difficulties in the preparation of the precursors to the trichlorocarbyne complex of molybdenum. The tungsten analogue is more easily prepared (see Section 2.6.2).[29] However, even the tungsten product is more conveniently prepared by another procedure [-H elimination from a bis(2,2-dimethylpropyl) precursor, Section 2.6.1.1].[17]
Scheme 7 Protonation of Carbyne Complexes[7,8,17]
CBut ButO W
HX (2 equiv), toluene, rt 5185%
ButO ButO
X W CHBut X 19
OBut OBut
18
X = Cl, Br, OAc, OBz, OPh, OC6F5, 4-ClC6H4O
R1 NH R1 Et2O, 40 oC TMS
R1 Me Cl H O N M CBut R1 O Cl Me 20
R1 Me Cl O N M CHBut O Cl R1 Me 21
M(
CBut)Cl
3(DME)
Et3N >95%
>95%
M = Mo, W; R1 = Me, iPr
The alkylidyne complex [W(Ct-Bu)(Ot-Bu)3] (1.00 g, 2.12 mmol) was added at rt as a solid to a CH2Cl2 soln (25 mL) of pyridine hydrochloride (4.2 mmol). After 10 min the solvent was removed in vacuo and the residue was recrystallized (pentane) to yield the product as orange crystals; yield: 0.92 g (79%); 1H NMR (benzene-d6, ): 10.76 (s, CHt-Bu); 13 C{1H} NMR (benzene-d6, ): 302.3 (CHt-Bu).
Applications of Product Subclass 1 in Organic Synthesis
2.6.1.5
Di-tert-butoxodichloro(2,2-dimethylpropylidene)(pyridine)tungsten(VI); Typical Procedure:[7]
Method 5: Alkene Metathesis
High-valent molybdenumcarbene complexes bearing electronegative ancillary ligands are efficient catalysts for alkene metathesis reactions (Scheme 8).[20,35] This reaction proceeds via [2 + 2] cycloaddition and formation of metallacyclobutane intermediates, some of which have been isolated under controlled conditions (see Section 2.6.5.3).[36] In order to make the reaction synthetically useful, it is necessary to have a driving force and high selectivities, and to suppress the self-metathesis if a cross-metathesis (e.g., R1 R2) is desired. The driving force may be provided by conjugation or by formation of polymeric materials. Selective processes often result from the removal of a volatile byproduct, such as ethene.
2.6.1
75
Scheme 8 Alkene Metathesis

R1 + R2 R
1
R2
H2C CH2
2.6.1.5.1
Variation 1: Ring-Opening Metathesis Polymerization (ROMP)
The living polymerization of strained cyclic alkenes such as norbornenes and substituted norbornadienes is catalyzed by molybdenum and tungsten carbene complexes (Scheme 9).[35] The living nature of this process allows control of the chain length and the preparation of block copolymers, which may also have a high level of tacticity.[37] A Wittig-like capping reaction with aldehydes can be used to cleave the metal fragment off the living polymer. Essentially monodisperse products 22 with x up to 500 have been obtained from norbornene by using di-tert-butoxo[(2,6-diisopropylphenyl)imido](2,2-dimethylpropylidene)tungsten(VI) as a ROMP initiator.[38] The catalyst does not attack the less reactive double bonds in the polymeric product. The use of 7,8-bis(trifluoromethyl)tricyclo[4.2.2.02,5]deca-3,7,9-triene as monomer gives oligomers from which polyenes with up to 15 conjugated double bonds have been obtained via a retro-DielsAlder ejection of an arene upon thermolysis.[39] Other substrates suitable for the ROMP process are substituted cyclooctatetraenes, leading to functionalized and soluble polyacetylenes of low polydispersities.[40]
Scheme 9 Ring-Opening Metathesis Polymerization of Norbornene[35]
[W]
CHBut
80 oC
[W]
CHBut
x
PhCHO
PhHC 22
[W] = W(Ot-Bu)2( NC6H3-2,6-iPr2)
CHBut
x
A soln of 1,4-dihydro-1,4-methanonaphthalene (291 mg, 2.05 mmol) in toluene (3.0 mL) was added dropwise to a rapidly stirred soln of [Mo(=CHt-Bu)(Ot-Bu)2(=NC6H3-2,6-iPr2)] (10 mg, 0.020 mmol) in toluene (3.0 mL) and the soln was stirred for 20 min. The polymerization was quenched by addition of pivalaldehyde (25 L). After 20 min, the soln was added to hexane (250 mL), and the precipitated polymer was isolated by centrifugation, washed with hexane, and placed under vacuum overnight; yield: 280 mg (94%).
2.6.1.5.2
1,4-Dihydro-1,4-methanonaphthalene, Homopolymer (x = 100); Typical Procedure:[41]
Variation 2: Alkyne Polymerization
Terminal alkynes have yielded polyenes 23 with up to 150 conjugated double bonds under molybdenumcarbene catalysis (Scheme 10).[42] The nature (in particular the size) of the ancillary ligands is important in controlling the selective -addition. Acetylene itself produces insoluble and air-sensitive polymers that are difficult to characterize. Cyclopolymerization of dipropargyl derivatives such as 24 have been shown to yield polyenes of low polydispersity containing only six-membered rings, following a selective -addition
76
of the first triple bond.[43] The nature of the coordination sphere on the carbene initiator is of capital importance, as polymers containing both five- and six-membered rings that are a consequence of an initial - or -addition, respectively, have been obtained with other initiators.[44]
Scheme 10 Alkyne Polymerization[42,43]
[Mo] CHCMe2Ph toluene, rt PhCHO
xR
[Mo] CHCMe2Ph R1
x
PhCH CHCMe2Ph R1 23
x
[Mo] =
OCMe(CF3)2 N Mo OCMe(CF3)2
; R1 = TMS
; x = up to 150
EtO2C x
CO2Et
[Mo] CHt-Bu
CO2Et EtO2C EtO2C [Mo]

-addition
EtO2C CHBut [Mo] CHBut

x
24
But [Mo] = N Mo(O2CCPh3)2
Polymerization stock solutions of diethyl 2,2-diprop-2-ynylmalonate (24; 0.406 M) and [Mo(=CHt-Bu)(O2CCPh3)2(=NC6H42-t-Bu)] (0.00676 M) in toluene that had been distilled over sodium benzophenone ketyl, stored over molecular sieves (4 ), and passed through alumina, were prepared. To the catalyst stock soln (3.007 mL), toluene (3 mL) was added and the monomer stock soln (1.0 mL) was squirted in. Within 30 s the mixture turned deep red. After 6 h, benzaldehyde (16 L) was added. After stirring for a further 3 h, the soln was concentrated in vacuo to about 1.5 mL. The polymer was precipitated in pentane (60 mL), collected on a frit, and dried in vacuo to yield a red, powdery material. All operations were carried out under a nitrogen atmosphere and the polymers were only briefly exposed to air for sample preparation for GC analysis; yield: 90 mg (91%); 13C{1H} NMR (CDCl3, ): 170.7 (CO2Et), 54.5 (Cquaternary).
2.6.1.5.3
2,2-Diprop-2-ynylmalonic Acid, Diethyl Ester, Homopolymer (x = 20); Typical Procedure:[43]
Variation 3: Ring-Closing Metathesis
Ring-closing metathesis (Scheme 11) affords cyclic products 25 in competition with intermolecular metathesis processes to form polymeric materials.[45] The reaction is also complicated by the possibility of ROMP (Section 2.6.1.5.1). Which products are obtained is the result of an interplay of thermodynamic and kinetic parameters. Entropy (the generation of two molecules from one) and evaporative subtraction of the volatile acyclic alkene from solution provide the necessary driving force for the desired cyclization. The ringclosing metathesis procedure can be applied to the construction of macrocyclic natural products, although mixtures of E- and Z-isomers are often obtained in these cases (see also Section 2.6.2.7).[46] The most widely used group 6 catalyst for this process is 26, although ruthenium-based catalysts are generally preferred owing to their greater func-
2.6.1
77
tional group tolerance and relatively low sensitivity to air, moisture, or solvent impurities.[47] The process has proven particularly useful for the formation of cyclic ethers, e.g. 27.[48] A number of functional groups, including tertiary alcohols, do not interfere with the course of the reaction. Amine and amide functional groups can be tolerated if they cannot form unreactive chelated adducts for steric reasons.[49] A variant of this method follows the initial ring-closing metathesis step with a carbonyl alkenation process, e.g. the synthesis of 28,[50] which is, however, stoichiometric in metal because of the formation of a catalytically inactive metaloxo byproduct. The success of this strategy rests on the fact that compound 26 metathesizes alkenes more rapidly than it alkenates ketones. Chiral analogues of 26 have been prepared using C2 symmetric diol ligands, and these complexes, 29[51] and 30,[52] have been used to perform the asymmetric ring-closing metathesis of dienes[5254] and the synthesis of chiral furans via enantioselective desymmetrization reactions.[55]
Scheme 11 Cycloalkenes by Ring-Closing Metathesis of Dienes[48,50]
[M ]
X 25
H2C CH2
Pri (F3C)2MeCO Mo (F3C)2MeCO CHCMe2Ph 26 (cat.) benzene, 20 oC, 15 min 92% N Pri
Ph
O Ph
27
Pri (F3C)2MeCO Mo (F3C)2MeCO CHCMe2Ph N Pri
Ph
Ph O O
26 benzene, 20 oC, 30 min 84%
O 28
F3C O O F3C
Pri CF3 N Mo CHCMe2Ph Pri
But Pri O Mo O But 30 CHCMe2Ph N Pri
CF3 29
1-[(2-Methyl-3-phenylallyl)oxy]oct-7-en-2-one (35 mg, 0.13 mmol) was added to a homogeneous yellow soln of catalyst 26 (100 mg, 0.13 mmol) in anhyd benzene (12 mL) under argon. The resulting mixture was stirred at 20 8C for 30 min, at which time TLC showed the reaction to be complete. The mixture was quenched by exposure to air, concentrated, and
1-[(2-Methyl-3-phenylallyl)oxy]methylcyclohex-1-ene (28); Typical Procedure:[50]
78
purified by flash chromatography (07% EtOAc/hexane) to yield the substituted cyclohexene as a colorless oil; yield: 27 mg (84%); 1H NMR (benzene-d6, ): 5.72 (br s, CHCH2), 2.051.45 (m, 8H, CH2CH2CH2CH2).
2.6.1.5.4
Variation 4: Other Selective Metathesis Processes
These processes are usually restrained to monosubstituted alkenes, yielding ethene as the byproduct. Fairly selective cross-coupling processes have been reported from a combination of an electron-poor alkene, especially one containing a -substituent (e.g., styrenes, acrylonitrile),[56,57] and a more nucleophilic one containing a small, electron-rich, nonconjugated substituent (see, for example, the synthesis of 31 in Scheme 12),[56] or with allylsilanes.[58] The electron-poor alkene self-metathesizes only slowly and, in addition, inhibits the self-metathesis of the nucleophilic alkene. Greater than 95% trans selectivity is observed in the reactions with styrene substrates,[56] while the cis-product is highly favored for cross-metatheses with acrylonitrile.[57] The formation of the homo dimer may also be significantly slowed down by steric bulk. For example, compounds 32 and 33 yield the cross-coupling product 34 without any self-metathesis of 32 and with only 26% yield of the 33 homo dimer.[59] The E/Z selectivities, however, are usually low for nonconjugated alkene products.
Scheme 12 Cross-Coupling Alkene Metathesis[56,59]
Pri (F3C)2MeCO Mo (F3C)2MeCO CHCMe2Ph 26 (cat.) CH2Cl2, rt, 1 h N Pri
Ph
( )5
Ph 31
()
( )5
2%
()
5
89%; E 100%
Pri (F3C)2MeCO Mo N Pri
O + 1.5 CO2Me 32 33 CO2Me
(F3C)2MeCO
CHCMe2Ph
26 (cat.) 83%
CO2Me
CO2Me 34
(E/Z) 2:1
2.6.1
79
To a mixture containing styrene (208 mg, 2 mmol) and oct-1-ene (112 mg, 1 mmol) in CH2Cl2 (2 mL) was added [Mo(=CHCMe2Ph){OCMe(CF3)2}2(=NC6H32,6-iPr2)] (7.7 mg, 1 mol%). The resulting mixture was stirred at rt for 1 h, then passed through a pad of silica gel and rinsed with CH2Cl2. The solvent was removed under reduced pressure, and the crude residue was chromatographed on silica gel to give 31 as a colorless oil; yield: 166 mg (89 %). A similar reaction run with styrene (9.29 g, 89.2 mmol), oct-1-ene (5 g, 44.6 mmol), and catalyst (342 mg, 1 mol%) in CH2Cl2 (60 mL) afforded 31; yield: 7.9 g (94%). 1H NMR (CDCl3, ): 2.16 (q, J = 6.8 Hz, 2H, allylic CH2), 6.20 (dt, J = 15.5 and 6.8 Hz, 1H, PhCH=CH), 6.33 (d, J = 15.5 Hz, 1H, PhCH=CH).
2.6.1.6
(E)-1-Phenyloct-1-ene (31); Typical Procedure:[56]
Method 6: Carbonylmethylenation
The reaction of methyllithium or trimethylaluminum with molybdenum(V), molybdenum(VI), tungsten(V), and tungsten(VI) chlorides in tetrahydrofuran or diethyl ether at low temperatures produces complexes that liberate methane and convert into thermolabile -methylene complexes upon warming. The exact nature of these reagents has not been determined, but their subsequent addition to aldehydes and ketones results in their methylenation at the carbonyl function. The low basicity of these compounds proves advantageous in carbonylmethylenation of base-sensitive substrates, such as readily enolizable ketones as in the synthesis of 35 (Scheme 13).[60] By comparison, methylidenetriphenylphosphorane (Ph3P=CH2) provides only a 16% yield of 35. The base-sensitive ketone 36 is cleaved via a retro-aldol process by methylidenetriphenylphosphorane as well as weakly basic chromium reagents. In contrast, molybdenum(V) and tungsten(V) reagents are capable of methylenating 36 with high regioselectivities.[61] The activity of these reagents is restricted only to a surprisingly small degree by alcohol and water, thus permitting carbonylmethylenation in aqueous or alcoholic media with useful applications to hydrophilic substances. The molybdenum reagents in particular display high aldehyde selectivities, paralleling those observed for alkylchromium(III) reagents in carbonylalkylation (Section 2.6.4.5). This is illustrated in Scheme 13 by the carbonylmethylenation of 37.[61,62] Basic groups such as hydroxy, alkoxy, dimethylamino, or alkylsulfanyl, in - or -positions relative to a carbonyl group, exercise an accelerating effect. This neighboring effect permits the selective monomethylenation of diketones such as 36, the selectivity depending on the solvent in the order dichloromethane < tetrahydrofuran < 1,2-dimethoxyethane. 1,3-Diketones and 1,3,5-triketones can be selectively monomethylenated. In the case of triketones, a peripheral oxo group is methylenated. Ketones react faster than enones. The reagents obtained from trichlorooxomolybdenum(V), tetrachlorooxomolybdenum(VI), or decachlorodimolybdenum(V) in tetrahydrofuran do not alter a number of functional groups that are attacked by other methylenating agents. These include acyl chlorides, anhydrides, esters, amides, diaryl-substituted 1,2-diketones, nitro aromatics, alkenes, and dienes, as well as the individual compounds diphenylketene, benzonitrile, diphenylacetylene, chlorobenzene, benzyl chloride, and dichloromethane.[60] The corresponding tungsten compounds have not been well investigated. The reason for this lack of reactivity is in some cases due to the formation of stable reagentsubstrate complexes, from which the substrate is released unchanged on addition of water. Functional groups that, on the other hand, interfere with the carbonylmethylenation reaction are azomethines, epoxides, and nitroso aromatics. A comparison of these molybdenum and tungsten reagents with other carbonylmethylenating agents in various applications is available.[60]
80

Scheme 13
O Ph Ph
Carbonylmethylenation[6062]
WOCl3/MeLi (1:2) (1.5 equiv) THF, 78 to 45 oC, 18 h 95%
Ph 35
Ph
OH O
1. A or B 2. H+, H2O
OH + O
OH
O 36
A: WOCl3/MeLi (1:2) (1 equiv) 43% B: MoOCl3/MeLi (1:2) (1 equiv) 38%
5% 9%
O Ph 37 O
MoOCl3/MeLi (1:2) (2 equiv) THF, 78 to 20 oC, 18 h
O Ph
89%
Ph
2%
To a red-brown suspension obtained by methylation of MoOCl3(THF)2 (1.57 g, 4.3 mmol) with MeLi (8.7 mmol) in THF (30 mL) at 70 8C was added dropwise a soln of 4-(4-acetylphenyl)-4-hydroxypentan-2-one (36; 0.48 g, 2.16 mmol) in THF (2 mL). The mixture was further stirred at 70 8C for 4 h, followed by warming to rt over 12 h. This was hydrolyzed with sat. aq NaHCO3 (10 mL). After separation of the two phases and Et2O extraction of the aqueous phase, the combined organic fractions were dried (Na2SO4), and the solvent was removed by rotary evaporation. Flash chromatography (3 cm 16 cm, silica gel, CH2Cl2/ acetone 40:1) afforded 2-(4-isopropenylphenyl)-4-methylpent-4-en-2-ol {fraction 1; yield: ~ 0.04 g (9%); IR max: 3500 cm1 (br, OH); 1H NMR (CDCl3, ): 4.77 [m, 1H, CH2C(CHH)CH3], 4.91 [m, 1H, CH2C(CHH)CH3], 5.09 [m, 1H, aryl-C(CHH)CH3], 5.40 (m, 1H, arylC(CHH)CH3]} as a colorless oil, 2-(4-acetylphenyl)-4-methylpent-4-en-ol [fraction 2; yield: ~ 0.18 g (38%); IR max: 3420 cm1 (br, OH); 1H NMR (CDCl3, ): 4.75 (m, 1H, C=CHH), 4.91 (m, 1H, C=CHH)] as a yellow oil, and unreacted 4-(4-acetylphenyl)-4-hydroxypentan-2one [fraction 3; yield: 0.08 g (17%)].
2.6.2
Carbonylmethylenation of 4-(4-Acetylphenyl)-4-hydroxypentan-2-one (36); Typical Procedure:[61]
Product Subclass 2: MetalCarbyne Complexes
As for the case of carbene complexes, carbonyl-free carbyne (Schrock-type alkylidyne) complexes are most common for high oxidation state (4) molybdenum and tungsten systems,[63] although chromium examples are known.[64] For the purpose of formal oxidation state assignment, the carbyne ligand is considered as (RC3). The majority of d0 complexes possess the formula M(CR)X3, but many adducts with neutral two-electron donor ligands L, M(CR)X3Ln (n = 1 or 2), are also known. Derivatives with more electronegative X groups (e.g., fluorinated alkoxides) form base adducts more readily. The most common supporting ligands (X) are bulky alkyl ligands, alkoxides, and halides, but derivatives with amides, and alkyl- and arylthiolates are also known. Typical ligands (L) are amines, ethers, and phosphines. In lower formal oxidation states (+4 and +5), phosphines and halides or cyclopentadienyl coligands are usually found. The halide derivatives are the most versa-
2.6.2
MetalCarbyne Complexes
81
tile for further transformations by ligand exchange. Exchange of the carbyne and an alkyl ligand by intramolecular scrambling of the -H atoms is possible.[65,66] Since the carbyne function is polarized as M(+)C(), these compounds are susceptible to electrophilic attack at the carbyne ligand (e.g., protonation) and nucleophilic attack at the metal center (e.g., ligand addition). The addition of acids (HX) converts carbyne complexes into carbene complexes (see Section 2.6.1.4),[7] although, in many cases, the reagents attack other ancillary ligands and the carbyne function remains intact. Examples are the reactions of trialkyl derivatives with hydrochloric acid, ammonium chloride, or carboxylic acids.[6769]
2.6.2.1
Method 1: By ,-Hydrogen Elimination from Alkyl Complexes
The increase of steric bulk in a high oxidation state complex containing alkyl ligands, or the in situ generation of encumbered complexes of this type by transmetalation reactions (see Section 2.6.1.1), induces ,-hydrogen elimination processes with formation of carbyne products. The alkylation reaction works better from oxo or alkoxo derivatives than from the corresponding chlorides, because these are less susceptible to competing reductive processes.[70] This reaction appears to be the preferred entry into 2,2-dimethylpropylidyne derivatives of molybdenum(VI) and tungsten(VI) through formation of the tris(2,2dimethylpropyl) derivatives 38 and 39 (see Scheme 14). Other 2,2-dimethylpropylidyne derivatives are then readily obtained by treating 38 and 39 with sufficiently strong acids, e.g. hydrochloric or carboxylic acid, or by further ligand exchange from the trichloride derivatives. This process is presumed to take place stepwise, via intermediate carbene complexes (see Section 2.6.1.4), even when these are not observed. Some carbyne products have been obtained by alkane elimination from carbene complexes,[15] although this strategy does not appear to have general synthetic utility. A particular case of ,-hydrogen elimination from an alkyl ligand leads to the formation of complex 40.[71] The two hydrogen atoms are eliminated as dihydrogen rather than being transferred to alkyl ligands. Thus, the reaction involves a formal metal oxidation and is so far limited to the system shown. The process is much faster for tungsten than for molybdenum, this being ascribed to a more favorable pre-equilibrium yielding the alkylidenehydride intermediate. While the alkyl precursors can be isolated for molybdenum, they may only be obtained in situ for tungsten by transmetalation from the corresponding chloride. Other related rearrangements for cycloalkyl derivatives, leading to carbyne products in some cases, have also been observed for this system (see Section 2.6.2.5).[72] The synthesis of 41[73] may be mechanistically related to the synthesis of 40, the dihydrogen byproduct being transferred to the vinyl group.
Scheme 14
,-Hydrogen Elimination Processes[67,68]

t-BuCH2MgCl (6 equiv) Et2O, 78 oC 34%
CBut ButH2C Mo CH2But CH2But
MoO2Cl2
38
t-BuCH2MgCl (6 equiv) Et2O, 78 oC 5070%
CBut ButH2C W CH2But CH2But
WCl3(OMe)3
39
82

R1CH2Li
TMS
TMS N N M N N
Cl
TMS
Et2O or THF
CH2R1 TMS TMS N N M N N TMS
2580 oC H2 7391%
TMS CR1 TMS TMS N N N M N 40
M = Mo, W; R1 = H, Me, Pr, Ph, TMS, t-Bu
TMS THF, 69 oC
WBr2(PMe3)4
90%
CEt PMe3 Me3P W PMe3 Me3P Br 41
A soln of WCl3(OMe)3 (19.1 g, 50 mmol) in a mixture of THF and Et2O was added very slowly to 1 M t-BuCH2MgCl (0.3 mol) in Et2O at 78 8C with vigorous stirring. The color of the soln gradually turned yellow-green. After the addition was complete, no significant amount of precipitate was apparent. The mixture was allowed to warm slowly from 78 to 25 8C over a period of 10 h to give a red-brown soln and abundant precipitate. After filtration from Celite followed by washing of the filter cake with Et2O, the solvent was removed in vacuo to give a thick red-brown oily liquid. Pentane (200 mL) was added to the residue, followed by another filtration and evaporation to dryness. The resulting oily red liquid was distilled at ca. 80 8C/0.001 Torr through a short-path distillation apparatus; yield 5560%. An additional 510% yield can usually be recovered by extracting the tarlike residue with pentane, filtering off the insolubles, removing the pentane in vacuo, and again distilling the residue as before. 1H NMR (benzene-d6, ): 1.66 (Ct-Bu); 13C{1H} NMR (benzene-d6, ): 316.2 (WC).
Ethylidyne(N-(trimethylsilyl)-N,N-bis{2-[(trimethylsilyl)amino-k N]ethyl}ethane-1,2-diamido-k N,k N)tungsten(VI) (40, M = W; R1 = Me); Typical Procedure:[71]
Tris(2,2-dimethylpropyl)(2,2-dimethylpropylidyne)tungsten(VI) (39):[68]
An Et2O (25 mL) soln of [WCl{N(CH2CH2NTMS)3}] (0.20 g, 0.345 mmol) was treated with EtLi (0.019 g, 0.52 mmol) at 25 8C. The mixture turned light yellow as gas evolved. The resulting mixture was stirred for another 3 h and then evaporated to dryness in vacuo. The yellow residue was extracted with pentane (60 mL), and the extract was filtered. The filtrate was concentrated to ca. 5 mL in vacuo and chilled at 40 8C for several h to yield the product as light yellow crystals; yield: 0.16 g (81%); 1H NMR (benzene-d6, ): 3.73 (WCCH3, 3JWH = 7.9 Hz); 13C{1H} NMR (benzene-d6, ): 274.33 (WC).
2.6.2.2
Method 2: By Addition of Alkynes to Compounds with Metal-Metal Triple Bonds
Symmetrical alkynes provide access to carbyne complexes 42 upon reaction with symmetrical triply bonded tungsten alkoxy, aryloxy, and mixed alkylalkoxy complexes (Scheme 15).[74,75] This reaction occurs readily when R1 is a simple alkyl group but also for functionalized alkynes, more easily so in the presence of nitrogen donors (in which case the base adducts are obtained).[74] This reaction is very sensitive to steric factors. The formation of alkyne adducts, bis-alkyne adducts, and products of C-C couplings are possible alternatives.[75,76] Other group 6 triply bonded dimers such as hexakis(dimethylamido)- or hexaalkylditungsten(III) and molybdenum alkoxides do not cleave internal alkynes.
2.6.2
83
Unsymmetrical alkynes can often be cleaved even if one of the substituents is bulky, giving a 1:1 mixture of the two carbyne products. However, use of an excess of the alkyne increases the yield of one carbyne product, e.g. 43, by the metathesis procedure described in Section 2.6.2.3, provided the lower-boiling alkyne is removed. Some of these reactions afford satisfactory results only in the presence of a stabilizing base, e.g. quinuclidine.[74] Terminal alkynes react with both tungsten and molybdenum alkoxides, but the CH product is not isolable unless a stabilizing base is present.[77] The triple bond of selected nitriles is also cleaved to afford a mixture of the carbyne and the sparingly soluble nitride products.[78,79]
Scheme 15 Addition of an Alkyne to a Compound Containing a Metal-Metal Triple Bond [74,79]
pentane, Et2O DME or THF 40 oC to rt 4791%
X3W
WX3 +
R1C
CR1
2 W(
CR1)X3 42
WX3 = W(Ot-Bu)3, W(CH2t-Bu)(O-iPr)2 R1 = Me, Et, Pr, CH2NMe2, CH2NEt2, MOM, CH2OTMS pentane, Et2O DME or THF 40 oC to rt
(ButO)3W
W(OBut)3
+ R1 C
CR2
W(
CR1)(OBut)3 + 43
W(
CR2)(OBut)3
R1 = t-Bu, TMS, Ph, CH CH2, CH(OEt)2, CO2Me, CH2CO2Me, Ac, St-Bu R2 = Me, Et
But-2-yne (80.1 L, 1.02 mmol) was added to a soln of [W2(Ot-Bu)6] (0.75 g, 0.93 mmol) in pentane (30 mL) at 40 8C. The soln was maintained at 40 8C for 1 h and allowed to warm to rt. The orange color faded to light amber, and after 2 h at rt the volatile components were removed in vacuo, leaving a light brown solid. Larger scale preparations sometimes yielded a brown oil initially, but the oil always crystallized with time in vacuo or when seeded. Sublimation of the light brown residue at 25 8C/106 Torr onto a 78 8C probe afforded the pure, white product; yield: 0.59 g (74%). This material is very oxygenand moisture-sensitive and darkens slightly when removed from the probe in a drybox. It was generally prepared in pentane or THF and utilized directly for further reactions, assuming a quantitative yield. 13C{1H} NMR (benzene-d6, ): 254.3 (WCMe).
2.6.2.3
Tri-tert-butoxy(ethylidyne)tungsten(VI) (42, X = Ot-Bu; R1 = Me); Typical Procedure:[74]
Method 3: By Stoichiometric Alkyne Metathesis
A variety of alkoxocarbyne complexes may be obtained from a preexisting carbyne complex and an alkyne by a metathesis process (Scheme 16). This exchange takes place via a metallacyclobutadiene intermediate 44, which has been observed or isolated for the corresponding aryloxo and fluorinated alkoxo systems. Such intermediates have greater stability for the tungsten systems.[67] This procedure is synthetically useful for symmetrical, unsymmetrical, and terminal alkynes. Like the reactions examined in Section 2.6.2.2, these are also sensitive to steric factors.[67,74] Electronic factors are also important, however, fluoroalkoxo complexes reacting more readily than the corresponding alkoxo complexes without fluorine substituents. Terminal acetylenes also react with bulkier carbyne complexes, but the reaction is often complicated and other products (e.g., deprotonated metallacyclobutadiene derivatives) may be obtained, limiting the synthetic utility.[67]
84

Scheme 16 Stoichiometric Alkyne Metathesis[67,74]
R2 M( CR2)(OR1)3(L) + R3C CR4 (excess) (R1O)3(L)M R3 44 R4
M( CR3)(OR1)3(L)
R2C CR4
R1
R2
R3
R4
Conditions
Yield (%) of [M(CR3) (=OR1)3(L)] 8090 quant. 64
Ref
Mo Mo W
a b
DME quinoline
CMe(CF3)2 t-Bu t-Bu
t-Bu t-Bu Me
Et2O, rt, 15 min Et2O, rt, 30 min pentane, rt, 2d
[67]
H Et
[67]
CCEt
[74]
R3 = R4 = Me, Et, Pr, Ph. R3 = Pr, iPr, Ph.
Addition of one equivalent of an internal alkyne, trichloro(1,2-dimethoxyethane-O,O)(2,2-dimethylpropylidyne)tungsten(VI) affords a stable tungstacyclobutadiene product, but reaction with additional alkyne yields 5-cyclopentadienyl products of further alkyne insertion rather than products of alkyne metathesis.[69,80]
Butylidynetris(1,1,1-trifluoro-2-methylpropan-2-olato)molybdenum(VI); Typical Procedure:[67]
Excess PrCCPr (125 L, 0.85 mmol) was added to [Mo(Ct-Bu){OCMe2(CF3)}3] (0.09 g, 0.16 mmol) dissolved in Et2O (3 mL). After 30 min, the solvent was removed in vacuo, leaving white needles that were pure by NMR; 13C{1H} NMR (benzene-d6, ): 299.3 (MoCPr).
2.6.2.4
Method 4: By Oxidation of Fischer-Type Carbyne Complexes
The dibromine oxidation of (alkylidyne)bromotetracarbonyl complexes of molybdenum and tungsten in the presence of 1,2-dimethoxyethane (DME) provides a direct access to DME-stabilized (alkylidyne)tribromo complexes, while the corresponding chromium systems lead to complete degradation.[81] The advantage of this procedure is the direct access to complexes with a wide variety of carbyne substituents starting from the corresponding, easily accessible Fischer-type carbyne precursor. The phenyl derivative 45, in particular, is easily synthesized in a one-pot procedure from the precursor as shown in Scheme 17.
Scheme 17 Oxidation of Fischer-Type Carbyne Complexes[81,82]
oxalyl bromide CH2Cl2, 78 oC Br2, DME CH2Cl2
Me4N[M(COPh)(CO)5]
MBr(
CPh)(CO)4
78 oC M = Mo 80% M = W 88%
MBr3(
CPh)(DME) 45
2.6.2
85
Me4N[W(COPh)(CO)5] (10.00 g, 19.87 mmol) was completely dissolved in CH2Cl2 (300 mL) then the soln was cooled to 78 8C. Oxalyl bromide (1.87 mL, 20.0 mmol) was dissolved in CH2Cl2 (40 mL) and cooled to 78 8C, then quickly added against a N2 stream to the acyl soln. This soln was left to stir at 78 8C for 15 min, then warmed in an ice bath just until a bright yellow color developed. It was immediately recooled to 78 8C; then this soln was filtered through a dry-ice jacketed frit, having a 2-cm layer of dry cellulose on it, into a cooled (78 8C) receiving flask (500-mL Schlenk). To the soln of [WBr(CPh)(CO)4] at 78 8C was added DME (10 mL). A freshly prepared 1.0 M soln of Br2 in CH2Cl2 (20 mL) with an additional quantity of CH2Cl2 (20 mL) was cooled to 78 8C and added (poured) against a strong N2 stream as quickly as possible. The color became red briefly then dark orange. The stirred soln was allowed to warm to rt under vacuum; much gas was evolved during the warming step. The solvent was removed in vacuo and the dark brown oily solid was washed with pentane (50 mL). The solid was then dissolved in CH2Cl2 (30 mL) and filtered. The volume was reduced to 15 mL and pentane (100 mL) was added gradually to precipitate the product as a green-brown solid. This precipitation process was repeated until the product in CH2Cl2 was emerald green. The final product was a dark green microcrystalline powder; yield: 10.49 g (88%); 13C{1H} NMR (benzene-d6, ): 331.7 (WCPh).
2.6.2.5
Benzylidynetribromo(1,2-dimethoxyethane-O,O)tungsten(VI) (45, M = W):[81,82]
Method 5: By Rearrangement of Vinyl Complexes
Vinyl complexes can, under favorable circumstances, rearrange by a [1,2]-H shift to carbyne complexes (Scheme 18).[83] The reaction appears to proceed via a 2-vinyl complex 46, which has been isolated in some cases,[84] and thus requires an open coordination site on the metal center. The vinyl precursors are often prepared in situ by hydride addition to alkyne complexes, e.g. for the synthesis of 47 and indenyl analogues,[84] by deprotonation of alkene complexes,[13] or by transmetalation, as for the synthesis of 48.[73] The vinyl complex intermediate may not be observed in some cases. 3-Allyl complexes are possible byproducts of this reaction when the substituents R2 and R3 bear -hydrogen atoms (e.g., 47),[85] in which case the rearrangement to the carbyne product is favored by the presence of free ligands and higher temperatures.
Scheme 18 [1,2]-H Shift from Vinyl Complexes[73,84]
R3 R [M] R1 46 + H (MeO)3P Mo Pri
2
R3 R2 [M] R1
[1,2]-R1 shift
[M]
R3 R2 1 R
NaBH4 P(OMe)3 (excess) THF, rt, 2 h 58%
(MeO)3P
Mo
CH2Pri
(MeO)3P
(MeO)3P 47
WCl2(PMe3)4
(5 equiv) Si(OMe)3 THF, reflux, 8 h 93%
CMe PMe3 Me3P W PMe3 Me3P Cl 48
86
5-Cyclopentadienyl(3,3-dimethylbutylidyne)bis(trimethyl phosphite-P)molybdeA soln of [MoCp{-(E)-CH=CHt-Bu}{P(OMe)3}3] (0.35 g, 0.5 mmol) in hexane (10 mL) contained in an evacuated sealed tube (50 mL) fitted with a Westoff stopcock was heated at 80 8C for 12 h. The mixture became bright yellow. The volatile material was removed in vacuo and the residue was dissolved in Et2O (5 mL) and chromatographed on an aluminapacked column. Elution with hexane gave a bright yellow band, which was collected and the volume of the solvent was reduced (to 5 mL); cooling (78 8C, 3 d) afforded the product as bright yellow crystals; yield: 0.21 g (85%); 1H NMR (benzene-d6, ): 5.2 (s, 5H, Cp), 2.2 (t, 2H, CH2t-Bu, 3JHP = 4.0 Hz); 13C{1H} NMR (benzene-d6, ): 299.8 (t, MoC, 2JCP = 27.0 Hz).
2.6.2.6
num(IV):[84]
Method 6: By Other Rearrangement Processes
The stability of the metalalkylidyne bond, especially for tungsten, induces other remarkable rearrangements from a variey of systems. The high-yield synthesis of compound 49 upon photolysis of hexamethyltungsten(VI) in neat trimethylphosphine involves a methyl migration onto a proposed carbyne intermediate (Scheme 19).[86] Other rearrangement processes have been established for selected cycloalkyl complexes.[13,72] For molybdenum complexes, the cyclobutyl complex 50 converts into the butylidyne product 52 without observation of a metallacyclopentene intermediate 51.[72] For tungsten complexes, on the other hand, alkylation of the chloro precursor complex with cyclobutyllithium yields the stable complex 51 directly, which is further transformed to the carbyne product 52 upon warming (Scheme 19).[71] Cyclopropyl derivatives undergo elimination of ethene and formation of a methylidyne product, while the cyclopentyl derivatives do not undergo the ring-opening step.
Scheme 19 Other Rearrangement Processes[71,72,86]
WMe6
Me3P (neat), h 2CH4
[W(
CH)(Me)3(PMe3)n]
[W(Me)2(
CHMe)(PMe3)n]
CH4 90%
W(Me)(
CMe)(PMe3)4 49
TMS TMS TMS N N N M N 50
TMS TMS N N M N 51
TMS N
M = W quant
TMS TMS TMS N N N M N 52

M = Mo 86%
Butylidyne(N-(trimethylsilyl)-N,N-bis{2-[(trimethylsilyl)amino-k N ]ethyl}ethane-1,2diamido-k N,k N)molybdenum(VI) (52, M = Mo); Typical Procedure:[72]
Compound 50 (M = Mo; 124 mg, 0.243 mmol) was dissolved in toluene (5 mL), and the soln was heated in a sealed tube to 60 8C for 2 h. The toluene was removed in vacuo, and the residue was dissolved in a minimum amount of pentane. The pentane soln was cooled to 40 8C to give brown crystals of the product after 24 h; yield: 107 mg (86%); 13C{1H} NMR (benzene-d6, ): 298.3 (MoC).
2.6.3
Metals-Alkyl and s-Aryl Homoleptic Complexes
87
The reactivity of Schrock-type carbyne complexes has to date been little exploited in organic synthetic applications in comparison with that of the corresponding carbene complexes (Section 2.6.1.5). For the most part, the interest has been limited to stoichiometric transformations to other organometallic products. Some carbyne compounds ([M]CR) undergo Wittig-like reactions with XY molecules, affording [M]X and RCY products.[63] As seen in Section 2.6.2.3, the addition of an alkyne (R2CCR2) to a carbyne complex ([M]CR1) may afford the metathetical products (R2CCR1 + [M]CR2). Some of these complexes catalyze the alkyne metathesis reaction.[87]
2.6.2.7
Method 7: Alkyne Metathesis
Medium-large cycloalkynes 53 have been synthesized from diyne precursors by a ringclosing metathesis process in which a tungsten carbyne complex acts as a catalyst (Scheme 20).[46] The cycloalkyne obtained by this methodology can be partially reduced to obtain the cycloalkene exclusively as the Z-isomer. The stereoselectivity of this route is particularly notable, since current molybdenum- and ruthenium-based ring-closing metathesis catalysts usually provide mixtures of E- and Z-configured cycloalkenes from diene precursors (see Section 2.6.1.5.3). The catalyst tolerates various functional groups: lactones, lactams, and silyl ethers have been obtained by this method. The catalyst is incompatible with terminal acetylenes; thus, it is necessary to use precursors with R1, R2 H. The use of a high boiling point solvent (e.g., 1,2,4-trichlorobenzene) allows the removal of the alkyl byproduct (R1CCR2) under reduced pressure, with a positive effect on the conversion.
Scheme 20
R1
W(
Cycloalkynes by Ring-Closing Metathesis of Diynes[46]

R1
Ct-Bu)(Ot-Bu)3 5297%
X R1
X 53
+ R1
R1 = Me, Et; X = (CH2)2OC(O)(CH2)4C(O)O(CH2)2
A soln of the diyne [MeCC(CH2)2O(O)C(CH2)2]2 (121 mg, 0.43 mmol) and [W(Ct-Bu)(OtBu)3] (12 mg, 6 mol%) in chlorobenzene (20 mL) was stirred under argon at 80 8C for 2 h. The solvent was removed in vacuo, and the residue purified by flash chromatography (Merck silica gel, hexane/EtOAc 4:1). This led to the recovery of some unchanged starting material (12 mg, 10%) and afforded the cycloalkyne product as colorless crystals; yield: 70 mg (73%); mp 106107 8C; 13C NMR (): 173.0 (alkyne).
2.6.3
1,6-Dioxacyclotetradec-9-yne-2,5-dione [53, X = (CH2)2OC(O)(CH2)4C(O)O(CH2)2]; Typical Procedure:[46]
Product Subclass 3: Metal-Alkyl and -Aryl Homoleptic Complexes
Compounds of this class are rather limited, their syntheses are generally low yielding, and have no general applications in organic synthesis. As is usually the case for any metal, the more robust complexes are those without -hydrogens and aryl complexes. Well-characterized members of this class have the stoichiometries MR6, MR4, [MR6]3, [MR5]2, [MR4], MR3, and [MR4]2. The MR6 complexes are known only for tungsten and have a
88
strong tendency to decompose by -hydrogen elimination. The tetrahedral MR4 complexes can only be obtained with sterically demanding ligands and are unexpectedly unreactive. While M(III) complexes with three unpaired electrons are common for chromium, no unambiguous example has been reported for molybdenum or tungsten. Delicate equilibria may exist between different species as a function of the size of R, the nature of the counterion, or even the solvent. For example, orange-yellow hexaphenylchromate(III), blue-green pentaphenylchromate(III), and cherry-red tetraphenylchromate(III) have been isolated under different conditions.[8890] Neutral trialkylchromium(III) compounds are known only with very bulky R groups, e.g. bis(trimethylsilyl)methyl [CH(TMS)2].[91] Unambiguous M(II) complexes exist only for chromium. These are either paramagnetic (S = 2) and square planar tetraalkylchromate(2) monomers or diamagnetic tetraanionic dimers. The choice of nuclearity is highly dependent on the counterion and the solvent; for example, the lithium salt of tetramethylchromate(II) adopts a monomeric or a dimeric structure depending on whether the lithium cations are surrounded by tetramethylethylenediamine or by diethyl ether molecules.[92] The relatively high polarity of the metal-alkyl bonds makes these derivatives rather sensitive toward proton sources including water, especially when the latter can be activated by coordination to the metal center. Thus, these compounds must generally be synthesized and handled under scrupulously dry conditions.
2.6.3.1
Method 1: By Transmetalation
The only synthetic method that allows access to homoleptic alkyl and aryl complexes of group 6 metals is the transmetalation reaction (Scheme 21). Competitive electron-transfer processes and equilibria of association/dissociation of the alkylating reagent are often the reasons for the moderate yields usually associated with these syntheses. There is no general rule as to the best reagents and conditions to use for a specific product. Lithium and magnesium reagents are typically used, although other alkylating sources have also been employed. This is exemplified by the synthesis of hexamethyltungsten(VI) (54)[93,94] and tetracyclohexylchromium(IV) (55).[95] As a general rule, lithium reagents are more reactive than Grignard reagents, but have a greater tendency to engage in single-electrontransfer (SET) side reactions. The choice of solvent may also be a determinant factor. Tetrahydrofuran, diethyl ether, and toluene are the most commonly used solvents, the latter disfavoring SET processes. The group 6 metal sources are typically the halides, but the alkoxides have also been used, the latter usually reducing the SET reactivity. Many neutral metal(IV) compounds are obtained from lower oxidation state precursors in <50% yield, e.g. 55,[95] via a disproportionation mechanism.
Scheme 21 Homoleptic Metal Alkyl and Aryl Complexes by Transmetalation[94,95]
ZnMe2 (3 equiv) pentane, 78 oC 53%
WF6
WMe6 54
CyMgBr
CrCl3(THF)3
22%
CrCy4 55
2.6.4
Metals-Alkyl and s-Aryl Non-homoleptic Complexes
89
Hexamethyltungsten(VI) (54):[94]
CAUTION: Hexamethyltungsten(VI) is known to decompose explosively. Proper safety precau-
tions should be taken during its synthesis, storage, and handling.
A 50-mL glass container with two openings was attached to a vacuum line, and WF6 (1.1 g, 3.7 mmol) and pentane (10 mL) were condensed into it in vacuo and with cooling (liq N2). A 1 M soln of ZnMe2 in heptane (11.5 mL) was slowly added dropwise at 78 8C. The mixture was stirred at 35 8C for 2 d, filtered at 10 8C, and concentrated in vacuo at 70 8C to afford an orange soln. The yield (53%) was determined by the quantitative reaction of 54 with NO and weighing the resulting product [WMe4{ON(Me)NO}2].
2.6.4
Product Subclass 4: Metal-Alkyl and -Aryl Non-homoleptic Complexes
Non-homoleptic (heteroleptic) complexes containing alkyl and aryl ligands are much more common, exist in a wider variety of formal oxidation states and coordination environments, and are more versatile in organic synthesis than the homoleptic complexes. The use of ancillary ligands with strong -donating properties increases the relative stability of high oxidation state derivatives. Thus, M(V) and M(VI) (M = Cr, Mo) alkyl and aryl complexes exist when supported by oxo, imido, or nitrido ligands,[9699] whereas no homoleptic counterparts are known. Non-homoleptic tungsten(VI) complexes are more common and stable than the homoleptic ones. Like the homoleptic complexes (Section 2.6.3), the non-homoleptic complexes tend to decompose more readily when they bear hydrogen atoms on the -position, via the ubiquitous -hydrogen elimination pathway. As this pathway necessitates an empty metal orbital cis relative to the alkyl group and a coplanar transition state, stable complexes with -hydrogen-bearing alkyl ligands may only be obtained when one or more of the above requirements are not met.[100] In particular, these compounds may be isolated when each valence-shell metal orbital is occupied by at least one electron and when the ligands cis to the alkyl group do not easily dissociate. Complexes whose alkyl substituents bear hydrogen atoms on the -position may also decompose, this process being especially favored for high-valent molybdenum and tungsten complexes, providing good synthetic methods for carbene and carbyne complexes (see Sections 2.6.1 and 2.6.2, respectively). Other methods of decomposition are associated with intramolecular C-H bond activation of ancillary ligands, which is promoted by the metal electron richness, e.g. see Scheme 22.[101] Finally, homolytic cleavage of the metal-alkyl bond may occur with production of radicals and reduced metal complexes. Aryl derivatives are more robust than the alkyl complexes toward this decomposition pathway.
Scheme 22 Decomposition of Alkyl Complexes by Alkane Elimination[101]
Mo Me Me3P Me3P PMe3
benzene-d6, >40 oC CH4
Mo Me3P Me3P P Me2
Like the homoleptic complexes, the transmetalation reaction represents the most convenient entry to alkyl and aryl non-homoleptic complexes of group 6 metals. The metal-alkyl and metal-aryl bonds may also be formed, however, by oxidative addition reactions.
90

2.6.4.1
The ancillary ligands often provide steric and electronic protection to the transition-metal center, resulting in a greater selectivity and higher yields for the transmetalation reactions relative to those leading to the homoleptic counterparts (see Scheme 23). A typical example is the synthesis of 56.[102] The empiricism in the choice of alkylating/arylating agent and conditions parallels that discussed for the homoleptic products in Section 2.6.3. In addition to lithium and magnesium reagents, the occasional use of dialkylzinc is also reported. The synthesis of compound 57 proceeds in good yields from the tri-tertbutoxo precursor, whereas no product is recovered when starting from the corresponding trichloride.[103] While the bis(imido)chromium(VI) precursors 58 afford products 59[96,97,104] and mesitylmagnesium bromide reacts cleanly with dichlorodioxomolybdenum(VI) to afford the corresponding dimesityldioxo product, use of mesitylmagnesium bromide with dichlorodioxochromium(VI) leads to chromium(V) and chromium(III) products.[97] The reaction between phenylmagnesium bromide and chromium(III) chloride in diethyl ether leads to chromium(I)--arene complexes as final products.[105,106] The initial reaction does, however, generate chromium(III)--phenyl species, and the greater coordinating ability of tetrahydrofuran permits the isolation of triphenyltris(tetrahydrofuran)chromium(III).[107] In some cases, the reduction accompanying transmetalation may be synthetically useful, e.g. the synthesis of 60.[108]
Scheme 23
W(Cp)2Cl2
Transmetalation[96,97,102,103,108]
MeLi (2 equiv), toluene 80 oC, 2 h 65%
WMe2(Cp)2 56
Mo(
N)(OBut)3
t-BuCH2MgBr (3 equiv) 83%
Mo(CH2But)3( 57
N)
CrX2( 58
NR1)2
R2MgY (2 equiv)
CrR22( 59
NR1)2
X = OTMS; R1 = t-Bu; R2 = Mes, 2,6-Me2C6H3 X = Cl; R1 = t-Bu, 2,6-iPr2C6H3; R2 = Me, Bn
MeLi or MeMgCl
MOCl4
M = Mo, W
2228%
[Mg(THF)4][MOMe4]2 60
[W(Cp*)2Cl2] (2.0 g, 3.8 mmol) and MeLi (0.40 g, 18.2 mmol) were treated with toluene (20 mL) and heated to 80 8C for 2 h, giving a red-orange soln. The mixture was filtered and the toluene was removed under reduced pressure. The residue was extracted into pentane and cooled to 78 8C, giving orange needles of [W(Me)2(Cp*)2]; yield: 1.2 g (65%); 1 H NMR (benzene-d6, ): 1.60 (s, 30H, C5Me5), 0.54 (s, 6H, WMe).
Dimethylbis(5-pentamethylcyclopentadienyl)tungsten(IV) (56); Typical Procedure:[102]
2.6.4
91
2.6.4.2
Method 2: By Oxidative Addition of Alkyl Halides
This method has mostly been used for the synthesis of chromium(III) compounds, with wide application in the NozakiHiyamaKishi reaction (Section 2.6.4.5). Other group 6 derivatives have been prepared as well.
2.6.4.2.1
Variation 1: One-Electron Oxidative Additions
Chromium(II) precursors react with alkyl halide reagents to afford a 1:1 mixture of chromium(III) halide and alkylchromium(III) products. The mechanism involves single-electron-transfer steps and radical intermediates (Scheme 24). Other radical sources may be used instead, including hydroperoxides or alkane/hydrogen peroxide mixtures under thermal, flash photolysis, or pulse radiolysis conditions.[109] This procedure has been used to produce the alkylpentaaquachromium(III) ion 61.[110] The latter is long-lived but cannot be isolated and must be generated in situ. Activated alkyl halides react thermally with the chromium(III) ion, while other alkyls require photolytic or radiolytic conditions. The addition of ligands such as ethylenediamine or saturated tetraaza macrocycles makes the process more favorable for both thermodynamic and kinetic reasons.
Scheme 24 One-Electron Oxidative Addition of Alkyl Halides[110]
R 1X
[Cr(OH2)6]2+ [CrX(OH2)5]
2+
R1
[Cr(OH2)6]2+
[CrR1(OH2)5]2+ 61
H2O (1 L) was freed of oxygen and then shaken with CHCl3 (10 mL). A 0.2 M soln of chromium(II) perchlorate (500 mL) was added in an atmosphere of N2 and the soln allowed to stand for 2 or 3 h at rt. The grayish-red soln gave no precipitate with AgNO3 soln at rt. A portion (100 mL) of this soln was placed on a column (15 cm 2 cm) of Dowex 50-X4 (200 400 mesh) in the hydrogen form and the column was eluted with 1 M HClO4 at the rate of 12 drops s1. A green fraction (100 mL) was soon eluted, followed by a colorless soln (150 mL), and then by a red fraction (110 mL). The green and red fractions were identified as containing [Cr(H2O)5Cl]2+ and [Cr(H2O)5(CHCl2)]2+, respectively, by UVvis spectroscopy and quantitative analysis with AgClO4 and KMnO4.
2.6.4.2.2
Reduction of Chloroform with Chromium(II) Perchlorate:[111]
Variation 2: Two-Electron Oxidative Additions
Electron-rich metal complexes containing at least one electron pair in a metal-based orbital may undergo a classical two-electron oxidative addition of alkyl halides, making a new metal-alkyl bond (Scheme 25). This synthetic strategy is thus generally limited to systems supported by electron-donating ancillary ligands. No synthetically useful examples of this type of reactivity have been described for noncarbonyl-containing group 6 organometallic species where the halide ion is incorporated in the coordination sphere of the metal. However, there are examples of two-electron oxidative addition reactions of alkyl halides where the halide remains as an outer sphere counterion, as in the preparation of 62.[102]
92

Scheme 25
W(Cp)2(
Two-Electron Oxidative Addition of an Alkyl Halide[102]

MeI, toluene rt, 12 h 77%
O)
[WMe(Cp)2( 62
O)]+ I
A soln of [W(Cp*)2(=O)] (150 mg, 0.32 mmol) in toluene (3 mL) was treated with MeI (0.2 mL, 3.2 mmol) and the mixture was stirred. After ca. 5 min a yellow microcrystalline deposit started to form. The stirring was continued for 12 h. The mixture was filtered and the solid was washed with pentane (3 2 mL) and dried in vacuo to give yellow crystals of 62; yield: 150 mg (77%); IR (Nujol) max: [W(=O)] 868 (s) cm1; 1H NMR (CDCl3, ): 2.13 (s, ~ 15H, C5Me5), 1.07 (s, 3H, WMe).
2.6.4.3
Methyloxobis(5-pentamethylcyclopentadienyl)tungsten(VI) Iodide (62):[102]
Method 3: By Oxidative Addition of Alkanes and Arenes
Alkanes and arenes may be able to add oxidatively to a suitable metal complex, forming an alkyl (or aryl) hydride product (Scheme 26). Arenes are more suitable than alkanes for this methodology, for both kinetic and thermodynamic reasons. The metal complex must be quite electron-rich to accomplish this process. Sufficiently reactive metal substrates are usually generated in situ from more stable precursors by either a thermal or a photochemical dissociation or reductive elimination process. For example, the tungstenocene leading to product 63 is generated by photolytic reductive elimination of dihydrogen from bis(5-cyclopentadienyl)dihydridotungsten(IV).[112] Tungstenocene may also be generated by thermal alkane elimination from a dicyclopentadienylalkylhydride system.[113] The product of the oxidative addition step may further evolve to afford more stable alkyl or aryl products, as is the case for the synthesis of compound 64.
Scheme 26 Oxidative Addition of Alkanes and Arenes[112,114]
H W(Cp)2H2
h, benzene H2
benzene >80%
(Cp)2W Ph 63
Me4Si (neat) 70 oC, 2.5 d
Me4Si
ON
CH2But CH2But
ON
90%
CHBut
ON
CH2TMS CH2But
64
In a glovebox an ampule (Teflon stopcock) was charged with [W(CH2t-Bu)2Cp*(NO)] (0.048 g, 0.098 mmol) and Me4Si (1 mL). The resulting wine-red mixture was stirred and heated at 70 8C for 2.5 d, during which time it changed to a darker red soln. The organic volatiles were removed under reduced pressure. The remaining dark wine-red solid was redissolved in pentane and filtered through Celite. The resulting soln was stored for several days to provide 64 as maroon crystals; yield: 0.045 g (90%); 1H NMR (benzene-d6, ): 1.54 (s, 15H, C5Me5), 1.35 (s, 9H, t-Bu), 0.38 (s, 9H, TMS).
(2,2-Dimethylpropyl)nitrosyl(5-pentamethylcyclopentadienyl)[(trimethylsilyl)methyl]tungsten(II) (64); Typical Procedure:[114]
2.6.4
93
2.6.4.4
Method 4: By Protonation of Carbene and Carbyne Ligands
Under suitable conditions, carbene and carbyne ligands can take up protons to generate alkyl derivatives. The proton source must be of low acidity to avoid further protonolysis of the alkyl product. This methodology is of rather limited synthetic utility. Two examples are shown in Scheme 27.[115,116] The formation of 65 involves loss of the pyridine ligand and proton transfer from the silanol to the carbene ligand, while even more extensive changes accompany the protonation of the carbyne ligand to give alkyl complex 66. Intramolecular proton transfer from other ligands (e.g., other alkyl groups) is also possible.[65,66]
Scheme 27 Protonation of Carbene and Carbyne Ligands[115,116]
Ph3SiOH, benzene rt, 90 min
Mo ON py
CHBut
75%
Mo ON
CH2But OSiPh3
65
Et4NOH, THF 6282%
W(
CR1)(OBut)3
[Et4N][W(CH2R1)O3] 66
R1 = t-Bu, TMS
5-Cyclopentadienyl(2,2-dimethylpropyl)nitrosyl(triphenylsilanolato)molybdenum(II)
In a glovebox, [Mo(=CHt-Bu)Cp(pyridine)(NO)] (102 mg, 0.30 mmol) and Ph3SiOH (83 mg, 1.0 equiv) were weighed into the reaction vessel. Benzene (20 mL) was vacuum-transferred onto the solids. The mixture was then warmed to rt and stirred for 1.5 h. Over the course of the reaction a color change from amber to dark red-brown occurred. The solvent was removed from the final mixture in vacuo, and the residue was extracted with Et2O (2 25 mL). The extracts were filtered through Celite and the filtrate was concentrated under reduced pressure to incipient precipitation. Well-defined red blocks formed over~ night and were isolated by cannulation; yield: 121 mg (75%); IR (Nujol) max: (NO) 1607 (vs) cm1; 1H NMR (benzene-d6, ): 3.79 (d, 1H, CHH, JHH = 9.9 Hz), 0.99 (d, 1H, CHH, JHH = 9.9 Hz).
(65); Typical Procedure:[115]
Alkylchromium(III) compounds are involved in the large-scale commercial polymerization of ethene and propene. Well-defined complexes that mimic the activity and selectivities of the commercial catalyst have been obtained.[117] An application of group 6 alkyl and aryl complexes that has been successfully applied to organic synthesis is the addition reaction to carbonyl compounds (see Sections 2.6.4.5 and 2.6.4.6). Other chromium-based systems have been developed for single-electron-transfer chemistry,[118] oxidation of alkanes via hydrogen atom abstraction,[119] and asymmetric ring opening of meso-epoxides.[120] Although these latter systems are of interest for synthetic organic chemistry, they do not involve the formation of direct Cr-C bonds, and consequently these applications are not treated here.[121]
94
2.6.4.5
Method 5: Addition of Organochromium(III) Compounds to Carbonyl Compounds
Under certain circumstances, organochromium(III) compounds transfer their alkyl or aryl groups to aldehydes and, less frequently, to ketones. The particular selectivity and tolerance of this reaction make it particularly useful in organic synthesis. The use of these chromium reagents may be advantageous for use with acid-sensitive substrates, because of their reduced Lewis acidity relative to other transfer reagents [e.g., trichloromethyltitanium(IV) or alkyltriisopropoxotitanium(IV)].
2.6.4.5.1
Variation 1: Reaction of Organochromium(III) Compounds Prepared from Organochromium(III) Chloride by Transmetalation
The organochromium(III) compound may be either isolated before the addition to the carbonyl compound or prepared in situ, as shown in Scheme 28. Triphenyltris(tetrahydrofuran)chromium(III) is able to react with ketones, viz. pentan-3-one (67) and cyclohexanone.[122] On the other hand, chlorodialkyl and dichloroalkyl derivatives are highly aldehyde selective, while alkylpentaaquachromium(III) is unreactive. The alkyldichlorochromium(III) reagent is particularly useful as it can be readily generated in situ by transmetalation from chromium(III) chloride and a Grignard reagent; see the formation of 68.[123] These reagents are able to transfer the alkyl group to the organic substrate even in an alcoholic medium or in the presence of water.[124] Dichloro[(trimethylsilyl)methyl]chromium(III) allows an aldehyde-selective alkenation process after acid hydrolysis.[125] This procedure has been more recently supplanted by those described in the following variations.
Scheme 28
O
Reaction of Organochromium(III) Complexes with Carbonyl Compounds[122,123]

Cr(Ph)3(THF)3 THF, 30 to 20 oC
Ph
OH +
Ph
OH HO Et
67 O ( )5 H
1. CrR1Cl2(THF)3, THF, 60 oC 2. H2O 6585%
70%
17%
OH H ( )5 R1 68
R1 = Me, Pr, Bu, Bn
A briskly stirred suspension of [CrPh3(THF)3] [from CrCl3(THF)3 (16 g, 43 mmol) suspended in THF (500 mL) and PhMgBr (129 mmol)] in THF at 30 8C was treated dropwise with freshly distilled pentan-3-one (67; 20 mL, 190 mmol). The mixture was then allowed to warm up to rt. After 2 h at 20 8C the solvent was removed by distillation under reduced pressure and the product hydrolyzed with H2O and filtered, both residue and filtrate being washed with Et2O. The dried ethereal layer was evaporated and the residue (21.2 g) separated by distillation. The volatile component, bp 5762 8C/0.01 Torr (14.9 g, 90 mmol, 70% relative to PhMgBr) was shown to be 3-phenylpentan-3-ol by a direct comparison of its IR spectrum with that of an authentic specimen. The semicrystalline residue (5.87 g) was chromatographed to give traces of oily products and 3-ethyl-4-methyl-5-phenylheptane-3,5diol; yield: 5.36 g (17% relative to PhMgBr); mp 9092 8C (hexane).
Reaction of Triphenyltris(tetrahydrofuran)chromium(III) with Pentan-3-one (67):[122]
2.6.4
95
2.6.4.5.2
Variation 2: Reaction of Organochromium(III) Compounds Prepared from Chromium(II) Chloride by Oxidative Addition (The NozakiHiyamaKishi Procedure)
This methodology was pioneered by Hiyama[126] and refined by Kishi[127] and Nozaki.[128] The organochromium reagent is readily formed from chromium(II) salts upon one-electron oxidative addition (Section 2.6.4.2.1) of a wide range of substrates including allyl, propargyl, alkenyl, and aryl halides, alkenyl trifluoromethanesulfonates, and allyl sulfonates and phosphates. The most convenient chromium(II) salt is the anhydrous chloride, which can either be purchased or prepared in situ from chromium(III) chloride and various reducing agents. The performance of the chromium(II) chloride reagent in forming the Cr-C bond is enhanced by the addition of a catalytic amount of nickel(II) chloride.[127,128] The alkylchromium(III) species are highly aldehyde selective, e.g. the formation of 69 in Scheme 29.[126] The most important feature, however, is the unparalleled compatibility with a wide array of functional groups in both reaction partners. In addition, the method features useful stereoselectivities. Substituted allyl reagents lead to the homoallyl alcohols. If the allyl reagent is -monosubstituted, the anti-alcohol is favored independent of whether the starting halide is E or Z configured; see the synthesis of 70 where the antiproduct is obtained in 100% selectivity.[129] Alkenyl halides or trifluoromethanesulfonates react with complete retention of their double-bond geometry, e.g. the synthesis of 71.[128] These useful features have made chromium-induced inter- or intramolecular C-C bond formations a frequent key step in the total synthesis of molecules of utmost complexity,[130] including the total synthesis of brevetoxin B.[131]
Scheme 29 The NozakiHiyamaKishi Reaction[126,128,129]
O OHC + Br
CrCl2 (1.2 equiv), THF 66%
OH 69
CrCl3/LiAlH4
OH Ph 70 Ph Ph HO 71
PhCHO
Br
THF, rt 87%
Ph + OTf PhCHO
CrCl2, NiCl2 (cat.) DMF, 25 oC 92%
3,3,6-Trimethylhepta-1,5-dien-4-ol; Typical Procedure:[126]
CrCl3 (4.28 g, 27 mmol) was reduced with LiAlH4 (513 mg, 13.5 mmol) in THF (20 mL). After stirring at rt for 10 min, 3-methylbut-2-enal (0.56 g, 6.1 mmol) and subsequently 1-bromo3-methylbut-2-ene (2.01 g, 13.5 mmol) in THF (10 mL) were added dropwise over 20 min. Stirring for 3 h, followed by workup and distillation (97100 8C/4 Torr, Kugelrohr), gave the product as an oil; yield: 0.90 g (88%).
96
2.6.4.5.3
Variation 3: Catalytic NozakiHiyamaKishi Reaction (The Frstner Procedure)
The examples outlined in Section 2.6.4.5.2 are stoichiometric in chromium(II) chloride and generally employ a large excess of this reagent. As shown in Scheme 30, reaction of the organic halide with two equivalents of chromium(II) halide yields the desired organochromium species 72 and one equivalent of chromium(III) halide. The nucleophile then adds to the aldehyde with formation of a chromium alkoxide species. The high stability of the oxygen-chromium(III) bond serves as the thermodynamic sink; the alcohol product is recovered by hydrolysis in the stoichiometric process. The use of halosilane, however, forces an exchange by virtue of the higher oxophilicity of silicon, producing an additional equivalent of chromium(III) halide. At this point the reaction can be made catalytic in chromium by simply using a reagent capable of reducing chromium(III) to chromium(II), e.g. metallic manganese. This modification does not compromise the scope, practicability, efficiency, and chemo- and diastereoselectivity of the C-C bond formation.[130,132,133] In addition, it reduces the consumption of the rather high-cost and toxic chromium reagent and paves the way for potential applications in enantioselective syntheses using chromium catalysts with chiral ancillary ligands.[134]
Scheme 30
R1X CrX3 CrX3 R1 MnX2 Mn OCrX2 R2 TMSX OTMS R1 R2
The Catalytic NozakiHiyamaKishi Reaction

CrR1X2 72 R2CHO
2 CrX2
A soln of 4-methoxybenzaldehyde (340 mg, 2.5 mmol), 2-[(trifluoromethyl)sulfonyloxy]hex-1-ene (1.06 g, 4.6 mmol), and TMSCl (0.75 mL, 6.0 mmol) in DMF (1.5 mL) and DME (5 mL) was dropped into a suspension of Mn powder (230 mg, 4.2 mmol), CrCl2 (46 mg, 0.38 mmol), and NiCl2 (10 mg, 0.07 mmol) in DME (5 mL) at 50 8C. After being stirred for 5 h at that temperature, the mixture was quenched with H2O (15 mL) and extracted with EtOAc (3 50 mL), and the combined organic layers were washed with brine. Aq TBAF (75% w/w) was added, and the soln was stirred at rt until TLC showed complete desilylation of the crude product. Standard workup followed by flash chromatography (hexane/ EtOAc 15:1) afforded the product as a colorless syrup; yield: 420 mg (76%).
2.6.4.6
2-Butyl-1-(4-methoxyphenyl)prop-2-en-1-ol: Typical Procedure:[130]
Method 6: AdditiveReductive Carbonyl Dimerization
In this reaction an alkyl group R3 is transferred from a suitable metalalkyl complex to the electrophilic carbon of a carbonyl substrate 73 (Scheme 31), resulting in the deoxygenation and dimerization to product 74 in a single step.[135] The substrate 73 can be an aromatic aldehyde or ketone, a conjugated enone, or a benzoic acid derivative. The alkyl transfer reagents [R3M] are tungsten(V) compounds formulated as dialkyldipropoxo(propoxo)tungsten(V) dimers 75. They are obtained in situ by alkylation of the correspond-
2.6.5
Metallacyclic Complexes
97
ing dichloro dimers with lithium or Grignard reagents and they are not isolated in view of their extreme thermolability. A large variety of alkyl groups, (trimethylsilyl)methyl, and phenyl have been used as R3, including ones where the -hydrogen elimination process is possible.[60] The procedure consists of the addition of the carbonyl substrate to 75 in tetrahydrofuran at 78 8C, followed by warming to reflux and room-temperature base hydrolysis. Various substituents (e.g., methoxy, dimethylamino, fluoro, chloro, and hydroxy) on phenyl groups are tolerated (e.g., see synthesis of 76), but the nitro and ethoxycarbonyl groups are not.[135] For R3 = Me, the carbonyl group must be conjugated with an unsaturated group, otherwise the monomeric carbinol is obtained. With R3 = Ph, however, even saturated ketones yield the additivereductive carbonyl dimerization product. Rearrangement products can also be obtained, depending on the substituents linked to the carbonyl group; see, for example, the reaction of 2-furaldehyde (77).[60]
Scheme 31
O 2 R1 73
Pr O R12(PrO)2W W(OPr)2R12 O Pr 75
AdditiveReductive Carbonyl Dimerization[60,135]

R1 R1 R2
R2
+ 2 [R
M]
R2
R3 R 3 74
O H Me2N
NMe2 Me2N 76
R1 = Me 82%
Pr O Me2(PrO)2W O Pr 75 R1 = Me W(OPr)2Me2
O 77
CHO O
43%
Et O
30%
[W2Cl4(-OPr)4(OPr)4] (2.2 g, 2.50 mmol) was dissolved in THF (100 mL) at 78 8C, followed by treatment with 1.5 M MeLi in Et2O (4 equiv), resulting in a color change to dark green. After 30 min, the Gilman test indicated the absence of MeLi. To this soln was added a THF soln (25 mL) of 4-(dimethylamino)benzaldehyde (2.50 mmol). After stirring for 15 min at 78 8C, the mixture was slowly warmed and refluxed for 3 h. The mixture was then hydrolyzed with 2 M NaOH (100 mL) at 20 8C. Et2O (50 mL) and petroleum ether were added and the mixture was stirred until dissolution of the amorphous hydrolysis product occurred. The organic phase was removed and the aqueous phase was extracted with Et2O (2 100 mL). The combined organic phases were washed with H2O and dried (Na2SO4). The solvents were removed by rotary evaporation, leaving a crude material which was identified (by GC in comparison with authentic samples) as a mixture of the title compound 76; yield: 82% and 1-[4-(dimethylamino)phenyl]ethanol; yield: 4%.
2.6.5
1,2-Bis[4-(dimethylamino)phenyl]-1,2-dimethylethane (76); Typical Procedure:[135]
Product Subclass 5: Metallacyclic Complexes
In many respects, the synthetic methods and reactivity of metallacyclic complexes parallel those of analogous dialkyl complexes. Metallacyclobutanes and metallacyclopentanes, on the other hand, display unique features. They may easily transform into, or be prefor references see p 112
98
pared from, carbenealkene and dialkene isomers, respectively (Scheme 32). The cyclic forms tend to be more stable for the heavier metal, with differences in stability of three orders of magnitude being reported for congeneric molybdenum and tungsten compounds.[8]
Scheme 32
M
Transformations of Metallacyclobutanes and Metallacyclopentanes

M
Metallacyclobutane complexes are involved as intermediates in alkene metathesis reactions catalyzed by alkylidene complexes and their use is equivalent to that of the carbene complexes in this particular organic application (see Section 2.6.1). Chromacyclopentane complexes are invoked as intermediates in the catalytic trimerization of ethene to hex-1ene.[136] This catalytic process takes place with good selectivity (74%), but has not yet found application for the oligomerization of other alkenes nor for cross-oligomerization processes.
2.6.5.1
This method is not as common as those described below for the preparation of group 6 metallacyclic derivatives. Dilithium and di-Grignard reagents have been used, as exemplified by the syntheses of 78, 79, and 80 (see Scheme 33).[104,137] The synthesis of metallacycles with large ring sizes suffers from the competitive formation of oligomers and from hydrogen elimination processes.
Scheme 33 Metallacycles by Transmetalation[104,137]
CH(TMS)Li(TMEDA)
TMS ButN Br Cr N ButN Br

CH(TMS)Li(TMEDA) Et2O, 30 oC 64%
ButN Cr ButN TMS 78
Li THF, 20
oC
Li
Cr N Me2 Cl
77%
Cl
Cr N Me2
79
2.6.5
Metallacyclic Complexes
99
MgCl
ClMg THF, 30 oC 49%
Cr N Me2 Cl
Cl
Cr N Me2 80
[CrCp*Cl2(THF)] (100 mL of a 0.085 M THF soln, 8.5 mmol) was treated with Me3P (1 mL, 9.88 mmol) and cooled to 50 8C. 1,4-Dilithiobutane (35 mL of a 0.277 M soln in Et2O) was added slowly and the mixture was stirred at 35 8C. The mixture was evaporated to dryness and the residue was extracted with pentane (2 150 mL) at 20 8C. The extract was filtered, cooled to 78 8C, and the resulting blood-red crystals isolated and dried under high vacuum; yield: 2.06 g (76%).
2.6.5.2
Butane-1,4-diyl(5-pentamethylcyclopentadienyl)(trimethylphosphine)chromium(III); Typical Procedure:[137]
Method 2: By Reductive Coupling of Alkenes
This method is specific for metallacyclopentanes. The alkene-coupling process is favored by metal reduction. A typical synthetic strategy is the in situ reduction of a metal halide precursor in the presence of the alkene; see, for example, the synthesis of 79 in Scheme 34.[137] An alkylidene precursor may also lead to a metallacycle with elimination of the carbene ligand as in the synthesis of 81, representing a deactivation pathway for alkene metathesis catalysts.[138] The two alkenes may be generated in situ in the coordination sphere by rearrangement processes, such as intramolecular hydrogen transfer from an alkylvinyl precursor.[139]
Scheme 34 Metallacyclopentanes by Reductive Coupling of Alkenes[137,138]
Mg, H2C CH2 (excess)
THF, 30 oC
Cr N Me2 Cl
90%
Cl
Cr N Me2 79
Ph TMS N N W N TMS
H2C CH2
Ph TMS N N TMS 81 CH2But CH2But

(excess), 80 oC
Ph TMS N N TMS N W
N W CH2
The compound described in the experimental procedure in Section 2.6.5.1 can also be prepared in 68% yield by reacting [CrCp*Cl2(THF)] with active Mg and Me3P in an Et2O soln saturated with ethene at 78 to 10 8C.
Butane-1,4-diyl(5-pentamethylcyclopentadienyl)(trimethylphosphine)chromium(III); Typical Procedure:[137]
100
2.6.5.3
Method 3: By Addition of Alkenes to Carbene Complexes
This method is specific for metallacyclobutane complexes. For stability reasons this method has been mostly applied to the preparation of high oxidation state tungstacyclobutane derivatives. Given the equilibrium shown in Scheme 32, the use of excess alkene may result in further exchange processes. The preparation of 82 in Scheme 35 is a two-step process involving the elimination of 3,3-dimethylbut-1-ene.[29]
Scheme 35 Metallacyclobutanes by Alkene Addition to Carbene Complexes[29]
Pri Pri N W ButHC OCMe(CF3)2 OCMe(CF3)2
(excess) TMS pentane, rt, 2 h ca. quant
Pri OCMe(CF3)2 N W Pri TMS
TMS OCMe(CF3)2 82
Trimethyl(vinyl)silane (124 L) was added to a soln of [W(=CHt-Bu)(=NC6H3-2,6-iPr2){OCMe(CF3)2}2] (212 mg) in pentane (15 mL). The solvent was removed in vacuo after 2 h to give a light yellow product that was recrystallized from pentane to give light yellow crystals. The yield of the crude product was essentially quantitative.
2.6.6
1,2-Bis(trimethylsilyl)propane-1,3-diyl(2,6-diisopropylphenylimido)bis(1,1,1,3,3,3-hexafluoro-2-methylpropan-2-olato)tungsten(VI) (82); Typical Procedure:[29]
Product Subclass 6: Complexes with Triply Bonded Heteroelement Ligands
The only known examples are nitride complexes, whereas terminal phosphide and arsenide complexes are known only without metal-carbon bonds. The lone pair on the nitride ligand retains sufficient Lewis basicity for coordination. Consequently, electronically unsaturated derivatives yield polymeric or oligomeric structures where nitrido groups bridge two metal centers symmetrically or asymmetrically.[140,141] Mononuclear complexes with terminal nitrido ligands are only found when the Lewis acidity of the metal center is suppressed by -donation from other ligands, e.g. amido ligands as in bis(diisopropylamido)[(dimethylphenylsilyl)methyl]nitridochromium(VI).[142] In addition, oligonuclear structures where the nitrogen atom forms bonds of lower order with more metal atoms may be preferred to a triply bonded mononuclear structure. Almost all organometallic nitride complexes have been obtained by adding the organic group(s) to inorganic substrates that already contain the MN function. An example is the synthesis of compound 57 shown in Scheme 23.[103] A large number of methods for assembling a metal-nitrogen triple bond in inorganic compounds are outlined in a review.[143] Some of these methods are also of potential applicability to organometallic substrates and are, therefore, briefly mentioned here (Scheme 36). The exchange of three halides with a nitride can be accomplished by use of the [Hg2N]+ ion, tris(trimethylsilyl)amine, or ammonia, with elimination of mercury(II) salts, trimethylsilyl halide, or hydrogen halide, respectively. In the latter case, excess ammonia is needed to neutralize the acid. The ammonolysis of trialkyl or alkylcarbene complexes has been used successfully to prepare organometallic nitride complexes of group 4 and 5 metals (see Sections 2.82.11) and could potentially be used for group 6 metals as well. Ammonolysis of a carbyne complex would appear to have the same potential. Nitride complexes are also obtained by exchange of a halide with groups capable of readily eliminating a stable byproduct while leaving a nitrogen atom bonded to the met-
2.6.7
Complexes with Doubly Bonded Heteroelement Ligands
101
al, with concomitant metal oxidation. Azide is the ubiquitous ligand with these characteristics, leading to the expulsion of dinitrogen. It can be administered either as a hydrophilic alkali metal salt or as the lipophilic trimethylsilyl derivative. The reaction between trichloro(5-pentamethylcyclopentadienyl)molybdenum(IV) dimer and trimethylsilyl azide generates dichloro(5-pentamethylcyclopentadienyl)nitridomolybdenum(VI) which, however, further evolves to more complex products.[140] An alternative to the azide reagent is the deprotonated 9,10-dihydro-9,10-epiminoanthracene,[144] leading to the elimination of anthracene. Other nitride compounds have been obtained by oxidation of coordinated ammonia ligands. The deoxygenation of a nitrosyl ligand is of potentially wide applicability. The oxygen-abstracting agent is an oxophilic metal complex such as trimesityl(tetrahydrofuran)vanadium(III).[145] Nitride compounds are also the byproducts of the addition of nitriles to triply bonded molybdenum and tungsten compounds (see Section 2.6.2.2). The splitting of the dinitrogen triple bond by a metal complex is a more recent achievement[146] but is so far limited to a sterically protected triamidomolybdenum system.[147] Other methods include the use of nitrogen trichloride, trithiazyl chloride, or aryl azide reagents.[143,148] Splitting of nitrous oxide (N2O) provides mixtures of nitrido and nitrosyl products.[148]
Scheme 36 Methods for Assembling the MN Function in Inorganic Compounds of Group 6 Metals
X [M] X R1 [M] R1 R1 X
[N3]
[M]
NO
[O]
[M]
1/2 N
N [M] N3
3X NH3 3R1H NH3 2R1Me
N3
N2
[M]
N [M]
N
[M]
3e 3H+
CH2R1 [M] CHR1 [M] NH3
Phosphide and arsenide complexes have also been synthesized for the first time in nonorganometallic complexes.[149,150] Organometallic derivatives have yet to be reported.
2.6.7
Product Subclass 7: Complexes with Doubly Bonded Heteroelement Ligands
The vast majority of examples in this subclass are oxo and imido derivatives. A fair number of sulfido derivatives are also known, whereas selenido and tellurido derivatives and compounds containing a double bond to phosphorus (phosphinidene complexes) are fewer. The relative small number of derivatives with phosphorus and the chalcogenides may be attributed to the weakness of the -interaction. The bonds between the aforementioned groups and a transition metal are considered double according to valency; however, these bonds are often relatively short and strong in electronically unsaturated systems, especially for oxo and imido ligands, because of the participation of an additional ligand lone pair to the bonding. In many cases a mononuclear structure with a terminal, doubly bonded heteroelement ligand may be unfavorable with respect to the alternative dinuclear structure where the ligand adopts a bridging, singly bonded conformation (Scheme 37). Facile interconversion of the two forms may occur, leading to analogous synthetic strategies and reactivity.
102
For this reason, bridged dinuclear compounds are also included in this section, although emphasis is placed on the terminally bonded derivatives. The mononuclear structure is favored by a sterically encumbering coordination sphere, whereas electronic configurations that allow the formation of metal-metal bonds lead preferentially to dinuclear structures. First-row heteroelement-containing ligands (oxo, imido) are found terminally bonded more frequently than their heavier congeners because of their superior -bonding ability. As seen for the triply bonded heteroelement derivatives, the most common synthetic method for the present subclass consists of the introduction of the organic fragment into an inorganic substrate that already contains the desired doubly bonded heteroelement ligand. This is especially true for the oxo compounds, as metal oxides or oxometalate precursors are readily available and inexpensive starting materials. The methods discussed in this section are those leading to the assembly of the metal-heteroatom double bond starting from substrates that already contain hydrocarbyl ligands.
Scheme 37
2 [M] E
MonomerDimer Dichotomy for Doubly Bonded Heteroelement Ligands

E [M] E [M]

2.6.7.1
Method 1: From Complexes Containing Singly Bonded Heteroelement Ligands
Singly bonded heteroelement ligands that contain a hydrogen substituent may be deprotonated by either an internal or an external base and transformed into doubly bonded ligands. In many cases the singly bonded hydrogen-bearing ligand is formed in situ by ligand exchange from a halide or alkoxide precursor. This is the case for the reaction between dichlorobis(5-pentamethylcyclopentadienyl)tungsten(IV) and potassium hydroxide, leading to the oxo derivative 83 by spontaneous elimination of water; see Scheme 38.[102] In this case the proton scavenger is a coordinated base (OH) and the conjugate acid is expelled. In high oxidation state systems, halides may be sufficiently good bases leading to the expulsion of the hydrogen halide, as in the hydrolysis of tetrabromo(5-cyclopentadienyl)molybdenum(V).[151] An intramolecular hydrogen transfer to a carbyne ligand furnishes the oxoalkyl derivative 66 (Scheme 27). For the synthesis of 84, aminolysis of tungsten-methyl bonds yields an imido and an amido ligand in a first step. An external base, however, is necessary to produce the second imido ligand, as neither the residual methyl ligand nor excess aniline is sufficiently basic to carry out the last deprotonation.[152] Imido derivatives have also been obtained from trimethylsilylamido derivatives, the elimination of the trimethylsilyl group (a proton equivalent) being favored by the presence of chloro, alkoxo, or oxo ligands. An external base may also serve as a catalyst for the intramolecular proton transfer to another ligand, as shown in the triethylamine-catalyzed isomerization of the amidocarbyne complexes 20 to the imidocarbene complexes 21 (Scheme 7).[8,17,29] A reverse strategy involves rearrangement from a precursor complex that contains the proton on the metal center and the base on the heteroatom ligand, as in the synthesis of the phosphinidene complex 85.[153] Ligand exchange from halide precursors with lithium disulfide has provided access to sulfido derivatives, occasionally involving metal oxidation, as in the formation of (5-pentamethylcyclopentadienyl)trisulfidotungstate(VI) 86.[154] The same transformation can also be performed, although in lower yield, using hydrogen sulfide in the presence of triethylamine.[155]
2.6.7
103
Scheme 38 Syntheses from Complexes Containing Singly Bonded Heteroelement Ligands[102,152154]

KOH (2 equiv) THF, H2O
W(Cp)2Cl2
(Cp)2W
OH OH
H2O 36%
W(Cp)2( 83 +
O)
+ PF6 WMe4
PhNH2 (2 equiv) CH2Cl2, rt, 2.5 h 87%
W Me NPh NHPh
PF6
Et3N, CH2Cl2 rt, 15 min 94%
W Me
NPh NPh
84
M(Cp)2HLi
R1PCl2
H (Cp)2M PR1Cl
HCl
(Cp)2M P R1 85
M = Mo, W; R1 = 2,4,6-t-Bu3C6H2
1. Li2S2, THF, rt, 1 h 2. Ph4PBr, MeCN 61%
WCpCl4
[Ph4P][WCpS3] 86
An excess of t-BuNH2 (0.08 mL, 0.76 mmol) and H2O (0.04 mL, 2.2 mmol) was added to a CH2Cl2 soln (25 mL) of [WCp*Cl(=O)2] (140 mg, 0.36 mmol). The soln was stirred for 1 h, dried (MgSO4), and filtered through a pad of Celite. The solvent volume was reduced to 23 mL and hexane was added to induce precipitation of [WCp*(=O)3][t-BuNH3], which was isolated; yield: 137 mg (86%).
2.6.7.2
tert-Butylammonium Trioxo(5-pentamethylcyclopentadienyl)tungstate(VI):[155]
Method 2: From Other Complexes Containing Doubly Bonded Heteroelement Ligands
Compounds containing a metal-heteroatom double bond may be obtained from analogous derivatives by exchanging the heteroelement ligand. This strategy is especially useful for preparing imido and sulfido derivatives from more easily available oxo compounds. In most cases, this method is used for the preparation of inorganic materials that are subsequently converted into organometallic compounds via metathetical reactions (see Section 2.6.1.5).[25] The new function (X) can be administered as either the diprotic acid (H2X) or the cumulene (O=C=X). The use of the acid presents potential problems in the presence of sensitive hydrocarbyl ligands. For particular systems, especially high oxidation state molybdenum and tungsten compounds, the metal-carbon bonds are sufficiently covalent and resist protonolysis. This is illustrated in the oxygen/sulfur exchange leading to products 87 in Scheme 39.[156] The relative strengths of the metal-heteroelement double bonds are against the exchange of oxygen by sulfur, whereas the weaker acidity of water vs hydrogen sulfide favors the exchange. Concerning the oxo/imido exchange, the acidity criterifor references see p 112
104
on favors the conversion of imido ligands into oxo ligands, especially when the amine byproduct is further consumed by protonation in an acidic medium.[152] The synthetically more useful reverse exchange is favored by trapping water with the chlorotrimethylsilane/triethylamine combination, leading to hexamethyldisiloxane and triethylammonium chloride.[25] This reaction could in fact involve the in situ conversion of the primary amine into a bis(trimethylsilyl)amine which subsequently carries out the exchange process. The direct use of a trimethylsilyl-substituted amine has also led to satisfactory results.[157] The use of cumulenes has practical synthetic use only for the conversion of oxo into imido derivatives by the use of isocyanates. Formation of carbon dioxide provides the necessary driving force to the reaction. An example is the synthesis of compound 88, where the incompleteness of the second step limits the yield.[158] A problem of this synthesis is the potential cycloaddition of the imido product with excess isocyanate, leading to metalated ureas.
Scheme 39 Syntheses from Other Complexes Containing Doubly Bonded Heteroelement Ligands[156,158]
MCpR1(
H2S, CS2
O)2
H2O M = W; = Me 77% M = W; R1 = CH2TMS 40% 1 = CH TMS 77% M = Mo; R 2 R1
MCpR1( 87
O)(
S)
R2NCO, hexane 140 oC, 1 week
R2NCO, hexane 125 oC, 20 d
R1
W O
52%
R1
W O
NR2
23%
R1
NR2 NR2
88
A soln of [Mo(CH2TMS)Cp*(=O)2] (25 mg, 0.071 mmol) in CS2 (10 mL) saturated with H2S was incubated at rt for 3 d, during which time the color of the soln changed from tinted yellow to red. The solvent was removed with a stream of N2. The red residue was spotted on a 0.25-mm-thick silica gel TLC plate and then developed with Et2O. The red band was collected to give [Mo(CH2TMS)Cp*(=O)(=S)]; yield: 20.2 mg (77%). X-ray crystallographic quality, dark red crystals were grown from a saturated soln in hexane at 20 8C.
2.6.7.3
Oxo(5-pentamethylcyclopentadienyl)sulfido[(trimethylsilyl)methyl]molybdenum(VI) (87, M = Mo; R1 = CH2TMS); Typical Procedure:[156]
Method 3: From Complexes Containing Triply Bonded Heteroelement Ligands
This method is restricted to the transformation of terminal nitrides to imide compounds. A rare example of the application of this method to organometallic substrates is the protonation of tris(2,2-dimethylpropyl)nitridomolybdenum(VI) to afford the imido complexes 89 (Scheme 40).[103,159]
2.6.7
105
Scheme 40 Synthesis from a Complex Containing a Triply Bonded Heteroelement Ligand[159]

H N Mo(CH2But)3( N)
HX, THF 4085%
ButH2C Mo X 89
CH2But CH2But
X = F, Cl, Br, I, OPh, OSiPh3
[Mo(CH2t-Bu)3(N)] (1.0 mmol) and triphenylsilanol (1.0 mmol) were placed in a Schlenk tube under argon and dissolved in THF (30 mL). The mixture was stirred at 60 8C for 48 h. Removal of the solvent under reduced pressure and extraction of the residue with hexane (5 mL) afforded [Mo(CH2t-Bu)3(=NH)(OSiPh3)] as a white powder. Recrystallization from ~ hexane at 0 8C gave white crystals; yield: 240 mg (40%); IR (Nujol) max: (N-H) 3371 cm1.
2.6.7.4
Tris(2,2-dimethylpropyl)imido(triphenylsilanolato)molybdenum(VI) (89, X = OSiPh3); Typical Procedure:[159]
Method 4: By Oxidative Processes
The most useful oxidizing agents for the preparation of organometallic oxo compounds have been nitrogen oxides such as trimethylamine oxide, nitrous oxide, and nitric oxide, allowing the preparation of compounds that cannot be accessed by other methods, although the oxidations are often accompanied by the formation of other products.[160] For selected systems, oxidation of a low-valent precursor with the heteroelement itself in its natural state (e.g., O2, S8) is sufficiently clean to be synthetically useful for the preparation of oxo and sulfido complexes. This is especially true for 5-cyclopentadienyl and 5-pentamethylcyclopentadienyl systems. The synthesis of 90 (Scheme 41), involving exhaustive decarbonylation, represents a typical example.[161] Photochemical activation of the carbonyl precursor is necessary in some cases.[162] Occasionally, elemental oxygen can be replaced by hydrogen peroxide, as, for example, in the synthesis of 91, but this requires the use of a strict stoichiometric ratio to avoid further conversion into peroxo analogues.[163] Hydrogen sulfide also leads to oxidation, with expulsion of dihydrogen, in the synthesis of compound 92.[164] The synthetic utility of the oxidation with a diazene to yield a bis(imido) product has only been illustrated for inorganic target systems.[165]
Scheme 41
{MCp(CO)2}2
Oxidative Processes[161,163,164]
air, CHCl3 or benzene, rt M = Mo 69% M = W 14%
(CpMO2)O 90
MCp(NO)R12
30% aq H2O2, rt, 1 h ca. 1050%
MCpO2R1 91
R1 = Me, CH2TMS; M = Mo, W
Me3P PMe3 PMe2 H Mo Me3P PMe3
S
H2S, pentane, 78 oC H2 60%
Me3P Me3P
Mo S 92
PMe3 PMe3
106
In a drybox, a 100-mL glass ampule (Teflon stopcock) was charged with a soln of [MoCp*Cl(CO)3] (0.980 g, 2.79 mmol) in toluene (50 mL). O2 was bubbled through the soln via a 24-gauge syringe needle at a rate of approximately 2 bubbles s1 while the soln was irradiated with a 450-W medium-pressure Hg immersion lamp at 5 8C. The reaction was monitored by IR spectroscopy and was stopped after 90 min when the absorbances due to the carbonyl ligands of the starting material at 17002000 cm1 had disappeared. During the reaction the soln turned from a red-orange to an amber shade with some blue solids precipitated on the walls of the reaction vessel. The toluene was removed under vacuum, leaving a brown solid. The solid was taken up in toluene in the drybox and the resulting soln filtered through a medium-porosity sintered-glass frit to remove insoluble blue impurities. Recrystallization (toluene/hexane) afforded [MoCp*Cl(=O)2] as a yel~ low solid; yield: 0.508 g (61%); IR (benzene-d6) max: (Mo=O) 920 (s), 890 (s) cm1; 1H NMR (benzene-d6, ): 1.63 (s, C5Me5).
Chlorodioxo(5-pentamethylcyclopentadienyl)molybdenum(VI):[162]
5-Cyclopentadienyldioxo[(trimethylsilyl)methyl]tungsten (91, R1 = CH2TMS; M = W);

To a stirred, purple soln of [W(CH2TMS)2Cp(NO)] (1.20 g, 2.65 mmol) in Et2O (50 mL) was added a 30% by weight aq soln of H2O2 (0.22 mL, 2.8 mmol of H2O2). The initial purple color of the mixture faded over the course of 1 h to pale yellow. An IR spectrum of the final yellow soln was devoid of absorptions due to the nitrosyl reactant. Volatiles were removed from the final mixture under reduced pressure to obtain a sticky yellow solid which was dried at 20 8C/0.005 Torr for 2 h. Recrystallization of the resulting pale yellow solid from Et2O/hexanes (1:1) at 20 8C afforded [W(CH2TMS)Cp(=O)2] as a white microcrystalline sol~ id; yield: 0.50 g (51%); IR (benzene-d6) max: (W=O) 948 (s), 907 (s) cm1; 1H NMR (benzened6, ): 5.69 (s, 5H, Cp), 0.88 (s, 2H, CH2), 0.28 (s, 9H, TMS).
2.6.7.5
Typical Procedure:[163]
Method 5: Catalytic Epoxidation of Alkenes
High oxidation state molybdenum oxo complexes are well-established catalysts for the epoxidation of alkenes by alkyl hydroperoxides, such as in the production of 2-methyloxirane (Halcon process). Chlorodioxo(5-pentamethylcyclopentadienyl)molybdenum(VI) provides an organometallic example of a catalytically active system. The epoxidation reaction is stereoselective, as shown by the selective formation of trans- and cis-1,2-diphenyloxirane from the respective E- and Z-alkenes, and can be applied to highly substituted alkenes; see Scheme 42.[162] Studies on this system have shown that the degradation of the catalyst involves oxidative poisoning to an unreactive peroxo complex.[162]
Scheme 42 Catalytic Epoxidation of Alkenes[162]
MCpO2Cl (cat.) benzene, 25 oC 72%
ButOOH
In a drybox, a soln of [MoCp*ClO2] (0.101 g, 0.338 mmol) in benzene (5 mL) was placed into a 50-mL bomb. Cyclooctene (1.77 mL, 13.6 mmol) was added via a syringe. Outside the drybox, 3 M t-BuOOH in 2,2,4-trimethylpentane (11.3 mL, 34 mmol) was added. The bomb was heated to 60 8C for 3 h. The soln was then diluted to a total volume of 150 mL with benzene. The organic layer was washed with H2O (6 100 mL) to remove excess hydroper-
1,2-Epoxycyclooctane; Typical Procedure:[162]
2.6.8
Complexes with Singly Bonded Heteroelement Ligands
107
oxide, and then washed with sat. NaCl soln (100 mL) and dried (MgSO4). The benzene was removed under vacuum, and the crude product was purified by flash chromatography (silica gel, EtOAc/hexane 1:9), to give 1,2-epoxycyclooctane; yield: 1.37 g (80%); >95% pure by 1H NMR spectroscopy. The epoxide was identified by comparison of its 1H NMR spectrum and GC retention time with those of an authentic sample.
2.6.8
Product Subclass 8: Complexes with Singly Bonded Heteroelement Ligands
The most important examples of this class are the halides, alkoxides, and amides, but derivatives with phosphorus, sulfur, selenium, and tellurium donors are also synthetically useful. Most hydrocarbyl functionalities are accessible from halide and alkoxide precursors.
2.6.8.1
Method 1: By Oxidative Addition of Compounds with Single Bonds between Heteroelements
The most practical synthetic route to halide derivatives is the oxidation of lower-valent carbonyl precursors either directly with the halogens or with other stoichiometric halogen sources such as phosphorus pentachloride or pentabromide, or iodobenzene dichloride. (5-Cyclopentadienyl)- and (5-pentamethylcyclopentadienyl)dicarbonylnitrosylchromium(I) are oxidized by iodine to the chromium(II) products 93,[166,167] while the analogous molybdenum and tungsten precursors react with a range of halogen sources to afford the dihalo derivatives such as 94 (Scheme 43).[168] The synthesis of tetrachloro(5pentamethylcyclopentadienyl)molybdenum(V) (95) requires easily available starting materials,[27,169] while the alternative transmetalation from MCl5 and cyclopentadienyl sources is precluded by competing reductive pathways. This oxidative procedure has also been used to access arylsulfido derivatives by use of disulfide reagents, as shown by the synthesis of 96.[170]
Scheme 43 Oxidative Addition[166170]
MeCN, rt
Cr(5-C5R15)(NO)(CO)2
I2
R1 = H 88% R1 = Me 62%
{Cr(5-C5R15)(-I)(NO)}2 93
MCp(NO)(CO)2
PCl5
Et2O, 20 oC M = Mo 90% M = W 83%
MCpCl2(NO) 94 MoCpCl4 95
{MoCp(CO)3}2
PhCl2
CH2Cl2, rt 82%
Me2Si Me2Si
PPh2 N CrMe PPh2 + 1/2 PhSSPh
toluene, 0 oC 66%
Me2Si Me2Si
PPh2 N Cr PPh2 96
Me SPh
108
1-[(Diphenylphosphino-k P)methyl]-N-{[(diphenylphosphino-k P)methyl]dimethylsilyl}1,1-dimethylsilanamido-k ,N](phenylsulfido)methylchromium(III) (96):[170]
To a red-brown soln of [CrMe{N(SiMe2CH2PPh2)2}] (0.16 g, 0.27 mmol) in toluene (10 mL) cooled to 0 8C was added a soln of PhSSPh (0.03 g, 0.14 mmol) in toluene (5 mL). Immediately, the soln changed to a dark purple color. After the mixture was stirred for 1 h at 0 8C, the soln was warmed to rt and the solvent was removed almost to dryness. The residue was quickly dissolved in hexane (1 mL) and filtered through Celite, and the solvent was removed in vacuo. Recrystallization from hexanes/toluene (1 mL: 3 drops) in a 40 8C freezer yielded a thick oil, which upon agitation gave 96 as purple crystals; yield: 0.12 g (66%).
2.6.8.2
Compounds that already contain a single bond between the metal and a heteroatom ligand may exchange the latter upon treatment with a suitable salt of the desired new ligand. The ubiquitous substrates are the halides, especially the chlorides which are easily accessible by oxidative procedures (Section 2.6.8.1 above) or from inorganic halide precursors. One example is the synthesis of 20 in Scheme 7. Like the alkylating agents discussed previously (Sections 2.6.3.1 and 2.6.4.1), some salts are potential reducing agents, especially alkyl and aryl sulfides, phosphides, and amides. The reaction of precursor 97 (Scheme 44) with a variety of lithium salts always affords the metathesis product in good yield when X1 = alkoxo or amido.[171,172] When X1 = chloro, 5% of reduction is afforded by the 4-tolylamide salt with the molybdenum system, while the diphenylphosphido reagent yields exclusively reduction products for both molybdenum and tungsten.[173]
Scheme 44 Transmetalation[171173]
+ M Cl X 97 NO
1
LiX2
2582%
X2
NO X1
M = Mo, W; X1 = Cl, NHt-Bu, Ot-Bu; X2 = NHt-Bu, Ot-Bu, PPh2
The lithium salt of 2,6-diisopropylphenoxide (1.60 g, 6.19 mmol) was added to [W(=CHtBu)Cl2(=NC6H3-2,6-iPr2)(DME)] (1.82 g, 3.09 mmol) in Et2O (50 mL) at 40 8C. The soln was warmed to 25 8C and stirred for 45 min. The mixture was filtered, and the filtrates were concentrated to afford an orange solid. Recrystallization of this material from a minimum of pentane afforded the product as a bright yellow solid in two crops; yield: 1.74 g (72%).
2.6.8.3
Bis(2,6-diisopropylphenolato)(2,6-diisopropylphenylimido)(2,2-dimethylpropylidene)tungsten; Typical Procedure:[17]
Method 3: From -Alkyl Complexes
Protonolysis of the typically polar bond between a group 6 metal and a hydrocarbyl ligand is usually considered to be an unwanted decomposition reaction. When metal-heteroatom bonds are desired, however, selective alkane-elimination reactions can sometimes offer significant advantages, such as ready availability and stability of the protonated source of the desired ligand (such as carboxylic acids, alcohols, or amines) and the absence of inorganic salts as byproducts (the resulting alkane is normally easily removed
2.6.8
Complexes with Singly Bonded Heteroelement Ligands
109
in vacuo). The synthesis of 84 proceeds via the protonolysis of the tungsten-methyl bond with aniline to form an arylamide ligand (Scheme 38),[152] and Scheme 45 illustrates related examples involving benzoic acid and ammonium chloride (98 and 99, respectively).[174,175] Hydrocarbyl groups other than -alkyls may also be used as precursors for this reaction, as demonstrated by the reaction of chromocene with tert-butyl alcohol to give 100.[176]
Scheme 45 Syntheses from -Alkyl Complexes[174176]
petroleum ether 60 oC 90%
W(Me)2(Cp)2 +
PhCO2H
WMe(Cp)2(O2CPh) 98
W(Me)2(Cp)2
NH4Cl
THF, 56 oC 61%
WMe(Cp)2Cl 99
Cr(Cp)2 +
ButOH
toluene, 110 oC 84%
{CrCp(OBut)}2 100
(Benzoato-O)bis(5-cyclopentadienyl)methyltungsten(IV) (98); Typical Procedure:[174]
The compound [W(Me)2(Cp)2] (0.52 g, 1.52 mmol) in petroleum ether (bp 100120 8C, 25 mL) was treated with benzoic acid (0.19 g, 1.51 mmol) and the mixture was warmed to 60 8C. Methane was evolved and the soln turned red. After 1 h the soln was filtered and slowly concentrated under reduced pressure. Red-brown crystals separated which were collected by filtration, washed with petroleum ether (2 15 mL), and finally recrystallized (petroleum ether/Et2O 2:1); yield: 0.61 g (90%).
2.6.8.4
Method 4: From Carbene or Carbyne Complexes
Addition of the conjugate acid of the desired ligand to a metalcarbene or carbyne compound results in protonation of the hydrocarbyl ligand (see also Sections 2.6.1.4 and 2.6.4.4), transforming it into an alkyl or carbene ligand with formation of a new metalheteroatom bond. Examples are the preparations of compound 19 (Scheme 7) and compound 65 (Scheme 27). The reaction of the carbene substrate 101 with tert-butyl alcohol produces product 102 (Scheme 46) which, upon heating, eliminates alkane and affords a new carbene compound in an overall process which resembles the protonolysis of an alkyl complex (Section 2.6.8.3).[19] The same reaction of 101 with triphenylsilanol at low temperatures leads to the protonolysis product directly.
Scheme 46 Synthesis from a Carbene Complex[19]
NMe2 CH2TMS W ButO N Ph 102 CH2TMS
NMe2 W N Ph 101 CH2TMS CHTMS + ButOH

pentane
110
5-Cyclopentadienyl(2,2-dimethylpropyl)nitrosyl(triphenylsilanolato)molybdenum(II)
See Section 2.6.4.4.
2.6.8.5
(65); Typical Procedure:[115]
Method 5: From Complexes Containing Doubly Bonded Heteroelement Ligands
Like the synthesis of alkyl compounds by selective protonation of carbene groups (Section 2.6.8.4), ligands with metal-heteroatom single bonds may be obtained from oxo or imido complexes via a single-proton-transfer reaction, as illustrated for 103 in Scheme 47. Alternatively, the metal-heteroatom bond may be protonated twice, with the external acid (HX) providing the M-X bond of the final product, as in the synthesis of 104. The replacement of an oxo or imido ligand with two singly bonded ligands may induce other modifications in the molecule, notably -hydrogen elimination from an alkyl group, transforming it into a carbene ligand (see Section 2.6.1.1.3).
Scheme 47 Syntheses from Complexes Containing Doubly Bonded Heteroelement Ligands[102,152]
W(Cp)2( O) + HBF4OEt2
Et2O 50%
[W(Cp)2(OH)]+ BF4 103
WMeCp(
NPh)2
TfOH
Et2O 80%
WMeCp(OTf)2( 104
NPh)
A soln of [W(Cp*)2(=O)] (120 mg, 0.26 mmol) in Et2O (10 mL) was treated with HBF4 OEt2 (excess) at 78 8C. The mixture was warmed to rt and the product was deposited as a white ~ solid which was isolated by filtration; yield: 75 mg (50%); IR (Nujol) max: (WO-H) 3340 (s, br) cm1; 1H NMR (benzene-d6, ): 1.88 (s, C5Me5).
2.6.9
Hydroxobis(pentamethylcyclopentadienyl)tungsten(IV) Tetrafluoroborate (103):[102]
Product Subclass 9: Miscellaneous Complexes Synthesis of Product Subclass 9
2.6.9.1
Method 1: Allylidene Complexes from Cyclopropenes
Ring-opening reactions of 3,3-disubstituted cyclopropenes yield allylidene complexes, a synthetic route of particular utility for the generation of ruthenium-based alkene metathesis catalysts.[47] This methodology has been extended to tungsten allylidene compounds using tungsten(IV) oxo[177] or imido[178] precursors (Scheme 48). These reactions proceed via initial formation of the 2-cyclopropene adduct 105, followed by ring opening. Metathesis of the chloride ligands with electron-withdrawing alkoxide groups furnishes alkene metathesis catalysts 106 (see Section 2.6.1.5).
2.6.9
Miscellaneous Complexes
Allylidene Complexes from Cyclopropenes[177,178]
Ph Ph
111
Scheme 48
X3P Cl W PX3 PX3 Cl
benzene
E X3P Cl W Cl PX3 105
Ph Ph
LiOR1 (2 equiv)
R1O R1O
E W PX3 106 Ph Ph
E = O, NC6H3-2,6-iPr2 PX3 = PMePh2, PEt2Ph, P(OMe)3 OR1 = OCMe(CF3)2
Dichloro(2,6-diisopropylphenylimido)(3,3-diphenylallylidene)bis(trimethyl phosphiteP)tungsten (105, E = NC6H3-2,6-iPr2; X = OMe); Typical Procedure:[178]
A soln of 3,3-diphenylcyclopropene (1.84 g, 9.55 mmol) in benzene (30 mL) was added via cannula to a soln of [WCl2(=NC6H3-2,6-iPr2){P(OMe)3}3] (7.12 g, 8.88 mmol) in benzene (60 mL), and the mixture was then stirred for 2 h at 80 8C. The solvent was removed in vacuo, and the resulting orange oil was left under dynamic vacuum for an additional 12 h. The product was then dissolved in THF (95 mL), and the resulting orange soln was filtered. After all but THF (10 mL) had been removed in vacuo, addition of pentane (150 mL) yielded an orange powder; yield: 5.50 g (72%); 1H NMR (90 MHz, toluene-d8, ): 12.85 (dt, 1H, JHH = 12.75, JHP = 6.37, H), 10.23 (dt, 1H, JHH = 12.75, JHP = 2.45, H), 3.65 [t, 18H, P(OMe)3].
112
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117
Table of Contents
14.11
Product Class 11: Selenopyranones and Benzoselenopyranones P. J. Murphy Product Class 11: Selenopyranones and Benzoselenopyranones . . . . . . . . . . 119
14.11 14.11.1 14.11.1.1 14.11.1.1.1 14.11.1.1.1.1
Product Subclass 1: 2H-Selenopyran-2-ones and 4H-Selenopyran-4-ones . 120 Synthesis by Ring-Closure Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 By Formation of Two Se-C Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 Method 1: 4H-Selenopyran-4-ones by Addition of Dibasic Selenide to Diethynyl Ketones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 2H-Selenopyran-2-ones from 2-Aminovinyl Selenoketones . . 122
14.11.1.1.2 14.11.1.1.2.1 14.11.1.2 14.11.1.2.1 14.11.1.2.1.1 14.11.1.2.1.1.1 14.11.1.2.1.1.2 14.11.1.2.1.1.3
By Formation of One Se-C and One C-C Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Method 1: Synthesis by Substituent Modification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Substitution of Existing Substituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Of Hydrogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Method 1: Method 2: Method 3: Lithiation of 4H-Selenopyran-4-ones . . . . . . . . . . . . . . . . . . . . . . . 122 4H-Selenopyran-4-ones by Oxidation of 4H-Selenopyrans . . . 123 4H-Selenopyran-4-ones by Oxidation of 1-Methyl-14-selenopyrans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
14.11.1.2.1.2 14.11.1.2.1.2.1 14.11.1.2.1.2.1.1
Of Metals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Of Lithium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Method 1: Reaction of (2,6-Di-tert-butyl-4-oxo-4H-selenopyran-3-yl)lithium with Electrophiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 4H-Selenopyran-4-ones by Oxidation of 4-Methylene-4H-selenopyrans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 4H-Selenopyran-4-thiones from 4H-Selenopyran-4-ones . . . . . 125
14.11.1.2.1.3 14.11.1.2.1.3.1
Of Carbon Functionalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Method 1:
14.11.1.2.2 14.11.1.2.2.1 14.11.2 14.11.2.1 14.11.2.1.1 14.11.2.1.1.1 14.11.2.1.1.1.1
Modification of Substituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 Method 1: Product Subclass 2: Benzo- and Dibenzoselenopyranones . . . . . . . . . . . . . . . . 126 Synthesis by Ring-Closure Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 By Annulation to an Arene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 By Formation of Two Se-C Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 Method 1: By Reaction of 2-Bromophenyl Ethynyl Ketones with Sodium Hydrogen Selenide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 By the Simonis Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
14.11.2.1.1.2 14.11.2.1.1.2.1
By Formation of One Se-C and One C-C Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 Method 1:
118
14.11.2.1.1.2.2 14.11.2.1.1.2.3 14.11.2.1.1.2.4 14.11.2.1.1.3 14.11.2.1.1.3.1 14.11.2.1.1.3.2 14.11.2.1.1.3.3 14.11.2.1.1.3.4 14.11.2.1.1.4 14.11.2.1.1.4.1 14.11.2.2 14.11.2.2.1
Method 2: Method 3: Method 4: Method 1: Method 2: Method 3: Method 4: Method 1: Method 1:
From 2-(Chloroselanyl)benzoyl Chloride via Electrophilic Aromatic Substitution . . . . . . . . . . . . . . . . . . . . . . . . 127 By Reaction of Se-Lithiated Selenosalicylamide Derivatives with Benzyne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 By Photochemical Rearrangement of Aryl Selenoesters . . . . . . 129 By Cyclization of Ethynyl 2-(Methylselanyl)phenyl Ketones . . . By Cyclization of Phenyl Selenocinnamates . . . . . . . . . . . . . . . . . By Electrophilic Cyclization of Methyl Selenides . . . . . . . . . . . . . By Selenolactonization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 130 130 132
By Formation of One Se-C Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
By Formation of One C-C Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 By Aromatic Electrophilic Substitution . . . . . . . . . . . . . . . . . . . . . . 132 By Rearrangement of Substituted Benzo[b]selenophen-3(2H)-ones . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 By Dehydrogenation of 2,3-Dihydro4H-1-benzoselenopyran-4-ones . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 Oxidation of Benzoselenopyrans . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Synthesis by Ring Transformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
14.11.2.3 14.11.2.3.1 14.11.2.3.2 14.11.2.4 14.11.2.4.1 14.11.2.4.1.1 14.11.2.4.1.1.1 14.11.2.4.1.1.2 14.11.2.4.1.1.3 14.11.2.4.1.2 14.11.2.4.1.2.1 14.11.2.4.1.3 14.11.2.4.1.3.1 14.11.2.4.2 14.11.2.4.2.1 14.11.2.4.2.2 14.11.2.4.3 14.11.2.4.3.1 14.11.2.4.3.2
Aromatization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 Method 1: Method 2:
Synthesis by Substituent Modification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Substitution of Existing Substituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Of Hydrogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Method 1: Method 2: Method 3: Method 1: Method 1: Method 1: Method 2: Method 1: Method 2: Lithiation of 4H-1-Benzoselenopyran-4-ones . . . . . . . . . . . . . . . . 138 Electrophilic Alkylation of 4-Hydroxy2H-1-benzoselenopyran-2-one . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Oxidation of Dibenzoselenopyrylium Salts . . . . . . . . . . . . . . . . . . 139 Decarboxylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Preparation of a 10H-Dibenzo[b,e]selenopyran-10-one Ylide . 139 Oxidation of the Selenium Atom . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 Addition of Dihalogen to the Selenium Atom . . . . . . . . . . . . . . . 140 Preparation of Benzo- and Dibenzoselenopyranthiones . . . . . . By Condensation of 2-Methyl-4H-1-benzoselenopyran-4-one with a Thiazolium Betaine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 141
Of Carbon Functionalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Of Oxygen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Addition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
Modification of Substituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
119
14.11
Product Class 11: Selenopyranones and Benzoselenopyranones

P. J. Murphy
General Introduction
The synthesis and chemistry of 2H-selenopyran-2-one (1; CAS name 2H-selenin-2-one), 4Hselenopyran-4-one (2; CAS name 4H-selenin-4-one), 1H-2-benzoselenopyran-1-one (3; CAS name 1H-2-benzoselenin-1-one), 2H-1-benzoselenopyran-2-one (4; CAS name 2H-1-benzoselenin-2-one), 4H-1-benzoselenopyran-4-one (5; CAS name 4H-1-benzoselenin-4-one), 10H-dibenzo[b,e]selenopyran-10-one, 6H-dibenzo[b,d]selenopyran-6-one (6; CAS name 6Hdibenzo[b,d]selenin-6-one), and (7; CAS name 9H-selenoxanthen-9-one; Scheme 1), have not been reviewed as a specific topic in an exhaustive manner, and there is no previous specific entry in the HoubenWeyl series. A monograph on general organic selenium chemistry is, however, worthy of note as it provides some coverage of the area.[1]
Scheme 1 Selenopyranones and Benzoselenopyranones
O
4 5 6 3 2 5 6 4 3
Se
1
Se
1
2 O
5 6 7 8
4 3 6 7 2
4 3 2 6 7
4 3
Se
1
Se
1
Se
8 1
O 3
9 8 7 6 4 10 1 2
4 O
9 3 8 7 6 10 1 2
Se
5
Se
5
3 4
O 6
Many methods exist for the formation of selenopyranones and benzoselenopyranones, but by far the most useful are those which involve the formation of one or two Se-C bonds in a heterocyclization process. SAFETY: The vast majority of organoselenium compounds should be handled using the standard precautions generally taken with other potentially hazardous substances found in a modern chemical laboratory. Inorganic selenium compounds, however, do present special hazards, as they are highly toxic, and exposure routes such as inhalation, ingestion, and skin or eye contact should be avoided. Common symptoms include drowsiness, headaches, nausea, abdominal pains, and a garlic odor of the breath, and these sub-
120
Science of Synthesis 14.11 Selenopyranones and Benzoselenopyranones
stances may have effects on the central nervous system. Long-term exposure has indicated that selenium and related compounds could cause malformations in human babies, and pregnant women should, therefore, avoid exposure to these substances. It is recommended that organoselenium compounds should be treated with similar care.
Some of the preparations included in this section use perchloric acid or inorganic perchlorate salts. Finely divided mixtures of perchlorates and organic matter frequently react explosively. Organic perchlorate salts are all potentially self-contained explosives, and should thus be handled with extreme care.
Product Subclass 1: 2H-Selenopyran-2-ones and 4H-Selenopyran-4-ones Synthesis by Ring-Closure Reactions By Formation of Two Se-C Bonds Method 1: 4H-Selenopyran-4-ones by Addition of Dibasic Selenide to Diethynyl Ketones
14.11.1
14.11.1.1 14.11.1.1.1 14.11.1.1.1.1
The most widely reported synthesis of 4H-selenopyran-4-ones involves the addition of sodium selenide to diynones 8, leading to the 4H-selenopyran-4-ones 10 (Table 1).[210] Sodium selenide is generated in situ by treatment of elemental selenium with sodium borohydride. This is then added to a sodium ethoxide solution, which is in turn added to the substrate 8, generally in ethanolic solution containing sodium ethoxide. An extensive study of this reaction[2] has found that the best method for the synthesis of the 4H-selenopyran-4-ones 10 is to allow 8 to react with the sodium ethoxide first, to give the intermediate enol ethers 9, which are then added to a solution of sodium selenide salt in ethanolic sodium ethoxide to give 10. The results of this study are shown in Table 1, together with several other preparations of symmetrical and unsymmetrical 4Hselenopyran-4-ones using a similar method.[6,7] Two early examples[8] of this reaction used a combination of hydrogen selenide and triethylamine; however, the yields are inferior to the newer method.
14.11.1
2H-Selenopyran-2-ones and 4H-Selenopyran-4-ones
121
Table 1 Synthesis of 4H-Selenopyran-4-ones by the Addition of Dibasic Selenide to Diethynyl Ketones[210]

O
step 1
O
step 2
R1 8
R2
R1
EtO 9
R2
R1
Se 10
R2
R1 t-Bu Ph 4-Me2NC6H4 2-thienyl Ph Me t-Bu Ph
R2 t-Bu Ph 4-Me2NC6H4 2-thienyl 4-Me2NC6H4 Me t-Bu Ph
Conditions 1. 0.07 M NaOEt/EtOH, 25 8C, 3 h; 2. Na2Se, 0.1 M NaOEt/EtOH, 15 min 1. 0.07 M NaOEt/EtOH, 25 8C, 450 s; 2. Na2Se, 0.1 M NaOEt/EtOH, 15 min
Yield (%) 89 89
mp (8C) 98102 147148 215 (dec) 153154 155156 8487 98102 147148
Ref
[2]
[2,3]
1. 0.25 M NaOEt/EtOH/THF, 50 8C, 30 min; 89 2. Na2Se, 0.1 M NaOEt/EtOH, 15 min 1. 0.25 M NaOEt/EtOH, 25 8C, 30 min; 2. Na2Se, 0.1 M NaOEt/EtOH, 15 min 87
[2,4]
[2]
1. 0.25 M NaOEt/EtOH/THF, 50 8C, 30 min; 68 2. Na2Se, 0.1 M NaOEt/EtOH, 15 min 1. 0.05 M NaOEt/EtOH; 2. Na2Se, 0.5 M NaOEt/EtOH, 1 h 1. 0.05 M NaOEt/EtOH; 2. Na2Se, 0.5 M NaOEt/EtOH, 1 h 1. 0.05 M NaOEt/EtOH; 2. Na2Se, 0.5 M NaOEt/EtOH, 1 h 56 70 70
[2,5]
[6]
[6]
[6]
Ph
N Me2Si
SiMe2 2. Na2Se, 0.25 M NaOEt, 2 h
1. 0.25 M NaOEt/EtOH/THF, 25 8C, 2 h;
63a
181183
[7]
Me Ph
a
Me Ph
H2Se, Et3N, MeOH, 20 min H2Se, Et3N, MeOH, 20 min
57 17
8889 145146
[8,9] [8,9]
Isolated as the amine, R2 = 4-H2NC6H4.
If the trimethylsilylated diynone 11 is used in this reaction, the final product obtained is the parent 4H-selenopyran-4-one (2) in 35% overall yield, the silyl groups being hydrolyzed during workup (Scheme 2).[10]
Scheme 2 Preparation of 4H-Selenopyran-4-one[10]
O O
Na2Se/0.25 M NaOEt EtOH, 1 h
TMS 11
TMS
35%
Se 2
2,6-Di-2-thienyl-4H-selenopyran-4-one (10, R1 = R2 = 2-Thienyl); Typical Procedure:[2]
A soln of Na2Se was prepared from the action of NaBH4 (0.08 g, 2.2 mmol) on powdered Se (0.174 g, 2.2 mmol) was suspended in 0.25 M NaOEt in EtOH (20 mL), which was stirred until a clear soln was obtained. Diynone 8 (R1 = R2 = 2-thienyl; 0.48 g, 2.0 mmol) was dissolved
122
in 0.25 M NaOEt in EtOH (20 mL) and after 30 min was added to the Na2Se soln. After 15 min, the mixture was added to H2O (200 mL), extracted with CH2Cl2 (3 30 mL), and the combined organic extracts were washed with brine, dried (MgSO4), and then concentrated; yield: 0.562 g (87%); mp 153154 8C (EtOH). NaBH4 (0.52 g, 15 mmol) and Se shot (0.79 g, 10 mmol) were added to 0.25 M NaOEt in EtOH (10 mL), which was refluxed for 1.5 h (until a clear soln was obtained), then cooled to rt. The diynone 11 (1.11 g, 5 mmol) was dissolved in EtOH (10 mL) and added to this soln. The resulting mixture was stirred for 1 h, then diluted with H2O (100 mL) and extracted with CH2Cl2 (3 50 mL), and the combined organic extracts were washed with brine, dried (Na2SO4), and concentrated. Recrystallization (toluene) gave 2 as a yellow crystalline solid; yield: 0.279 g (35%); mp 114115.5 8C.
14.11.1.1.2 14.11.1.1.2.1
4H-Selenopyran-4-one (2):[10]
By Formation of One Se-C and One C-C Bond Method 1: 2H-Selenopyran-2-ones from 2-Aminovinyl Selenoketones
The only known synthesis of non-benzoannulated 2H-selenopyran-2-ones 14 occurs on treatment of 2-aminovinyl selenoketones 12 with the acid chlorides 13 and triethylamine in acetonitrile; the yields for this process are generally poor and only three examples have been reported (Scheme 3).[11]
Scheme 3 Preparation of 2H-Selenopyran-2-ones from 2-Aminovinyl Selenoketones[11]
( )n N + R
1
R2 Cl O 13
Et3N, MeCN, heat R1 = R2 = Ph; n = 2 46% R1 = Ph; R2 = 4-Tol; n = 2 16% R1 = 4-Tol; R2 = Ph; n = 1 47%
R2 R1 Se 14 O
Se 12
14.11.1.2
Synthesis by Substituent Modification
There are very few reports relating to the modification of preformed selenopyranones and no addition reactions have been described. The only known reactions are limited to one report of substitution via a metalation sequence.[12]
14.11.1.2.1 14.11.1.2.1.1 14.11.1.2.1.1.1
Substitution of Existing Substituents Of Hydrogen Method 1: Lithiation of 4H-Selenopyran-4-ones
2,6-Di-tert-butyl-4H-selenopyran-4-one (15) can be metalated at the 3-position by treatment with lithium diisopropylamide at 78 8C to give (2,6-di-tert-butyl-4-oxo-4H-selenopyran-3-yl)lithium (16), which is in equilibrium with the ring-opened form 17 (Scheme 4).[12]
14.11.1
123
Scheme 4 Lithiation of a 4H-Selenopyran-4-one[12]

O
LDA, THF 78 oC
O Li But Se 16 But But
But
Se 15
But
SeLi 17
But
BuLi (1 equiv) was added dropwise to a stirred and cooled (78 8C) soln of iPr2NH (1 equiv) in THF (5 mL mmol1), and the mixture was warmed to 0 8C for 30 min, then cooled again to 78 8C. 2,6-Di-tert-butyl-4H-selenopyran-4-one (15; 1 equiv) dissolved in THF (5 mL mmol1) was then added dropwise, and the resulting soln was stirred for 1 h to generate (2,6-di-tert-butyl-4-oxo-4H-selenopyran-3-yl)lithium (16), which was used immediately (see Section 14.11.1.2.1.2.1.1).
14.11.1.2.1.1.2
(2,6-Di-tert-butyl-4-oxo-4H-selenopyran-3-yl)lithium (16):[12]
Method 2: 4H-Selenopyran-4-ones by Oxidation of 4H-Selenopyrans
4H-Selenopyrans 18 are reported to be oxidized to the corresponding 4H-selenopyran-4ones 19 in fair yields by either potassium permanganate[13] or hydrogen peroxide;[14] however, very limited experimental details are given (Scheme 5).
Scheme 5 Preparation of 4H-Selenopyran-4-ones by Oxidation of 4H-Selenopyrans[13,14]
R2 R
1
O R1 R1 Ph Se 19 R1 Ph
Ph
Se 18
Ph
R1 H H H Me H
a
R2 H H H H OMe
Conditions KMnO4, MeCN, heat H2O2, benzene, 24 h H2O2, acetone, 24 h KMnO4, acetone, heat H2O2, benzene, 24 h
Yield (%) 45 40 48 62 38
mpa (8C) 145147 n.r. n.r. 141143 n.r.
Ref
[13] [14] [14] [13] [14]
n.r. = not reported.
14.11.1.2.1.1.3
Method 3: 4H-Selenopyran-4-ones by Oxidation of 1-Methyl-14-selenopyrans
The 1-methyl-14-selenopyran 20 undergoes hydrolysis and oxidation on exposure to oxygen for one week to give 2,6-dibenzoyl-4H-selenopyran-4-one (21) in 36% yield (Scheme 6).[15]
124

Scheme 6 Preparation of a 4H-Selenopyran-4-one by Oxidation of a 1-Methyl-14-selenopyran[15]
O
O2, MeOH rt, 1 week
Bz
Se Me 20
Bz
36%
Bz
Se 21
Bz
14.11.1.2.1.2 14.11.1.2.1.2.1 14.11.1.2.1.2.1.1
Of Metals Of Lithium Method 1: Reaction of (2,6-Di-tert-butyl-4-oxo-4H-selenopyran-3-yl)lithium with Electrophiles
(2,6-Di-tert-butyl-4-oxo-4H-selenopyran-3-yl)lithium (16, see Section 14.11.1.2.1.1.1) reacts with either benzaldehyde, carbon dioxide, or diphenyl diselenide to give the substituted 4H-selenopyran-4-ones 22 in good to excellent yields (Scheme 7).[12] Attempted reaction with methyl trifluoromethanesulfonate gave a methylated ring-opened product.
Scheme 7 Reaction of (2,6-Di-tert-butyl-4-oxo-4H-selenopyran-3-yl)lithium with Electrophiles[12]
O Li But Se 16 But
A: PhCHO B: CO2 C: (PhSe)2 A: R1 = CH(OH)Ph 74% B: R1 = CO2H 75% C: R1 = SePh 44%
O R1 But Se 22 But
CO2 gas was bubbled into a stirred, cooled (78 8C) soln of (2,6-di-tert-butyl-4-oxo-4H-selenopyran-3-yl)lithium (16; 5 mmol, see Section 14.11.1.2.1.1.1) in THF until the color of the mixture faded. The mixture was poured into 0.1 M NaOH (100 mL) and the aqueous layer was extracted with CH2Cl2 (3 25 mL). The aqueous layer was acidified with cold 10% aq HCl and extracted with CH2Cl2 (3 50 mL). The combined organic extracts of the acid layer were washed with brine, dried (Na2SO4), and concentrated. Purification by recrystallization (MeCN) gave 22 (R1 = CO2H); yield: 1.18 g (75%); mp 165 8C (dec).
14.11.1.2.1.3 14.11.1.2.1.3.1
2,6-Di-tert-butyl-4-oxo-4H-selenopyran-3-carboxylic Acid (22, R1 = CO2H):[12]
Of Carbon Functionalities Method 1: 4H-Selenopyran-4-ones by Oxidation of 4-Methylene-4H-selenopyrans
The selenopyrylium salt 23 is deprotonated in basic buffer to give the 4-methylene-4H-selenopyran 24. This undergoes air oxidation to give the dioxetane intermediate 25, which in turn is thought to eliminate formaldehyde to give the 4H-selenopyran-4-one 15 in 15% yield (Scheme 8).[16]
14.11.1
125
Scheme 8 Preparation of a 4H-Selenopyran-4-one by Oxidation of a 4-Methylene-4H-selenopyran[16]

O O
O2 pH 8.2
But
+ Se
But PF6
But
Se
But
But
Se
But
23
24
25
CH2O 15%
But
Se 15
But
14.11.1.2.2 14.11.1.2.2.1
Modification of Substituents Method 1: 4H-Selenopyran-4-thiones from 4H-Selenopyran-4-ones
4H-Selenopyran-4-ones 26 can be converted into the corresponding 4H-selenopyran-4thiones 27 (Scheme 9) by treatment with Lawessons reagent [2,4-bis(4-methoxyphenyl)1,3-dithia-2,4-diphosphetane 2,4-disulfide][6] or diboron trisulfide.[9,17]
Scheme 9 Preparation of 4H-Selenopyran-4-thiones from 4H-Selenopyran-4-ones[6,9,17]
O
A: Lawesson's reagent, toluene, heat, 1 h B: B2S3, heat, 2 h
R1
Se 26
R1
A: R1 = Me 51% A: R1 = t-Bu 79% A: R1 = Ph 87% B: R1 = Me 76% B: R1 = Ph 76%
R1
Se 27
R1
2,6-Dimethyl-4H-selenopyran-4-one (26, R1 = Me; 0.505 g, 2.7 mmol) was dissolved in CHCl3 (50 mL) and B2S3 (1.0 g, 8.5 mmol) was added. The mixture was then refluxed under argon for 2 h in the absence of light. The mixture was then cooled to rt, filtered, and concentrated to dryness. The residue obtained was then extracted by trituration with hot CHCl3, and the extracts were concentrated and purified by column chromatography (silica gel, petroleum ether then benzene). The fractions containing the product were concentrated, and the product 27 (R1 = Me) was purified by recrystallization (petroleum ether/ EtOH 1:1) to give violet crystals; yield: 0.417 g (76%); mp 115 8C.
2,6-Dimethyl-4H-selenopyran-4-thione (27, R1 = Me):[17]
126
14.11.2
Product Subclass 2: Benzo- and Dibenzoselenopyranones Synthesis by Ring-Closure Reactions By Annulation to an Arene By Formation of Two Se-C Bonds Method 1: By Reaction of 2-Bromophenyl Ethynyl Ketones with Sodium Hydrogen Selenide
14.11.2.1 14.11.2.1.1 14.11.2.1.1.1 14.11.2.1.1.1.1
A very convenient synthesis of 2-substituted 4H-1-benzoselenopyran-4-ones 29 is found in the reaction of 2-bromophenyl ethynyl ketones 28 with sodium hydrogen selenide in dimethylformamide at 100 8C. The reaction is general for alkyl and aryl substituents (Scheme 10) and reaction of the trimethylsilylated ketone 28 (R1 = TMS) leads to the parent compound 29 (R2 = H) in excellent yield.[18]
Scheme 10 Preparation of 4H-1-Benzoselenopyran-4-ones by the Reaction of 2-Bromophenyl Ethynyl Ketones with Sodium Hydrogen Selenide[18]
O
NaSeH, DMF 100 oC
Br 28
R1
Se 29
R2
R1 Me Bu t-Bu (CH2)5Me (CH2)7Me Ph TMS
R2 Me Bu t-Bu (CH2)5Me (CH2)7Me Ph H
Yield (%) 48 90 93 79 86 84 59
mp (8C) 9798 oil 8991 oil oil 133134 9293
Ref
[18] [18] [18] [18] [18] [18] [18]
A soln of a 2-bromophenyl ethynyl ketone 28 (10 mmol) in DMF (20 mL) was slowly added over 1 h at 100 8C to a stirred soln of NaSeH [12 mmol; prepared from Se powder (0.95 g) and NaBH4 (0.54 g)] in DMF (40 mL). After 25 h, the mixture was cooled, diluted with H2O (100 mL), filtered, and extracted with benzene (3 100 mL). The combined organic extracts were washed with H2O (3 200 mL) and brine (2 200 mL), then dried (MgSO4), concentrated, and purified by column chromatography (silica gel, hexane/acetone 50:1); yield: 4893%.
4H-1-Benzoselenopyran-4-ones 29; General Procedure:[18]
14.11.2
Benzo- and Dibenzoselenopyranones
127
14.11.2.1.1.2 14.11.2.1.1.2.1
By Formation of One Se-C and One C-C Bond Method 1: By the Simonis Reaction
It has been reported[1922] that reaction of benzeneselenols with either -oxo esters or malonic acid derivatives in the presence of a strong acid (a Simonis-type reaction) leads to 1benzoselenopyran-4-ones and/or 1-benzoselenopyran-2-ones. For example, reaction of the substituted benzeneselenols 30 with -oxo esters 31 or diketene 32 leads to the 4H-1-benzoselenopyran-4-ones 33; however, the yields are always low (Scheme 11).[19,20] Similarly, reaction of the benzeneselenols 34 with malonic acids 35 leads to the 4-hydroxy-2H-1benzoselenopyran-2-ones 36; again, the yields for this process are poor.[21] A slightly different reaction occurs when the malonic esters 37 are utilized in this reaction, in that the 2-(phenylselanyl)-4H-1-benzoselenopyran-4-ones 38 are obtained in 2030% yield (Scheme 11).[22]
Scheme 11 Preparation of Benzoselenopyranones by the Simonis Reaction[1922]
O R
1
O R2 or O O 32
PPA, heat 537%
R2 R1 Se 33 R3
+ SeH 30
EtO O 31
R1 = H, Me, (CH CH)2 ; R2 = H, Me, Et, Ph; R3 = H, Me, Ph
O R1 + SeH 34 HO HO 35 R
2
OH R1
PPA, heat 321%
R2 Se 36 O
R1 = H, Me; R2 = H, Me, Et, Bu, Pr, Ph
O R1 + SeH 34
R1 = H, Me; R2 = H, Me, Et
O R
2
EtO EtO 37
PPA, heat 2030%
R1 Se 38
R2 Se
R1
14.11.2.1.1.2.2
Method 2: From 2-(Chloroselanyl)benzoyl Chloride via Electrophilic Aromatic Substitution
In one of the earliest reported preparations of 10H-dibenzoselenopyran-10-ones, 2-(chloroselanyl)benzoyl chloride (39) was reacted with benzene to give the parent 10H-dibenzo[b,e]selenopyran-10-one (7) in 73% yield (Scheme 12).[23] Also reported was the reaction of the benzoyl chloride 39 with toluene to give a substituted product in an unreported yield, a reaction which was later repeated,[24] in which the structure was shown to be 3for references see p 142
128
methyl-10H-dibenzo[b,e]selenopyran-10-one (40). The yields for this reaction were generally found to be very poor, which limit its usefulness.
Scheme 12 Preparation of 10H-Dibenzoselenopyran-10-ones from 2-(Chloroselanyl)benzoyl Chloride via Electrophilic Aromatic Substitution[23,24]
O
benzene, AlCl3, 5060 oC 73%
O Cl SeCl 39
toluene, AlCl3, 5060 oC 15%
Se 7
Se 40
14.11.2.1.1.2.3
Method 3: By Reaction of Se-Lithiated Selenosalicylamide Derivatives with Benzyne
Treatment of the dimeric selenosalicylamide derivatives 41 with a fourfold excess of lithium isopropylcyclohexylamide generates the corresponding Se-lithiated selenosalicylamides 42 (Scheme 13), which on reaction with benzyne, generated in situ from bromobenzene, leads to 10H-dibenzoselenopyran-10-ones 43.[25]
Scheme 13 Preparation of 10H-Dibenzoselenopyran-10-ones by the Reaction of Se-Lithiated Selenosalicylamide Derivatives with Benzyne[25]
R1 O NEt2 R2 41 Se )2
LICA (4 equiv) THF, 78 oC
R1
O NEt2
PhBr THF, 20 oC
R2 42
SeLi
R1
R2 43
Se
R1 = R2 = H 40% R1 = H; R2 = OMe 22% R1 = OMe; R2 = H 42%
A soln of diselenide 41 (R1 = R2 = H; 1.18 g, 4.61 mmol) in THF (30 mL) was added to a soln of LICA (16.59 mmol) in THF (50 mL) at 78 8C. After 1 h at this temperature, the cooling bath was removed and the mixture was warmed to 20 8C over 10 min, at which point a soln of PhBr (1.45 g, 9.22 mmol) in THF (20 mL) was added. The mixture was stirred overnight at rt, quenched with sat. NH4Cl soln, concentrated, and the residue was extracted with CHCl3. After drying (Na2SO4) and concentration, the product 7 was isolated by chromatography (benzene), followed by recrystallization (EtOH/hexane); yield: 0.48 g (40%); mp 182185 8C.
10H-Dibenzo[b,e]selenopyran-10-one (43, R1 = R2 = H):[25]
14.11.2
129
14.11.2.1.1.2.4
Method 4: By Photochemical Rearrangement of Aryl Selenoesters
Photolysis of the aryl selenoesters 44 in benzene leads to the formation of the 10H-dibenzo[b,e]selenopyran-10-ones 45 [R1,R2 = (CH=CH)2] or the annulated 4H-1-benzoselenopyran-4-ones 45 [R1,R2 = (CH2)3, N=CH-CH=CH, CH=CH-Se, Se-CH=CH] in poor yields (Scheme 14).[2630] A number of byproducts are formed in these reactions, with the most prevalent being diaryl diselenides.
Scheme 14 Preparation of Annulated 4H-Benzoselenopyran-4-ones by Photochemical Rearrangement of Aryl Selenoesters[2630]
O R3 Se X 44 O R2 R1 45 R3
benzene, h
R2 Se R1
R1,R2 (CH=CH)2 (CH=CH)2 (CH2)3 N=CH-CH=CH CH=CH-Se Se-CH=CH

a
R3 H Me Me Me Me Me
X Cl SOMe S-4-Tol Cl Br H
Yield (%) 19 3 14 25 4 16
mp (8C) a 108110 120125 128130 126127 149150
Ref
[26] [27] [28] [29] [30] [30]
mp not reported.
14.11.2.1.1.3 14.11.2.1.1.3.1
By Formation of One Se-C Bond Method 1: By Cyclization of Ethynyl 2-(Methylselanyl)phenyl Ketones
Reaction of the ethynyl 2-(methylselanyl)phenyl ketones 46 with concentrated hydrobromic acid effects cyclization to the 4H-1-benzoselenopyran-4-ones 47 in good yields (Scheme 15).[31]
Scheme 15 Formation of 4H-1-Benzoselenopyran-4-ones by Cyclization of Ethynyl 2-(Methylselanyl)phenyl Ketones[31]
O
HBr, AcOH
SeMe 46
R1
R1 = H 66% R1 = Ph 43%
Se 47
R1
130
14.11.2.1.1.3.2
Method 2: By Cyclization of Phenyl Selenocinnamates
The phenyl selenocinnamates 48 undergo cyclization on treatment with aluminum trichloride to give the parent 2H-1-benzoselenopyran-2-one (49, R1 = H) in 60% yield or 3methyl-2H-1-benzoselenopyran-2-one (49, R1 = Me) in 35% yield (Scheme 16).[32]
Scheme 16 Formation of 2H-1-Benzoselenopyran-2-ones by Cyclization of Phenyl Selenocinnamates[32]
O SePh R1 48
PhCl, AlCl3, 100 oC R1 = H 60% R1 = Me 35%
R1 Se 49 O
The phenyl selenocinnamate 48 (R1 = H; 1.0 g, 3.5 mmol) was added to AlCl3 (3 g, 22.5 mmol) in PhCl (25 mL) and heated on a steam bath for 30 min. When the color of the mixture changed from yellow to red, and TLC indicated the consumption of 48 (R1 = H), the mixture was diluted with ice-cold dil HCl and extracted with CHCl3. The extracts were washed with H2O, dried, and concentrated. Column chromatography, eluting first with hexane to remove diphenyl diselenide (0.09 g) and then with benzene/hexane (1:1), gave the product; yield: 0.42 g (60%); mp 6971 8C.
14.11.2.1.1.3.3
2H-1-Benzoselenopyran-2-one (49, R1 = Me):[32]
Method 3: By Electrophilic Cyclization of Methyl Selenides
One of the most convenient methods for the formation 2H-1-benzoselenopyran-2-ones 51 is from the aluminum trichloride or phosphoryl chloride catalyzed electrophilic cyclization of aryl methyl selenides 50.[33] This reaction, first reported in the late 1960s,[33,34] appears to be a fairly general method for the preparation of alkyl-, aryl-, and cyano-substituted 2H-1-benzoselenopyran-2-ones (Scheme 17).
Scheme 17 Preparation of 2H-1-Benzoselenopyran-2-ones by Electrophilic Cyclization of Aryl Methyl Selenides[33,34]
R2 R1 R3 COX SeMe 50
R1 = H, 6-Me, 7-Me, 8-Me; R2 = H, Me, Ph; R3 = H, Me, Ph, CN
R2
X = Cl: AlCl3, benzene or CS2, 030 oC X = Cl, OH: POCl3, heat, 67 h ~50%
R3 R1 Se 51 O
A similar cyclization of the substrates 52 using trimethylsilyl polyphosphate (PPSE) gave, in reasonable yield, the annulated 2H-1-benzoselenopyran-2-ones 53, which are selenium analogues of the psoralen class of compounds used in photochemotherapy.[35,36] The bis(2H-selenopyran-2-one) derivative 55 has also been prepared, from 54, using this methodology, however the yield was very poor (Scheme 18).[37]
14.11.2
131
Scheme 18 Preparation of Psoralen Analogues by Electrophilic Cyclization of Aryl Methyl Selenides[3537]

CO2H X SeMe 52 HO2C MeSe 54 SeMe CO2H
PPSE, 120 oC, 522 h X = O 43% X = S 44% X = Se 34%
X 53
Se
PPSE, 180 oC, 16 h 14%
Se 55
Se
It has been reported that 6H-dibenzo[b,d]selenopyran-6-one (6) can be prepared by the zinc chloride mediated cyclization of the acid chloride derived from carboxylic acid 56 (R1 = Me), and that the carboxylic acid 56 (R1 = Bn) is converted into 6 on treatment with thionyl chloride;[38] however, no details or yields were given for these processes (Scheme 19).
Scheme 19 Preparation of 6H-Dibenzo[b,d]selenopyran-6-one[38]
R1 = Me: MeOCHCl2, ZnCl2, CH2Cl2 R1 = Bn: SOCl2
Se HO2C R1Se 56 O 6
The parent heterocyclic system 1H-2-benzoselenopyran-1-one (3) has been prepared in 58% yield using a related process whereby the methyl vinyl selenide 57 was treated sequentially with anhydrous zinc chloride and dichloromethyl methyl ether, followed by aluminum trichloride (Scheme 20).[39]
Scheme 20 Preparation of 1H-2-Benzoselenopyran-1-one[39]
SeMe CO2H O 57 3
1. MeOCHCl2, ZnCl2 2. AlCl3, CH2Cl2, 80 oC 58%
Se
2-[2-(Methylselanyl)vinyl]benzoic acid (57; 2.4 g, 10 mmol) and anhyd ZnCl2 (100 mg) were dissolved in MeOCHCl2 (10 mL) and the mixture was stirred overnight at rt. The excess MeOCHCl2 was removed by evaporation, and dry CH2Cl2 (50 mL) was added to the residue. This soln was cooled to 80 8C, and AlCl3 (1.33 g, 10 mmol) was added with efficient stirring. After the mixture had warmed slowly to rt, it was poured into ice H2O (100 mL) and extracted with CHCl3. The extracts were dried and concentrated; yield: 1.21 g (58%); mp 7980 8C (hexane).
1H-2-Benzoselenopyran-1-one (3):[39]
132
14.11.2.1.1.3.4
Method 4: By Selenolactonization
6H-Dibenzo[b,d]selenopyran-6-one (6) is conveniently prepared from the aryl methyl selenide 58 via a two-stage process to give initially the selenyl bromide 59, which on subsequent reduction with hypophosphorous acid yields the selenol 60 (Scheme 21). This is not isolated, but undergoes cyclization to give 6 in 60% yield, together with the diselenide 61 in 26% yield, which can also be converted into 6 in 76% yield by treatment with hypophosphorous acid in acetic acid.[38]
Scheme 21 Preparation of 6H-Dibenzo[b,d]selenopyran-6-one by Selenolactonization[38]
Br2, CH2Cl2 CCl4, reflux, 2 h H3PO2, AcOH reflux, 20 h
Pri2NOC SeMe 58
Pri2NOC SeBr 59
O 60 6
60% H3PO2, AcOH 76%
61
26%
The aryl methyl selenide 58 (8.0 g, 21 mmol) was dissolved in CH2Cl2/CCl4 (1:1, 60 mL), following which Br2 (1.2 mL, 24 mmol) was added. This mixture was refluxed for 2 h, then evaporated to dryness and redissolved in AcOH (30 mL), to which was added H3PO2 (15 mL), and the resulting mixture was refluxed for 20 h. The mixture was then poured into ice H2O (150 mL), extracted with CH2Cl2, and the extract was washed with 8.4% aq NaHCO3, dried (MgSO4), filtered, and concentrated. The residue was purified by column chromatography (toluene) to give 6; yield: 3.4 g (60%); mp 113115 8C and the diselenide 61; yield: 2 g (26%); mp 210 8C.
14.11.2.1.1.4 14.11.2.1.1.4.1
6H-Dibenzo[b,d]selenopyran-6-one (6):[38]
By Formation of One C-C Bond Method 1: By Aromatic Electrophilic Substitution
Many examples of the synthesis of benzoselenopyranones and dibenzoselenopyranones by electrocyclization onto an aromatic ring have been reported. 4H-1-Benzoselenopyran-4-ones 63 are formed from the electrocyclization of the acid derivatives 62 (X = OH) on treatment with polyphosphoric acid,[40] or from the acid chlorides 62 (X = Cl) with aluminum trichloride,[41] together with the ipso-substitution products in some cases (e.g., compound 64 in 36% yield where R1 = Me and R2 = F) (Scheme 22). This reaction is, however, very limited as most other examples have led to the formation of the ipso-substitution products exclusively.[40,41]
Pri2NOC
SeH
Se
Pri2NOC Se
14.11.2
133
Scheme 22 Preparation of 4H-1-Benzoselenopyran-4-ones by Aromatic Electrophilic Substitution[40,41]

O R2 Se COX 62 R1
A: R1 A: PPA, MeSO2F B: AlCl3, CH2Cl2, 78 oC = Ph; R2 = H; X = OH 64%
R2 Se 63 R1
A: R1 = 4-MeOC6H4; R2 = H; X = OH 40% B: R1 = Ph; R2 = H; X = Cl 85% B: R1 = Me; R2 = F; X = Cl 24%
Se Cl O + 64 F
An excellent method for the preparation of 4-hydroxy-2H-1-benzoselenopyran-2-one (66) is the aluminum trichloride mediated cyclization of the diphenyl propanediselenoate 65, which proceeds in 80% yield (Scheme 23).[42] Attempts to extend the scope of this reaction to substituted diphenyl propanediselenoates were largely unsuccessful with yields of 0 5% being reported.[21]
Scheme 23 Preparation of 4-Hydroxy-2H-1-benzoselenopyran-2-one[42]
OH O PhSe 65 O SePh
AlCl3, 170 oC 80%
Se 66
The first reported synthesis of 10H-dibenzo[b,e]selenopyran-10-ones 68 was from the electrocyclization of 2-(phenylselanyl)benzoic acids 67 (X = OH) using strong acids (Table 2).[23,24,4347] In the case of reactions involving unsubstituted precursors, or those containing electron-donating substituents (Table 2, entries 110), cyclization can be effected using a range of conditions including polyphosphoric acid, sulfuric acid, or a mixture of trifluoroacetic anhydride and trifluoroacetic acid. The presence of electron-withdrawing groups on selenide 67 (Table 2, entries 1122) has a detrimental effect on the yield of the product 68 under the standard acidic conditions [PPA, polyphosphate ester (PPE), P2O5/ MsOH, or TFA/TFAA]; however, it was found that trimethylsilyl polyphosphate (PPSE) was by far the most superior reagent for effecting this cyclization (Table 2, entries 19 22).[47] One example of a FriedelCrafts reaction has been reported (Table 2, entry 23);[24] however, the authors of this paper suggest the methodology and yields are inferior to the acid-catalyzed processes.
134
Table 2 Preparation of 10H-Dibenzo[b,e]selenopyran-10-ones by Electrocyclization[23,24,4347]

R1 R2 Se R3 R4 67 R5 R6 O X R8 R R7 R3 R4 68 Se R5 R6 R1
2
R8 R7
Entry R1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
a b
R2 H H H H H H H H H H H H H H H H H H H H
R3 H H H Me H H H H H H OMe H H H H H
R4 H H H H H H H H H H H H H H H H NO2
R5 H H H H H H H OMe NO2 NO2 NO2 NO2 NO2 NO2 H NO2 NO2 H NO2 NO2 H
R6 H H H H H H H
R7 H H Me H H H H Cl
R8 H H H H H H H H
X OH OH OH OH OH OH OH OH
Conditionsa PPA, heat PPA, 100 8C, 3h PPA, heat PPA, heat H2SO4 H2SO4
Yieldb mpb (8C) (%) 82 97 53 65 n.r. n.r. 191192 190 111 110111 n.r. n.r. 190191 156 139141 101102 229232 222224 196197 196197 196197 196197 196197 241243 196197 196197 229232 222224 191192
Ref
[24] [44]
H H H H H H H H H H H H H H H H Cl H H Cl H H H
[24] [24] [23,43] [23,43] [45] [45]
CO2H H
H2SO4, 95 8C 88 H2SO4, 95 8C, 88 90 min TFAA, TFA TFAA, TFA PPA PPE PPA PPE P2O5, MsOH TFA, TFAA TFA, TFAA TFA, TFAA, H3PO4 PPSE, P2O5, 210 8C PPSE, P2O5, 210 8C PPSE, P2O5, 210 8C PPSE, P2O5, 210 8C ZnCl2 88 83 18 12 43 44 40 55 70 55 99 87 94 63 38
(CH=CH)2 Me H H H H H H H H H H H H H H H H H H H H H H H H H H
OMe OH OMe OH Cl Cl Cl Cl Cl Cl H Cl Cl H Cl Cl H OH OH OH OH OH OH OH OH OH OH OH OH Cl
[46] [46] [47] [47] [47] [47] [47] [47] [47] [47]
OMe Me
OMe H
OCH2O H H OMe H NO2 H H H
[47]
[47]
[47]
OMe H H H
[47]
[24]
PPSE = trimethylsilyl polyphosphate. n.r. = not reported.
The sulfuric acid mediated electrocyclization of 2-(phenylselanyl)benzaldehyde (69) leads to a mixture of 10H-dibenzo[b,e]selenopyran-10-one (7) in 49% yield and 10H-dibenzo[b,e]selenopyran (9H-selenoxanthene, 72) in 46% yield.[48] The reaction is thought to proceed via the corresponding dibenzoselenopyrylium intermediate 70; this is hydrolyzed to 10H-dibenzo[b,e]selenopyran-10-ol (9H-selenoxanthen-9-ol, 71), which acts as a hydride-
14.11.2
135
transfer reagent reducing a further molecule of 70 to the dibenzoselenopyran 72 and yielding 7 (Scheme 24).
Scheme 24 Preparation of 10H-Dibenzo[b,e]selenopyran-10-one and 10H-dibenzo[b,e]selenopyran[48]
OH CHO SePh 69
80% H2SO4 95 oC
+ Se 70 O
70
Se 71
+ Se 7
49%
Se 72
46%
When a similar cyclization of the selenoacetoacetate ester 73 was attempted using polyphosphoric acid,[20] the reaction took a different course and instead of the expected benzoselenopyran-2-one product, the rearranged 2-methyl-4H-1-benzoselenopyran-4-one (74) was obtained in 40% yield (Scheme 25).
Scheme 25 Preparation of 2-Methyl-4H-1-benzoselenopyran-4-one[20]
O O PhSe 73 O
PPA 40%
Se 74
Carboxylic acid 67 (R1 = R3 = R4 = R6 = R7 = H; R2 = OMe; R5 = NO2; R8 = Cl; X = OH; 6.0 g, 15.5 mmol) was added to a heated (210 8C), mechanically stirred mixture of PPSE syrup (200 g) and P2O5 (24 g) and stirred for 20 min. The mixture was then poured onto an icecold soln of HCl and stirred for a further 3 h. The resulting orange precipitate was collected by filtration and recrystallized (MeCN); yield: 3.58 g (63%); mp 222224 8C. 2-(Phenylselanyl)benzaldehyde (69; 10.0 g, 38.3 mmol) was added to 80% H2SO4 (100 mL) and heated to 95 8C for 30 min. The mixture was then poured onto crushed ice and extracted with CH2Cl2, following which the extracts were washed with H2O, dried (MgSO4), and concentrated to dryness. Column chromatography of the residue (benzene/hexane 1:5) gave 72; yield: 4.3 g (46%). Further elution with neat benzene gave 10H-dibenzo[b,e]selenopyran-10-one (7); yield: 4.9 g (49%), which was recrystallized (EtOH) to give pale yellow needles; mp 192193 8C.
10H-Dibenzo[b,e]selenopyran-10-one (7) and 10H-Dibenzo[b,e]selenopyran (72):[48]
1-Chloro-8-methoxy-4-nitro-10H-dibenzo[b,e]selenopyran-10-one (68, R1 = R3 = R4 = R6 = R7 = H; R2 = OMe; R5 = NO2; R8 = Cl; Table 2, Entry 22):[47]
136
14.11.2.2 14.11.2.2.1
Synthesis by Ring Transformation Method 1: By Rearrangement of Substituted Benzo[b]selenophen-3(2H)-ones
The substituted benzo[b]selenophen-3(2H)-ones 75 undergo rearrangement to the corresponding 4-hydroxy-2H-1-benzoselenopyran-2-ones 76 in quantitative yield on treatment with hypophosphorous acid (Scheme 26).[49]
Scheme 26 Preparation of 4-Hydroxy-2H-1-benzoselenopyran-2-ones by Rearrangement of Substituted Benzo[b]selenophen-3(2H)-ones[49]
O CO2Et Se 75
R1 = H, Me, CO2Et H3PO2 ~100%
OH R1 Se 76 O
R1
14.11.2.3 14.11.2.3.1
Aromatization Method 1: By Dehydrogenation of 2,3-Dihydro-4H-1-benzoselenopyran-4-ones
Preparation of 4H-1-benzoselenopyran-4-one (33, R1 = R2 = R3 = H) in 67% yield by the triphenylcarbenium perchlorate oxidation of 2,3-dihydro-4H-1-benzoselenopyran-4-one (77, R1 = R2 = R3 = H; Scheme 27) has been reported,[50] a reaction which was used later[51] to prepare a range of substituted 4H-1-benzoselenopyran-4-ones 33 in somewhat lower yields (1530%).
Scheme 27 Preparation of 4H-1-Benzoselenopyran-4-ones by Oxidation of 2,3-Dihydro-4H-1-benzoselenopyran-4-ones[50,51]
O R2 R
1
O
Tr+ ClO4, MeCN R1 = R2 = R3 = H 67% R1 = R2 = H; R3 = Me 23% R1 = = H; = Me 15% R1 = 6-Me; R2 = R3 = H 30% R1 = 7-Me; R2 = R3 = H 27% R1 = 8-Me; R2 = R3 = H 25% R3 R2
R2 R
1
Se 77
R3
Se 33
R3
Triphenylcarbenium perchlorate (CAUTION: explosive) (3.42 g, 10 mmol) was added to a soln of 2,3-dihydro-4H-1-benzoselenopyran-4-one (77, R1 = R2 = R3 = H; 2.11 g, 10 mmol) in MeCN (15 mL), and the mixture was heated to 50 8C for 15 min. After cooling, charcoal was added and the soln was filtered. Dry Et2O (30 mL) was added to precipitate 4-hydroxybenzoselenopyrylium chloride [mp 118 8C (dec)], which was removed by filtration. The salt was neutralized by addition to an excess of aq NaHCO3, followed by extraction with Et2O, drying, and concentration. Recrystallization (ligroin) gave the product; yield: 1.40 g (67%); mp 9394 8C.
4H-1-Benzoselenopyran-4-one (33, R1 = R2 = R3 = H):[50]
14.11.2
137
14.11.2.3.2
Method 2: Oxidation of Benzoselenopyrans
Oxidation of the 2H-1-benzoselenopyrans 78 using chromium(VI) oxide in pyridine leads to the 2H-1-benzoselenopyran-2-ones 79 in 50% yield;[52] a similar oxidation of the substrate 80 led to the 4H-1-benzoselenopyran-4-one 81 in 43% yield.[53] The parent 1H-2-benzoselenopyran-1-one (3) has been prepared from 1H-2-benzoselenopyran (82) by oxidation with sulfuryl chloride (Scheme 28).[54]
Scheme 28
R1
CrO3, py
Preparation of Benzoselenopyranones by Oxidation of Benzoselenopyrans[5254]

R1
Se R2 78
R1 = Me; R2 = H 50% R1 = H; R2 = Me 50%
Se R2 79 O
CrO3, py
Se 80
SPh
43%
Se 81
SPh
SO2Cl2 (1 equiv), TMSCN (2.3 equiv) SnCl4 (0.3 equiv), CH2Cl2
Se
37%
Se O
82
CrO3 (2 g, 20 mmol) was dissolved in pyridine (30 mL) and cooled (0 8C), whereupon 2(phenylsulfanyl)-2H-1-benzoselenopyran (80; 1 g, 3.3 mmol) was added in small portions over 10 min with stirring. After 2 h at this temperature the reaction was warmed to rt and stirred for a further 4 h. After addition of H2O (50 mL) and CH2Cl2 (50 mL), sufficient 1 M HCl was added to dissolve any precipitate and the organic layer was separated. The aqueous layer was extracted with further CH2Cl2 (3 25 mL) and the combined extracts were washed with 1 M HCl (50 mL) and H2O (100 mL), dried, and concentrated. Recrystallization of the residue (hexane/benzene) gave 81; yield: 0.45 g (43%); mp 107108 8C.
14.11.2.4 14.11.2.4.1
2-(Phenylsulfanyl)-4H-1-benzoselenopyran-4-one (81):[53]
Synthesis by Substituent Modification Substitution of Existing Substituents
No general methods exist for the substitution of existing substituents on benzo- or dibenzoselenopyranones and only a limited number of examples of substitution reactions have been reported. Several useful oxidative preparations of benzo- and dibenzoselenopyranones are known (see Sections 14.11.2.3.2 and 14.11.2.4.1.1.3). The hydrolysis of a dibenzoselenopyran-10-imine derivative yields 10H-dibenzo[b,e]selenopyran-10-one (7) in 95% yield.[55] Similarly, the hydrolysis of a cyanohydrin derivative of a dibenzoselenopyran-10-one can be achieved using aqueous sodium hydroxide solution.[56]
138
14.11.2.4.1.1 14.11.2.4.1.1.1
Of Hydrogen Method 1: Lithiation of 4H-1-Benzoselenopyran-4-ones
Metalation of 2-phenyl-4H-1-benzoselenopyran-4-one (83) using lithium diisopropylamide at 78 8C has been reported and leads to the 3-metalated product 84. However, reactions of this intermediate are known to lead to a complex mixture of products and are generally not synthetically useful; for example, methylation using methyl trifluoromethanesulfonate led to the 3-methyl product 85 in only 11% yield (Scheme 29).[12]
Scheme 29
O
LDA, THF 78 oC
Lithiation of a 4H-1-Benzoselenopyran-4-one[12]
O Li Se 84 Ph
TfOMe 11%
Se 83
Ph
Se 85
Ph
14.11.2.4.1.1.2
Method 2: Electrophilic Alkylation of 4-Hydroxy-2H-1-benzoselenopyran-2-one
Reaction of 4-hydroxy-2H-1-benzoselenopyran-2-one (66) with aqueous formaldehyde leads to the dimeric product 86 in quantitative yield, whilst reaction with malonyl dichloride gives the lactone 87 in 90% yield. Attempted chlorination of 66 with phosphoryl chloride gives the dimerized product 88 in 88% yield (Scheme 30).[42]
Scheme 30 Electrophilic Alkylation of 4-Hydroxy-2H-1-benzoselenopyran-2-one[42]
OH
CH2O, H2O, heat, 1 h ~100%
HO
Se
O O 86 O
Se
OH
CH2(COCl)2 130140 oC, 0.5 h 90%
O OH Se 87 O Cl
POCl3, 70 oC, 30 min 88%
Se 66
Se
Se 88
14.11.2
139
14.11.2.4.1.1.3
Method 3: Oxidation of Dibenzoselenopyrylium Salts
Oxidation of dibenzoselenopyrylium salts 89 using either manganese(IV) oxide[57] or potassium permanganate[58] leads to the parent 10H-dibenzo[b,e]selenopyran-10-one (90, R1 = H) in excellent yield or amine 90 (R1 = NMe2) in poor yield (Scheme 31).
Scheme 31 Preparation of 10H-Dibenzo[b,e]selenopyran-10-ones by Oxidation of Dibenzoselenopyrylium Salts[57,58]
A: MnO2, MeCN, reflux, 10 min B: MnO2, CH2Cl2, reflux, 2 h C: KMnO4, NaOH, H2O
R1
+ Se 89
R1
A: R1 = H; X = ClO4 99% B: R1 = H; X = ClO4 88% C: R1 = NMe2; X = ZnCl3 21%
R1
Se 90
R1
14.11.2.4.1.2 14.11.2.4.1.2.1
Of Carbon Functionalities Method 1: Decarboxylation
The decarboxylation of 10-oxo-10H-dibenzo[b,e]selenopyran-4-carboxylic acid (91) by pyrolysis in the presence of calcium hydroxide is reported to give 10H-dibenzo[b,e]selenopyran-10-one (7, Scheme 32), although a detailed experimental procedure was not given.[23]
Scheme 32
O
pyrolysis
Preparation of 10H-Dibenzo[b,e]selenopyran-10-one by Decarboxylation[23]

O
Se CO2H 91
Se 7
14.11.2.4.1.3 14.11.2.4.1.3.1
Of Oxygen Method 1: Preparation of a 10H-Dibenzo[b,e]selenopyran-10-one Ylide
Treatment of 10H-dibenzo[b,e]selenopyran-10-one 5-oxide (92) with 2 equivalents of dimethylacetylene dicarboxylate in refluxing dichloromethane for 10 hours generates the selenium ylide 93 in 21% yield (Scheme 33).[59]
Scheme 33
O
DMAD (2 equiv), CH2Cl2, 10 h 21%
Preparation of a 10H-Dibenzo[b,e]selenopyran-10-one Ylide[59]

O
Se O O
+ Se
CO2Me CO2Me 93
92
140
14.11.2.4.2 14.11.2.4.2.1
Addition Reactions Method 1: Oxidation of the Selenium Atom
10H-Dibenzo[b,e]selenopyran-10-one 5-oxide (92) was originally prepared by treatment of 10H-dibenzo[b,e]selenopyran-10-one (7) with chromium(VI) oxide.[23,43] It is more conveniently prepared by oxidation of 7 with 3-chloroperoxybenzoic acid[59] which is reported to give 92 in high yield, although no experimental details were given (Scheme 34).
Scheme 34
O
MCPBA
Preparation of 10H-Dibenzo[b,e]selenopyran-10-one 5-Oxide[59]

O
Se
Se O
92
14.11.2.4.2.2
Method 2: Addition of Dihalogen to the Selenium Atom
Chlorine, bromine, and iodine all react with 10H-dibenzo[b,e]selenopyran-10-one (7) to give the corresponding Se,Se-dihalides in excellent yield;[6063] however, the nature of the species formed is dictated by the halogen in question. The structure of the chlorine adduct is trigonal bipyramidal in which two Se-Cl bonds exist (i.e., 94); however, iodine and bromine both form molecular complexes 95, which are tetrahedral at selenium (Scheme 35).
Scheme 35 Halogenation of 10H-Dibenzo[b,e]selenopyran-10-one[6063]
O
X = Cl
Se Cl 94 Cl
O
X2, CH2Cl2 or CCl4
Se 7 O
X = Br, I
Se X X 95
14.11.2.4.3
Modification of Substituents
Very few substituent modification reactions have been reported for benzo- or dibenzoselenopyranones, with only two of interest being discussed in detail. It has, however, been reported that a range of derivatives of 10-oxo-10H-dibenzo[b,e]selenopyran-4-carboxylic acid (91) including the acid chloride, esters, and amides can be prepared using standard methods.[23,43]
14.11.2
141
14.11.2.4.3.1
Method 1: Preparation of Benzo- and Dibenzoselenopyranthiones
The preparation of 2H-benzoselenopyran-2-thiones by the action of phosphorus pentasulfide on the corresponding 2H-benzoselenopyran-2-ones has been reported,[34] however, no preparative details and only limited analytical data were given for these reactions.[64] It was later reported (Scheme 36)[65] that 10H-dibenzo[b,e]selenopyran-10-one (7) can be converted into the corresponding dibenzoselenopyran-10-thione 96 in 91% yield by treatment with Lawessons reagent [2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide] under similar conditions to those used for the preparation of 4H-selenopyran-4-thiones (see Section 14.11.1.2.2.1).
Scheme 36 Preparation of 10H-Dibenzo[b,e]selenopyran-10-thione Using Lawessons Reagent[65]
O
Lawesson's reagent benzene, heat, 9 h
Se 7
91%
Se 96
14.11.2.4.3.2
Method 2: By Condensation of 2-Methyl-4H-1-benzoselenopyran-4-one with a Thiazolium Betaine
2-Methyl-4H-1-benzoselenopyran-4-one (74) undergoes reaction with the thiazolium betaine 97 on heating to give the condensation product 98; no yield was reported for this process (Scheme 37).[66]
Scheme 37 Betaine[66]
O Et N+ + Se 74 S 97 SO3
160 oC, 1 h
Condensation of 2-Methyl-4H-1-benzoselenopyran-4-one with a Thiazolium

O EtN Se 98 S
142
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The People
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Table of Contents
1 2 3 4 5 6 7
The Editorial Board of Science of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 The Volume Editors of Science of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 The Advisory Board of Science of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 The Authors of Science of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162 The Science of Synthesis Team . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 How to Get Further Information on Science of Synthesis . . . . . . . . . . . . . . . . . . . 171 Who to Contact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
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The Editorial Board of Science of Synthesis

Prof. Daniel Bellus Mhlestiegrain 10 4125 Riehen Switzerland Phone: + 41 (61) 641-1029 Fax: + 41 (61) 641-2529 E-mail: bellus.daniel@freesurf.ch
Prof. Eric N. Jacobsen Harvard University Dept. of Chemistry and Chemical Biology 12 Oxford Street Cambridge, MA 02138 USA Phone: + 1 (617) 496-3688 Fax: + 1 (617) 496-1880 E-mail: jacobsen@chemistry.harvard.edu Prof. Steven V. Ley University of Cambridge Chemical Laboratory Lensfield Road Cambridge CB2 1EW UK Phone: + 44 (1223) 336-398 Fax: + 44 (1223) 336-442 E-mail: svl1000@cam.ac.uk Prof. Ryoji Noyori Nagoya University Department of Chemistry Chikusa Nagoya 464-8602 Japan Phone: + 81 (52) 789-2956 Fax: + 81 (52) 783-4177 E-mail: noyori@chem3.chem.nagoya-u.ac.jp Prof. Manfred Regitz Fachbereich Chemie Universitt Kaiserslautern Erwin-Schroedinger-Strae 67663 Kaiserslautern Germany Phone: + 49 (631) 205-2431 Fax: + 49 (631) 205-3921 E-mail: regitz@rhrk.uni-kl.de
The Editorial Board of Science of Synthesis
149
Dr. Paul J. Reider Vice President, Chemistry Research Amgen, M/S 29-M-B One Amgen Center Drive Thousand Oaks, California, 91320-1799 USA Phone: + 1 (805) 447-1043 Fax: + 1 (805) 480-1331 E-mail: reider@amgen.com Prof. Ernst Schaumann Institut fr Organische Chemie der TU Clausthal Leibnizstrae 6 38678 Clausthal-Zellerfeld Germany Phone: + 49 (5323) 72-2383/72-2519 Fax: + 49 (5323) 72-2858 E-mail: ernst.schaumann@tu-clausthal.de Dr. Ichiro Shinkai 1-11-6-1809, Tsukuda Chuo-ku Tokyo 104-0051 Japan Phone: + 81 (3) 5560-8028 Fax: + 81 (3) 5560-8029 E-mail: ishinkai@tkk.att.ne.jp Prof. E. Jim Thomas Victoria University of Manchester Oxford Road Manchester M13 9PL UK Phone: + 44 (161) 275-4613/-4614 Fax: + 44 (161) 275-4939 E-mail: e.j.thomas@man.ac.uk Prof. Barry M. Trost Stanford University Department of Chemistry Stanford CA 94305-5080 USA Phone: + 1 (650) 723-3385 Fax: + 1 (650) 725-0259 E-mail: bmtrost@leland.stanford.edu
150
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The Volume Editors of Science of Synthesis

Category 1: Organometallics
Volume 1: Compounds with Transition Metal-Carbon -Bonds and Compounds of Groups 108 (Ni, Pd, Pt, Co, Rh, Ir, Fe, Ru, Os)
Prof. Mark Lautens Department of Chemistry University of Toronto Toronto Ontario M5S 1A1 Canada Phone: + 1 (416) 978-6083 Fax: + 1 (416) 978-6083 E-mail: mlautens@alchemy.chem.utoronto.ca
Volume 2: Compounds of Groups 73 (Mn , Cr , V , Ti , Sc , La , Ac )
Prof. Tsuneo Imamoto Department of Chemistry Faculty of Science Chiba University Inage Chiba 263-8522 Japan Phone: + 81 (43) 290-2791 Fax: + 81 (43) 290-2791 E-mail: imamoto@scichem.s.chiba-u.ac.jp
Volume 3: Compounds of Groups 12 and 11 (Zn, Cd, Hg, Cu, Ag, Au)
Dr. Ian ONeil Donnan and Robert Robinson Laboratories Department of Chemistry University of Liverpool Crown Street Liverpool L69 7ZD UK Phone: + 44 (151) 794-3485 Fax: + 44 (151) 794-3588 E-mail: ion@liverpool.ac.uk
151
Volume 4:
Compounds of Group 15 (As, Sb, Bi) and Silicon Compounds
Prof. Ian Fleming Pembroke College University of Cambridge Department of Chemistry Cambridge CB2 1RF UK Phone: + 44 (1223) 336-372 Fax: + 44 (1223) 336-362 E-mail: if10000@cus.cam.ac.uk
Volume 5: Compounds of Group 14 (Ge, Sn, Pb)
Dr. Mark G. Moloney University of Oxford Department of Chemistry Dyson Perrins Laboratory South Parks Road Oxford OX1 3QY UK Phone: + 44 (1865) 275-656 Fax: + 44 (1865) 275-674 E-mail: mark.moloney@chem.ox.ac.uk
Volume 6: Boron Compounds
Prof. Dieter E. Kaufmann Institut fr Organische Chemie der TU Clausthal Leibnizstrae 6 38678 Clausthal-Zellerfeld Germany Phone: + 49 (5323) 72-2027 Fax: + 49 (5323) 72-2834 E-mail: dieter.kaufmann@tu-clausthal.de Prof. Donald S. Matteson Department of Chemistry P. O. Box 644630 Washington State University Pullman, WA 99164-4630 USA Phone: + 1 (509) 335-3365 Fax: + 1 (509) 335-8867 E-mail: dmatteson@wsu.edu
152
Volume 7:
Compounds of Groups 13 and 2 (Al, Ga, In, Tl, Be Ba)
Prof. Hisashi Yamamoto Arthur Holly Compton Distinguished Professor Department of Chemistry The University of Chicago 5735 South Ellis Avenue Chicago IL 60637 USA Phone: + 1 (773) 702-5059 Fax: + 1 (773) 702-0805 E-mail: yamamoto@uchicago.edu
Volume 8: Compounds of Group 1 (Li Cs)
Prof. Victor Snieckus Bader Chair in Organic Chemistry Queens University Kingston Ontario K7L 3N6 Canada Phone: + 1 (613) 533-2239 Fax: + 1 (613) 533-2837 E-mail: Snieckus@chem.queensu.ca Prof. Marek Majewski Department of Chemistry University of Saskatchewan 110 Science Pl. Saskatoon, SK S7N 5C9 Canada Phone: + 1 (306) 966-4671 E-mail: majewski@sask.usask.ca
153
Category 2: Hetarenes and Related Ring Systems

Volume 9: Fully Unsaturated Small-Ring Heterocycles and Monocyclic Five-Membered Hetarenes with One Heteroatom
Prof. Gerhard Maas Abteilung Organische Chemie I Universitt Ulm Albert-Einstein-Allee 11 89069 Ulm Germany Phone: + 49 (731) 502-2790 Fax: + 49 (731) 502-2803 E-mail: gerhard.maas@chemie.uni-ulm.de
Volume 10: Fused Five-Membered Hetarenes with One Heteroatom
Prof. E. Jim Thomas Victoria University of Manchester Oxford Road Manchester M13 9PL UK Phone: + 44 (161) 275-4613/-4614 Fax: + 44 (161) 275-4939 E-mail: e.j.thomas@man.ac.uk
Volume 11:
Five-Membered Hetarenes with One Chalcogen and One Additional Heteroatom
Prof. Ernst Schaumann Institut fr Organische Chemie der TU Clausthal Leibnizstrae 6 38678 Clausthal-Zellerfeld Germany Phone: + 49 (5323) 72-2383/72-2519 Fax: + 49 (5323) 72-2858 E-mail: ernst.schaumann@tu-clausthal.de
154
Volume 12:
Five-Membered Hetarenes with Two Nitrogen or Phosphorus Atoms
Prof. Reinhard Neier Institut de Chimie Universit de Neuchtel Av. de Bellevaux 51 CH-2007 Neuchtel 7 Switzerland Phone: + 41 (32) 718-2428 Fax: + 41 (32) 718-2511 E-mail: reinhard.neier@ich.unine.ch
Volume 13: Five-Membered Hetarenes with Three or More Heteroatoms
Dr. Richard C. Storr Donnan and Robert Robinson Laboratories Department of Chemistry University of Liverpool Crown Street Liverpool L69 7ZD UK Phone: + 44 (151) 794-3479 Fax: + 44 (151) 794-3588 E-mail: rcstorr@liverpool.ac.uk Dr. Tom L. Gilchrist 57 Cunningham Drive Bromborough Wirral Merseyside CH63 0JX UK Phone: + 44 (151) 334-4126 Fax: + 44 (151) 794-3588 E-mail: tlg57@liverpool.ac.uk
Volume 14: Six-Membered Hetarenes with One Chalcogen
Prof. E. Jim Thomas Victoria University of Manchester Oxford Road Manchester M13 9PL UK Phone: + 44 (161) 275-4613/-4614 Fax: + 44 (161) 275-4939 E-mail: e.j.thomas@man.ac.uk
155
Volume 15:
Six-Membered Hetarenes with One Nitrogen or Phosphorus Atom
Prof. David St. Clair Black School of Chemistry The University of New South Wales Sydney NSW 2052 Australia Phone: + 61 (2) 9385-4657 Fax: + 61 (2) 9385-6141 E-mail: d.black@unsw.edu.au
Volume 16: Six-Membered Hetarenes with Two Identical Heteroatoms
Prof. Yoshinori Yamamoto Department of Chemistry Graduate School of Science Tohoku University Sendai 980-8578 Japan Phone: + 81 (22) 217-6581 Fax: + 81 (22) 217-6784 E-mail: yoshi@yamamoto1.chem.tohoku.ac.jp
Volume 17: Six-Membered Hetarenes with Two Unlike or More than Two Heteroatoms and Fully Unsaturated Larger-Ring Heterocycles
Prof. Steven M. Weinreb Department of Chemistry Eberly College of Science The Pennsylvania State University 152 Davey Laboratory, University Park PA 16802-6300 USA Phone: + 1 (814) 863-0189 Fax: + 1 (814) 863-8403 E-mail: smw@chem.psu.edu
156
Category 3: Compounds with Four and Three Carbon-Heteroatom Bonds

Volume 18: Four Carbon-Heteroatom Bonds: X-CX, X=C=X, X2C=X, CX4
Dr. Julian G. Knight University of Newcastle Dept. of Chemistry Bedson Building Newcastle upon Tyne NE1 7RU UK Phone: + 44 (191) 222-7068 Fax: + 44 (191) 222-6929 E-mail: j.g.knight@ncl.ac.uk
Volume 19: Three Carbon-Heteroatom Bonds: Nitriles, Isocyanides, and Derivatives
Prof. Shun-Ichi Murahashi Department of Chemistry Faculty of Engineering Science Osaka University Toyonaka Osaka 560 Japan Phone: + 81 (6) 6850-6220 Fax: + 81 (6) 6850-6224 E-mail: mura@chem.es.osaka-u.ac.jp
Volume 20: Three Carbon-Heteroatom Bonds: Acid Halides; Carboxylic Acids and Acid Salts; Esters, Polyesters, and Lactones; Peroxy Acids and R(CO)OX Compounds; R(CO)X, X = S, Se, Te
Prof. James S. Panek Department of Chemistry Metcalf Center for Science and Engineering Boston University Boston, MA 02215 USA Phone: + 1 (617) 353-2484 Fax: + 1 (617) 353-6466 E-mail: panek@chem.bu.edu
157
Volume 21:
Three Carbon-Heteroatom Bonds: Amides and Derivatives; Polyamides and Peptides; Lactams
Prof. Steven M. Weinreb Department of Chemistry Eberly College of Science The Pennsylvania State University 152 Davey Laboratory, University Park PA 16802-6300 USA Phone: + 1 (814) 863-0189 Fax: + 1 (814) 863-8403 E-mail: smw@chem.psu.edu
Volume 22: Three Carbon-Heteroatom Bonds: Thio-, Seleno-, and Tellurocarboxylic Acids and Derivatives; Imidic Acids and Derivatives; Ortho Acid Derivatives
Prof. Andr B. Charette Dpartement de Chimie Universit de Montreal P.O. Box 6128 Station Downtown Montreal, Quebec, H3C 3J7 Canada Phone: + 1 (514) 343-2432 Fax: + 1 (514) 343-5900 E-mail: andre.charette@umontreal.ca
Volume 23: Three Carbon-Heteroatom Bonds: Ketenes and Derivatives
Prof. Rick L. Danheiser Department of Chemistry Massachusetts Institute of Technology Room 18-297 Cambridge, MA 02139-4307 USA Phone: + 1 (617) 253-1842 Fax: + 1 (617) 252-1504 E-mail: danheisr@mit.edu
158
Volume 24:
Three Carbon-Heteroatom Bonds: Ketene Acetals and Yne-X Compounds
Prof. Armin de Meijere Institut fr Organische Chemie der Georg-August-Universitt Tammannstrae 2 37077 Gttingen Germany Phone: + 49 (551) 39-3231 Fax: + 49 (551) 39-9475 E-mail: Armin.deMeijere@chemie.uni-goettingen.de
Category 4: Compounds with Two Carbon-Heteroatom Bonds

Volume 25: Aldehydes
Prof. Reinhard Brckner Institut fr Organische Chemie und Biochemie der Albert-Ludwigs-Universitt Albertstr. 21 79104 Freiburg Germany Phone: + 49 (761) 203-6029 Fax: + 49 (761) 203-6100 E-mail: reinhard.brueckner@organik.chemie. uni-freiburg.de
Volume 26: Ketones
Prof. Janine Cossy Lab. de Chimie Organique, Associ au CNRS ESPCI 10, rue Vauguelin 75231 Paris Cedex 05 France Phone: + 33 (140) 794429 Fax: + 33 (140) 794660 E-mail: janine.cossy@espci.fr
159
Volume 27:
Heteroatom Analogues of Aldehydes and Ketones
Prof. Albert Padwa Emory University Department of Chemistry 1515 Pierce Drive Atlanta, GA 30322 USA Phone: + 1 (404) 727-0283 Fax: + 1 (404) 727-6586 E-mail: chemap@emory.edu
Volume 28: Quinones and Heteroatom Analogues
Prof. Axel G. Griesbeck Institut fr Org. Chemie der Universitt Kln Greinstr. 4 50939 Kln Germany Phone: + 49 (221) 470-3083 Fax: + 49 (221) 470-5057 E-mail: griesbeck@uni-koeln.de
Volume 29: Acetals: Hal/X and O/O, S, Se, Te
Dr. Stuart Warriner School of Chemistry University of Leeds Leeds LS2 9JT UK Phone: +44 (113) 233-6437 Fax: +44 (11)3 233-6565 E-mail: S.L.Warriner@chem.leeds.ac.uk
Volume 30:
Acetals: O/N, S/S and S/N and Higher Heteroatom Analogues
Prof. Junzo Otera Okayama University of Science 1-1 Ridai-cho Okayama 700-0005 Japan Phone: + 81 (86) 256-9525 Fax: + 81 (86) 256-4292 E-mail: otera@high.ous.ac.jp
160
Category 5: Compounds with One Carbon-Heteroatom Bond

Volume 34: Fluorine
Prof. Jonathan Percy Department of Chemistry University of Leicester Leicester LE1 7RH UK Phone: + 44 (116) 252-2140 Fax: + 44 (116) 252-3789 E-mail: jmp29@leicester.ac.uk
Volume 39:
Sulfides, Selenides, and Tellurides
Prof. Nobuaki Kambe Osaka University Graduate School of Engineering 2-1 Yamada-oka Suita 565-0871 Japan Phone: + 81 (6) 6877-5111 (Ext. 3416) Fax: + 81 (6) 6879-7390 E-mail: kambe@ap.chem.eng.osaka-u.ac.jp
Volume 42: Organophosphorus Compounds
Prof. Edwin Vedejs Chemistry Department College of LS & A University of Michigan 930 N. University Ann Arbor, MI 48109-1055 USA Phone: + 1 (734) 615-2177 Fax: + 1 (734) 615-1628 E-mail: edved@umich.edu
The Advisory Board of Science of Synthesis

3
161
The Advisory Board of Science of Synthesis

Dr. Andreas Barth Fachinformationszentrum Karlsruhe Information Systems D-76344 Eggenstein-Leopoldshafen Germany Phone: + 49 (7247) 808-450 Fax: + 49 (7247) 808-272 E-mail: ab@fiz-karlsruhe.de Grace Baysinger Swain Library of Chemistry and Chemical Engineering Stanford University Organic Chemistry Building Stanford, CA 94305-5080 USA Phone: + 1 (650) 725-1039 Fax: + 1 (650) 725-2274 E-mail: graceb@leland.stanford.edu Dr. Alexander Mullen Bayer AG Business Group Pharma Research Scientific Information and Documentation D-42096 Wuppertal Germany Phone: + 49 (202) 368-495 Fax: + 49 (202) 364-200 E-mail: alexander.mullen.am@bayer-ag.de Dr. Henry Rzepa Imperial College Department of Chemistry London SW7 2AY UK Phone: + 44 (171) 594-5774 Fax: + 44 (171) 594-5804 E-mail: rzepa@ic.ac.uk Dr. Engelbert Zass Informationszentrum Chemie Biologie ETH Hnggerberg HCI G 5.4 CH-8093 Zrich Switzerland Phone: + 41 (1) 632-2964 Fax: + 41 (1) 633-1287 E-mail: zass@chem.ethz.ch
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The Authors of Science of Synthesis

Prof. T. Takahashi, Sapporo, Japan Prof. K. H. Theopold, Delaware, USA Prof. Y. Wakatsuki, Saitama, Japan Volume 3 Dr. S. Christie, Loughborough, UK Prof. J. P. Fackler, Texas, USA Dr. M. Glenn, Brisbane, Australia Prof. H. Heaney, Loughborough, UK Prof. W. Kitching, Brisbane, Australia Prof. P. Knochel, Munich, Germany Prof. C. W. Liu, Taiwan, RoC Dr. M. A. Malik, Manchester, UK Prof. P. OBrien, Manchester, UK Dr. I. A. ONeil, Liverpool, UK Dr. A. Schier, Garching, Germany Prof. H. Schmidbaur, Garching, Germany Volume 4 Dr. H. Adolfsson, Stockholm, Sweden Dr. D. Ager, Hoffman Estates/IL, USA Prof. J. M. Aizpurua, San Sebastin, Spain Prof. T. Aoyama, Nagoya, Japan Prof. K. Baines, Ontario, Canada Dr. B. Bennetau, Talence Cedex, France Prof. W. E. Billups, Texas, USA Dr. J. Burton, Cambridge, UK Dr. R. Carter, Corvallis/OR, USA Prof. T. H. Chan, Quebec, Canada Dr. K. S. Ethiraj, Taipei, Taiwan, RoC Prof. I. Fleming, Cambridge, UK Prof. P. Gaspar, St. Louis/MO, USA Prof. T. Hiyama, Kyoto, Japan Prof. J. R. Hwu, Taiwan, RoC Dr. T. Ikegami, Sakyo-ku, Kyoto, Japan Dr. M. Jaspars, Old Aberdeen, UK Prof. B. A. Keay, Alberta, Canada Prof. S. Kobayashi, Tokyo, Japan Prof. P. Kocienski, Leeds, UK Dr. C. de Koning, Johannesburg, South Africa Prof. Y. Landais, Talence Cedex, France Dr. N. J. Lawrence, Manchester, UK Prof. E. Lukevics, Riga, Latvia Dr. M. McKenzie, Leicestershire, UK Prof. J. P. Michael, Johannesburg, South Africa Prof. C. Moberg, Stockholm, Sweden
Volume 1 Dr. C. Aubert, Paris Cedex, France Dr. D. Bonafoux, Stony Brook/NY, USA Dr. N. Chatani, Osaka, Japan Dr. R. Friesen, Kirkland, Canada Dr. J. Gonzalez, Virginia, USA Prof. W. D. Harman, Virginia, USA Prof. T. Hirao, Osaka, Japan Dr. X. Jiang, Lincoln, Nebraska, USA Prof. M. Lautens, Toronto, Canada Prof. M. Malacria, Paris Cedex, France Prof. J. Montgomery, Detroit/MI, USA Prof. J. OConnor, La Jolla/CA, USA Prof. A. Ogawa, Osaka, Japan Prof. I. Ojima, Stony Brook/NY, USA Dr. M. Perseghini, Zurich, Switzerland Dr. J.-L. Renaud, Paris Cedex, France Dr. G. R. Stephenson, Norwich, UK Prof. J. Takacs, Lincoln, Nebraska, USA Prof. A. Togni, Zurich, Switzerland Dr. S. Vayalakkada, Lincoln, Nebraska, USA Dr. A. T. Vu, Radnor/PA, USA Volume 2 Dr. D. Barbier-Baudry, Dijon, France Prof. A. Dormond, Dijon, France Dr. I. D. Gridnev, Inage Chiba, Japan Prof. W. A. Herrmann, Munich, Germay Dr. Z. Hou, Saitama, Japan Prof. T. Imamoto, Inage Chiba, Japan Prof. T. Ito, Yokohama, Japan Dr. F. E. Khn, Garching, Germany Prof. E. P. Kndig, Geneve, Switzerland Prof. K. Mashima, Osaka, Japan Dr. Y. Matsumoto, Tokyo, Japan Prof. K. Mikami, Tokyo, Japan Prof. M. Minato, Yokohama, Japan Dr. A. Mommertz, Delaware, USA Prof. A. Nakamura, Osaka, Japan Prof. E. Negishi, Indiana, USA Prof. K. Oshima, Kyoto, Japan Dr. S. H. Pache, Geneve, Switzerland Prof. R. Poli, Dijon, France Dr. C. C. Romo, Oeiras, Portugal Dr. B. Salisbury, Delaware, USA Dr. T. Shiono, Tokyo, Japan Prof. K. M. Smith, Davis/CA, USA
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Volume 6 Dr. K. Albrecht, Clausthal-Zellerfeld, Germany Dr. G. Alcaraz, Rennes Cedex, France Dr.Y. N. Bubnov, Moscow, Russian Federation Mr. Chr. Burmester, Clausthal, Germany Dr. B. Carboni, Rennes Cedex, France Dr. F. Carreaux, Rennes Cedex, France Dr. S. Ceccarelli, Milano, Italy Dr. G. Chen, South Plainfield/NJ, USA Prof. D. Gabel, Bremen, Germany Dr. A. C. Gaumont, Rennes Cedex, France Prof. C. Gennari, Milano, Italy Dr. C. Habben, Clausthal-Zellerfeld, Germany Dr. K. Ishihara, Nagoya, Japan Prof. D. E. Kaufmann, Clausthal-Zellerfeld, Germany Mr. M. Kster, Clausthal-Zellerfeld, Germany Dr. M. Krzeminski, Torun, Poland Prof. T. B. Marder, Durham, UK Prof. D. S. Matteson, Pullman/WA, USA Dr. J. Meller, Torun, Poland Prof. N. Miyaura, Sapporo, Japan Dr. P. J. Murphy, Gwynedd, UK Prof. H. Nth, Munich, Germany Prof. M. Periasamy, Hyderabad, India Dr. U. Piarulli, Milano, Italy Dr. B. Schilling, San Francisco/CA, USA Prof. B. Singaram, Santa Cruz/CA, USA Prof. M. Srebnik, Jerusalem, Israel Prof. F. Teixidor, Bellaterra, Spain Dr. M. Vaultier, Rennes Cedex, France Prof. B. Wrackmeyer, Bayreuth, Germany Prof. H. Yamamoto, Chicago, US Prof. M. Zaidlewicz, Torun, Poland Volume 7 Prof. Ch.-J. Li, New Orleans/LO, USA Prof. T.-P. Loh, Singapore, Singapore Prof. I. E. Marko, Louvain-la-Neuve, Belgium Prof. K. Maruoka, Kyoto, Japan Prof. N. Miyoshi, London, UK Prof. K. Mochida, Tokyo, Japan Dr. M. Oishi, Evanston/IL, USA Prof. K. Oshima, Kyoto, Japan Prof. S. Saito, Nagoya, Japan Prof. M. Shimizu, Mie, Japan Prof. T. Takahashi, Sapporo, Japan Prof. S. Tsuboi, Okayama, Japan Prof. M. Yamaguchi, Sendai, Japan
Prof. A. Mori, Yokohama, Japan Prof. M. Nilsson, Gteborg, Sweden Dr. M. North, London, UK Prof. K. Oshima, Kyoto, Japan Prof. P. Page, Leicestershire, UK Prof. C. Palomo, San Sebastin, Spain Dr. J. Pietruszka, Stuttgart, Germany Dr. J.-M. Pons, Marseilles Cedex, France Prof. Dr. J. Pornet, Poitiers, France Dr. O Pudova, Riga, Latvia Prof. A. Ricci, Bologna, Italy Dr. R. Saini, Texas, USA Ms. M. S. Samuel, Ontario, Canada Prof. T. K. Sarkar, Kharagpur, India Prof. T. Shioiri, Nagoya, Japan Dr. R. Singer, Canada Prof. T. Skrydstrup, Aarhus, Denmark Dr. M. Smith, Cambridge, UK Prof. H. Suzuki, Nishinomiya, Japan Prof. K. Tamao, Kyoto, Japan Prof. D. Wang, Bejing, PRC Prof. J. White, Corvallis/OR, USA Dr. G. Whitham, Oxford, UK Volume 5 Dr. A. Clark, Coventry, UK Dr. I. Coldham, Exeter, UK Dr. G. T. Crisp, Adelaide, South Australia Dr. C. Diaper, Nottingham, UK Mr. P. Eagle, Shropshire, UK Dr. P. J. Guiry, Dublin, Ireland Prof. B. Jousseaume, Talence Cedex, France Dr. R. Marshall, Toowoomba, Australia Mr. P. J. McCormack, Dublin, Ireland Dr. M. G. Moloney, Oxford, UK Prof. R. Okazaki, Tokyo, Japan Prof. K. Oshima, Kyoto, Japan Dr. J. Podlech, Stuttgart, Germany Dr. A. C. Spivey, Sheffield, UK Dr. N. Takeda, Kyoto, Japan Prof. E. J. Thomas, Manchester, UK Dr. P. Thornton, London, UK Prof. N. Tokitoh, Kyoto, Japan Dr. G. P. Vennall, Exeter, UK Dr. M. Wood, Exeter, UK Dr. P. B. Wyatt, London, UK Dr. D. Young, Brisbane, Australia
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Prof. H. Yamamoto, Chicago, US Prof. A. Yanagisawa, Nagoya, Japan Prof. H. Yasuda, Hiroshima, Japan Volume 8 Dr. U. Bergstrer, Kaiserslautern, Germany Prof. L. Brandsma, Bilthoven, The Netherlands Prof. D. Caine, Tuscaloosa, Alabama, USA Prof. J. V. Comasseto, Sao Paulo, Brazil Prof. K. Dieter, Clemson, USA Prof. T. Durst, Ottawa/ON, Canada Prof. J. Eames, London, UK Dr. R. Friesen, Kirkland, Canada Prof. R. E. Gawley, Florida, USA Prof. G. W. Gribble, New Hampshire, USA Dr. H. Heydt, Kaiserslautern, Germany Prof. A. Jonczyk, Warsaw, Poland Dr. E. Juaristi, Mexico, Mexico Prof. R. M. Kellogg, Groningen, The Netherlands Dr. A. Kowalkowska, Warsaw, Poland Prof. A. P. Krapcho, Burlington, Vermont, USA Prof. M. Majewski, Saskatoon, Canada Mr. R. Melgar-Fernandez, Mexico, Mexico Dr. A. Mordini, Firenze, Italy Dr. B. Mundy, Waterville/ME, USA Dr. O. Munoz-Muniz, La Jolla/CA, USA Prof. C. Njera Domingo, Alicante, Spain Prof. N. Ono, Matsuyama, Japan Dr. Rittmeyer, Frankfurt, Germany Prof. V. Snieckus, Ontario, Canada Dr. A. Streitweiser, Berkeley/CA, USA Dr. D. M. Thamattoor, Waterville/ME, USA Dr. U. Wietelmann, Frankfurt, Germany Volume 9 Prof. W. Ando, Tsukuba, Japan Dr. U. Bergstrer, Kaiserslautern, Germany Prof. D. StC. Black, Sydney, Australia Dr. H. Heydt, Kaiserslautern, Germany Prof. B. Knig, Regensburg, Germany Prof. G. Maas, Ulm, Germany Prof. F. Mathey, Palaiseau Cedex, France Prof. M. Regitz, Kaiserslautern, Germany Dr. J. Schatz, Ulm, Germany Prof. N. Tokitoh, Kyoto, Japan Prof. K. P. Zeller, Tbingen, Germany
Volume 10 Dr. R. A. Aitken, Fife, UK Dr. M. Andrews, Kent, UK Dr. C. Dell, Surrey, UK Dr. T. J. Donohoe, Manchester, UK Dr. P. Gallagher, Surrey, UK Dr. T. L. Gilchrist, Liverpool, UK Dr. M. A. Graham, Leeds, UK Dr. S. J. Higgins, Liverpool, UK Prof. K. Jones, Surrey, UK Dr. J. A. Joule, Manchester, UK Dr. P. J. Murphy, Gwynedd, UK Dr. C. M. Rayner, Leeds, UK Dr. M. Shipman, Warwick, UK Dr. P. Steel, Durham, UK Prof. E. J. Thomas, Manchester, UK Volume 11 Prof. G. V. Boyd, Givataim, Israel Dr. D. W. Brown, Bath, UK Prof. E. Fanghnel, Halle (Saale), Germany Dr. D. Gudat, Bonn, Germany Prof. D. Kikelj, Ljubljana, Slowenien Dr. C. Klenke, Marburg, Germany Prof. C. Th. Pedersen, Odense, Danmark Prof. H. Perst, Marburg, Germany Dr. W.-D. Pfeiffer, Greifswald, Germany Prof. M. Sainsbury, Bath, UK Prof. E. Schaumann, Clausthal-Zellerfeld, Germany Dr. G. Schukat, Halle (Saale), Germany Dr. R. K. Smalley, Manchester, UK Dr. H. Ulrich, Guilford/CT, USA Prof. U. Urleb, Ljubljana, Slovenia Dr. B. J. Wakefield, Cheshire, UK Volume 12 Prof. M. R. Grimmett, Dunedin, New Zealand Dr. G. Hajos, Budapest, Hungary Dr. K. Karaghiosoff, Munich, Germany Prof. F. Mathey, Palaiseau Cedex, France Prof. R. Neier, Neuchtel, Switzerland Dr. Z. Riedl, Budapest, Hungary Prof. A. Schmidpeter, Munich, Germany Dr. W. Stadlbauer, Graz, Austria Prof. B. Stanovnik, Ljubljana, Slovenia Dr. J. Svete, Ljubljana, Slovenia
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Volume 16 Dr. S. von Angerer, Bad Abbach, Germany Prof. N. Haider, Vienna, Austria Prof. W. Holzer, Vienna, Austria Prof. T. Ishikawa, Chiba, Japan Dr. S. Ito, Sendai, Japan Prof. D. Kikelj, Ljubljana, Slowenien Prof. M. Matsumoto, Kanagawa, Japan Prof. M. Sako, Gifu, Japan Prof. N. Sato, Yokohama, Japan Prof. R. Sato, Morioka, Japan Prof. F. Seela, Osnabrueck, Germany Prof. U. Urleb, Ljubljana, Slovenia Prof. Y. Yamamoto, Sendai, Japan Prof. M. Yoshifuji, Sendai, Japan Volume 17 Dr. S. von Angerer, Bad Abbach, Germany Dr. M. Bohle, Berlin, Germany Dr. R. M. Borzilleri, Princeton/NJ, USA Prof. D. Dpp, Moers, Germany Dr. M. da Graa Henriques Vicente, Louisiana, USA Dr. J. Herr, Albany/NY, USA Dr. R. H. Hutchings, Ann Arbor/MI, USA Dr. C. Lindsley, West Point/PA, USA Dr. N. McKeown, Manchester, UK Dr. J.-P. K. Meigh, Rochdale, UK Prof. A. L. Schwan, Guelph, Ontario, Canada Prof. K. M. Smith, Louisiana, USA Dr. M. D. Surman, Albany/NY, USA Prof. Y. Tominaga, Nagasaki, Japan Dr. H. Ulrich, Guilford/CT, USA Prof. S. M. Weinreb, Pennsylvania, USA Prof. K. Yamamoto, Osaka, Japan Prof. S. Yamazaki, Nara, Japan Volume 18 Prof. S. Braverman, Ramat-Gan, Israel Dr. Y. Charalambides, Cambridge, UK Prof. Dr. N. Furukawa, Ibaraki, Japan Dr. T. L. Gilchrist, Liverpool, UK Prof. G. Guichard, Strasbourg Cedex, France Prof. A. Y. IlChenko, Kiev, Urkaine Prof. K. W. Jung, Tampa/FL, USA Dr. B. A. Kashemirov, Los Angeles/CA, USA Dr. J. G. Knight, Newcastle, UK Dr. R. Maggi, Parma, Italy Prof. Ch. E. McKenna, Los Angeles/CA, USA Dr. St. C. Moratti, Cambridge, UK
Volume 13 Dr. R. A. Aitken, Fife, UK Prof. N. G. Argyropoulos, Thessaloniki, Greece Prof. R. K. Bansal, Jaipur, India Dr. M. Begtrup, Copenhagen, Denmark Dr. P. Bradley, Nottingham, UK Dr. A. Brigas, Faro, Portugal Dr. S. J. Collier, Albany, US Dr. L. Christiano, Faro, Portugal Dr. A. Curtis, Staffordshire, UK Dr. T. L. Gilchrist, Liverpool, UK Dr. N. Gupta, Jaipur, India Dr. K. Hemming, Hatfield, Herts, UK Dr. P. Koutentis, Nicosia, Cyprus Dr. ONeill, Liverpool, UK Dr. R. M. Paton, Edinburgh, UK Dr. R. C. Storr, Liverpool, U.K. Dr. A. C. Tom, Aveiro, Portugal Dr. G. W. Weaver, Loughborough, UK Dr. D. J. Wilkins, Cornwall, U.K. Volume 14 Dr. K. Afarinkia, London, UK Prof. A. T. Balaban, Bucharest, Romania Dr. T. S. Balaban, Karlsruhe, Germany Dr. N. Camp, Windlesham, UK Dr. S. Faulkner, Manchester, UK Dr. P. J. Murphy, Gwynedd, UK Dr. A. Nelson, Leeds, UK Prof. M. Ngrdi, Budapest, Hungary Dr. W.-D. Rudorf, Halle, Germany Prof. E. J. Thomas, Manchester, UK Dr. R. C. Whitehead, Manchester, UK Dr. A. C. Williams, Surrey, UK Volume 15 Prof. M. Banwell, Canberra, Australia Dr. U. Bergstrer, Kaiserslautern, Germany Prof. D. StC. Black, Sydney, Australia Dr. H. Ihmels, Wrzburg, Germany Dr. P. A. Keller, Wollongong, Australia Prof. M. Kozlowski, Philadelphia/PA, USA Dr. R. D. Larsen, Rahway/NJ, USA Prof. F. Mathey, Palaiseau Cedex, France Prof. R. Prager, Adelaide, Australia Prof. D. Spitzner, Stuttgart, Germany Prof. R. Streubel, Braunschweig, Germany Dr. C. M. Williams, Brisbane, Australia
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Prof. L. Rossi, Moneluco di Roio/LAquila, Italy Prof. Dr. G. Sartori, Parma, Italy Dr. S. Sato, Ibaraki, Japan Dr. J. G. Schmidt, Los Alamos/NM, USA Dr. J.-P. Senet, Vert-le-Petit, France Dr. L. A. Silks, Los Alamos/NM, USA Dr. Y. Wu, Baltimore/MD, USA Volume 19 Dr. U. Bergstrer, Kaiserslautern, Germany Dr. H. Heydt, Kaiserslautern, Germany Prof. Y. Ito, Kyoto, Japan Prof. S. Kanemasa, Fukuoka, Japan Dr. P. Langer, Gttingen, Germany Prof. S. Murahashi, Okayama, Japan Dr. M. North, London, UK Dr. J. Podlech, Stuttgart, Germany Dr. A. Schmidt, Clausthal-Zellerfeld, Germany Dr. L. R. Subramanian, Tbingen, Germany Volume 20 Dr. S. R. Chemler, Buffalo/NY, USA Prof. R. S. Coleman, Columbus/Ohio, USA Dr. R. M. Garbaccio, West Point/PA, USA Prof. P. R. Hanson, Lawrence/KS, USA Dr. N. K. Jain, Raritan/NJ, USA Prof. M. E. Maier, Tbingen, Germany Prof. S. J. Miller, Chestnut Hill/MA, USA Mr. D. C. Myles, Hayward/CA, USA Prof. S. G. Nelson, Pittsburgh/PA, USA Prof. J. Panek, Boston, USA Prof. A. Phillips, Boulder/CO, USA Volume 21 Prof. J. Aube, Lawrence/KS, USA Prof. D. J. Austin, New Haven/CT, USA Dr. T. R. Bailey, Exton./PA, USA Prof. J. K. Cha, Tuscaloosa/AL, USA Prof. V. O. Cesare, Jamaica/NY, USA Prof. G. R. Cook, Fargo/ND, USA Prof. P. R. Hanson, Lawrence/KS, USA Prof. R. V. Hoffman, Las Cruces/NM, USA Prof. R. P. Hsung, Minneapolis/MN, USA Dr. Y. H. Kim, Wilmington/DE, USA Prof. W.-R. Li, Chung-Li, Taiwan Prof. J. Liebscher, Berlin, Germany Dr. M. F. Lipton, Kalamazoo/MI, USA Prof. W. D. Lubell, Montreal/Quebec, Canada
Prof. F. A. Luzzio, Louisville/KY, USA Prof. M. J. Miller, Notre Dame/IN, USA Dr. M. Paetzel, Berlin, Germany Mr. S. Pritz, Berlin, Germany Prof. M. P. Sibi, Fargo/ND, USA Prof. M. B. Smith, Storrs/CT, USA Dr. D. Stien, Montpellier, France Prof. E. Turos, Tampa/FL, USA Prof. S. M. Weinreb, Pennsylvania, USA Prof. T. Ziegler, Tbingen, Germany Volume 22 Prof. V. K. Aggarwal, Bristol, UK Dr. R. A. Aitken, Fife, UK Prof. A. B. Charette, Quebec, Canada Dr. S. Cicchi, Florence, Italy Dr. F. M. Cordero, Florence, Italy Prof. R. S. Glass, Tucson/AZ, USA Mr. M. Grenon, Montreal, Canada Dr. J. Hu, Los Angeles/CA, USA Prof. W. Kantlehner, Aalen, Germany Dr. A. Kolasa, Krakw, Poland Prof. H. Lebel, Montreal, Canada Prof. T. Murai, Gifu, Japan Dr. N. Nakajima, Toyama, Japan Dr. K. Ostrowska, Krakw, Poland Prof. G. K. S. Prakash, Los Angeles/CA, USA Mr. J. Richardson, Bristol, UK Dr. M. Ubukata, Toyama, Japan Prof. T. Wirth, Cardiff, UK Volume 23 Prof. J. M. Aizpurua, San Sebastin, Spain Dr. D. M. Bennett, Worcester/MA, USA Prof. R. L. Danheiser, Cambridge/MA, USA Dr. G. B. Dudley, New York/NY, USA Prof. I. Ganboa, San Sebastian, Spain Dr. E. Gomez-Bengoa, San Sebastian, Spain Prof. G. Kollenz, Graz, Austria Prof. H. W. Moore, Irvine/CA, USA Dr. M. Oiarbide, San Sebastian, Spain Prof. C. Palomo, San Sebastin, Spain Prof. H. Perst, Marburg, Germany Prof. E. Schaumann, Clausthal-Zellerfeld, Germany Dr. C. Spanka, Basel, Switzerland Prof. T. T. Tidwell, Toronto, Canada
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Volume 27 Dr. K. Abbaspour Tehrani, Gent, Belgium Prof. V. K. Aggarwal, Bristol, UK Prof. M. J. Dabdoub, Sao Paulo, Brazil Prof. L. Fisera, Bratislava, Slovak Republic Dr. H. Heydt, Kaiserslautern, Germany Dr. C. O. Kappe, Graz, Austria Dr. S. Kim, Chungnam, Korea Prof. N. De Kimpe, Gent, Belgium Dr. J. J. Li, Ann Arbor/MI, USA Prof. P. Merino, Zaragoza, Spain Prof. K. Narasaka, Tokyo, Japan Prof. E. Niecke, Bonn, Germany Prof. A. Padwa, Atlanta/GA, USA Prof. R. A. Pilli, Campinas, SP, Brazil Mr. J. Richardson, Bristol, UK Prof. J. G. Schantl, Innsbruck, Austria Prof. R. Schobert, Bayreuth, Germany Dr. D. M. Wilson, San Diego/CA, USA Dr. Y. Zhang, San Diego/CA, USA Prof. B. Zwanenburg, Nijmegen, The Netherlands Volume 28 Prof. C. Avendano, Madrid, Spain Prof. M. Balci, Ankara, Turkey Dr. N. Bker, Saint Jean Trolimon, France Prof. A. G. Griesbeck, Cologne, Germany Dr. S. Kawasaki, Sendai, Japan Prof. K. Krohn, Paderborn, Germany Prof. C.-C. Liao, Hsinchu, Taiwan Dr. J. C. Menendez, Madrid, Spain Prof. G. V. Nair, Trivandrum, India Dr. R. K. Peddinti, Hsinchu, Taiwan Prof. T. R. R. Pettus, Santa Barbara/CA, USA Prof. E. A. Theodorakis, La Jolla/CA, USA Prof. M. Yoshifuji, Sendai, Japan
Volume 24 Prof. K. Banert, Chemnitz, Germany Dr. W. Dlling, Halle (Saale), Germany Prof. W. Kantlehner, Aalen, Germany Prof. R. R. Kostikov, St. Petersburg, Russia Prof. T. Murai, Gifu, Japan Prof. Dr. M. Pietrusiewicz, Lublin, Poland Prof. V. A. Potapov, Irkutsk, Russia Prof. J. G. Schantl, Innsbruck, Austria Dr. C. Schneider, Gttingen, Germany Prof. B. A. Trofimov, Irkutsk, Russia Dr. B. Witulski, Kaiserslautern, Germany Prof. Dr. M. Yoshimatsu, Gifu, Japan Dr. R. Zimmer, Berlin, Germany Volume 26 Dr. D. Cahard, Mont-Saint-Aignan, France Dr. J. M. Campagne, Gif sur Yvette, France Dr. P. Capdevielle, Paris, France Dr. I. Chataigner, Mont St. Aignan Cedex, France Dr. T. Constantieux, Marseille, France Prof. J. Cossy, Paris Cedex, France Dr. D. Desmaele, Chtenay-Malabry, France Dr. W. Eberbach, Freiburg, Germany Dr. B. Figadre, Saint Chron, France Dr. X. Franck, Chatenay Malabry, France Dr. A. Harrison-Marchand, Mont St. Aignan Cedex, France Prof. Y. Landais, Talence Cedex, France Dr. J. Maddaluno, Mont St. Aignan Cedex, France Dr. S. P. Marsden, Leeds, UK Prof. C. Njera, Alicante, Spain Dr. A. Nelson, Leeds, UK Dr. J.-L. Parrain, Marseille, France Dr. J.-C. Plaquevent, Mont-Saint-Aignan, France Dr. J. Rodriguez, Marseille, France Dr. J. Salan, Orsay, France Dr. Y. Six, Gif sur Yvette, France Dr. J. Suffert, Illkirch Cedex, France Dr. J.-M. Vincent, Talence Cedex, France Prof. P. Vogel, Lausanne-Dorigny, Switzerland Prof. M. A. Yus Astiz, Alicante, Spain
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173
Appendix
List of All Volumes of HoubenWeyl Methods of Organic Chemistry
Appendix
175
1st Edition
Vol. I Vol. II Analytical Methods, Purification 1909 Oxidation, Reduction, Special Topics 1911 Oxygen, Sulfur-, Halogen-Compounds Nitrogen Compounds, Organometallics (2 Vols.) 350 p 1400 p out of print out of print
2nd Edition
Vol. I Vol. II Vol. III Vol. IV Analytical Methods, Purification Oxidation, Reduction, Special Topics Oxygen-, Sulfur-, Halogen-Compounds Nitrogen Compounds, Organometallics 1921 1922 1923 1924 1121 p 1115 p 1117 p 1046 p out of print out of print out of print out of print
3rd Edition
Vol. I Vol. II Vol. III Vol. IV Analytical Methods, Purification Oxidation, Reduction, Special Topics Oxygen-, Sulfur-, Halogen-Compounds Nitrogen Compounds 1924 1925 1929 1941 1217 p 1431 p 998 p 1034 p out of print out of print out of print out of print
4th Edition
I
General Laboratory Methods Materials Science, Methods of Separation General Laboratory Practice 1 Analytical Methods General Laboratory Practice 2 Physical Methods Physical Methods 1 Physical Methods 2 General Chemical Methods Nonmetallic Oxidation Agents Metallic and Organic Oxidation Agents, Antioxidants Reduction I Reduction II General Chemical Methods Carbocyclic Three-ring Compounds Homocyclic Four-ring Compounds Photochemistry I Photochemistry II 1981 1975 1980 1981 1955 1971 1971 1975 1975 1046 p 1244 p 912 p 1000 p 1004 p 879 p 567 p 917 p 1043 p 1955 1955 954 p 1078 p 1953 1070 p 1958 1959 1048 p 1017 p
Vol. I/1 Vol. I/2

II
Vol. II
III
Vol. III/1 Vol. III/2

IV
Vol. IV/1 a Vol. IV/1 b Vol. IV/1 c Vol. IV/1 d Vol. IV/2 Vol. IV/3 Vol. IV/4 Vol. IV/5 a Vol. IV/5 b
176
V
List of All Houben-Weyl Volumes: Houben-Weyl Methods of Organic Chemistry
The Chemistry of Compound Classes Alkanes, Cycloalkanes Alkenes, Cycloalkenes, Arylalkenes Conjugated Dienes, DielsAlder Reactions Open-chain and Cyclic Polyenes; Enynes Alkynes, Di- und Polyynes, Allenes, Cumulenes Arenes and Arynes Carbocyclic -Electron Systems Fluorine and Chlorine Compounds Bromine und Iodine Compounds Part 1: Alcohols I (Formation of the C-O Bond) Part 2: Alcohols II (Retention of the C-O Bond) Alcohols III Phenols (2 Vols.) Enols and their O-Derivatives; Ene Diols (Reductones); Biosynthesis of Hydroxy Compounds O-Metal Derivatives of Organic Hydroxy Compounds; Lactones Ethers, Acetals, Orthoesters, Oxonium Salts, Cyclic Three- to Five-membered Ethers Cyclic Six- and Higher-membered Ethers; Acetals Aldehydes Ketones I (Formation of C-C and C=O Bonds) Ketones II (C-C Cleavage) Ketones III (Reactions with Retention of the Carbonyl Function) p-Quinones o-Quinones, Dipheno- and Stilbenequinones, Higher Ring Ketones, Quinoles, Quinone Derivatives Anthraquinones, 10-Anthrones Isatins, Thionaphthoquinones; Ketenes Peroxides, Carbonic Acid Derivatives, Carboxylic Acids, Carboxylic Acid Derivatives Sulfur, Selenium, Tellurium Compounds Nitro, Nitroso and Hydroxylamine Compounds Hydrazines, Azines; Azo-, AzoxyCompounds I; Diazenes I Diazonium Salts; Azo-, AzoxyCompounds II; Diazenes II; Azides; Nitrile Oxides Oximes; Diazo Compounds; N-Oxides Amines I Amines II (Aziridines, Azedidines, Amino Acids, Lactams, Quaternary Ammonium Salts, Nitrogen-Sulfur Compounds) 1970 1972 1970 1972 1977 1981 1985 1962 1960 1979 1980 1984 1976 1978 690 p 1308 p 1296 p 775 p 1247 p 757 p 870 p 1217 p 894 p 769 p 882 p 1134 p 1366 p 539 p
Vol. V/1 a Vol. V/1 b Vol. V/1 c Vol. V/1 d Vol. V/2 a Vol. V/2 b Vol. V/2 c Vol. V/3 Vol. V/4 Vol. VI/1 a Vol. VI/1 b Vol. VI/1 c Vol. VI/1 d
Vol. VI/2 Vol. VI/3 Vol. VI/4 Vol. VII/1 Vol. VII/2 a Vol. VII/2 b Vol. VII/2 c Vol. VII/3 a Vol. VII/3 b
1963 1965 1966 1975 1973 1976 1977 1977 1979
952 p 832 p 787 p 556 p 1286 p 789 p 818 p 832 p 911 p
Vol. VII/3 c Vol. VII/4 Vol. VIII Vol. IX Vol. X/1 Vol. X/2 Vol. X/3
1979 1968 1952 1955 1971 1967 1965
414 p 508 p 775 p 1337 p 1484 p 964 p 971 p
out of print
Vol. X/4 Vol. XI/1 Vol. XI/2
1968 1967 1958
1044 p 1178 p 840 p
Appendix
177
1963 1964 1970 1973 1974 1982 1983 1984 1970 1980 1978 1975 683 p 1132 p 904 p 1042 p 438 p 910 p 893 p 932 p 430 p 502 p 599 p 570 p out of print
Vol. XII/1 Vol. XII/2 Vol. XIII/1 Vol. XIII/2 a Vol. XIII/2 b Vol. XIII/3 a Vol. XIII/3 b Vol. XIII/3 c Vol. XIII/4 Vol. XIII/5 Vol. XIII/6 Vol. XIII/7
Vol. XIII/8 Vol. XIII/9 a Vol. XIII/9 b
Phosphorus Compounds I (PhosphorusCarbon Compounds) Phosphorus Compounds II (Derivates of Phosphorous and Phosphoric Acid) CH-Acidity, Organometallic Compounds of Group I of the Periodic Table Organometallic Compounds of Group II of the Periodic Table (except mercury) Organomercury Compounds Organoboron Compounds I Organoboron Compounds II Organoboron Compounds III Organometallic Compounds of Group III of the Periodic Table (except boron) Organosilicon Compounds Organogermanium and -tin Compounds Organolead Compounds and Organometallic Compounds of Groups IVVI of the Periodic Table Organoarsenic, -antimony, -bismuth Compounds -Organomanganese, -rhenium, -iron, -ruthenium, -osmium, -platinum Compounds -Organocobalt, -rhodium, -iridium, -nickel, -palladium Compounds Macromolecular Compounds Macromolecular Compounds I Macromolecular Compounds II The Synthesis of Peptides Synthesis of Peptides, Protection Groups I Synthesis of Peptides, Protection Groups II Indexes
1978 1986 1984
703 p 980 p 1057 p
VI
Vol. XIV/1 Vol. XIV/2

VII
1961 1963
1360 p 1251 p
Vol. XV/1 Vol. XV/2

VIII
1974 1974
1006 p 806 p
Vol. XVI/1 Vol. XVI/2
Index of Experimental Procedures, 1986 Vol. IXV, E 15, E 11 Index of Compound Classes, 1987 Vol. IXV, E 15, E 11 (2 Vols.) Part a: General and Open-chain Compounds Part b: Cyclic as well as Spiro and Bi Compounds; Steroids; Named Reactions
689 p 2003 p
178
Additional and Supplementary Volumes to the 4th Edition

Vol. E 1 Vol. E 2 Vol. E 3 Vol. E 4 Vol. E 5 Vol. E 6 Organic Phosphorus Compounds I Organic Phosphorus Compounds II Aldehydes Carbonic Acid Derivates Carboxylic Acids, Carboxylic Acid Derivates (2 Vols.) Hetarenes I (Five-membered Rings with One Heteroatom in the Ring System) a) Hetarenes I, Part 1 b1) Hetarenes I, Part 2 a b2) Hetarenes I, Part 2 b Hetarenes II (Six-membered Rings with One Heteroatom in the Ring System) a) Hetarenes Part 1 b) Hetarenes Part 2 Hetarenes III (Five-membered Rings with Two and More Heteroatoms in the Ring System) a) Hetarenes III, Part 1 b) Hetarenes III, Part 2 c) Hetarenes III, Part 3 d) Hetarenes III, Part 4 Hetarenes IV (Six-Membered and Larger Hetero-Rings with Maximum Unsaturation)
(in English)
1982 1982 1983 1983 1985
972 p 1156 p 837 p 1395 p 1817 p
Vol. E 7
1994 1994 1994
1154 p 848 p 714 p
Vol. E 8
1991 1992
938 p 1174 p
Vol. E 9
1993 1994 1994 1994
1361 p 1238 p 938 p 913 p
Vol. E 10
Vol. E 11
a) Vol. E 9 a b/1) Vol. E 9 b/Part 1 b/2) Vol. E 9 b/Part 2 c) Vol. E 9 c d) Vol. E 9 d e) Vol. E 9 e Organo-Fluorine Compounds (in English) a) Fluorinating Agents b/1) Synthesis of Fluorinated Compounds, Transformations of Fluorinated Compounds b/2) Synthesis of Fluorinated Compounds, Transformations of Fluorinated Compounds c/1) Methods Index I c/2) Methods Index II Organic Sulfur Compounds (2 Vols.) General Index for E 4/Author Index for E 4, E 5, E 11
1997 1998 1997 1997 1997 1998 1998 1999
796 p 373 p 550 p 923 p 846 p 604 p 740 p 720 p
1999 1999 1999 1985 1987 1990 1988
896 p 812 p 909 p 1821 p 612 p 1004 p 1768 p
Vol. E 12 b Vol. E 13
Organotellurium Compounds (in English) Organic Peroxo Compounds (2 Vols.)
Appendix
179
Vol. E 14
Vol. E 14 Vol. E 15 Vol. E 16
Vol. E 17
Carbonyl Derivates I Part 1 O/O- and O/S-Acetals Part 2 O/N-Acetals Part 3 Hal/X-, N/S(N)- and anomeric Sugar Acetals b) Carbonyl Derivates II: C=N Double-bond Systems (2 Vols.) Ene-X and Yne-X Compounds (3 Vols.) a) Organic Nitrogen Compounds I (2 Vols.) b) Organic Nitrogen Compounds II: - and -Lactams c) Organic Nitrogen Compounds III: Nitrous/Nitric Acid Esters, Nitrenes, 3-,4-Membered Ring Systems with at Least One N-Atom in the Ring System d) Organic Nitrogen Compounds IV: Amines, Nitro, Azo, Azoxy Compounds (2 Vols.) Carbocyclic Three-membered Ring Compounds
(in English)
a)
1991 1991 1992 1990 1993 1990 1991 1992
922 p 1006 p 1282 p 1857 p 3946 p 1516 p 1085 p 1176 p
1992
1546 p
a) b) c) d)
Cyclopropanes: Synthesis Cyclopropanes: Synthesis Cyclopropanes: Transformations Cyclopropenes, Author Index, Compound Index Carbocyclic Four-Membered Ring Compounds
(in English)
1996 1996 1996 1996
966 p 981 p 746 p 941 p
Vol. E 18 Vol. E 19
Vol. E 20 Vol. E 21
e) Cyclobutanes f) Cyclobutenes, Cyclobutadienes, Author Index, Compound Index Organo--Metal Compounds as Auxiliaries in Organic Chemistry (2 Vols.) Low-valent Carbon Compounds a) C-Radicals (2 Vols.) b) Carbenes, Carbenoids (2 Vols.) c) Carbocations d) Carbanions Macromolecular Compounds (3 Vols.) Stereoselective Synthesis (in English) a) Nomenclature, Principles, Analytic, Axially Chiral Compounds, Bond Disconnection, Alkylation Reaction, Insertion into C-H Bonds b) C-C Bond Formation c) C-C Bond Formation, Cycloaddition Reactions, Ene Reactions d) C-C Bond Formation by Sigmatropic Rearrangements, Electrocyclic Reactions, C-H, C-Hal Bond Formation e) Bond Formation, C-N, C-O, C-P, C-S, C-Se, C-Si, C-Sn, C-Te f) Appendix, Author Index and Compound Index
1996 1997 1986
614 p 707 p 1428 p
1989 1989 1990 1993 1987 1995
1567 p 2214 p 550 p 1313 p 2958 p 1150 p
1995 1995 1995
1052 p 1096 p 1196 p
1995 1996
1262 p 1231 p
180
Vol. E 22
Synthesis of Peptides and Peptidomimetics

(in English)
Vol. E 23
Synthesis of Peptides and Peptidomimetics 2002 Synthesis of Peptides and Peptidomimetics 2002 Synthesis of Peptides and Peptidomimetics 2002 Synthesis of Peptides and Peptidomimetics 2003 Synthesis of Peptides and Peptidomimetics 2003 (Index Volume) Indexes to the Complete E-Series (in English) a) Index of Experimental Procedures 1998 General Compound Classes (alphabetically) Individual Compounds (C1C13) b) Index of Experimental Procedures 1998 Individual Compounds (> C13) c/1) Substance Index 1999 Aliphatic Compounds I Carbonyl Compounds I (Derivatives of Carbonic Acids, Carboxylic Acids) c/2) Substance Index 2000 Aliphatic Compounds I Carbonyl Compounds II (Derivatives of Ketenes, Ketones, Aldehydes) d/1) Substance Index 2000 Aliphatic Compounds II Alkynes, Alkenes, Alkanes d/2) Substance Index 2000 Aliphatic Compounds II Alkynes, Alkenes, Alkanes d/3) Substance Index 2000 Aliphatic Compounds II Alkynes, Alkenes, Alkanes e) Substance Index 1998 Cyclic Compounds I 3- and 4-Membered Monocyclic Compounds f) Substance Index 1998 Cyclic Compounds II 5-Membered Monocyclic Compounds g) Substance Index 1999 Cyclic Compounds III 6-Membered Monocyclic Compounds Without Heteroatoms h) Substance Index 1999 Cyclic Compounds IV 6-Membered Monocyclic Compounds With Heteroatoms n-Membered Monocyclic Compounds (n > 6) i) Substance Index 1999 Cyclic Compounds V Bicyclic Compounds I j) Substance Index 1999 Cyclic Compounds VI Bicyclic Compounds II
a) b) c) d) e)
976 p 785 p 847 p 395 p 497 p
1204 p
925 p 1154 p
1228 p
750 p
1123 p
714 p
521 p
952 p
504 p
828 p
1160 p
629 p
Appendix
181
2000 551 p
k)
Substance Index Cyclic Compounds VII Tricyclic Compounds I l) Substance Index Cyclic Compounds VIII Tricyclic Compounds II m) Substance Index Cyclic Compounds VIII Polycyclic Compounds I n) Substance Index Cyclic Compounds IX Polycyclic Compounds II o) Synopsis of the Structure of HoubenWeyl I General Overview and 4th Edition p) Synopsis of the Structure of HoubenWeyl II General Overview and Additional and Supplementary Volumes to the 4th Edition
2000
558 p
2001
772 p
2001
600 p
2000
872 p
2001
1074 p
Please contact the editorial office to receive a free HoubenWeyl Users Guide.
183
Index
Index A Abbreviations 44 49 ACS Style Guide 43, 44, 52 Addition Reactions 25 Advisory Board 161 American Spelling 43 Aromatization 29, 30 Atom Economy 51 Authors 162 167 B Biochemical Nomenclature 43 -Bonds 22 Books 52 C CahnIngoldPrelog System 17 Carbohydrates 44 Categories 19, 21 ChemDraw 55, 59 Chemical Abstracts 43, 52 Citation 52 Classification Principles 17 Completed Manuscript 57 -Conjugation 22 Copyright 51 D Databases 52 Delivery of Manuscripts 56 Disposition of Manuscripts 42 Document Template 43 E Editorial Board 148, 149 Editorial Description 11 Editorial Office 168 171 Electric Charges, Presentation 55 Electronic Division 170 Electronic Journals 52 Elements 24 Elimination 25 Examples 32 Experimental Procedures 49 F Figures 56 Format, Disks 59 Formulas 54 Functional Groups 22 Conjugated 23 Priority 24 G Galley Proofs 57 General Criteria 41 Graphs 56 Greek Symbols 59 H Hapticity 25 Hazardous Compounds 51 Hazards 51 Health Effects of Chemicals 51 Heteroatoms 21 Homepage 171 HoubenWeyl 15 I Information for Authors 37 Inorganic Compounds 44 Introductory Texts 42 ISIS/Draw 59 Isolable Products 21 IUPAC Rules 44 M Macros 43 Managing Director 168 Managing Editor 168 Manuscript Submission 57 Mechanism 42 Metal 25 Methods 19, 24 Modular Organization 42 Molfile 59 Multifunctional Compounds 22 N Natural Compounds 44 Nomenclature 43 Numbering 43, 54 O Organization 19 Organization of the Manuscripts 42 Organizational Principles 16 Oxidation State 17, 25 P Page Proofs 57 Patents 41, 52 Abstracts 41 Literature 41 Peptides 44 Permission for Reproduction 56 Permission to Publish (Imprimatur) 57 Physical and Reactive Chemical Hazards 50 Preparation of Manuscripts on Disks 59 Pressure 44 Product Classes 19, 24, 25 Product Subclasses 19, 25
185
R Reaction Centers 59 Rearrangement 25 References 52 Retention 25 Ring Transformation 29, 30 Ring-Closure Reaction 29, 30 -Rule 23 S Safety 50 Sample Contributions 61 Sample Pages 56 Scheme Tables 53 Schemes 54 Slash 50 Solid-Phase Reactions 42, 50 Spectroscopic Data 50 Steroids 44 Style 43 Consistency of 41 Style Templates 59 Substituent Modification 29, 30 Substitution 24 SYNTHESIS 49 T Table of Contents 42, 56 Tables 53 Temperature 44 Trademarks 43 Transition Metals 25 Trivial Names 44 U Units 44 V Variations 19, 24 Volume Editors 150 160 Volume List Houben-Weyl 175 181 Science of Synthesis 34 36 Volumes 19 W Web site 171 Who to Contact 172 Word Processors 43, 59 Word-Processing Programs 59 Workflow Chart 58 Workup 50

Science of Synthesis

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Science of Synthesis

Georg Thieme Verlag Stuttgart New York

Managing Director Managing Editor

2004 Georg Thieme Verlag Stuttgart New York

Selenopyranones and Benzoselenopyranones (P. J. Murphy) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Complete Volume List of Science of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Editorial Description of Science of Synthesis

Editorial Description of Science of Synthesis

HoubenWeyl Methods of Organic Chemistry Entering the New Millennium

Houben-Weyl Methods of Molecular Transformations

Organizational Principles of Science of Synthesis, HoubenWeyl Methods of Molecular Transformations

Editorial Description of Science of Synthesis

Classification Principles of Science of Synthesis (Volume 9 Given as an Example)

Organometallics (Vols 18)

Hetarenes (Vols 917)

Products of Organic Synthesis Vol. 10 etc. 9.2 etc. METHOD 9.1.1.1

4/3 C-X bonds (Vols 1824)

Rule 1: hierarchical organization

2 C-X bonds (Vols 2533)

1 C-X bond (Vols 3442)

All C bonds (Vols 4348)

Rule 2: six categories

organization of product classes/subclasses Also: Rules 110 apply

Selected Products and Reactions

Houben-Weyl Methods of Molecular Transformations

Rules 310: classification of products within categories

* Rule 15 applies to Category 1 Rule 16 applies to Category 2 Rule 17 applies to Categories 3 6

Editorial Description of Science of Synthesis

Houben-Weyl Methods of Molecular Transformations

Editorial Description of Science of Synthesis

Classification of Products into Compound Categories Categories

Houben-Weyl Methods of Molecular Transformations

Ac Unq Unp Unh

Lanthanide Series Actinide Series

Two or More Functional Groups

C-X and C-C -Bonds

Editorial Description of Science of Synthesis

Conjugated Functional Group

or transforming a second functional group (FG2, Scheme 5),

Houben-Weyl Methods of Molecular Transformations

Product Classes within the Categories

Priority Among Elements

Priority Among Functional Groups

Priority for a Carbon-Bound Heteroatom

Editorial Description of Science of Synthesis

x.y.z.5 x.y.z.6 x.y.z.7 x.y.z.8

x.y.z.9 x.y.z.10 x.y.z.11 x.y.z.12

Houben-Weyl Methods of Molecular Transformations

Editorial Description of Science of Synthesis

The table of contents should take the following format:

Houben-Weyl Methods of Molecular Transformations

x.y.12.1 x.y.12.n Rule 16

Editorial Description of Science of Synthesis

x.y.1.3 x.y.1.4 x.y.1.5 x.y.1.6 x.y.1.7 x.y.1.8

x.y.3 x.y.4 x.y.4.1 x.y.4.1.1

x.y.4.1.3 x.y.4.1.4 x.y.4.2

x.y.4.2.1 x.y.4.2.2 x.y.4.2.3

Houben-Weyl Methods of Molecular Transformations

x.y.1 x.y.1.1 x.y.1.1.1

x.y.1.1.3 x.y.1.1.4 x.y.1.1.5 x.y.1.1.6 x.y.1.1.7 x.y.1.1.8

x.y.3 x.y.4 x.y.4.1

Editorial Description of Science of Synthesis

x.y.4.1.3 x.y.4.1.4 x.y.4.2

ONeil Fleming Moloney Kaufmann/ Matteson H. Yamamoto Snieckus/ Majewski