This page intentionally left blank Copyright 2008, New Age International (P) Ltd.

., Publishers Published by New Age International (P) Ltd., Publishers All rights reserved. No part of this ebook may be reproduced in any form, by photostat, microfilm, xerography, or any other means, or incorporated into any information retrieval system, electronic or mechanical, without the written permission of the publishe r. All inquiries should be emailed to rights@newagepublishers.com PUBLISHING FOR ONE WORLD NEW AGE INTERNATIONAL (P) LIMITED, PUBLISHERS 4835/24, Ansari Road, Daryaganj, New Delhi - 110002 Visit us at www.newagepublishers.com ISBN (13) : 978-81-224-2647-2 PREFACE For a very long time the need was felt by graduate and postgraduate students of Chemistry of almost all colleges and of I ndian Universities for a book dealing with advanced mechanistic organic chemistry written in understandable language and with suitable examples which can be easily grasped to make their conc ept clear. Besides students, this has also been the requirement of teachers teaching advanc ed organic chemistry. Till about 1959 there appears to be the only book by E.S. Gould (St ructure and Mechanism of Organic Chemistry) but the examples mentioned in it are so difficul t at several places that they elude the comprehension of even teachers, not to talk of students. Around sixties appeared the book by J erry March (Advanced Organic Chemistry, Reactions, Mechanism and Structure). I t was definitely a mu ch better advance over that of Gould, but it has been made so bulky that its cost has beco me prohibitive. I t adores the racks and shelves of libraries. I n view of the abov e difficulties of teachers and students, the present book has been brought out. Some of its special chapters are the Pericyclic Reactions, which includes Chelet ropic, Electrocyclic, Sigmatropic and Cycloaddition reactions. The concept of Stereoche mistry and Conformation deserve special attention not because they cater to the needs o f higher students, but they are immensely useful for candidates trying for UGC and CSI R sponsored competitive examinations, but also those preparing for Union Pub lic Service Commission and State Public Service Commission Exams. The candi dates will find the chapters immensely useful and is sure to rouse interest in them in knowing more about mechanistic chemistry. Spectroscopy is another topic, a good knowledge of which is expected from any go od

chemist. The spectroscopy finds immense applications in the identification of se veral unknown compounds in the field of research and medicine. Here one has to be very careful in elucidating the correct structure of entities. Moreover in every exam ination (competitive or regular) one has to show his skill in the area of s pectroscopy and therefore chapters on spectroscopy giving a clear and lucid account is also note worthy. (v) To the best of my knowledge, a book written by an I ndian author and covering al l the chapters covered in it is not known. Part I deals with chapter involving typical complex organic reactions. Part I I deals with various aspects of spectroscopy and the use of this technique in identifica tion of compounds. Miscellaneous reagents used in organic synthesis are disc ussed in Part I I I . The author is immensely grateful to Prof. R.P. Rastogi for writing th e forward for this volume. R.P. Narain (vi) FOREWORD The present book deals with mechanistic principles of organic reactions in an exhaustive and systematic manner. I t would be equally useful for the study of complex reactions where inorganic reactions are also involved in the reaction ne twork including biochemical reactions. The author had long teaching and resea rch experience in Gorakhpur University. The subject matter has been clearly presente d. The book is divided into three parts. Part I deals with typical com plex organic reactions such as (i) reactions involving carbocations and carbanions, (ii) Peri cyclic and electrocyclic reactions and (iii) Sigmatropic and Chelotropic reactions. Thi s part also includes material useful for characterization of products from structural p oint of view such as Geometrical isomerism, Stereochemistry and Conformation. Part I I is concerned with spectroscopic methods of structure determination such as U.V., I .R., N.M.R. and Mass spectroscopy, which is quite useful from the a ngle of identification and characterization of reaction intermediates. I n part I I I , detailed treatment of commonly used oxidizing and reducing agents along with in volved reaction mechanism has been presented. Treatment of each part is comprehensive and thorough. The book would be useful for teaching at post-graduate level and also as reference book for un dergraduate level. I t would be extremely useful for reference for research scientists in co

nnection with organic synthesis, reaction mechanism of complex reactions involving inorga nic and organic reactions and also bio-chemical reactions. R.P. Rastogi (vi i ) This page intentionally left blank CONTENTS Preface (v) Foreword (vii) PART ITYPICAL COMPLEX ORGANIC REACTIONS Chapter 1. Carbocations (Carbonium Ions) 311 Nomenclature 3 Structure and Stability 4 Generation of Carbocations 8 Reactions of Carbocations 8 Reactions with Nucleophiles Elimination Reactions Rearrangement Reactions Addition to Unsaturated Systems Non-Classical Carbocations 10 Generation of a Non-classical Carbocations 11 Chapter 2. The Carbanion Chemistry 1220 Stability 12 Generation of Carbanion 13 Abstraction of Hydrogen by a Base From Unsaturated Compounds Reactions of Carbanions with Electrophiles 15 Substitution Reactions of Alkyl Anions Addition Reactions of Alkyl Anions Reactions of Carbanians with Electrophiles Elimination Reactions Oxidation Reactions of Carbanions Rearrangement Reactions 19 I ntermolecular Rearrangements I ntermolecular Additions I ntramolecular Eliminations Sigmatropic Carbanion Rearrangement (ix) (x) Chapter 3. Theory of Concerted Reactions 2129 What are Concerted Reactions ? 21 Concerted Mechanism Stepwise Mechanism Stereoselective and Stereospecific Reactions 23 Theory of Concerted Reactions 24 Homo and Lumo Structures 25 Ethylene Butadiene System Frontier Orbital Approach 28 Conjugated Triene Chapter 4. Pericyclic Reactions 3054 I ntroduction 30 Cycloaddition Reactions 31 Classification Classification based on the Number of Electrons General Rule for Pericyclic Reactions 32 What is Symmetry Allowed and Symmetry Forbidden Reactions 33

 Woodward Hoffmann Rule Bond involved in Cycloaddition Reaction Some more Example of 2 + 2 Cycloaddition Photochemical Cycloaddition 2 + 3 Cycloaddition 2, 1 Cycloaddition 4 + 2 Cycloaddition Diel -Alder Reaction Scope of Diel -Alder Reaction 44 Stereochemi try of Endo and Exo Addition Orientation (Regio electivity) Diene Reactivity Dienophile Reactivity I ntra Molecular Diel -Alder Reaction Chapter 5. Electrocyclic Reaction 5570 I ntroduction 55 Thermal Electrocyclic Reaction 57 2 Systems 4 System 6 System (xi ) Electrocyclic Reaction of Radicals 67 Metal Catalysed Electrocyclic Reactions 68 Photochemical Electrocyclic Reactions 69 Cha ter 6. Sigmatro ic Rearrangements 7193 I ntroduction 71 Nomenclature The Homo of Allylic Radicals 72 Hydrogen Migrations Other Views about Sigmatro ic Transition State 74 Formation of a Cyclic Transition State Structure Frontier Orbital A roach Some Exam les of Hydrogen Shifts Migrations in Cyclo ro ane rings Migrations of Atoms or Grou s other than Hydrogen Selection Rules 79 Shifts in Neutral S ecies Shifts in Charged S ecies Shifts in Electron Deficient Centers A lication of FMO Method Co e and Claisen Rearrangements 83 Co e Rearrangement Oxy-Co e Rearrangement Claisen Rearrangement Some Other Exam les Abnormal Claisen Rearrangement 91 [2, 3] Sigmatro ic Rearrangement Photochemical Rearrangements 92 The Ene Reactions Cha ter 7. Cheletro ic Reactions 94100 I ntroduction 94 Symmetry Allowed Cycloaddition of SO 2 to a diene Cheletro ic Reactions involving 4 Electrons Addition of Carbenes or Nitrenes Reactions involving 6 Electrons Cycloaddition and Elimination Reactions involving 8 Electroncs (xi i ) Cha ter 8. Geometrical Isomerism 101120

General I ntroduction 101 Com ounds having Double Bonds Relative Stabilities of I somers Nomenclature of I somers 105 Determination of Configuration of Geometrical I somers 106 Physical Methods of Determination of Configurations Stability and I nter Conversion of cis-trans I somers 111 Pre aration of cis-trans I somers by Physical and Chemical Methods Stereochemistry of Addition to Double Bonds 114 Cis Addition Trans Addtion Stereochemistry of Cyclic Com ounds 120 Cha ter 9. Basic Conce ts of Stereochemistry 121157 I m ortance of Sterochemistry 121 Asymmetry and Chirality 123 Diasteroisomers Pro erties of Diastereoisomers What Com ound dont show O tical Activity 125 Plane of Symmetry Centre of Symmetry Alternating Axis of Symmetry Nomenclature of O tical I somers 129 Fischer Projections Stereoisomerism in Cyclic Com ounds 137 Methods of Determining Absolute Configuration 139 Asymmetric Synthesis 144 Asymmetric Transformation Mechanism of Asymmetric Synthesis Absolute Asymmetric Synthesis Stereoselective and Stereos ecifc Reactions 148 Resolution of Racemic Mixtures 149 Racemisation 152 Mechanism of Racemisation Walden I nversion Mechanism of Walden I nversion (xi i i ) Cha ter 10. Conformation 158194 Conformation and Conformational Analysis 158 Conformation of Ethane Conformation of Pro ane Conformation of Butane Ecli sed and Staggered Forms Ring Strains in Cycloalkanes Princi les of Conformation 165 Rotation about Bonds involving carbon aatoms in a state of s 2 hybridisation Methods for Determining Confirmation 167 Conformational Asymmetry 172 Conformations of Three to Five Memmbered Rings 173 Stereochemistry of Cyclic Com ounds 175 Cyclo ro ane Rings Cyclobuane Rings Cyclo entane rings Cyclohexane Rings Monosubstituted Cyclohexanes Disubstituted Cyclohexanes 1, 3 Disubstituted Cyclohexanes Conformational Energies of Substitutents 185 Conformation and Chemical Reactivity 185

Six Membered Heterocyclic Rings 187 Cyclooctane and Cyclononane 188 Cyclodecane 189 Conce t of I Strain 190 Bayers Strain Theory 190 Limitations of Strain Theory 192 Fused Ring Systems 193 Stability of Ring Systems 194 Cha ter 11. Some Novel Reactions in Organosilicon Chemistry 195209 Ex edited Organic Synthesis with Organosilicon Com ounds 195 Creation of a Bond 196 Protection of Grou s 197 Activation 197 Some A lications of Organosilicon Com ounds to Organic Synthesis 198 Why Silicon Com ounds are Reactive (xi v) Formation and Cleavage of Bonds to Silicon Organosilicon Protecting Grou s Electro hilic Substitution Reactions Synthesis of Olefins Reactive I ntermediates in Organosilicon Chemistry Silylenes Silenes Silanones Disilenes Silyl Amino Silyl Radicals Thermolysis Photolysis, Pyrolysis and Electron Transfer PART IISPECTROSCOPY Cha ter 12. General Considerations 211213 General Consideration 211 S ectrosco y 212 Ty es of Molecular S ectra Lasers, I m ortance and Uses 213 Cha ter 13. Ultraviolet S ectrosco y 214224 Ultraviolet and Visible S ectrosco y 214 Ultraviolet S ectrosco y 216 Origin of U.V. Absor tion S ectra Colour in Organic Com ounds Absor tion in Organic Molecules Energy Levels in Different Molecular Orbitals Difference between n * and * transition Choice of Solvent and Solvent Effects A lication of U.V. S ectrosco y 223 Cha ter 14. Infrared Absor tion S ectrosco y 225241 I ntroduction 225 Origin of I nfrared S ectra 227 Molecular Vibrations Ty es of Vibrations in Polyatomic Molecules 228 (xv) Vibrational Degrees of Molecule Factors I nfluencing Vibrational Frequencies I nstruments 236 Source of Radiation Sam ling Techniques Finger Print Region A lications of S ectrosco y 240 I R S ectra of Some Com ounds

Cha ter 15. Nuclear Magnetic Resonance S ectrosco y 242263 I ntroduction 242 Hydrogen Nuclei 245 Chemical Shifts and Number of Signals 245 I nstrumentation Ex ression of Chemical Shifts Acetylene in Magnetic Field Benzene in Magnetic Field Factors I nfluencing Chemical Shift Solvents Used S litting of Signals and S in-s in Cou ling Origin of Multi let Peaks Cou ling Constants Vicinal Cou ling I nter renation of NMR S ectra A lications of NMR S ectrosco y 260 13 C NMR S ectrosco y 262 31 P Phos horus 263 11 B Boron 263 Cha ter 16. Mass S ectrometry and Lasers 264271 I ntroduction 264 A lications of Mass S ectrometry 264 Some I m ortant Points in Mass S ectrometry 265 Mass S ectrometer Princi le of O eration I nter retation of Some S ectra Mass S ectrum of Benzene, of 2,2,4 Trimethyl Pentane Some Binding Princi les for finding the Base Peaks 270 Use of a S ark Sam le (xvi ) PART IIIMISCELLANEOUS REAGENTS USED IN ORGANIC SYNTHESES Cha ter 17. Some Oxidising Agents And their Mechanism 275284 Ozone 275 Lead tetra-acetate 276 Periodic Acid 278 Osmium Tetraxide 279 Selenium Dioxide 281 Perbenzoic Acid 282 Cha ter 18. Some Reducing Agents and their Mechanism 285297 Lithmium Aluminium Hydride 285 Sodium BoroHydride 288 Metal/Liquid Ammonia 290 Some Metal Catalysts used in Hydrogenation 292 Raney Nickel Catalysts 293 Platinum and Platinum Black 294 Palladium 295 Aluminium I so ro oxide 296 Cha ter 19. Miscellaneous Com ounds 288314 Diazomethane 298 Liquid Ammonia 300 N-Bromosuccinimide 304 Trifluoroacetic Acid 307 Trifluroacetic Anhydride 308 Sodium Amide (Sodamide) 309 Dimethyl Sul hoxide (DMSO) 311 Boron Trifluoride 313

Index 315-317 PART-I TYPICAL COMPLEX ORGANIC REACTIONS This age intentionally left blank C H A P T E R Carbocations (Carbonium Ions) The carbonium ions are ositively charged highly reactive intermediates and have six electrons in the outer shell of central carbon. They may be re resented as C R H H + C H H R C R H H + 120 + So they are very reactive toward any nucleo hilic reagent i.e., one t hat will donate a air of electrons to carbon to form a fourth covalent bond. Being ositively charged they are stabilized inductively by electron-donating substances and rendered less stable by electron-withdrawing substituents. Since carbon of a carbonium ion is in an s 2 hybrid, the ion air is lanar with a vacant orbital (as in ethylene) which is er endicular to the lane of three covalen t bonds to the carbon. NOMENCLATURE As early as 1902 Gomberg suggested that the word carbonium was ina r o riate for such s ecies because onium signifies a covalency greater than that of the neutral atom. But the nomenclature went on till about 1964 when George Olah and his coworkers found evi dence by mass s ectrosco y the existence of a ositively charged intermediate, the CH 5 + ion. It was su osed to have been formed by the attack of H + on CH bond to give the s ecies

CH 5 + also called the methanonium ion. CH H + H 3 H C 3 H H + CH 3 H 2 + It has a three centre, two electron bond. In this the formal covalen cy of carbon is five rather than three. ro osed that the word carbonium ion should be re On this basis Olah served for such enta3 4 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY coordinated s ecies, while other ositively charged s ecies originally c alled carbonium ions be given the name carbenium ions. Olah also suggested the nomenclature carbocation s to encom ass both the ty e of s ecies and the IUPAC has acce ted this ro osal. Although entacovalent ions are much rarer than other ositively charged ions, t he general word carbocation is used for all such s ecies. It is interesting to note that another s ecies, the ethanonium ion 2 5 C H has also been re orted in the gas hase by IR s ectrosco y. So now the word carbocation is used to cover all such electron defic ient and ositively charged s ecies, although some authors still refer to use the word carbonium ions. The difference between carbenium and carbonium ions is summarized as f ollows: Carbocation ro erty Carbenium ions Carbonium ions Exam le CH 3 C CH 3 CH 3 CH 5 Number of covalent 3 5

bonds to carbon No. of electrons 6 8 in outer shell Electron deficiency electron not electron deficient deficient The sim lest exam le of carbenium ion is CH 3 which is so unstable that it is rarely formed even in gaseous hase. The more stable ones have been re ared in solution and in some cases even in the solid state. When in solutions they are formed in olar solvents where they get solvated. They may also be associated with a negative ion called gegenion. The ion airs are formed in non olar solvents. STRUCTURE AND STABILITY The carbocations being reactive intermediates have short life and so t hey are unstable. But they have been rendered stable after being tra ed in strongest su er acids which are mixtures of fluorosul huric and antimony entafluoride dissolved in SO 2 or chlorofluorosul huric acid SO 2 CIF. Under these conditions their structure and stability have been correlat ed. In general, the greater the resonance and hy er-conjugation the greater is the stability of carbocation. The stability also de ends on the field strengths. The fo llowing exam les illustrate this oint. 1. Stability de ending on the number of canonical forms We know that among the sim le carbocations the order of stability is tertiary carbocation secondary carbocation rimary carbocation 6 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY CH 2 CH CH 2 CH 2 CH CH 2 allyl cations (Two canonical structures) So the order of reactivity is: CH H CH 6 5 2 > CH =CHCH 2 2

 > CH CH CH 3 2 2 and the above is also their stability. Now lest us study the stability of tri henyl and henylalkyl cations. The tri henylmethyl carbocation shows its stability because the ositive charge on the carbon is distributed uniformly over a number of structures. C C C C etc. C Thus a number of canonical structures is ossible. Like tri henylmethyl cation, di henylmethyl cation is also very stable. In some cases the carbocations are so st able that their salts have been isolated in the solid state. The solid salt of tri henylmethyl cation with boron fluoride as 4 6 5 3 (C H ) C BF A is available commercially. Arylmethyl cations are further stabilized if they have electron donating groups in ortho and para positions. 2. The stability increases when the positive charge is in conjugation with a dou ble bond This is due to increased delocalization of the positive charge over t wo atoms instead of being concentrated at one. R R C R C R R R C R C R C R R R C R C R C

R R C 3. The presence of a heteroatom adjacent to the cationic centre and bearing an unshared pair of electrons, like nitrogen, oxygen or halogen increases stability Such ions are stabilized by resonance C R R O .. .. CH 3 R C R O .. CH 3 CARBOCATI ONS (CARBONI UM I ONS) 7 Simple acyl cations have been prepared in solution and even in the s olid state. It has been found that acetyl cation CH CO 3 is as stable as ter butyl cation. Their canonical forms are represen ted as: C R R C O .. O .. .. It has been shown that although the positive charge is located on cation, this s tructure contributes more than that containing a triple bond. Therefore in general the carbocation stability is increased due to res onance. 4. Conjugation between the bent orbitals and p orbitals of the cation In this connection the case of cyclopropylalkyl cation and substituted cyclopropyl cations is interesting. Cyclopropylmethyl cation has been found to be more stable than benzyl cation and the stability increases with each addition of cyclopropyl groups. Thus C CH 3 CH 3 CH C

Dimethylcyclopropyl cation Dicyclopropyl cation Thricyclopropyl cation This increased stability has been explained between the bent orbitals of cyclopropyl rings and the vacant p orbital of the cation carbon. The vacant p orbital lies parallel to C 2 C 3 bond of the cyclopropane ring and not perpendicular to it. Thus the geometry becomes similar to that of a cyclopropane ring conjugated with an oblefinic bond. The structure of carbocation has been measured by 13 C nmr shift of the carbon atom carrying the positive charge. The shift agrees with the electron density on th is carbon. The following table given by Olah and J. Denovan (J. Amer. Chem. Soc . 1977.90.5026) shows that substitution of an ethyl for a methyl group or a methyl for hy drogen causes a downfield shift showing that the central carbon becomes somewhat more positive. Table 1.1 Ions Chemical shift Temperature C (C 2 H 5 ) 2 C CH 3 139.4 20 (CH 3 ) 2 C C 2 H 5 139.2 60 (CH 3 ) 3 C 135.4 20 HC(OH) 2

+17.0 30 C(OH) 3 +28.0 50 The presence of hydroxy group decreases the positive character of the central carbon. Vacant p orbital C 2 C 3 8 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY GENERATION OF CARBOCATIONS Following are some of the methods used to generate carbocations. 1. By direct ionisation: The direct ionisation of alkyl halides gives carbocations. R X R + X Solvent (x = Cl, Br, I) The process is accelerated due to the presence of metal ions like Ag . 2. Form alkenes: A proton or other positive species adds to one atom of an unsaturated system leaving a positive charge on the adjacent carbon. C Z + H C Z H 3. Decomposition of an alkyl diazonium ions: R N R + N 2 N 4. By protonation of alcohols: The protonated alcohols give carbocation s on decomposition. R OH + H .. .. R OH .. H R + H O 2 5. By reaction of acyl halides in presence of anhydrous aluminium chl oride: The Frielel Crafts acylation reactions came under this heading. R COCl RCO AlCl 4 RCO + AlCl 4

AlCl 3 anhydrous REACTIONS OF CARBOCATIONS The carbocations being highly reactive intermediates of very short life react further without being isolated and give stable products. In general they give the fol lowing reactions: 1. Reaction with nucleophiles 2. Elimination of a proton 3. Rearrangements 4. Addition to unsaturated systems. 1. Reaction with nucleophiles The carbocations react with species, the nucleophiles R + Y R Y Y = OH , halide ion or may be even a neutral species. CARBOCATI ONS (CARBONI UM I ONS) 9 CH 3 C H CH 3 + Br CH 3 C H CH 3 Br CH 3 C CH 3 CH 3 + . . O H .. H CH 3 C H CH 3 CH 3 O CH 3 C CH 3

CH 3 H OH + H 2. Elimination of a proton In this process the elimination of a proton results in the formation of an alkene. Thus the dehydration of alcohols gives rise to alkene in presence of conc. H 2 SO 4 . R CH 2 CH 2 OH .. .. RCH 2 CH 2 OH .. .. H O 2 R CH 2 CH 2 H or R C CH 2 RCH = CH 2 H It may rearrange RCH CH 3 2cation 1cation H H So carbocations can adopt two pathways to give the stable product. 3. Rearrangements As shown in the example due to rearrangement 1 carbocation rearranges to 2 cation. This rearrangement may involve the migration of a hydrogen with its pair o f electron when it is called the hydride shift or it may involve the migration of an alkyl group

with its bonding electrons in which case it is called the alkyl shift. They hydride shift is given in the above example. The alkyl shift may be represented as C C H R C C R H H H 4. Addition to unsaturated systems A carbocation may add to an alkene producing a new positive charge at a new posi tion as shown in the following example. 10 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY R C H CH 2 + C R CH CH 2 C CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 Formed by any of the two methods, the new carbocation reacts further to stabilize itself. This generally happens either by reacting with a nucleophile or by the los s of a proton. If the new cation formed by union with an alkene further combines wi th an alkene, this will result in the formation of a polymer. A number of reactions have been explained on the basis of generation of carbocations. The examples include the Friedel Crafts alkylation and arylation reactions. Besides pinacol pinacolne re arrangement, Beckmann rearrangement and Wagner Merwein rearrangement are other examples. NON CLASSICAL CARBOCATIONS OR BRIDGED CARBOCATIONS The carbocations so far studied are called classical carbocations in w hich the positive charge is localized on one carbon atom or delocalized by resonance involving an unshared pair of electrons or a double or triple bond in the allylic positions (resonance in ph enols or aniline). In a non classical carbocation the positive charged is delocalized by double or triple bo nd that is not in the allylic position or by a single bond. These carbocations are cyclic, bridged

ions and possess a three centre bond in which three atoms share two electrons. The examples are 7 nor bornenyl cation, norbornyl cation and cyclopropylmethyl cation. 1 2 3 4 7 5 6 1(a) H H 1(b) 1(c) (1) 5 6 4 3 2 1 CH 2 CH CH 2 CH 2 CH 2 CH CH 2 CH 7 norbornenyl cation 7 norbornyl cation 2 2(a) 2(b) cyclopropylmethyl cation 3 3(a) 3(b) CH 2 CH 2 CH 2

CH 2 H CARBOCATI ONS (CARBONI UM I ONS) 11 It we accept the existence of bridged ions, the question to be answe red is why should such ions be formed in preference to classical carbocations in any particul ar reaction. One reasonable answer is that when several intermediates are possible, the most stabl e one is the one likely to be formed. Since charge is most diffuse in the bridged ion than in the classical io n, the bridged structure would be expected to be more stable than the classical structure. GENERATION OF NON CLASSICAL CARBOCATIONS The non classical carbocations can be generated if proper substrate is chosen. For example the norbornyl carbocation can be generated by the departure of a leaving group from an exosubstitued substrate X route X route exo ub tituted norbornyl compund 4 4(a) 4(b) Y Thi i called the route to a non-cla ical carbocation becau e of t he participation of a bond. If a bond is involved then it is called a route. Many chemist s aruge that the structure written from 7-norbornenyl cation are not non-classical carbocations bec ause they are not canonical forms but real structures and there is ra id EQUILIBRIUM between them. Distinction between neighbouring grou artici ation and non-classical carbocati on It is im ortant to distinguish between neighbouring grou artici ation and non-classical carbo-cation. A non-classical carbocation can be formed due to artici ation of several s ecies as a neigh-bouring grou . Some of these neighbouring grou s are 1. C = C as a neighbouring grou Here we have a c = c grou attached to a carbon atom which is adjacent to be carbon atom where nucleo hilic substitution can occur and during the course of the reaction becomes bonded of artially bonded to the reaction centre to form a non-classical or bridged ion (Fig. 1 to 1(c)). Thus the rate and/or the stereochemistry may be affected. This ex lains why the acetolysis of 5 is 10 11 times faster than that of 5(a), because it involves the formation of a non-classical carbocation 2. The carbon-carbon single bond as a neighbouring grou This has been ex lained in Fig. (2 2(b)) and also in Fig. (3 to 3 (b)). 3. The 2-nor-bornyl system This is given in Fig. (2 to 2(b)).

5(a) H X 5 X H 12 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY 12 C H A P T E R The Carbanion Chemistry The carbanions are formed during heterolytic fission of a CX bond in which the carbon atom is more electronegative than X. R C X H H R C H H X + : The shared air of electron goes to the carbon atom which acquires a n octet with a negative charge and X goes out as a ositive ion. The above s ecies containin g the carbon with the octet and a negative charge is called a carbanion. So, it is a tricovalent carbon with a air of electrons and the geometry has been found to be yramidal resembling ammonia and amines in which the unshared air occu ies one a ex of the tetrahedron. Therefore, the central carbon atom is in a state of s 3 hybridisation, but when it is stabilized by declocatization, the hybridization becomes, s 2 for effective resonance. STABILITY Being electron-rich it is a very reactive intermediate and forms the basis of many im ortant organic synthesis. It can combine with a great variety of electro hile s e.g., alkyl halides and ketones and can form com ounds having carbon-carbon bonds in high yields. R C O RCR R R O R X R R + X R

a carbanion R = alkyl X = halogen. C R R R Carbanion THE CARBANI ON CHEMI STRY 13 Because of the unshared electron airs, it can also function as a ba se and can abstract a roton to form a conjugate acid. R 3 C H + B : R 3 C + BH The benzyl carbanion has been found to be most stable because of the extensive delocalization of the negative charge over the various resonating structures. CH 2 CH 2 CH 2 CH 2 The stability becomes greater due to the resence of electron attracti ng grou s like NO 2 , CN or carbonyl group in the molecule and it decreases due to electron r eleasing groups. CH 2 N C O O CH 2 C N O O The stability of the carbanions has been found to be in the order benzyl > vinyl > phenyl > C 2 H 5 > n propyl > isobutyl > neopentyl. The effect of groups on the stability of carbanions when present in position is in the order. NO > R C > SO > CN CONH > h logens > H > R

2 2 2 O GENERATION OF CARBANIONS The c rb nions h ve been gener ted s intermedi tes in l rge number of re ctions. In recent ye rs new types of c rb nions h ve been prep red which re p ired with different met ls nd this h s found the b sis for the prep r tion of m ny nove l org nomet llic compounds. Some of these met ls include group IA, IIA met ls besides luminium, zinc nd c dmium. ( ) Abstr ction of hydrogen by b se In org nic compounds h ving CH bonds, the c rbon tom being more electroneg tive will pull the bonding electron tow rds itself nd so hydrogen c n go out s proton. Therefore, in presence of b se this H will be ttr cted by the b se nd c rb nion wil l be obt ined. This cidic hydrogen will be bstr cted by b ses like N OH, t-BuO or lkyl lithium where the lkyl r dic l will beh ve like b se. 14 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY A simple ex mple of such bstr ction of proton is the form tion of t riphenylmethyl c rb nion by N NH 2 in presence of liquid mmoni . Ph C H + N NH 3 2 Ph C N + NH 3 3 lig. NH 3 In the Grign rd re gent, the lkyl r dic l cts like c rb nion s shown by its re ctions with CO 2 le ding to the form tion of c rboxylic cids O C O + RMgX O C O MgX + R HOH RCOOH + Mg OH X C rboxylic cid Therefore deproton tion is method used most often for the prep r tio n of reson nce nd inductively st bilized c rb nions. R H + M RM + H 2 Dimethyl sulphide, Me 2 S (with estim ted pK v lue s high s 49 in the medium of DMSO) loses proton with lkyl lithium, the ide h s been put forw rd th t ny type of

non-met l tom bonded to c rbon tom will m ke proton tt ched to th t c rbon tom c idic to be repl ced by strong b ses like butyl lithium. Deproton tion of very we kly cidic CH cids is ccomplished by met ll tion with org nolithium nd org nosodium compounds. (b) From Uns tur ted Compounds The c rb nions c n be gener ted from uns tur ted compounds either by r eduction or by ddition. (i) M ny uns tur ted compounds t ke up two electrons (reduction) from ctive met ls to form dic rb nions. It is illustr ted s follows: C C + 2M M C C M The nion from one electron tr nsfer is prob bly n intermedi te. Simp le lkenes do not form such st ble di nions, but some conjug ted deriv tives do form di nions s with cyclooct tetr ene forming di nion with lk li met ls. + 2 N 2 2 N + Benzene ( rom tic) does not yield its nti rom tic di nion nd n phth l ene reduces only to its nion r dic l. (ii) By ddition: The ddition of nucleophile to n uns tur ted C = C bond gener tes c rb nion. THE CARBANI ON CHEMI STRY 15 R + Nu Nu R + Nu Nu N N REACTIONS OF CARBANIONS WITH ELECTROPHILES These re ctions re of two types: ( ) Substitution, nd (b) Addition. 1. Substitution re ctions of lkyl (sp 3 ) nions The c rb nions re involved in number of substitut ion re ctions. Th e ex mple re the form tion of mono nd di lkyl m lonic esters. H H C COOEt COOEt OEt H C COOEt COOEt

RBr R H C COOEt COOEt + Br etc R C COOEt COOEt C rb nion intermedi te Simil rly with other re ctive methylene groups like diketones we get mono and dialkylated derivatives. H H C COOEt COOEt OEt H C COCH 3 RBr R H C etc. Car anion intermediate COCH 3 Br COCH 3 COCH 3 diketone In such reactions the leaving group is a halide ion ut many other groups such as sulphonates, sulphates or alkoxides have also een used. A ond is formed etween R and some non-metallic or metallic element. Virtually all elements except no le gases can e onded to car on. Some su stitution reaction are as follows: (i) YH R RH + Y (ii) In (i) there is an a straction of a proton y a strong organometalli c ase like BuLi ecause they are readily availa le. It is an extremely important reaction ecause it is used to generate other anions. 2. Addition Reactions of Alkyl (Sp 3 ) Anions

The formation of an aldol y the union of two molecules of aldehyde in presence of alkalies is an important example under this heading. The formation of acetaldol from acetaldehyde is as follows: 16 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY CH CHO + HCH CHO 3 2 OH CH CHOH CH CHO 3 2 H O 2 CH CH CH CHO 3 Acetaldol hydroxy utraldehyde The mechanism is as follows: CH CHO 3 OH CH CHO + H O 2 2 a car anion The car anion then attracts the second molecule of aldehyde. CH 3 C H O CH CHO 3 CH 3 C H O CH CHO 2 H O 2 CH 3 C H OH CH CHO 2 Acetaldol The acetaldol again having hydrogen tom to the ldehyde repe ts the process nd long ch in polymers re formed. Here the c rb nion obt ined form the first molecule dds t the ldeh ydic c rbon tom of the second molecule. Other re ctions involving the ddition of c rb nions re re ctions like Perkins re ction, Cl isen condens tion, benzilic cid re rr ngement nd Mich el ddition. 3. Re ctions of carbanions with Electro hiles

The ty e carbanions undergo most of the reactions given by alkyl an ion . An example i + FeCl 3 Fe 4. Elimination Reaction of Carbanion The elimination reaction of carbanion have been put under different cla e . The e are: (a) elimin tions (b) eliminations (c) eliminations (d) eliminations THE CARBANI ON CHEMI STRY 17 Besi es these cycloeliminations are also known. Many of elimination rea ctions procee rapi ly at room temperature but are slow at ry ice temperatures. Thus permit ting carbanions containing goo leaving groups to be use in substitution. Out of the above the elimination is most common. These eliminations result in the formation of alkenes and alkynes. When phenylethyl romide is heated with an alcoholic sol ution of an alkali first a car anion is formed y the loss of a proton followed y the loss of a halide ion and simultaneous formation of a dou le ond. Ph C H H CH 2 Br OH Ph CH CH 2 Br Ph CH CH 2 + Br The presence of a positively char ed su stituent on the c rbon tom promotes the cidity of hydro en. 5. Oxidation Reactions of Car anions One electron oxidation of monocar anions leads to car on radicals and two electron oxidation ives car ocations. In most of these oxidations, the mechanism is no t known, thou h pro ress is ein made on some mechanisms. But there appears to e a parallelism etween ase stren th and ease of oxidation of car anions. (i) Oxidation of Car anions to Hydroperoxides, Alcohols and Ketones The car anions take up O 2 and these take up protons to ive hydroperoxides in ood yields. But ecause they are explosive in nature, they are not usually isolat ed and on reduction with sodium sulphite on trialkyl phosphite ive alcohols. Alcohols can also e pre pared via hydroperoxy moly -

denum complexes and alkyl oranes. These reactions are summarized as f ollows: O 2 R MoO Py 5 RO Mo 2 CIB < RB < H O 2 2 ROH [H] [H] RO H 2 Ketones can e prepared from special car anions types y elimination r eactions which follow oxy enation. 18 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY R R R R R R 1. O 2 2. Sn 2+ R R OH CN HCN C O R R CO , H O 2 2 R R COOH OOH 1O 2 O 2 CN NO 2 CO 2 (ii) Oxidative Couplin s The simple couplin reaction works well in certain cases RR R ()

[O] One of the most useful couplin reactions is the E lintion reaction i n which the oxidation of acetylene anions with ferric ion proceeds very satisfactorily. RC C RC C C R Fe 3+ (iii) Dianion Oxidations Oxidation of dianions, in which oth the electrons are oxidized ives products which are iolo ically important: O O [O] O O O O 2 O O O O BrCH CH Br 2 2 O O 2 C C 2 THE CARBANI ON CHEMI STRY 19 When the product of two electron oxidation is a diradical, the isolat ed product can e thou ht of as ein formed y intra or intermolecular couplin of this diradi cal. BrCH CH Br 2 2 2 2 2 REARRANGEMENT REACT ONS OF CARBAN ONS These rearrangement reactions are classified under different classes. 1. ntermolecular Rearrangements The reaction between a cation and carbanion can result in more a les s tight association. Therefore stereochemical changes in the carbon species will take place. Two conditions will arise: (a) with carbanion no doubt a tight tructure R-M will be formed, b ut if the carbanion R

ha a chiral centre, then due to loo e form or R (n) , inver ion of group will take place and thi will be detected by racemi ation. R + M RM (b) with carbanions geometrical isomerisation can take lace either ho to-chemically or thermally. R + M M R R M + M R 2. Intramolecular Additions 5-membered rings are kinetically formed over 6 and so a five membered ring is formed at least 2800 times faster then a six membered ring as is seen in the following and other systems 20 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY 3. Intramolecular Eliminations These reactions are reverse to those written in section 2 above. Thes e reactions take lace because of either release of ring strain or by elimination of grou s, the s ecie s formed is more stable. O O 4. Sigmatro ic Carbanion Rearrangement In shar contrast to carbonium ions, the carbanions undergo (1, 2) si gmatro ic shifts very rarely if ever. An exam le is as given below: Ph C CH Cl 3 2 Na Ph C CH 3 2 Ph C CH 3 2 Ph Tri henyl ethyl chloride Carbanion Rearranged

carbanion It is to be noted that after the formation of the carbanion the mig rating grou goes to the carbanion carbon without a electron air. This is in shar contrast to re-arran gements in carbocations where the migrating grou moves with the electron airs. The above re arranged carbanion may combine with a roton to com lete the reaction. Ph C 2 CH 2 Ph Ph CH 2 CH Ph 2 H Thus the carbanion owe their im ortance in the synthesis of great var iety of bond-forming reactions. Unlike carbocations most carbanions do not undergo rearrangem ents but in many cases react in substitution and addition reactions in high yields. Changing the cation and solvent can greatly affect the reaction. WHAT ARE CONCERTED REACTIONS ? Reactions in which more than one bond is broken or formed can be di vided into two classes. 1. Those in which all bonds are broken and new ones are formed simul taneously so that no intermediates are involved. Such reactions are called concerted or mult icentre reactions because the changes occur in concert or at the same time at more th an one center. In such rocesses there is only one energy barrier and one transition st ate. (Fig. 3.1). Free energy A + B AB Reaction coordinate Fig. 3.1 2. This class includes reactions in which the bond forming and bond breaking rocesses other consecutively so that one or more intermediates are involved. These intermediates may be highly stable and ca able of isolation or they may be reactive s ecies of only transient existence. When the intermediate is stable, it is convenient to regard the entire rocess as consisting of two or more consecutive concerted rocesses. But where the intermediates are unstable, the entire rocess is regarded as one reaction which roceeds in a ste wise manner. The energy curve for such a reaction is as shown (Fig. 3.2). ! C H A

P T E R Theory of Concerted Reactions 21 Free energy A D Reaction coordinate B C Fig. 3.2 22 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY In such a reaction C is formed from A via an unstable intermediate B which has a short life time. Since B lies in a shallow energy well, it is unstable. I t has a small energy barrier to surmount by which if can ass on to the roducts or it can reve rt to the reactants. The more stable an intermediate is, the dee er is the energy well, so C is relativel y more stable than B. Although C is the first isolable roduct to be formed it can ass t o the more stable form D. C is called kinetically controlled roduct of the reaction of A. D i s the roduct isolated after the system reaches equilibrium, it is called thermodynamically controlled r oduct. Generally thermodynamically controlled roduct is more stable than the kinetically controlled one although the latter is formed faster then the former from a reac tant. 1. Concerted Mechanism Let us take a reaction in which a cyclic transition state is formed. a b c d a = b c = d In the concerted fragmentation, the breaking of the ac and bd bond are going on at the same time. The overall reaction does not involve an intermediate. Ther e is only one energy barrier (Fig. 1) in which both bond are partially broken and new a = b and c = d are a rtially formed. When the two bond break imultaneou ly and at an exactly the ame rate, it i called a ynchronou proce . If, however the reactant i un ymmetrical, the two bond do not break at the ame rate. In 1969 R.B. Woodward and R. Hoffmann developed a general theory of concerted reaction which proceed through a cyclic tran ition tate proce which they tur ned pericyclic. They u ed the concept of orbital ymmetry to predict which type of cyclic tran itio n tate are energetically fea ible. 2. Stepwi e Mechani m If the two bond ac and bd break in two ucce ive independent tep ,

then we have an intermediate in which only one of the bond i broken and the e nergy profile will have two tran ition tate a follow (Fig. 3.3). Free energy Reaction coordinate Fig. 3.3 24 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY tereoi omeri m. So we can ay that all tereo pecific reaction are n ece arily tereo elective but the conver e i not true. However if both maleic and fumaric acid gave the dl pair or a mixtu re in which the dl pair predominated, the reaction would be tereo elective but not tereo pecif ic. If more or le equal amount of dl and me o form were produced in each ca e, the reactio n would be tereo elective but not tereo pecific. If more or le equal amount of dl and me o form were produced in each ca e, the reaction would be non tereo elective. Thi mean that if a reaction i carried out on a compound that ha no tereoi omer , it cannot be tereo pecific but at mo t tereo elective. The concerted reaction , including S N 2 di placement , E2 elimination of alkyl halide , anti and Syn addition to alkene are all tereo elective. In the ca e of chiral or geometric ub trate the nature of the product depend o n the unique tereoelectronic requirement of the reaction. The e are example of tereo pecific react ion . THEORY OF CONCERTED REACTIONS Having learnt about the concerted reaction , we can now undertake the theory of the e reaction . The development of the theory of concerted reaction ha been due chiefly to the work of R.B. Woodward and R. Hoffmann. They have taken the ba ic idea of mo lecular orbital theory and u ed them, mainly in a qualitative way, to derive election rule whi ch predict the tereochemical cour e of variou type of concerted reaction . The e rule are be t under tood in term of ymmetrie of interacting molecular orbital . Here are will ee ome of the mo t important theoretical approache and ee how they are interrelated. Molecular Orbital We are familiar with and p orbital . The p orbital are dumb-bell haped each having a node, a region in pace in which the probability of founding an election i extremely mall. The lobe of a p orbital are labeled a + and . The e ign do not refer to the po itive and n egative charge ince both lobe of an electron cloud are negatively charged. They are ign of the wa ve function . When two parts of an orbital are separated b a node alwa s has opposit e signs on the two sides of the lobe.

+ We know that atomic orbitals combine to form a molecular orbital. Whe n two atomic orbitals of comparable energ combine, the form two molecular orbitals, one of which is called the bonding molecular orbital and is of lower energ than each of the combining atomic orbitals and the other is of higher energ called the antibonding molecular orbital. Energ Atomic orbital of A Atomic orbital of B Antibonding orbital Bonding orbital Energ THEOR OF CONCERTED REACT ONS 25 The orbitals of lower energ fill first. This means that the antibond ing orbitals remain empt in the ground state. Molecular orbitals formed b the overlap of two atomic orbi tals when the centers of electron densit are on the axis common to the two nuclei are ca lled ( igma) orbital and the bond are bond . The corre ponding anti orbital are de ignated or an tibonding orbital . It i to be noted that orbital are formed not only by the overlap of two orbital but by the overlap of any of the atomic orbital ( , p, d or f) whether ame or different, but the two lobe mu t have the ame ign. A + orbital can form a bond only by ov erlapping with another po itive orbital or with a + lobe of a p, d or f orbital. In molecular orbital calculation , a wave function i formulated which i a linear combination of the atomic orbital (al o called LCAO) and i written a : = C A A + C B B The functions A and B are functions of atomic orbitals of atoms A and B and C A C B are numerical coefficients which indicate the relative contributions of A and B to the molecular orbital. HOMO and LUMO STRUCTURES The highest occupied molecular orbital is designated as HOMO and the

lowest unoccupied molecular orbital is designated as LUMO. A positive overlap between the orbitals gives rise to the bonding orb itals while lack of overlap forms antibonding orbitals. Now let us illustrate the HOMO and LUMO structures of same alkenes. 1. Eth lene S stem We know that the parallel overlap of two p orbitals from two carbon atoms provides a double bond. + C H H + C H H M.O. (bonding) Fig. 3.4 The HOMO is that which results from the overla of two atomic orb itals of like hase, while LUMO is constructed from these two orbitals with o osite hases. + + HOMO (C C) + + LUMO (C C) Thus in ethylene the combination of two orbitals gives a bonding orbital and a antibonding orbital. An im ortant difference between the bonding and antibonding or bitals is their symmetry. 26 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY It is therefore ossible to classify the various molecular orbitals ac cording to their two indeendent symmetric ro erties which are as follows : (a) Some molecular orbitals are symmetric about a mirror lane (m) which bisects the molecular orbitals and is er endicular to the lane of the atoms forming the molecular orbital. m (b) On the other hand molecular orbitals, are known which do not have m symmetry as above but they show another ty e of symmetry about a two fold axis (called C 2 ) which asses at right angle in the same lane and through the centre of the framework of atom s forming the molecular orbital. Symmetry of this ty e will be resent if rotation of the molecule around the axi

s by 180 360 2 . H G I K J gives rise to a molecular orbital identical with the original. m C 2 So the icture of symmetry of orbitals of bonding and antibonding wil l be as follows: Orbital * m A S C 2 S A Fig. 3.5 A = antisymmetric ; S = symmetric Symmetry Pro erties of Ethylene So we find that the ground state () orbital would be symmetric (S) w ith res ect to the mirror lane m and antisymmetric (A) with res ect to C 2 axis. On the other hand the antibonding orbital ( ) would be antisymmetric with res ect to m and symmetric with res ect to C 2 axis. Symmetry Pro erties of Sigma Orbitals The symmetry ro erties of sigma orbital of a CC-covalent bond is havi ng a mirror lane symmetry and because a rotation of 180 through its mind oint regenera tes the same orbital, it i al o having C 2 ymmetry. The orbital would be anti ymmetric with re pect to both m and C 2 hown a follow : Orbital m A S C 2 A

S THEORY OF CONCERTED REACTI ONS 27 For a linear conjugated system the wave function n will have n1 nodes. f n1 is zero or an even integer n would be s mmetric with respect to m and antis mmetric with respect of C 2 . f n1 is an odd integer n will be having the s mmetr exactl reversed. Table 3.1 Node (n1) m C 2 Zero even integer S A Odd integer A S 2. Butadiene S stem The -MO of butadiene are shown as below where the adjacent lobes of the same sign ( hase) of orbitals overla while the adjacent lobes with o osite signs roduce a nod e in the resulting MO. The 4 electrons of butadiene are accommodated in the two bonding MOs i.e., 1 and 2 . For 1 there is zero node, and one node for 2 and so on upto n1 nodes for n . + + + + 4 + + 3 LUMO + + 2 +

 + 1 HOMO + + + + + + E n e r g

Nodes S mmetr 3 m 2 C 2 A S 2 S A Antibonding MOs 1 A S 0 S A Bonding MOs 1 2 3 4 Fig. 3.6 The molecular orbitals of 1, 3 butadiene. For pol enes in their ground state, the highest occupied MO (HOMO) wi ll be s mmetric with respect to m 2 for 2, 6, 10 ... electron systems and antisymmetric for 4, 8, 12 . .. electron systems. The lowest unoccu ied MO (LUMO) has the symmetry o osite to that of HOMO. In the first excited state, the LUMO of the ground state will become singly occu i ed because of the romotion of an electron and it will thus become the new highest occu ied orbital. Therefore in the circumstances the symmetry of the highest occu ied orbital is o osite to that of the ground state. m C 2 4 A S 3 S A

 2 A S 1 S A 28 MECHAN SMS N ADVANCED ORGAN C CHEM STR The coefficients of the various p orbitals of complex molecules contai ning systems are obtained by com uter rogramming based on a roximate solutions of the Schroding er wave equation. FRONTIER ORBITAL APPROACH Just as the outermost elections in an atom decides its chemistry, so the highest occu ied molecular orbital (HOMO) decides its reactivity. This is called the fr ontier orbital. The Frontier Molecular Orbital (FMO) a roach was develo ed by K. Funk ui for quickly redicting if a given ericyclic reaction (i.e., reaction which involve s a concerted reorganisation of elections within a closed loo of interacting orbitals) is allowed b y examining the symmetry of the highest occu ied molecular orbital (HOMO) and if the reaction is bimolecular, th e interaction between the two com onents should be re resented by interaction between suitable molecul ar orbitals of each. The rule is that (for cycloaddition reaction) the reactions are allowed only whe n all overla s between the highest occu ied molecular orbital (HOMO) of one reactant and the lowest uno ccu ied molecular orbital (LUMO) of the other are such that a ositive lobe overla s o nly with another ositive lobe and a negative lobe only with another negative lobe. Thus these HOMOLUMO interaction are termed frontier orbital interactions. The extent of the interaction de ends u on the geometry of a roach o f the com onents, since this affects the amounts of ossible a roach. It also de ends u on t he hase relationshi s of the orbitals and u on their energy se arations. A small energy se aration forms greater interaction. Let us consider two ethylene molecules a roaching each other in such a way that the to of one system interacts with the bottom of the other. The HOMO of one system must be matched with the LUMO of the other as shown. In both the cases the hase r elationshi s at one end of the system are wrong for bond formation. So a concerted rocess in which both new bond are formed imultaneou ly i not po ible and the reaction will be termed a ymmetry -forbidden reaction. LUMO HOMO HOMO LUMO Fig. 3.7 Now let u take the ca e of a reaction between ethylene and an ally l anion. In both ca e the HOMO-LUMO interaction lead to bonding at both terminal . LUMO

HOMO LUMO HOMO Fig. 3.8 THEORY OF CONCERTED REACTI ONS 29 The e like pha e are combining. Therefore the ymmetry i allowed. It i to be noted that the term ymmetry allowed and ymmetry forbidden only refer to the concerted proce e . Conjugated Triene Now let u draw the molecular orbital of a conjugated triene like 1 , 3, 5 hexatriene. CH 2 = CHCH = CHCH = CH 2 . The configuration of ix elections in the ground and the first excit ed state is as follows: + + + + 6 + + 5 + + 3 + + 2 + + + + E n e r g

+ + + + + + + 4 + + + + + + + + + + + 1 + + + + Antibonding Homo bonding A 1, 3, 5 hexatriene Fig. 3.9 t is to be noted that the relative s mmetr about the terminal carb on atoms of HOMO of 1, 3 butadiene ( 2 ) and 1, 3, 5 hexatriene ( 3 ) is opposite. Based on the number of electrons in olyenes, we can redict which

ty e of intermolecular cycloadditions will be symmetry allowed. The close in energy the front ier orbitals are, the stronger will be the interaction between them and therefore the more easily th e reaction will occur. The orbital coefficients at the interacting centres can also influence the rate and the direction of addition. Summarising we have the symmetry ro erties in hexatriene as follows: m C 2 6 A S 5 S A 4 A S 3 S A 2 A S 1 S A 30 MECHAN SMS N ADVANCED ORGAN C CHEM STR NTRODUCT ON t has long been known that unsaturated compounds containing a delocal ized s stem of electrons can rearrange into cyclic com ounds or other systems. Such reactions were only incidentally studied until 1930. O. Diels and K. Alder ublished their first a er on diene synthesis (which was later given the name Diels-Alder reaction) in 1928. Subsequ ent work of K. Alder and G. Stein (1933 and 1937) roved the generality of the reaction and i ts high regio and stereo selectivity. This led to the interest on thermal transformations in un saturated com ounds. Pericyclic Reactions In 1969 R.B. Woodward and R. Hoffmann introduced the term ericyclic reactions to differentiate those reactions which have a (i) a common cyclic transition state; (ii) are highly stereos ecific; and (iii) their stereochemistry de ending on the total number of and elec tron involved in the formation or breaking of bond . Thu pericyclic reaction are intra or intermolecular proce e which i nvolve concerted reorgani ation of electron within a clo ed loop of interacting orbital . Five cla e of pericyclic reaction have been recognized. (a) Cycloaddition reaction (b) Sigmatropic reaction (c) Electrocyclic reaction (d) Cheletropic reaction (e) Group tran fer reaction

" C H A P T E R Pericyclic Reaction 30 PERI CYCLI C REACTI ONS 31 CYCLOADDITION REACTIONS Cycloaddition form a very exten ive and rapidly expanding area of che mi try, the ynthetic potential and theoretical ignificance of which have been recognized on ly recently. Carbanion reaction , reaction of alkene with electrophile , nucleophili c addition to carbonyl compound , metal promoted and organomettalic reaction fall in thi cat egory. The reaction to be di cu ed under thi heading re ult in the formation of a new ring f rom two reacting molecule . In general the cyclic tran ition contain four, five or ix atom . Energy required to reach the tran ition i provided by thermal or photochemical excitation of the reacting mol ecule . Other polar or radical generating reagent having high chemical potential energy are not u ual ly involved. A concerted mechani m require that a ingle tran ition tate and therefore no int ermediate lie on the reaction path between reactant and adduct. In uch reaction the bond are formed but not broken. Example According to the above definition the example include : (a) Dimeri ation of olefin + (b) Diel -Alder reaction + (c) + a + c: b d e b c e a d Reaction b and c are example of diene ynthe i : (d) + : CR 2 CR 2 Cla ification Cycloaddition involve the generation of a cyclic y tem tructure at the termin i of two i olated system. The new bond ari e at the expen e of electrons of the re acting molecules. Thus cycloadditions are n n tran formation with n 2.

Hui gen fir t tried to cla ify cycloaddition according to the termini of one reaction partner, u ually with longer chain. Thu Diel -Alder reaction i a 4 + 2 cycl oaddition. + 32 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY Similarly olefine dimeri ation i a 2 + 2 cycloaddition. However thi nomenclatu re i ometime ambiguou . Cla ification ba ed on the Number of Electron The y tem generally adopted recognized the fundamental importance of t he number of electron involved in cycloaddition and cla ifie the reaction on thi b a i . Table 4.1. Cla ification of Cycloaddition Name Example Type of ring involved Type of tran for mation 2 + 2 dimeri ation of olef ine + ( ) a (1) 2 2 cycloadditions 4 + 2 + 4 + I fragment + SO 2 SO 2 (2) 2 2 fragmentation 2 + 2 + 2 cycloaddition + (3) 3 3 cycloaddition ( ) b In many of the above example the number of electron happen to be the ame a the number of atom in each component. But thi i not alway the ca e. For example in 1, 3 dipolar cycloaddition, the 1, 3 dipole ha four electron di tributed on three atom . The a ddition of a 1, 3 dipole to an olefine will give 3 + 2 carbon atom in the ring but it will have 4 +2 electrons according to the ado ted system 4 electron system a b c + 2 electron

system a c b Cycloadditions are usually reversible, the reverse reaction being called fragmention or cycloreversion. The latter can be designated in the same manner as fo r cycloaddition. GENERAL RULE FOR PERICYCLIC REACTIONS A general rule for determining the stereochemical course of concerted reactions has been ut forward by R.B. Woodward and R. Hoffmann. PERI CYCLI C REACTI ONS 33 Let us consider a ericyclic reaction in which the electrons of a s ystem are used in the transition state and new bonds are being formed. The question arises in how many ways the orbitals can react? There are only two ways in which the orbitals will react. 1. When the orbitals undergoing the change lie on the same face of t he molecules which are reacting (called su rafacial way). or 2. When the overla of the reacting orbitals or roduct orbitals occur s on the o osite faces of the reacting molecules (called antarafacial way). (+) () (+) () Su rafacial attack (+) () (+) () Antarafacial attack Bonding orbital overla of ethene with atomic S orbital. Fig. 4.1 The same definitions a ly to longer systems Su rafacial use of a b ond involve bonding in the ame way at both terminal . So there i retention of configur ation at both end or inver ion a both end . Suprafacial Fig. 4.2 Antarafacial u e of a bond involve retention at one end and inver i on at the other. Antarafacial Fig. 4.3 Sub cript and a are u ed to indicate a upra and an antara proce re pectively. Suprafacial, uprafacial ( , ) approach of two polyene i normally terically uitable for efficient orbital overlap. The va t majority of concerted addition involve the , approach. WHAT IS SYMMETRY ALLOWED AND SYMMETRY FORBIDDEN REACTION? A pericyclic reaction i allowed if orbital ymmetry i con erved. In uch reaction there i conver ion of the ground (electronic) tate of reactant into the groun d tate of the product. Such reaction are aid to be thermally allowed, or there i the conver io n of the fir t excited tate of

the reactant into the fir t excited tate of the product. There are photo-chemically allowed reaction . A pericyclic reaction i forbidden if it orbital ymmetry i not con erved. In uch reaction the occupied orbital of the reactant do not tran form into the occup ied orbital of the product with the ame ymmetry. 34 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY The detail of ymmetry forbidden reaction will be clear when we tud y the cycloaddition of ethene de cribed later. Woodward-Hoffmann Rule It i a general rule for pericyclic reaction and predict if a give n pericyclic reaction will be allowed under a given et of condition . The rule i a follow : A ground tate pericyclic change i ymmetry allowed when the total nu mber of (4q + 2) uperfacial and 4r antarafacial component i odd (q and r being zero or any integer). To apply the rule we fir t draw the orbital picture of the reactant and how a geometrically fea ible way to achieve overlap. Then the (4q + 2) uprafacial electron and 4r antarafacial electron of the component i counted. If the total i an odd number, the re action i thermally allowed. Let u take the hypothetical cycloaddition of ethene to give cyclobuta ne. CH 2 CH 2 + CH 2 CH 2 ( + ) 2 2 CH 2 CH 2 CH 2 CH 2 (2 + 2) cycloaddition If the two molecules a roach each other with their molecular lanes arallel, the LUMO of one will react with the HOMO of the other as shown. (+) () (+) () Bonding LUMO () (+) (+)

() HOMO Re ulsion Reaction is symmetry forbidden Fig. 4.4 C C C C 2 1 Parallel overla of ethylene C C H H H H C C H H H H H H H H H H H H PERI CYCLI C REACTI ONS 35 The reaction via a lanar transition state is 2 s + 2 s. Here only one of the two new CC bonds can be formed. This will raise its activation energy im ossible to be reached. So there are two (4q + 2) electron su rafacial com onents and no antarafacial com o nent. Since the total number of counting com onents is two, an even number, the reaction is thermally disallowed. But if the a roach of the molecular lanes is er endicular, i.e., w hen one surface of the orbital of one molecule interacts with both surfaces of the orbital of the other molecule, then cycloaddition will be allowed here but the geometry of the a roach w ill be the deciding factor and geometrically it is inaccessible. (+) () HOMO (+) () (+) () (+) () or (+) () (+) () (+) () (+) () HOMO [ s + a] 2 2 Fig. 4.5 The above interaction is su rafacial with res ect to one com onent and

antarafacial with res ect to the other and is therefore a [ 2 s + 2 a] rocess. A bonding interaction could occur between two airs of lobes of the same sign, but the nearer alkene molecule would need to twist about its original bond, and so it will make it geometrically inacce ssible. So summarizing we see that in thermal [2 + 2] cycloaddition, a su ra -su ra rocess is geometrically ossible but symmetry forbidden. But in su ra-antar roces s, symmetry is allowed but geometrically difficult. Now we have to ex lain how the hotochemical formation of cyclobutane takes lace from 2 com onents. In hotochemical rocess there is an excitation of an electron from t he HOMO of one comonent to the next higher orbital which now makes this the HOMO havi ng the o osite symmetry. This change will ermit a reviously forbidden reaction to become an allowed rocess. Thus a ( 2 s + 2 s) cycloaddition is symmetry allowed under hotochemical conditions, whi ch was not ossible under thermal conditions. (+) () (+) () LUMO (ground state) C C (+) () () HOMO (excited state) C C () The hotochemical combination Fig. 4.6 The flanking grou s from the same lobe (su rafacially) or from o osit e lobes (antarafacially). 36 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY Su rafacial Antarafacial Fig. 4.6 The symbols , and are given respectively to the systems, bond lone p orbital which participate in the tran ition tate and the ymbol ( ) and (a) are indica ted for their uprafacial and antarafacial u e. The notation i completed by the number of elec tron upplied by each component. Thu 2 s denotes a two electron system used in a su rafacial way. wo a indicates a

and

vacant orbital used in an antarafacial way and so on. The cyclodimerisation of ethylene via a lanar transition state is the refore a 2 s + 2 s reaction. Since there are two (4q + 2) electron su rafacial com onents and no antarafacial com onents, the total number of counting com onents is two, an even number. Hence the reaction is thermally disallowed. In antarafacial cycloaddition new bonds develo on o osite sides of t he system. If the number of com onents in a cycloaddition is considered, the ossible a thways become still more numerous. For m+n cycloadditions, where m and n are different, four d ifferent athways are conceivable, distinguished by the stereochemistry of the resulted adduct s : m s + n s , m a + n a and m a + n s and m s + n a . m n m + n s s m n m + n a a m n m + n a s m n m + n s a Possible interactions in an m + n cycloaddition ; ; Fig. 4.7 In this way Hoffmann and Woodward have established the following sim l e rule : a concerted m + n cycloaddition will be symmetry allowed in the ground state and

symmetry forbidden in the excited state if m + n = 4q + 2 (q = 0, l, 2...); if m + n = 4q the reaction will be symmetry allowed in the excited state and symmetry forbidden in the ground state. This rule a lies to ms + ns cycloadditions and to m a + n a rocesses. The following table summerises all the rules for cycloaddition reaction s. PERI CYCLI C REACTI ONS 37 Table 4.2. Generalized rules for cycloaddition reactions m + n Allowed in the ground state Allowed in the excited state Forbidden in the excited state Forbidden in the ground state 4q m s + n a m s + n s m a + n s m a + n a 4q + 2 m s + n s m s + n a m a + n a m a + n s The antara-su ra rocesses, even if less studied than the more common su ra-su ra reactions are frequently encountered in recent works on cycloaddition reactions a nd confirm in their turn the utility of orbital symmetry considerations. Bond Involved in Cycloaddition Reaction The theory of concerted cycloaddition may be extended to other reacti on involving bond . For in tance, let u con ider the cyclobutane fragmentation into two m olecule of ethylene. R H

H H R R H H H R R + H H R R A + a R H H H R R H R H R H + Inver ion R R H H B R Retention R 2 a 2

+ Fragmentation of ub tituted cyclobutane into ethylene . A bond i con idered to be involved in a cycloaddition in a upra manner if configuration i either retained or inverted at both of it termini in the cour e of the reaction. The retention of the configuration at one terminu and the inver ion at the other will indicate an antara addition. The all ci . cyclobutane will yield only a ci alkene. Configuration i retained (or inverted) at both termini of the two bond involved, the reaction i a upra- upr a proce a in A. In B a ci alkene and a tran alkene are formed. Thu at both the termini of one bond the configuration i retained only at one terminu and not at the other. The proce will be upra-antara. During cycloaddition (addition of bonds to bonds, a subscri t ( or ) preceding the number of electron in the relevant orbital i added, for example 2 s; 2 ; 2 a etc. 38 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY

Energy Level Diagram in Cycloaddition The energy level diagram i con tructed by placing on the left ide the energy level of the orbital of the reactant and on the right ide the energy level of the product which indicate their ymmetry. We notice that a bonding reacting level in the reactant i correlated with the antibonding level in the product. 4 3 1 + 2 + AA AS SA SA 0 AA SA + AS SS ++ + SS + + + 4 * 3 * 2 1 Energy level diagram of 2 + 2 cycloaddition Fig. 4.8 Orbital 1 and 2 are combinations of the bonding orbitals of ethylene and are theref ore of equal energy. 3 and 4 are combinations of antibonding orbitals and are also of equal ener gy. Similarly 1

and 2 are bonding * 3 and * 4 antibonding. Thu the dimeri ation of ethylene to cyclobutane involve the tran form ation of four orbitals (two bonding and two antibonding) into 4 orbital . The orbital of a ingle ethylene molecule do not relate to the ymmetry of the reaction a a whole, nor doe a ingle bond of the cyclobutane. We need to combine the eparate orbital in appropriately ymmetrical way . Thi i illu trated in the above diagram which indicate that the 2 orbital air of ethylene transforms into high energy 3 orbital pair of cyclobutane. Thi ugge t that the ground tate the rmal reaction i ymmetry forbidden and the diagram al o reveal a high activation energy reachi ng up into the cro over region. However if the electron are promoted to antibonding orbital, a in a ph otochemical reaction, the proce i ymmetry allowed in the excited tate, (already di cu ed). The theory again accord the ob ervation that dimeri ation i almo t i nvariably a photochemical proce . Such conclu ion can al o be reached qualitatively without det ailed calculation , but for preci e e timation of the energie involved in the more complex ca e , elabor ate calculation are nece ary. Some More Example of 2 + 2 Cycloaddition The cyclodimeri ation of fluorinated alkene and formation of cyclobutan e from alkene activated by electron withdrawing group ha formed great application in l aboratory and indu try PERI CYCLI C REACTI ONS 39 recently. Either dipolar intermediate or diradical may re ult in the rate determining tep. The example are afforded by the 2 + 2 cycloaddition of ketene with al kene . a = b + c = d a c b d or a c b d Dipolar intermediate

Diradical intermediate Dipolar pecie have been ob erved in the cycloaddition of polar intermediate . Thu cyclobutane can be formed by non concerted proce e involving zwitter ionic inter mediate . The combination of an electron rich alkene (enamime , enol ether ) and an alkene having electron withdrawing group (nitro a cyano ub tituted alkene ) fir t give a zwitter ion which c an rotate about the newly formed bond before cyclization and give both a ci and a tran adduct. C C ERG H + C C EWG H C C C C ERG EWG H ERG = electron relea ing group (OR, NR ) 2 EWG = electron with drawing group (NO ,C N) 2 = H ERG EWG H H ERG EWG H or Ketene are e pecially reactive in 2 + 2 cycloaddition becau e they offer a low degree of teric hindrance at one center-the carbonyl group and a low energy LUMO. + (CH ) C C O 3 2 CH 3 CH 3 O (77%) C H OC CH + H C C O 2 5 2 C H 5 2 O O (30%) In reaction with tetracyanoethylene, the tereochemi try of the double bond of an enol ether i retained in the cyclobutane product when the reaction i carried out in non p

olar olvent . In polar olvent , cycloaddition i non tereo pecific becau e of the longer lif e time of the zwitter ion. Diradical intermediate are found more commonly in thermal 2 + 2 cycl oaddition . The be t ub trate for uch addition are fluoroalkene and allene . Thu P.D. Bartlett and hi coworker have demon trated that the cycloaddition of 1,1-dichloro-2,2 difluroethyl ene to tereoi omeric hexa2, 4 diene yield a mixture of i omeric product in a non tereo pe cific way. 40 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY CCl = CF + CH CH = CH CH = CH CH 2 2 3 3 CF CCl 2 2 CH CH = CH CH CH 3 = H C 3 Product Thermal concerted 2 + 2 reaction are predicted to occur between an alkene and a ketene. According to Woodward-Hoffmann rule , addition mu t be uprafacial to o ne component and antarafacial to the other if the proce i to be concerted. H R H R O HOMO of alkene LUMO of ketene Frontier orbital of alkene and ketene Minimizing the teric interation in the tran ition tate (between R a nd R), it lead to a cyclobutanone product in which the e ub tituent are ci H R O R H H R H R O O R R Fig. 4.9 Ketene are e pecially reactive in 2 + 2 cycloaddition becau e they o ffer a low degree of teric hindrance at one center-the carbonyl group and a low energy LUMO. Photochemical Cycloaddition The reaction type which include 2 + 2 cycloaddition and carried out by photoch emical mean have al o great ynthetic potentiality. The photodimeri ation of cinnami c acid were among the earlie t photochemical reaction to be tudied. The e compound give go od yield of dimer when

irradiated in the cry talline tate. In olution, ci -tran i omeri atio n i the dominent reaction. Ph.CH = CHCOOH h H O 2 HOOC Ph COOH Ph (56%) Cycloadditio of carbo -carbo double bo ds ca also occur i tramolecula rly. If the two double bo ds are i the same molecule, the co certed reactio may hav e high yields as i the followi g examples. PERI CYCLI C REACTI ONS 41 H O CCH 2 3 h pe ta e H O CCH 2 3 (74%) h Yields are best for aromatic keto es a d aldehydes. CO CH 2 3 + CO CH 2 3 (67%) h CH Cl 2 2 Such 2 + 2 cycloadditio s also co firm the ge erality of Woodward-Hoff ma rule. 2 + 3 Cycloadditio s (1, 3 dipolar cycloadditio s) The 2 + 3 cycloadditio implies a reactio betwee 1, 3 dipole a d a u saturated compou d called dipolarophile. The product of the reactio is a five membered heterocycl e. Its theory has bee develoed by R. Huisge . Accordi g to him there are four classes of d ipoles disti guished by their bo ds a d the way they are stabilized by co jugatio . (a) Dipoles with double bo d i which the electro deficie t atom acqu ires the octet by co jugatio with u shared electro s from the adjace t atom. a = b c a b c = The ce tral atom must have a lo e pair of electro s a d must be abl e to develop for bo ds. It ca therefore be o ly a itroge atom. Atoms a a d c ca be carbo , itroge or oxyge . C N C = itrile ylides C N N = itrile imi es C = N C C = N N

 

 

 

 

   

 

C N O = itrile oxides C = N O (b) Dipoles with double bo ds a d without octet stabilizatio . Such dip oles are similar to vi yl carbo s. a b c a b c 42 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY The examples are vi yl carbe es, keto carbe es or ketoimi es. C C C C C C H vi yl carbe es C C C C C C H keto carbe es N C O keto imi es N C O (c) Dipoles without double bo d a d with octet stabilizatio . The ce tr al atom ca be either itroge or oxyge , where as the margi al atom may be carbo , itroge or oxyge . a b c a b c The electro deficie t atom is stabilized by co jugatio with the u sh ared electro s of the adjace t atom. The examples are azoxy compou ds, itro compou ds or ozo e. N N O N N O O N O O N O O O O O O O azoxy compou ds itro compou ds ozo e (d) Dipoles without double bo d a d without octet stabilizatio . A exa mple of this class is trimethyle e. a b c a b c CH CH CH 2 2 2 CH CH CH 2 2 2 Such 1, 3 dipolar additio s show a striki g similarity with die e add itio s. If the 1, 3 dipolar species is a stable compou d, the reactio takes place just by mixi g the compo e ts with or without heati g. They take place i abse ce of a y catalyst or light. Ki etic measureme ts have show that the reactio is a seco d order ( first order i each compo e t), the rate co sta t is slightly affected by polarity of the solve t. The 1, 3 cycloadditio s are highly stereospecific a d the co certed ess of the reactio is demo strated by the orie tatio of the reage ts i the tra sitio stat e. The formatio of the adduct (c) ca be explai ed by the steric dema ds i the two compo e ts as i the die e additio , the reage ts must approach each other from the least hi dered side. PERI CYCLI C REACTI ONS 43 Ph C N CH

 

 

 

 

  

 

 

  

 

   

2 Cl NO Ph C N CH 2 Et N 3 NO 2 (a) (b) b + Ph.CH O NO 2 Ph C PhHC N CH O (c) + There also appears to be great similarity betwee 1, 3 dipolar additi o a d the Diels-Alder reactio (which is 4 + 2 cycloadditio ) described i the later pages. Some Other Examples of Cycloadditio s Before describi g 4 + 2 cycloadditio , we also have examples of 2 + 1 cycloadditio . 2, 1 cycloadditio These cycloadditio s lead to the formatio of three membered ri gs com mo ly see i the carbe e additio to double bo ds. C C + CR 2 C C CR 2 We k ow that carbe es have either a si glet or triplet structure. The additio of si glet carbe e gives a haloge ium io a d is therefore stereospecific. C C + Br C C B C R R C R R R si glet carbe e It leads to the formatio of carbe ium io s which is trigo al. The additio of a triplet carbe e is similar to the additio of atom ic oxyge . C C + O C C O C R R C R R R triplet carbe e R R

    

  

It is o stereospecific. So the stereochemistry of the product reveal s us whether the carbe e was si glet a triplet. 44 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY The cycloadditio of methyle e :CH 2 to ethyle e has i dicated that the compo e ts ca be correlated i the grou d state with the grou d state trimethyle e. The reactio is thus symmetry allowed i the grou d state. CH CH CH 2 2 2 I the tra sitio state, the reage ts should approach each other i a o -symmetric way as proposed by P.S. Skell a d A.Y. Gar er. C C C R R 4 + 2 Cycloadditio s Diels-Alder Reactio Ge eral Features The reactio betwee a co jugated die e with a mo oe e to give a six membered ri g compou d is the best k ow example of 4 + 2 cycloadditio a d bears th e ame of two workers DielsAlder who first recog ized the scope of the reactio a d bega i vest igati g i to its mecha ism. Most of the evide ce goes to show that it is a co certed reactio w hich i volves simulta eous formatio of two ew bond . + diene dienophile Diel -Alder reaction The reaction i carried out imply by heating a diene or another con jugated y tem of bonds with a reactive unsaturated com ound (dieno hile). Usually the reaction is not sensible to catalysts and light does not affect the course. De ending on the s ecific com o nents, either carboxylic or heterocyclic roducts can be obtained. The stereos ecificity of the rea ction was firmly established even before the im ortance of orbital symmetry was recognized. In term s of orbital symmetry classification, the Diels-Alder reaction is a 4 s + 2 s cycloaddition, an allowed rocess. SCOPE OF DIELS ALDER REACTION The great advantage of Diels Alder reaction in organic synthesis lies in its high stereoselectivity. Exam les of Diels-Alder reactions are known for almost all ty es of bonds acting as dieno hiles. The diene system may be all carbon or there may be many variations as shown in t he following tables. Table 4.3 Exam les of Dieno hiles >C=C< O=O (singlet O 2 ) CC N=S

 

  

 

 

 

    

 

    

>C=N >Si=C< >C=O >C=S N=N PERI CYCLI C REACTI ONS 45 Table 4.4 Systems acti g as die es C C C C O C C C N C C C O C C O C N C C N C C O C N N C O N N C Thus the co siderable variatio possible i the structures of both die e a d die ophile makes the Diels-Alder reactio a very versatile sy thetic route to both carb oxylic a d heterocyclic compou ds. Some examples are: + COOMe C C COOMe 150 Tolue e H Me COOMe CooMe 85% + CN C C below room temp. , NC CN NC CN CN CN CN + 80 Be ze e O H

 

 

 

45% + O C 20 , CN NC O CN CN O CHO 92% The sy thetic utility of Diels-Alder reactio becomes still greater whe a adduct gives compo e ts differe t from those from which it was formed. This is called retro-Diels-Alder reactio a example of which is a follows : + COOEt C C COOEt COOEt COOEt MeOOC MeOOC O O COOEt COOEt MeOOC O O If i the reactio s of a substituted die e with a alke e, if chiral ce ters developed i the reactio are co sidered, the the umber of isomers developed becomes very large. For example i the followi g case, four chiral ce ters are developi g a d so the umber of isomers formed becomes 32 depe di g upo differe t orie tatio s. 46 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY H H R 1 R 2 + CHR 3 CHR 4 H R 1 R 3 H R 4

 

 

 

 

 

      

H R 2 H + H R 1 R 4 H R 3 H R 2 H Actually o e orie tatio predomi ates (called high regioselectivity) a d o ly o e diastereoisomer is produced (called high stereoselectivity). The Diels-Alder reactio is revers ible a d may be carried out u der thermody amic or ki etic co trolled co ditio s. Ki etic Studies The Diels-Alder reactio is a seco d order reactio , first order i e ach compo e t. Rate = k 2 [die e] [die ophile] The prese ce of Lewis acids, through ot ecessary may accelerate the reactio rate a d affect regioselectivity. The reverse reactio , the retro-Diels-Alder reactio is a clea first order reactio , both i the gaseous a d co de sed phase. Rate = k 1 [adduct] The above two rate reactio s are i agreeme t with a co certed reacti o . Stereochemistry a d E do a d Exo Additio A ormal Diels-Alder reactio is a ( 4 s + 2 s) cycloaddtion and the stereochemistry of both the diene and alkene is retained in the cyclization rocess. The diene and alken e a roach each other in arallel lanes. The bonding ineraction involves between C 1 and C 4 of the diene and carbon atoms of the dieno hilic double bond are in a six center arrangement as il lustrated below : LUMO of dieno hile HOMO of diene ( of diene) 2 Fig. 4.10 A normal Diels-Alder reaction, c cloaddition of ethane and 1 ,3 butadiene. Thus we find that the reaction is a s n (suprafacial) addition with

 

 

 

 

  

  

respect to both the diene and dienophile. The frontier orbitals involved shows that the reaction occurs b interaction of HOMO and LUMO. So there is no possibilit of substituents to change their position. Substituents which are on the same side of the diene or dienophile will be cis on the newl formed ring as is seen between the reaction of dimeth l maleate (a cis dienophile) w ith 1,3 butadiene. The product formed is cis 4,5 dicarbomethox c clohexane. PER C CL C REACT ONS 47 HC HC CH 2 CH 2 + C C COOMe COOMe H H COOMe H COOMe H Cis 4, 5 dicarbomethox c clohexane. No trans isomer is formed But 1, 3 butadiene with dimeth l fumarate gives a trans product + C C H COOMe MeOOC H H COOMe COOMe H trans How the relative orientation of substituents is preserved in the adduc t is also illustrated b the combination of c clopentadiene with the two isomers of 1, 2 disubstitu ted dienophile. Here the cis isomer gives the cis product and the trans isomer, the trans adduct. CH CH CH CH CH 2 maleate diester (cis) fumarate diester (trans) COOR COOR COOR COOR

cis trans Cis-addition is the normal result of a s nchronous bond formation in a 4 s + 2 s cycloaddition and needs no further comments. Variations to the cis addition have been found in the transtition sta te in some cases and a mixture of roducts has been re orted. Two ossible stereochemical vari ations have been re orted because of endo and exo addition. Thus in the dimerisation of butadie ne Hoffmann and Woodward have shown that besides the rimary orbital interactions between C 1 and C 4 of the diene and C 1 and C 2 of the dieno hile, there are also secondary interactions (shown by dotted lines and also called endo addition) between C-2 of the dieno and C-3 of the dieno hile. S uch orientations are only ossible in endo orientation and this will stabilize the transition st ate. 1 2 3 4 3 2 1 dieno hile diene endo addition exo addition 4 Fig. 4.11 Such addition will not be ossible in exo-orientation. 48 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY These secondary interactions lay an im ortant role in cycloadditions h aving highly electron deficient dieno hiles. The indimerization of cyclo entadiene again two roducts are formed, th e major being formed by the endo addition. Here also there are secondary bonding interactio ns. Fig. 4.12 The exoaddition will be as follows : Fig. 4.13 In these dimerisations one molecule acts as a diene and the other as the dieno hile. The endo roduct is thermodynamically less stable and secondary interactions tend to reduce the activation energy. No such interactions are ossible for the exo transition state .

Some more exam les of endo addition (1) Addition of maleic anhydride to cyclo entadiene. Here also two orientations are ossible and the endo roduct redominates. Sometimes the exo adducts are com letely excluded. Sometimes the initially formed endo adduct may isomerise to the less sterically hindered and more stable exo adducts followed by a retro Diels-Alder reaction followed by recombination. HOMO LUMO Minor roduct endo exo Cyclo endiene Primary bonding interaction Secondary bonding interaction HOMO LUMO endo addition (Major roduct) H H PERI CYCLI C REACTI ONS 49 (2) Whatever may be the ex lanation of actual stereochemistry, the endo or ientation is consistent with a concerted mechanism. It is to be noted that the endo addition rule is not as universal as the cis-addition rule. It can be finished by the more general rule according to which the reagents a roach each other from the less hindered side. If that side a ears to corres ond to an exo -orientation, then exoaddition will occur both under and thermodynamic conditions. The attack from the less-hindered side and in which how the roducts formed by exo or endo additions vary has attracted great attention and a very interesting ca se of the reaction between na hthalene derivatives and 4 henyl-1, 2, 4 triazoline 3, 5 dione (d ) acting as dieno hile has been re orted by B.M. Jacobson in 1973. In all the above cases the attack from the less-hindered side (exo-or ientation) was referred and the ratio exo/endo varied from 19 (for a) to 4 (for c). The increase in wei ght of endo-orientation for c cannot be ex lained only on secondary overla interactions. But they are accounted for by decrease of geometrical constraints. The steric requirements of saturate d cyclohexane ring are higher than the steric requirements of s 2 carbon atoms in C. While studying the stereochemistry of the endo addition, it has been found that the bulky side of the olefine is normally under the ring as in the following exam l es : benzene 40 97%

C O N C O N Ph a b c d CH 3 O C C O O CH 3 O C C O O CH 3 CH 3 COOCH 3 CH 3 COOCH 3 CH 3 N 50 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY Steric factors have also been studied in several cases. It has been found that dienes which easily ado t the s-cis confirmation undergo Diels-Alder reaction readily . The cyclic dienes undergo the reaction if they have cis conformation. If they are frozen into a trans-conformation, the reaction does not occur. This ex lains why e and f undergo the reaction easil y but g fails to react. Besides the above configurational and steric factors electronic effects of substituents have also been studied on Diels-Alder reaction. How the electronic and steric fa ctors both o erate is best afforded by cyclobutadiene which is a highly reactive s ecies and unde rgoes Diels-Alder reaction even at very low tem erature to give a mixture of the following two roducts. The case of this dimerisation can be related to the closeness in ene rgy of cyclobutadiene HOMO and LUMO. In contrast, the tritertiary butyl cyclobutadiene in which the bulky t-butyl grou s hinder dimerisation ca n be isolated at room tem erature. Orientation (Regioselectivity) A question of regioselectivity arises when both the diene and alkene are unsymmetrically substituted and two different orientations are ossible. Thus a 1-substituted

diene with a mono substituted dieno hile may form an ortho and a meta adduct. The same dieno hile with a 2-substituted diene can yield a meta and a ara roduct. Actually it has been observed that 1 sustituted dienes referentially form ortho adducts whereas with 2-substituted derivatives ara adducts are formed. O O e f g Bu t Bu t Bu t H Ph COOMe Ph Ph COOMe and COOMe HOMO LUMO (favoured) COOH Ph COOH COOH Ph and LUMO HOMO (favoured) Ph PhS COOMe PhS COOMe and PhS COOMe HOMO LUMO (favoured) * * * * * * PERI CYCLI C REACTI ONS 51 robl This regioselectivity was originally one of the greatest unsolved ems in Diels-Alder reaction but with the a lication of FMO theory, it has now been solved satis factorily. Calculations made on systems containing heteroatoms give a set of coefficients which account for the observed orientation. The regioselectivity of a diene addition has also been ex lained on a concerted mechanism. The transition state involves a six -electron system similar to benzene exc e t for the fact that besides

a - overla , - overlap mu t al o be con idered. A in benzene, the ub tituent in ortho and para will be better con jugated than tho e in meta. The e qualitative a pect of regio electivity have been tudied quantitatively b y quantum mechanical tudie . Further the molecular orbital con ideration have hown that t he favoured tran ition tate will be that in which there i tronge t interaction between the HOMO of the diene and LUMO of the dienophile. In the mo t common ca e the dienophile bear an elec tron withdrawing ub tituent and the diene an electron relea ing one. Here the interation i betwe en the LUMO of the dienophile and the HOMO of diene. Diene Reactivity In a ynchronou Diel -Alder reaction, the following fact have come t o light about diene : 1. Simple diene react readily with good dienophile and they mu t ado pt a ci oid geometry about the bond ( -ci ). But in the ub tituted diene like ci -1- ub tituted diene , the -ci conformation i di favoured with re pect to the -ci form of corre ponding tran form due to the nonbonding interaction between the ub tituent and the 4-hydrogen. In a concerted reaction the tran i omer hould be therefore more reactive than the ci -deriva tive. 2. The conformation of cyclic and polycyclic diene i frozen either i n the ci oid or in the tran oid form (i). h i But irre pective of the mechani m (concerted or tepwi e) the reaction i only po ible from ci oid form . In the frozen tran oid conformation, the reaction d oe not occur. Thi i why the following doe not react. j 3. Diene can al o be generated under the condition of Diel -Alder reaction fro m precur or . An example of exceeding reactive diene i quinodimethane which ha bee n ynthe ized from the pyroly i of benzocyclobutene. Ph CH=O Ph CH=O Ph CH=O 52 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY In a Diel -Alder reaction from it a benzenoid ring ha been e tabli h ed having aromatic tabilization. Another example of a diene with extra ordinarily high reactivity i d iphenyl benzo (c) furan (diphenyl i obenzofuran) Here again the high reactivity i due to the gain of aromatic tabil ization in the adduct. Polycyclic aromatic are moderately reactive a the diene component in Diel -Alder

reaction . Anthracene form adduct with a number of dienophile . The addition occur at the centre ring. The naphthalene ring y tem i much le reactive . 4. The formation of Diel -Alder adduct i now u ed in the determinati on of the po ition of double bond in polycyclic hydrocarbon . 5. Polar ub tituent al o have a marked effect on cycloaddition. The diene component i electron rich wherea the dienophile i electro n deficient. Electron relea ing ub tituent favour the reaction, while the electron with dra wing group decrea e the rate. Thi may be due to their effect in rai ing the energy of the diene HOMO to make it more compatible with the dienophile LUMO. Thi explain why 2 methyl butadiene react with maleic anhydride (the dienophile) at 30C in the medium of dioxane with twice the peed a compared with butad iene. But under the ame condition butadiene react 10 time fa ter a compared with 2-chlorobu tadiene which ha an electron withdrawing group. Thermodynamically un table compound are the mo t reactive diene . Dienophile Reactivity The reactivity of the dienophile depend on the electron demand of th e reaction. Electronwithdrawing group in the dienophile will accelerate the reaction rate. Simple alkene and alkyne uch a ethylene and acetylene are poor dienophile . In the following table ome repre entative dienophile have been tabulated along with their reaction with cyclopen tadiene. All of the e compound bear at lea t one trongly electron withdrawing ub tituent or a double or a triple bond. Thu tetra cyanoethylene i about 4.6 10 8 time a reactive a cyclopentadiene. A a re ult of en ual tudie , the following conclu ion have been o btained. CH 2 CH 2 quinodimethane CH 2 CH 2 X X Ph Ph Ph Ph O O 69% PERI CYCLI C REACTI ONS 53 Table 4.5. Reactivity of ome repre entative dienophile toward cyclope ntadiene

in dioxane at 20C No. Rate A. 1. 460000000 2. 910 3. 806 4. 628 5. 742 B. 6. Dienophile Sub tituted Alkene NC NC C C CN CN NC H C C CN H NC H C C H CN HOOC H C C COOH H HOOC H C C H COOH Sub tituted Alkyne F CC CCF 3 3 Hexaflur o- 2 butyne 1. A di ub titutd derivative, RCH = CHR hould react twice a fa t a a mono ub tituted compound RCH = CH 2 . 2. If a reaction proceed through a cyclic tran tion tate k and l re pectively, two ub tituent hould be more efficient in tabilizing it than a ingle ub tituent. 3. Sub tituted tran ethylene react at lea t 50100 time a fa t a t he corre ponding monoderivative which indicate a concerted mechani m. 4. Tran ient intermediate like benzyne or cyclobutadiene are extremely reactiv e dienophile. 5. In diene reaction with inver e electron demand imple alkene are mo t reactive. Thi i why the e reaction have been u ed to identify imple alkene . 6. Functionalized dienophile have long been u ed in ynthetic organic chemi try . For example

a ub tituted benzoquinone (a dienophile) underwent cycloaddition with 1,3 butad iene and wa the fir t tep in the early ynthe i of teroid . R R R k l O O CH 3 CH 3 C 6 H 6 100C CH 3 CH 3 O O O H (86%) 54 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY Intramolecular Diel -Alder Reaction An area of Diel -Alder Chemi try that ha received a good deal of at tention recently i in the ynthe i of polycyclic natural product . Thi involve intramolecular v ariant. Thu a p eudotropine ha been ynthe ized. The oxygen-nitrogen bond of i oxazoline can be c leaved by reduction. Cyclopropanone are al o reactive toward cycloaddition of variou type . Probably a dipolar pecie i fir t formed from rever ible cleavage of cyclopropanone ring . O O O O N CH 2 CH CH 2 toluene N O 1. H 2 -Pd/c 2. CH 2 O, HCOOH CH 3 N

OH + INTRODUCTION An electrocyclic reaction i defined a a concerted clo ure of a ring tarting from a conjugated open y tem in which a orbital is converted into a orbital. It i therefore an example of intramolecular cycloaddition or retroaddition. Some example are: 1. 2. 3. h 1,3 butadie e Cyclo bute e 100C h So if the system of the o en chain artner is having n electrons, t he cyclic artner will have (n 2) electrons and one additional bond. Electrocyclic reaction can be brought about by heat, by ultraviolet i rradiation and ometime by u e of metal cataly t . The thermal reaction i generally not reve r ible and a written above cyclobutene have been converted to 1, 3 diene by heating between 10 0 and 200C. But the photochemical conver ion can be carried out in either direction. Genera lly 1, 3 diene can be converted to cyclobutene rather than the rever e becau e the diene b ecau e of electrons are strong absorbers of light at the used wavelengths. These reactions are nearly always stereos ecific and the stereos ecifici ty in the roduct has been confirmed by n.m.r. studies. The interest in these reactions has grown during the last about # C H A P T E R Electrocyclic Reactions 55 56 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY two decades; firstly because of their many synthetic uses and secondly they have aved the way for the confirmation of the theory of orbital symmetry. The highly stereos ecific nature of the reaction is illustrated in the thermal conversion of cis 3, 4 dimethylcyclobutene into cis-trans, 2, 4 hexadiene Me H H H H Me H Me H

H H Me trans cis H Me H H H Me 3 cis 4 But the trans isomer gave only the trans-trans diene. Me H H H H Me trans H H Me H H Me 3 trans In the following disrotatory motion, the movement can be in any of t he ways, either by inward or outer ward rotation. (O ening by movements in different directions). A C B D A C B D or B A C D A B D C Fig. 5.1 ELECTROCYCLI C REACTI ONS 57 For conrotatory motions, the icture will be as follows: A C B D A C B D or B A D C A B C D Fig. 5.2 If A, B, C and D are all identical, then there will be only one ossible roduct, but if they are all different, then there are four ossible roducts. Basically the theory disti nguishes only the disrotatory modes or conrotatory modes. But redictions can be made on the basis of steric effects. Electrocyclic rocesses are also observed with ionic systems, both cati onic and anionic. The decisive factor in the stereochemistry is the number of electrons in the delocalized olyenic system. Thus the mode of ring o ening or ring closure de ends on the electr ons in the o en olyene. THERMAL ELECTROCYCLIC REACTIONS

Table 5.1. Electrocyclic reactions No. of Reaction ty e Exam les Ground State Excited State electrons in the relevant M.O. of olyene 2 [1, 3] D C 4 [1, 3] C D 4 [1, 4] C D 4 [1, 5] C D 6 [1, 5] D C 58 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY 6 [1, 6] D C 6 [1, 7] D C C = Conrotatory; D = Disrotatory 2 System The most sim le electrocyclic reaction involving a 2 electron system is the formation of an alkyl cation from a cyclo ro yl cation The reaction is an im ortant one, es ecially in bicyclic system where it leads to ring ex ansion The change of cyclo ro yl cation to allyl cation is an irreversible reaction bec ause only the ring o ening is observed. It is irreversible cyclo ro yl cation, is thermody namically unstable with res ect to allyl cation and also because the ring is under strain. Other factors which affect the case of electrocyclic ring o ening include the na ture of substituents which can stabilize or destabilize the develo ment of ossible charge and the re lease of strain in small cyclic systems. Thus different stereochemistries have been observed in the ring o ening of cyclo ro yl derivatives. All cis derivatives generate an all-cis allyl cation but the anti d erivatives will form the all trans cation. A X B cis cis B A A X B trans B A trans Thus outward disrotatory reaction is favoured over the inward rocess, if A and B are bulky grou s. P.R. Schleyer et al [J.Amer.Chem. Soc 88, 2868 (1966)] have c onfirmed this ex erimentally showing that the anti derivatives solvolyse faster than the syn deriva tives. But the outward motion will be disfavoured over the inward rocess if A and B form a mediu m-sized ring. The effect of substituents and the relief of strain is also visible in certain cyclic ethers. The resence of adjacent oxygen in the following cyclic ether assists ring o ening smoothly at 60C and ELECTROCYCLI C REACTI ONS 59 the strained bicyclo entane is unstable even at 0C. The ring o ening has been fac

ilitated by the relief of strain. Cl Cl Cl Cl O 4 System The sim lest exam le of an electrocyclic reaction involving 4 electron system is the thermal o ening of cyclobutenes to 1,3 butadienes. The reaction can be done t hermally or hotochemically and under either conditions, it is stereos ecific. h The two reactio s ca be separately carried out. The cyclobute e must be thermody amically u stable with respect to the die e. Therefore i a thermal process o ly a ri g ope i g of cyclobute e is observed. But u der photochemical co ditio s die es are more efficie t i abs orbi g radia t e ergy tha are simple alke es. This is why ri g closure of die es ca be carried out i high yields photochemically. A bond of cyclobutene break to form the open chain diene. Thi bre aking will be either con or di rotatory. The conrotatory thermal opening will be a follow : con. rehybridi ation Fig. 5.3 After the ring opening, rehybridi ation will occur to give the product . In di rotatory motion one p orbital will rotate in clockwi e and the other in anticlockwi e direction. di . rehybridi ation Fig. 5.4 The tereochemical ignificance of ring opening or ring clo ure become marked by taking ub tituted reactant . The identification of the product will indicate whether the reaction ha taken place in con or di rotatory manner. In mo t ca e the ring opening goe to completion and there are very few example of the rever e reaction i.e., the thermal cycli ation of butadiene . The ring opening take place moothly in olution or in the ga pha e at temperature between 120 and 200C. 60 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY In attempt to carry out cycli ation from butadiene 1,3 in the ga eou pha e and under photochemical condition R.Sriniva an (J.Amer.Chem.Soc. 88, 3765 (1966) howed that irradiation yield a complex mixture of ethylene, acetylene, but-l ene, hydrogen a nd polymer . The quantum yield of acetylene and ethylene formation increa e with pre ure. butadiene + polymer CH CH CH 2

   

CH 2 + The effect of ub tituent on ring opening i marked in the following example : CH 3 CH 3 H H h dis CH 3 CH 3 H H con. CH 3 H H CH 3 trans-trans 2,4 hexadiene cis 3,4dimethylcyclob tene cis-trans 2, 4hexadiene This is beca se that in thermal reaction, the change is conrotatory hile in photochemical process, it is disrotatory, ill strated as follo s: H C 3 CH 3 H H con. H C 3 CH 3 H H h dis CH 3 H CH 3 H cis-trans 2-4 hexadiene HOMO for thermal

2 CH 3 H H CH 3 HOMO for photo chemical 2 trans-trans 2-4 hexadiene Fig. 5.5 For photochemical reaction 3 is the first excited state and the two shaded lobes being on the same side of the plane are forced to undergo disrotator change. ELECTROC CL C REACT ONS 61 From this it should not be inferred that all electroc clic reactions under thermal conditions proceed in a conrotator manner and under irradiation the proceed in a disrotator fashion. This is clear from the following example: rradiation of trans, cis, trans 1,6 dimeth lhexa-l,3,5 triene ( ) give s rise to trans-5, 6 dimeth lc clohexa 1,3 diene ( ) while thermal ring closure gives rise to cis 5, 6 dimeth l c clohexa 1,3 diene . T pical examples occur with the trans and cis 3,4 dichloroc clobutenes which open stereo specificall to trans, trans and cis, trans-1,4-dichlorobutadiene respect ivel . Cl Cl Cl Cl Cl Cl Cl Cl Fused c clobutenes are thermall rather stable, speciall those in whic h the second ring is five or six membered. For example the following c clobutene does not isomer ise below 380C. H H This appears to be surprising because the fusion of a second ring should increase the strain and make the ring opening easier. However the allowed ring opening is conrotator which would required the formation of dienes containing a trans fused double bond under drastic conditions. CH 3 CH 3 H H dis CH

3 CH 3 H H

 

CH 3 CH 3 CH 3 CH 3 H H h con CH 3 H CH 3 H H H CH 3 H H CH 3 II H H 400C H 62 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY The f sed cyclob tenes prefer a path hich leads to disallo ed cis, cis cyclic diene. Th s bicyclo-octane(IV) opens at 230260C to give cis, cis l,3 cyclooctadiene and not cis-trans diene. The activation energy 180 K J mole -l is m ch higher than for opening of simple cyclob tenes. Cyclob tenes are thermally converted into b tadienes and the ring openi ng corresponds to a conrotatory process. ROOC COOR COOR COOR 130C con. H H (cis-trans) So in electrocyclic processes the reactant orbitals change into prod ct orbitals thro gh an intermediate transition state and in the most stable transition state the symmetry of the reactant orbitals is conserved hile passing to prod ct orbitals. Th s a symmet

rical orbital in the reactant m st change into an antisymmetric orbital. The transformation cyclob tene b tadiene can be either con- or disrot atory (see Fig. above). In con-rotatory motion C 2 symmetry is maintained thro gho t hile in disrotatory motion m symmentry is maintained. The directly involved orbitals of cyclob tene are and and their rela ted antibonding orbitals and *. The corres onding molecular orbitals are re resented by 1 , 2 , 3 and 4 . The picture in a disrotator change will be as follows: Fig. 5.6 S mmetr properties of M.Os of c clobutene and butadiene. H H ( V) *(m-A; C 2 -A) *(m-A; C 2 -S) 4 (m-A; C 2 -S) 3 (m-S; C 2 -A) 3 (m-A; C 2 -S) 1 (m-S; C 2 -A) (m-S; C 2 -A) (m-S; C 2 -S) E ELECTROCYCLI C REACTI ONS 63 On the ba i of the above the following correlation diagram can be c

on tructed howing correlation between orbital of the ame ymmetry having minimal differ ence in a di rotatory interconver ion. The line connecting the orbital how imilar ymmetry . m- ymmetry maintained * S * S A 4 S 3 A 2 S 1 S S E O Fig. 5.7 Correlation diagram between cyclobutene-cyclobutadiene system in a disrotatory interconversion. A thermal transformation will be ex ected when the ground state orbita ls of the reactants will correlate with the ground state orbitals of the roduct. In the above exam le although the ground state orbital of cyclobutene, , correlate with the ground tate orbital of butadiene 1 , the orbital of the former does not correlate the 2 orbital of the latter, but rather it correlates with the 3 which is an excited state. So in such a case the thermal transformation b disrotator processes will be a s mmetr forb idden reaction. On the other hand in a photochemical transformation b a disrotator process, one electron is promoted from to * orbital and so the , and * orbitals of cyclobuten e would correlate with 1 , 2 and 3 orbitals of butadiene. Thus the first excited state of c clobutene, since it correlates with the first excited state of butadiene, therefore, the process woul d be a photochemicall s mmetr allowed process. The same arguments can be applied to construct the correlation diagram for the conrotator process in the transformation of c clobutene butadiene s stem. n suc h a case, as we have seen, a C 2 s mmetr is maintained throughout. C S mmetr maintained

2 con. Here two things are clear: 1. There is a correlation between the ground state orbitals of c clobu tene and butadiene i.e. 2 2 2 2 1 2 . Therefore a thermal conrotator process would be a s mmetr allowed process. 64 MECHAN SMS N ADVANCED ORGAN C CHEM STR 2. The first excited state of c clobutene ( 2 *) is correlated with the u er excited state 2 1 2 3 ( ) of butadiene making it a high energ s mmetr forbidden process. * A * S A 3 S 4 S 2 A 1 S A E O Fig. 5.8 Correlation diagram between cyclobutene-butadiene system in a conrotatory interconversion Similarly the first excited state of butadiene 2 1 2 3 is correlated with a high energ upper excited state 2 * of cyclobutene. Thu a photochemical conrotatory proce in either dir ection would be a ymmetry forbidden reaction. So a thermal opening of cyclobutene take place in a conrotatory fa h ion while photochemical inter conver ion involve a di rotatory fa hion. The e generalization h old good for all y tem having 4q electrons where q is any integer like 0, 1, 2 etc. For systems having (4q + 2) electrons theoretical redictions are ent irely different and they are in conformity with the ex erimental facts. 6 System The equilibration of a hexa-1,3,5 triene with a cyclohexa-1,3 diene differs in s ome res ects from the electrocyclic rocesses discussed above. To study the above reaction, besides knowing their symmetry, we have to look into the geometry of the acyclic triene. The following facts have come to ligh t. A. Cyclization in the ground state is ossible only from the cis isom

er. B. Under hotochemical conditions and in excited state, the trans chang es to cis ra idly and it is then followed by cyclization. ELECTROCYCLI C REACTI ONS 65 h trans cis h There seems to be no great difference in the free energy bet een acy clic triene and the cyclic diene. This is beca se of smaller strain in the six-membered ring as compared ith the fo rmembered one. On the other hand in 6 electron system in electrocyclic rocess there is more efficient absor tion in the near regions of u.v. s ectrum. This is wh y under both thermal and hotochemical conditions, the (1, 6) electrocyclic reactions are reversi ble. Side reactions are more frequent in reversible. Side reactions are more frequent in reversible transformations of trienes than in dienes. The dehydrogenation of cyclic dienes to aromatic com ounds may also occur in the thermal rocess. On heating cyclohexadiene yields benzene and hydrogen. The electrocyclic ring o ening is revented by the energetically more favourable rocess, the aromatisation. The cis-hexa-l,3 diene is stable at 100C but undergoes e lectrocyclic closure at higher tem erature. Hexa-l,3,5 triene gives on irradiation benzene, hydrogen and hexa 1,2,4 -triene. The rocess is conrotatory in both the directions. It is ossible to construct the correlation diagram of Cyclobutadiene 1,3,5 cyclohexatriene dis m symmetry maintained The symmetry ro erties of molecular orbitals of cyclohexadiene are giv en in the following table. Table 5.2 M C2 * A A 4 A S 3 S A 2 A S 1 S A S S Correlation diagram for di rotatory motion of cyclohexadiene-hexatriene y tem ymmetry maintained.

66 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY * A 4 A 3 S A 6 S 5 A 4 E O 2 A 1 S S S 3 A 2 S 1 fashion: From the correlation diagram we find that in disrotator 1. The ground state bonding orbitals of c clohexadiene is correlated wi th the ground state bonding orbitals of hexatriene and so it will be a thermall allowed reaction. 2. For a 1,3,5-triene the s mmetr of the HOMO is 3 . Therefore a thermal cleavage of c clohexadiene should be such that the positive lobes must lie on the same side of the plane which requires a disrotator motion. 3 Fig. 5.9 HOMO for thermal reaction 3. n the photochemical process the lobes of the same sign must overl ap and this is possible b conrotator motion. 4 * HOMO Fig. 5.10 HOMO for photochemical reaction Here the electron gets promoted to 3 in cyclohexadiene. ELECTROCYCLI C REACTI ONS 67 The correlation of the conrotatory diagram of interconversion of cycloh exadiene-hexatriene is as follows where C 2

symmetry is maintained. * A S 4 A 3 S 2 A 1 S A 3 S 2 A 1 S 6 A 5 S 4 E O Although a few other ac clic examples of stereospecific isomerisation of hexatri enes are known, speciall in the field of natural product like steroid chemistr , the commonest reactions of this t pe are in c clic hexatrienes. C clooctatriene and c clooctatetraene are s stems in which the electroc clic reaction goes ver readil and the show an interesting trend. H H H H bic clo [4, 2, 0] octatriene The reverse reaction is more favourable for the c clooctatriene equilib rium. For c clooctatetraene and its product, so the equilibrium strongl favo urs the former to such an extent that the half life of the bic cloisomer is onl a few min utes at 0C. Thus as the bic clic s stem becomes ver strained, the equilibrium lies more in favour of the reverse reaction. ELECTROC CL C REACT ONS OF RAD CALS The electroc clic reactions of systems containing an im aired electron are diffi cult to inter ret using the above sim le theories. The symmetry of the HOMO of the rad ical system corres onds to that of the corres onding anion. Thus the allyl radical would be ex e cted to cyclize in the same manner as the alkyl anion i.e., in a conrotatory manner. In fact the interconversion takes lace in a disrotatory manner. Theoretical calculations based on Huckets theory also give ambiguous or incorrect redictions. And therefore more so histicated calculations are required to obtain reliable results.

68 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY For exam le in cyclo ro yl cations, it can be seen that grou s situat ed on the same side of the ring as the leaving grou will move inwardly. The same rocess will im ose an ontoward disrotatory motion to the grou s situated in anti as follows. Fig. 5.11 METAL-CATALYSED ELECTROCYCLIC REACTIONS Transition metal catalysts can alter the normal thermal reactions of a olyene system in several ways. (a) First the catalysed reaction can give roducts which are not relat ed to any ericyclic rocess. (b) Catalysts can also give a roduct resulting from a formally disallowed therm al reaction: the catalysed ring o ening of strained cyclobutene rovides exam les. (c) Finally there are a few exam les of reformed transition metal com lexes whi ch follow the same course as the thermal reactions of the ligand, but with differen t rate. The disrotatory o ening of fused cyclobutenes (V) and (VI) is catalyse d by Ag + . The conversion of (V) to dibenzocyclochatetraene is an instantaneous re action at room tem erature in resence of Ag ions. Various suggestions have been ut forward to ex lain how a catalyst o erates. Some of these are as follows: (a) In resence of metal, a com letely different mechanism o erates, wh ich is a root of low energy involving one or more intermediates. This ha ens in some metal catalysed sigmatro ic and cycloaddition reactions. (b) The metal su lies filled and em ty orbitals of right symmetry to interact with the LUMO and HOMO of the diene. This rovides a good mechanism for the transf er of electron (V) Ag + (not isolated) dibenzocyclooctatetraene Ag + (VI) ELECTROCYCLI C REACTI ONS 69 density from the HOMO to the LUMO. By this a forbidden disrotatory r eaction becomes an allowed one. Fig. 5.12 Interaction of d orbitals with diene orbitals (c) Another theory given by van der Lugt and coworkers (Tetrahedron Le tt., 1970, 2281) says that the reaction remains forbidden in resence of metal. The activati on energy is lowered because the excited electronic configurations of the metal substrate co m lex are much

lower in energy than those of the substrate alone. PHOTOCHEMICAL ELECTROCYCLIC REACTIONS It has already been ointed out that if a thermal reaction is disrot atory, then the hotochemical reaction would be conrotating and vice-versa. This has been utilized i n synthetic organic chemistry, because by choosing the a ro riate conditions, the stereochemistry of the roduct can be selected. The LUMO of a conjugated linear olyene has a symmetry o osite to t hat of HOMO. Thus the excitation of an electron into the LUMO will reverse the direction of ring c losure or ring o ening com ared with that of ground state system. For 2,6, ..... (4n + 2) s ystems, hotochemically induced ring closure should be conrotatory and for 4, 8, ... 4n systems it should b e disrotatory. Table 5.3. Woodward-Hoffmann Rules for Electrocyclic Reactions No. of electrons Motion Thermal Photochemical 4n con d is Thermally allowed but hotochemically forbidden 4n + 2 dis con Thermally allowed but hotochemically forbidden The sim le icture given above agrees remarkably well with the observe d ex erimental facts; but it has raised certain roblems. For exam le, let us consider buta diene-cyclobutene ring closure d-orbitals of the catalyst HOMO LUMO 70 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY butadiene cyclobutene h ring clos re disrotatory B t the reverse conversion does not proceed smoothly. This is beca se the diene is a stronger absorber of light at ave lengths sed in the reaction. So it is th e diene hich is excited. The most instr ctive examples are those here the diene forms part of a ring so that a f sed cyclob tene is formed. H H (CH ) 2 n (CH ) 2 n h Since the reverse reaction is thermally disallo ed, the prod cts may b e nexpectedly stable. Th s cyclopentadiene can be partially converted photochemically into bic yclo [2,1,0] pentene, hich in spite of having a strained str ct re has a half life of abo t t o ho rs at room temperat re. h EtOH Ma y other examples of co trasti g behaviour have bee discovered. For example all-cis-

 

 

 

cyclodecape tae e (VII) photochemically equilibrate at low temperatures w ith tra s 9, 10 dihydro apthale e by a co rotatory six electro electrocyclic reactio b ut it is co verted thermally i to cis-9, 10 dihydro aphthale e by disrotatory closure. H H h con 2 1 10 9 8 7 6 5 4 3 dis VII INTRODUCTION Rearrangements in hich a sigma bonded gro p is transferred from one end of a conj gated system to the other are called sigma bond rearrangements. Some exam l es are: 1. 1, 5 hydrogen shift in a conjugated diene H 5 4 3 2 1 H 2. Co e rearrangement. This is a 3, 3 sigma-tro ic rearrangement. Here there is an interaction between a air of allyl radicals. 2 3 3 2 1 1 R R 2 3 3 2 1 1 R R 3. The migration of hydrogen through an allyl system is rearrangement of order 1, 3 because the univalent hydrogen move from C-1 to C-3. 3 2 1 H H 4. The ylide rearrangement is a sigmatro ic change of the order (3, 2 ) since the new bond

 

 

i two and one atom away from the original po ition. 2 S R 1 2 3 S R $ C H A P T E R Sigmatropic Re-arrangement 71 72 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY All the e rearrangement are uncataly ed thermal rearrangement and occu r intra-molecularly and include a large variety of tructural type . Woodward and Hoffmann have given the name of igmatropic rearrangement to uch reaction becau e they involve the movement of a igma bond which i adjacent to one or more system. Originally very few ty es of such rearrangements were known e.g., Co e s rearrangement, Claisen rearrangement and some 1, 5 hydrogen shift in some dienes, bu t now many others have been discovered. The common feature of such reactions is that they are con certed, uncatalysed and involve a bond migration through a cyclic transition state. Nomenclature There is a well defined formal system of nomenclature given by R.B. Woodward and R. Hoffmann (J.Amer.Chem.Soc, 87, 4389 (1965) and this is widely used. The numbering is written by the order [i, j] written in a bracket. The letter i and j denote the number of atoms across which the bond migrate . Let u take the ca e of cope-rearrangement of 1, 5 hexadiene. 2 3 3 2 1 1 3 3 2 1 1 In thi ca e the bond which ha migrated i to carbon atom 3 and 3 and the original bond wa between C-1 and C-1. Therefore, thi hift i repre ented a [3, 3]. So here i = 1 and j = 1. The numbering alway tart from the original termini of the bond. Each of the original termini i given the number 1.

In the (1, 3) hift of the inivalent hydrogen i = 1 and j = 3. 3 2 1 H H Thu the termini of the original bond are labelled fir t and thi i followed by numbering the chain ub equently. THE HOMO OF ALLYLIC RADICALS The homo of allylic radical with everal carbon atom can be depicte d a follow : 1 2 3 1 2 3 4 5 1 2 3 4 5 6 7 Let u ee the migration of a hydrogen atom and how the election r ule have been put forward to explain the formation of an imaginary tran ition tate in a igmat ropic reaction. SI GMATROPI C RE-ARRANGEMENTS 73 Hydrogen migration Let there be the migration of hydrogen (or deuterium atom or an alky l radical) in an alkene of the type. CH CH CH CH CH CH 3 2 3 M 1 2 3 [1, 3] Breaking bond CH CH CH CH CH CH 3 2 3 1 2 3 M New bond Thi i called (1, 3) hift becau e the original bond attached at c arbon 1 ha been broken and it ha attached it elf at the carbon 3. But in a petadiene of the type given below (1, 5) igmatropic rearrangement can take place. CH CH CH CH CH 2 2 M 3 4 5 [1, 5] M 2 1 CH CH CH CH CH 2 2 3 4 5 2 1 Thu in the rearrangement, in the tran ition tate, there will be an overlap between the orbital of the atom or free radical (R) of the group which i migrating and the orbital of an allylic free radical. So there will be an overlap between the HOMO of one compone nt and the HOMO of the other. It will be in the following tep : 1. There will be the homolytic cleavage of the bond giving two free radical . So one

electron remain with the original migrating group and the other i a ociated with the framework. It is necessary that the framework must have the correct symmetry to give a n interaction. 2. For a [1, 5] shift of hydrogen or deuterium the entadienyl system must accommodate the six electrons, four from already two bonds and one each obtained dur ing homolytic cleavage. 3. In entadienyl the Homo will be that which have 3 function. 4. Thus the 1s orbital of h drogen or an other species will simultan eousl interact with C-1 or C-5 of the all l s stem. 5. Bonding interaction will be b suprafacial mode. H CH 2 CH CH CH CH 2 H + CH 2 CH CH CH CH 2 CH 2 CH CH CH CH 2 H CH 2 CH CH CH CH 2 H [1,5] [1,3] How [1, 5] rearrangement will be favoured is clear from the following arrangemen t of p orbitals in pentadiene in which the HOMO of one component will react with the HOMO of the other suprafaciall . 3 will be the highest HOMO orbital in pentadiene and the reaction wil l be facilitated easil . 74 MECHAN SMS N ADVANCED ORGAN C CHEM STR (+) H drogen free radical 3 2 1 E Fig. 6.1 [1, 5] sigmatropic reaction

n some molecular orbitals the hase at a given carbon atom may be zero and hence the orbital in such a case is left unmarked. This view also ex lains satisfactorily why a [1, 3] sigmatro ic shift of a hydrogen in 1, 3 entadiene will not be ossible. In this case, a [1, 3] shift would have to be antarafacial and such a rearrangement would be structurally rohibited. (+) H in 1 S orbital Fig. 6.2 [1, 3] sigmatro ic migration of hydrogen So a [1, 5] or larger rearrangements su rafacial shift is symmetry al lowed but a [1, 3] shift would be structurally rohibited, because geometrically it will not be feasible. This would require the hydrogen to migrate to the o osite side of the allyl system and thi s is sterically difficult. Another advantage of this a roach is that it allows the ossibility of introducing substituent effects. Substituents which alter the energies of allyl orbitals relat ive to the S orbital will increase the chances of interaction either with 1 or with 3 . OTHER V EWS ABOUT S GMATROP C TRANS T ON STATE 1. Formation of a c clic transition state structure Let us take again a [l, 5] shift of a h drogen atom on a pentadien e, studied earlier. CH CH CH CH CH 2 2 [1, 5] CH CH CH CH CH 2 2 H H The bonding h drogen orbital overlaps simultaneousl with the p-orbitals on both the terminal carbon atoms and a c clic transition structure is formed in which the C-1 becomes a p-orbital and S GMATROP C RE-ARRANGEMENTS 75 C j becomes sp 3 h bridised bonding orbital. These terminal p orbitals also overlap the other p orbitals coming in between. Thus these are two stereochemicall different wa s in which the overlap can take place in the formation of a c clic structure. (a) Suprafacial overlap of h drogen orbital (b) Antarafacial overlap of h drogen orbital Fig. 6.3 n structure (a) the h drogen orbital overlaps suprafaciall with the terminal p orbitals of the

 system while in structure (b) the overla is antarafacially. Therefore the geometry of the two transition systems becomes different. While the su rafacial overla has a lane of symmetry, the antarafacial migration has two fold axis. The transition state in su rafacial attack is designated as of Huckel ty e in which no sign inversion of the cycle has taken lace. The other ty e of migration involves one sign inversion. This is called mobius ty e inversion. The Huckel ty e of inversion occurs when the total number of electrons is 2, 6, ... , (4n + 2). This is also called aromatic tr ansition state. In mobius ty e the artici ating electrons is 4, 8, ... i.e. 4n. The advantage of the method in this system is that it does not requ ire a knowledge of the symmetries of HOMO and LUMO of the reactants. So it is the number of electrons and not the number of atoms which determines the selection rule. Therefore, the selection rules for hydrogen migration in thermal sigmatro ic shifts can be summarized as follows; as given in the table: Table 6.1 Selection rules for sigmatro ic hydrogen migration No. of electrons Sigmatro ic migration Nature of attack Neutral com ound 4 (1, 3) Antarafacial 6 (1, 5) Su rafacial 4n (1, (4n1)) Antarafacial 4n + 2 (1, (4n + 1)) Su rafacial Cation Polyene 4 (1, 4) Antarafacial 6 (1, 6) Su rafacial 4n [1, 4n] Antarafacial Contd... 76 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY Anion Polyene 4 [1, 2] Antarafacial 6 (1, 4) Su rafacial 4n (1, (4n 2)) Antarafacial 2. Frontier orbital a roach The above selection rules can also be derived from frontier orbital t heory. For transitions involving 4n + 2 and 4n electron systems, the icture s will be as fallows. The First leads to Su rafacial overla while the second to antarafacial ov erla . LUMO HOMO HOMO LUMO Fig. 6.4 FMO a roach for 4n + 2 electrons showing su rafacial overlao . LUMO HOMO HOMO LUMO Fig. 6.5 FMO a roach for 4n electrons showing antarafacial overla . Some other exam les of hydrogen shifts The above selection rules, therefore, redict that [l, 5] hydrogen shifts in neu

tral olyenes would be thermally allowed and the reaction would be facile, but thermal [1 , 3] and [l, 7] shifts must go by an antarafacial rocess and they will be difficult to attain because of the geometric strain. This is also confirmed by many ex erimental observations. Thus concerted uncatal ysed [1, 3] hydrogen shifts have not been seen in the diene of the following ty e, [1, 5 ] shifts are well known. 1 H 5 4 3 2 H This also ex lains why in a thermal reaction a cyclo entadiene derivat ive shows only a singlet for the methyl grou in PMR s ectrum. This is also a [l, 5] thermal migration of hydrogen. The hydrogen mi grates so fast in reference to the methyl grou that at room tem erature one sees a singlet for the methyl grou . CH 3 CH 3 H 5 4 3 2 CH 3 H H CH 3 H H SI GMATROPI C RE-ARRANGEMENTS 77 In acyclic dienes [1, 5] su rafacial nature of hydrogen shift has als o been demonstrated. In acyclic 1, 3 diene with a chiral grou at one terminal gave two iso mers ex ected from a su rafacial [1, 5] shift but gave neither of isomers that would result from an antarafacial migration. In this reaction chirality is first transferred from one terminal to the other . Me D Et H Me [1, 5]H Me D Et Me H Me D Et

H Me [1, 5]H Me D Et Me H In both cyclic and acyclic dienes which can achieve the necessary geo metry the [1, 5] shift is commonly observed because the activation energy is lowest for the transition states involving minimal distortion. This is articularly so in cyclo entadienes and ind enes. The reference for [1, 5] over [1, 3] shifts is demonstrated by thermal rearrangement of 1-duterioindene. At 200C, deuterium became scrambled over all three non-benzenoid carbons. 2 3 4 1 5 H D H D [1, 5]D D [1, 5]D As a result of the movement of hydrogen to an adjacent carbon atom, the activation energy becomes lower by about 40 k Jmol -1 than in o en system. The substituents also considerably affect the activation of the rearran gement. In cyclohexa-1, 3-diene, the [l, 5] hydrogen migration takes lace on a non adjacent carbon atom so that activation energies become com arable with those of acyclic dienes. Thus the acti vation energy for rearrangement of 5 methyl-cyclohexa, 1, 3-diene is 143 kJ mol -1 . Me 6 5 4 3 2 1 Me [1, 5]H With seven membered rings, because the ring size becomes flexible, the activation energy becomes slightly less. Thus for 2 methyl cyclohe tadiene, the value is 124 k J mol -1 . Migrations in cyclo ro ane rings Since cyclo ro ane rings can often artici ate in lace of double bond s, ericyclic reactions

have been extended to them also. Atleast they show olefinelike characte r and in their ability to transmit conjugation. 78 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY In the Walash model each carbon atom has an s 2 orbital which is directed towards the centre of the ring and a orbital the lobes of which overla with the orbitals of the adjacent carbons. These lobes can overla with other lobes in a conjugated system . So the lane of the ring becomes arallel to the lane in which the rest of the system lies. Fig. 6.6 [1, 5] H shifts have been observed in such systems. Such reactions have been cal led homodienyl [1, 5] hydrogen shifts and selection rules for them have been a lied as in other dienyl shifts. 3 2 1 H [1, 5]H 2 1 3 4 5 H Homodienyl [1, 5] shift 4 5 Migrations of atoms or grou s other than hydrogen Sigmatro ic migrations are not confined to hydrogen atoms only. Grou s of nearly every ty e have been found to migrate. These include alkyl, aryl, vinyl, acyl or alkoxy carbonyl grou s. Organometallic functions, such as trialkylsilyl grou s R 3 Si also migrate readily. But in attem ting to ex lain such migrations, we have to take into c onsideration several factors. For exam le while considering the migration of an alkyl grou , we hav e to consider whether the configuration is retained or inverted in the roduct. There is also t he question of s eed of migration, why should they migrate at different rates and whether the relative r ates are likely to be the same in all cases. Answers to some of these roblems have started to come . SELECTION RULES We have seen that in the migration of a hydrogen atom in entadiene, the IS orbi tal of hydrogen overla s the orbitals in entadiene su rafacially in a [1, 5] shift . If in lace of hydrogen one has a carbon of an alkyl radical, then a carbon free radical will have is odd electron in a orbital which has two lobes of o osite sign. In such a condition during a thermal [1, 5] su rafacial rocess, symmetry will be conserved if the migrating carbon moves in a manner that the lobe which was originally attached to the system remains attached to it.

Thus the configuration of the migrating grou will be retained. But in a [1, 3] thermal su rafacial migration the rocess would involve o osite lobes. So if the migrating carbon w as originally bonded via its ositive lobe it must now use its negative lobe to form the new C-C bond. This will mean an inversion of configuration in the migrating grou . So in a [1, 5] su rafacial thermal rearrangement, there is retention of configuration but in a [1, 3] su rafacial rocess, there is inversion of configuration. SI GMATROPI C RE-ARRANGEMENTS 79 A thermal su rafacial [1, 5] migration with retention of configuration (a) A thermal su rafacial [1, 3] migration with inversion of configuration (b) Fig. 6.7 In general four ty es of transition states can be envisaged for sigma tro ic migrations of the order (i, j), two in which the migrating grou moves su rafacially (a ) and (b) and two in which it means antarafacially (c) and (d) Antarafacial migration with retention of configuration (c) Antarafacial migration with inversion of configuration (d) Fig. 6.8 These selection rules based on their classification as aromatic or ant iaronatic transition state are given in the following table. Table 6.2 Selection rules for sigmatro ic grou migration No. of electrons Shift Thermally allowed migrations Neutral com ound 4 (1, 3) (Su rafacial with inversion) (Antarafacial with retention) 6 (1, 5) (Su rafacial with ratention) (Antarafacial with inversion) 4n (1, (4nl)) (Su rafacial with inversion) (Antarafacial with retention) 4n + 2 (1, 4n + 1) (Su rafacial with retention) (Antarafacial with inversion) Cation 4 (1, 4) Same as in neutral 6. (1, 6) Same as in neutral Anaion 4 (1, 2) Same as in neutral 6 (1, 4) Same as in neutral 80 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY The redictions of the orbital rules are straightforward when a lied to migrations in which transition states involve relatively little strain. Difficulty arises wh en the allowed states are difficult to achieve.

Shifts in neutral s ecies [1, 3] shifts These are not common. An exam le of a su rafacial shift with inversio n of configuration is the thermal rearrangements of bicyclo-hexene, studied by W.R. Roth and A. Friedrich (Tetrahedron Letters 1969, 2607). H CH 3 120C CH 3 CH 3 H CH 3 bicyclo (2.1.1) hexene bicyclo (3.1.0) hexene H The substituted methylene bridge migrates in such a way that the meth yl grou is almost exclusively exo in the roduct. Another exam le of su rafacial migration with inversion is the rearrangement of bicyclo octenone to give again a ketone and re orted by J.A. Berson (1972). H CH 3 CH 3 less stable ketone CH 3 H O O The ketone which is formed as a result of [1, 3] rearrangement is due to the int eraction between the methyl grou and a hydrogen atom in a bridging methylene grou . The migration with inversion is articularly favoured by overla with the carbonyl orbital. (1, 5) shifts We have already seen that in [l, 5] alkyl shifts with symmetry allow ed will lead to retention of configuration. Another such exam le with retention of configuration in a [1, 5] alkyl shift is the rearrangement of s irodienes. Thus the conversion of cis-6, 9 dimethyls iro [4, 4] nona-1, 3 diene to dimethyl bicyclo nonadiene is an exam le. The first roduct is a su rafacial [1, 5] carbo n shift with retention of configuration at the migrating carbon. This is then followed by a [l, 5] h ydrogen shift which becomes the major roduct. SI GMATROPI C RE-ARRANGEMENTS 81 CH 3 1

2 3 4 5 CH 3 200C [1, 5] C-shift [1, 5] H-shift CH 3 CH 3 cis cis CH 3 CH 3 cis Generally [1, 5] alkyl shifts are followed by migration of hydrogen o r other grou s, the hydrogen migrates much more readily than an alkyl grou . Now results have been obtained which show that the relative ease of migration differs with different grou s . The grou s which migrate readily are those in which the carbon atom is s 2 hybidised i.e., acyl, aryl and vinyl and so on. In the indene system the order in which the grou s migrate is CHO > CO Me > H > CH = CH 2 > CO 2 Me > CN > Me. It is likely that similar order is followed in other ring systems. The other grou s which undergo [1, 5] shifts readily include Me 3 Sn, Me 3 Si and NO 2 . [1, 5] shifts occur most readily in five membered rings, both carbocy clic and heterocyclic, because these arrangements require movement of grou s to an adjacent a tom in the ring. Migrations in cyclohexadienes require about 4060 KJ mol1 more activation energy then in cyclo enadienes and this makes migration of alkyl and similar grou s difficult in six mem bered rings. Activation energy is also influenced on whether aramatic character is created or destroy ed by migration. [1, 7] and higher order shifts This has been brought out by C.W. S angler in chem. Reviews 76, 187 (1976). Exam les of shifts of higher order than [1, 5] are relatively rare. But an exam le of a thermal su rafacial rocess involving [1, 7 shift and inversion of the migrat

ing grou is afforded by bicyclononatrienes. 8 7 6 5 4 3 2 1 CH 3 CN [1, 7] CH 3 CN CH 3 Shifts in charged s ecies Many im ortant molecular rearrangements show alkyl or aryl shifts in c arbocations and other electron deficient s ecies. Thus in this grou we have exam les of Wa gner-Meerwein rearrangement, inacol- inacolone rearrangement and ex ansion and ring contraction of s mall rings. They roceed by a carbocation rearrangement. The electron deficient centre need not be a carbenium ion. The only requirement is that it has a vacant orbital. The [l, 2] shifts in singlet carbenes, nitrenes and nitrenium ions are of the same general ty e. Molecular orbital calculations have shown that in all these electron-de ficient centres su rafacial [1, 2] shift occurs with retention of configuration through a two e lectron Huekel ty e transition state: 82 MECHANI SMS I N ADVANCED ORGANI C CHEMI STRY Carbenium ion C R C R 2 Carbene C R C R C C R 2 R C C R R Nitrene C R N C NR Nitrenium ion C R NR C N R R [1, 2] shifts to electron deficient centres In all these reactions the migrating grou moves with retention of configuration . It also ex lains

why concerted [1, 2] shifts to electron rich centres will be unfavour able or why 1, 2 shifts of hydrogen or alkyl grou s in radicals or anions are rare. [1, 4] shifts in cationic olyenes are allowed either by antarafacial rocess when the configuration of the migrating grou will be maintained or as su rafacial wh en inversion in the migrating grou will occur. R R Fig. 6.7 A lication of FMO method According to Huckels rule a monocyclic laner conjugated system having (4n + 2) electrons is aromatic and hence stable in the ground state. A system having 4n electrons is unstable and will be antiaromatic. But these rules are reversed by the resence of a node in the arran gement of atomic orbitals. Thus a system having (4n + 2) electrons and a node would be antiarom atic while that with 4n electrons and a node would be aromatic and hence stable in the ground state. A lying these rules in ericyclic reactions it has been shown and a generalization given that thermal reactions occur via aromatic transition states while hotochemic al reactions roceed via antiaromatic transition state. A cyclic transition state is considered to be aromatic or isoconjugate with the corres onding aromatic system if the member of conjugated ato ms and that of the SI GMATROPI C RE-ARRANGEMENTS 83 electrons involved ha en to be the same as in the corres onding aromatic system . On the other hand a cyclic transition state will be regarded to be antiaromatic or isoc onjugate with the corres onding antiaromatic system if the member of conjugated atoms and that of the electrons involved ha en to be the same as in the corres onding antiaromatic system. Let us a ly the rules in some cases: R C CH CH 2 2 [1, 3] shift su rafacial H R C CH CH 2 2 H 0 node. Total 4 electrons (3 from and one from H) hence antiaromatic and allowed hv R C CH CH 2 2 [1, 3] shift antarafacial H R C CH CH 2 3 H

0 node. Total 4 electrons hence aromatic allowed H 0 no e. Total 6 electrons (5 from orbitals an 1 from H) hence aromatic allowe p R C (CH CH)CH CH 2 2 [1, 5] shift suprafacial H R C CH CH CH 2 CH 3 Summary of all these is given in the following table: Table 6.3 Selection rules for sigmatropic change by FMO metho No. of electrons No. of no es Aromaticity Shift mo e 4n 0 or even Antiaromatic Supra, hV 4n O Aromatic Antara, 4n + 2 0 or even Aromatic Supra, 4n + 2 O Antiaronatic Antara, hV These selection rules have been foun to be remarkably successful in thermolytic reactions (symmetry allowe ones) photolytic reactions have been foun to be mor e complex. [3, 3] SIGMATROPIC CHANGES : THE COPE AN CLAISEN REARRANGEMENTS (3, 3) sigmatropic changes are an important group of thermal rearrange ments which involve a six membere cyclic transition state. The transition state can be cons i ere as two interacting allyl systems. 84 MECHANI SMS I N A VANCE ORGANI C CHEMI STRY 2 1 1 3 3 2 The principles of orbital symmetry conservation establish that concerte suprafacial [3, 3]sigmatropic arrangements are allowe processes. Base on these principles an th e results of numerous experiments their stereochemistry is highly pre ictable. H C 2 CH CH 2 H C 2 CH 2 CH Various geometries are possible for the transition state an they can be classifie on whether each of the allyl systems interacts with lobes of the other system o n the same si e (suprafacially) or on opposite si es (antarafacially). Three transition states have bee n given. All have been classe

on Huckels system, on the basis of aromatic transition state approach a n so all are thermally allowe . The following picture gives the allowe transition state for thermal [3, 3] shifts. (a) (b) (c) (a) Represents suprafacial, suprafacial chair form. (b) Represents suprafacial, suprafacial boat form. (c) Represents antarafacial, antarafacial twiste form. Of all these (c) is much less likely to be forme because it involves twisting o f the allyl system while (a) an (b) are strain free. Again of these (a) is more favou re because the six p lobes are in a quasi planar arrangement. Moreover the molecular orbital calculati ons ma e by ewar have shown that the central p lobes of the two allyl systems in the boat form appear to have a slight estabilizing effect an this has also been confirme by Woo war an Hoffmann with the ai of correlation iagrams. But both the chair an boat forms have been fou n in practice. Therefore, the [3, 3] sigmatropic rearrangement has become a useful to ol in synthetic organic chemistry. The following are some examples which inclu e Cope an Clai sen rearrangement. SI GMATROPI C RE-ARRANGEMENTS 85 The Cope Rearrangement The 1, 5 ienes isomerise on heating up to 300. The reaction is norm ally reversible an gives an equilibrium mixture of starting material an the pro uct. The tempe rature nee e to bring about epen s on the substituents. If the substituent R is a conjugate grou p (i.e., consisting of ouble bon s) then they lower the energy of the transition state an rearran gement goes at 165185C. Some examples are: 1. Cope rearrangement 2. Oxy. Cope rearrangement HO HO O 3. Anionic oxy. Cope rearrangement, O O O H + 4. 150 1 hr CH 2 CH 2 CH 2 2 CH 100% 5. OH CH CH 2 CH CH 2 320

O 90% 6. KH, THF 98% OH reflux 18 hrs O H H Cope rearrangements are generally reversible processes an there are no changes in the number of single an ouble bon s as a result of the reaction, so roughly the total bon energy is unchange . The position of the final equilibrium is governe by the relative stability of t he starting materials an the pro ucts. 86 MECHANI SMS I N A VANCE ORGANI C CHEMI STRY When the ring strain is relieve , Cope rearrangements occur at much l ower temperatures an there is complete conversion to ring opene pro ucts. A common example of Cope rearrangement involving [3, 3] sigmatropic re arrangement in a 1, 5 iene is the pyrolysis of meso 3, 4 imethyl hexa-1, 5 iene giving exclusively cis, trans isomer of 2, 6 octa iene. The process involves a six electron transition sta te which has a chair like configuration an substituents occupy equatorial sites. H Z CH 3 R CH 3 H 13% H CH 3 S CH 3 H E cis trans 87% or CH 3 CH 3 H CH 3 CH 3 H CH 3 CH

3 H H meso-3, 4 imethyl 1, 5 hexa iene Chair form of 6-membere cyclic transition ZE 2, 6-octa iene us-trans major pro uct The preferre ouble bon geometry in the pro uct usually has the mor e bulky substituent trans to the main carbon chain since this is the sterochemistry which arise s from an equatorial-like orientation in the transition state. In some cyclic system the chair transition is sterically impossible to attain, a n the Cope reaction still goes but by a boat transition state. a boat like geometry Thus a Cope rearrangement procee ing through a boat-like transition sta te is the rearrangement of cis 1, 2 ivinyl cyclo-propane. H H < 0 The structure of the molecule is such that it oes not allow the at tainment of a chair shape transition state. The above pro uct Similarly the conversion of cis 1, 2 ivinylcyclobutane also involves a boat transition state. SI GMATROPI C RE-ARRANGEMENTS 87 120 H H In both the above examples the conversion takes place easily because of the release of strain in small rings. The rearrangement of ivinyl cyclopropane may also be regar e as an electrocyclic ring closure in which the cyclopropane ring takes the place of a ouble b on . But reactions of this type have been regar e as Cope rearrangement. Therefore the course of most Cope rearrangements can thus be regar e as a concerte [3, 3] shift with the chair transiti on state being more favourable than the boat. There are also instances where a system un ergoes Cope rearrangement t hrough ifferent possibilities. This is affor e by the examples of hexa iene. The alte rnatives are of two types. (a) issociation into a pair of allylic ra icals or into a cation-anio n pairs followe by recombination or (b) Formation of a new bond before the fir t ha tarted to cleave giving a diradical or a

zwitter ion intermediate. Stepwi e alternative for the Cope rearrangement A diradical intermediate appear to be formed in the rearrangement of 2, 5 diphenyl-1, 5hexadiene