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W A B A W B
terminus.
These rearrangements can be of following types, i.Nucleophilic or Aninotropic : in which migrating group migrates with its electron pair. ii.Electrophilic or cationotropic : in which migrating group migrates without its electron pair. iii.Free radical : in which migrating group migrates with only one electron.
ii. Intermolecular : In these migrating group is completely detached from migration origin and migration of group can take place to different molecule.
A W A B+ U A C A B U+ A C W B W+ A C U+
given below.
R C C C
1.
2.
C R
O R
3.
CR
4.
x a x b y a x b y a
x b + y
5.
+ y
Reactions 1 to 3 show first reason for 1,2-rearrangement to take place viz. formation of valence electron sextet at one of the carbon atoms of substrate i.e. either carbocation or carbenium ion. Thermodynamic driving force for potential 1,2-rearrangement will be significant if
newly generated carbocation is stabilized electronically by its substituents than old carbocation or angle strain is reduced due to rearrangement in cyclic carbocation or newly generated carbocation is captured in subsequent irreversible reaction. Reaction 4 & 5 show second cause for occurrence of rearrangement. In these reactions atom b is bonded to good leaving group. Heterolysis of such a bond would give a carbocation. Departure of leaving group is then assisted by neighboring group. This sometimes gives a positively charged three membered ring as in reaction 5. Rearrangement in such reactions is possible only if group x is present at new position in product than in reactant.
Broadly these reactions consists of three steps ; a)First step is generation of electron deficient centre in molecule. As the migrating group migrates with electron pair, the migration terminus must have an incomplete octet. This can be obtained in two ways ,
i.Through carbocation : Carbocations can be formed in various ways. The most common being dehydration of alcohol. This step is similar to that of SN1 or E1 reaction.
R C C OH H R C C OH2 -H2O R C C
Me C Me Me C C H CH2
Me C Me CH2Me
Me
b)Migrating group migrates to the previously formed electron deficient centre with its electron pair creating new electron deficient centre. c)In third step, newly formed electron deficient centre acquires octet either by accepting a nucleophile or excluding proton. It is observed in many cases that either two or all three steps take place simultaneously. As seen in many cases SN1 type of first step is very common followed by rearrangement to give more stable carbocation. It is proved by fact that rate of reaction increases with
ionizing power of solvent and it is unaffected by concentration of base. It has been shown that rate of migration increases with degree of electron deficiency at migration terminus.
Most of rearrangements are intramolecular. It can be shown by cross over experiments. But, one more evidence for this fact is that, if migrating group is chiral, its configuration is retained in the product. In molecules where stearic nature of migration origin and terminus can be investigated, mixed results are found i.e. either inversion or racemisation takes place.
Ph Ph C OH H C NH2 Me HNO2 Ph O C Ph C H Me
This shows the concertedness of reaction. So, if, racemisation is found at migration terminus, then it is probable that first step takes place before second step, as in SN1 reaction.
R A B X R A B A R B product
And, if inversion occurs at migration terminus, then two steps might be concerted, as in SN2.
R R A B X A B A
R B product
In this case, neighboring group assists departure of leaving group, as in neighboring group nucleophilic substitution reaction. This
In many reactions like Hofmann, Curtis, there is no question which group migrates but in certain cases, like Beckman reaction, there are more than one choices. But, of them, which migrates depends upon geometry of molecule. In Beckman reaction, only group anti to hydroxyl migrates, whereas in case of Wagner-Meerwein and Pinnacol rearrangement, there are many choices, as substrate contains several groups, that have equal probability of migration. Such reactions are used for direct study of relative migratory aptitude. In Pinacol rearrangement, there is one more question which hydroxyl group leaves. As it will create electron deficient centre for migration to take place. The hydroxyl group lost will be that which generates more
stable carbocation.
Ph H Ph C C H Ph
Ph H C C OH H Ph
Ph C H C O H
OH OH
Ph Ph C OH
H C H
In this example, hydroxyl group is lost from carbon bearing two phenyl
reaction. In order to study migratory aptitude in such reactions, substrate should have structure R1RC(OH)C(OH)RR1 . In this case whichever hydroxyl group leaves, it will give same carbocation and hence comparison on migratory tendencies of R and R1 can be done. Many factors are responsible in deciding migratory aptitude. One of them is conformational effect. Another factor is, relative ability of group that remains at migration origin, to stabilize positive charge. Sometimes, if group that stabilizes positive charge is present on migration origin, then group which actually is not having good migratory ability, migrates. Along with this, migratory aptitude is
Me Ph C Me * C H CH2 H
Ph
C Me +
* C Me * C Me
Me
Me
C Me
Ph
Only migration of phenyl group in first case is due to the fact that,
phenyl group assists in departure of tosyl group. Whereas, no such possibility for second reaction.
All these factors costs no particular answer to migrating aptitude. Though, in most cases, aryl migrates preferentially to alkyl group, but it is not always true. Migratory aptitude of hydrogen is unpredictable. Hence, mixtures are always obtained. However, it is seen that in migration of aryl group, those having electron donating substituents at meta or para position migrates Preferentially, over those containing substituents on ortho position. While, aryl group containing electron withdrawing groups show less migratory aptitude.
A. Wagner-Meerwein rearrangement : When alcohol containing more than two alkyl or aryl group on carbon are treated with acid, the product formed is generally a rearranged product, rather than simple substitution or elimination product. This reaction is called Wagner-Meerwein rearrangement. Newly generated carbocation is stabilized generally by loss of proton to give olefin and less often by nucleophilic substitution or loss of some other positive group.
R R1 R2 H OH R3 H R2 R3 R1 R
OH
Isoborneol
Camphene
H3C C H3C C
H CH3
H OH Camphenilol
Santene
rearrangement in triterpene, 3- -friedelanol. This compound on treating with acid, 13(8)-oleanene is formed by seven successive 1,2 shifts.
20 19 12 11 18 13 14 8 7 6 15 21 12 22 17 1 16 9 10 5 3 4 6 8 2 15 11 13 14 16 17 19 18 22 20 21
H
1 2 3 10 5 4 9
H
7
HO
H 13(18)-oleanene
3-friedelanol
then hydride shift from 4 to 3; methyl shift from 5 to 4; hydride shift from 10 to 5; methyl shift from 9 to 10; hydride shift from 8 to 9; methyl shift from 14 to 8 and hydride shift from 13 to 14 takes place, generating carbocation at C-13, which is stabilized by loss of proton
AlCl3
group.
Tricyclic molecules containing more than 10 carbon atoms give alkyl substituted adamantane.
AlCl3
AlCl3
AlCl3 tBuBr
These reactions take place because of great thermodynamic stability of adamantane, diamentane and similar diamond like molecules. Some examples of Wagner-Meerwein rearrangement are given below.
O O OEt HO TFA, DCM 72h O O OEt
76%
OH
EtOOC
Ph
COOMe OH Br HN O N N COOMe Br HN O N N O 86% O N N H OMe OMe OMe O N O N H OMe OMe OMe CH3SO3H 1,2-DCE 500C
B.Pinacol rearrangement :
OH Pinacol
The migrating group can be alkyl, aryl, hydrogen or ethoxycarbonyl etc. In case of symmetrical diols which hydroxyl is protonated and which group migrates does not have much significance, but in case of unsymmetrical diols it is important. Generally. Hydroxyl group is protonated which gives more stable carbocation.
O OH OH Ph Ph H2SO4 Ph Ph
Migration of alkyl group from initially formed carbocation takes place because, carbocation containing hydroxyl group are more stable than that of 30 carbocation. Also, these carbocation can readily lose proton to give corresponding carbonyl compound.
O OH OH H
OH OH H Me2C C Ph COOEt
Ph O Me2C C COOEt
O Ph Ph Ph Ph OH OH TsOH, CDCl3 O + Ph Ph
O Ph
N SO2Ph
N SO2Ph 90%
Synthetically useful Pinacol rearrangement reaction is syntheses of bridged bicyclic compound from a diol in following way.
OH OH H O LiAlH4 OH H
OH2 -H2O
-H
Similar type of reaction is also shown by compounds containing different group than hydroxyl on adjacent carbon of that containing hydroxyl group on it. This reaction is known as Semipinacol rearrangement and involves 1,2 shift of H or alkyl from oxygenated carbon atom to neighboring C atom i.e. carbocation to carboxonium ion rearrangement.
BF3.Et2O O
-BF3 O BF3 H
H H
HO
HO O O
-H
O O O
AgNO3 I OH O
Similarly, when positive charge is present on carbon to alicyclic ring, then migration of alkyl group can give ring larger than original one.
CH2
This newly formed carbocation can then be stabilized by either elimination or substitution.
This reaction represents special case of Wagner-Meerwein rearrangement. Generally, a mixture of rearranged and non rearranged products is formed.
NH2 HNO2 OH + CH2OH HNO2 CH2NH2
OH + OH
Mechanism is as follows.
H N HO O H2O H O N O -HNO2 HN N O N O -H2O O N O N
+O NH2
O N N
NH2 HNO2
OH +
OH
+ HO
HO
NH2
It is found that, expansion reaction give good yields in smaller rings where expansion gives relief from angle strain and contraction reaction give otherwise good yields except for cyclopentyl cation. An example of such ring expansion is; treatment of 16-methylpentaspiro[2.0.2.0.2.0.2.0.2.1]hexadecan-16-ol with p-toluenesulfonic acid in acetone-water to give 2-methylhexacyclo[12.2.0.02,5.05,8.08,11.011,14]hexadecan-1-ol.
H3C OH H CH3 OH
OH H H 40%H2SO4
H OH
Reaction of certain amino alcohols give analogous reaction to semipinacol rearrangement. This reaction is known as Tiffeneau-Demjanov rearrangement.
CH2NH2 HNO2 OH
OH
NH2
60%
Certain aldehyde or ketone are converted in this way to other ketones. But, conversion of ketone to aldehyde is not seen in any case. Mechanism of the reaction goes through protonation of carbonyl oxygen. Two pathways are possible. One in which migration of two groups is in opposite direction and other in which migration is in same direction.
Actual pathway is not certain. But, it is found that in certain cases only one operates while in others both operate at same time. This can be demonstrated by labeling carbonyl carbon. In first case, labeled
OH C R4
Pathway 2:
R1 R2 C R3 R3 R2 C OH C R4 R1 -H R2 C O O C R4 H R2 R1 C R3 C OH R3 C R4 R1 R4 R2 R3 C O H R1 C R4
In case of hydroxy aldehyde or ketone process may stop after one migration. This is called ketol rearrangement.
R1 R2 C OH
O C R3 H R3
R1 C OH
O C R2
80%
E.Dienone-phenol rearrangement : Cyclohexadienone containing two alkyl groups at position two or four,
Mechanism is as follows;
O H OH OH
R H R R
R OH
R R
OH H H2SO4 H O H HO 1-methyloestradiol H H
OH
F.Wolff rearrangement : Wolff rearrangement is rearrangement reaction, in which a diazo ketone is converted into ketene.
R' R O N2 -N2 R R O R' R' C C O
The rearrangement reaction takes place in presence of light, heat or transition metal catalyst such as Ag2O.
O N2 h / MeOH N O 90%
COOMe O N
47%
G.Homologation of aldehyde or ketone : Aldehyde or ketone can be converted to their higher analogs on treatment with diazomethane.
O CH2N2 R O CH2N2 R H R R' R O O R'
Though, it appears to be an insertion reaction, it is purely rearrangement reaction. Carbene is not formed in the reaction.
Mechanism is as follows,
O R C R' + H2C N N R CH2 C O CH2 R C O R' R O C H2 C R' R' N N -N2
In case of aldehyde, hydrogen migrates preferentially which is evident from good yields of methyl ketone.
An interesting example of this reaction is, preparation of bicyclic ring compound using alicyclic compound containing diazo group in side chain.
CHN2
rearrangement is seen.
Cl H3C CH CH2 ONs CF3COOH H3C OOCCF3 CH CH2 Cl
ONs :- RO2SO
NO2
I.Migration of boron to electron deficient carbon: On heating non terminal boron at about 100-2000C, boron moves towards end of chain.
C B
C B
C B
C B
C C
C C
C B
CH3 H3C C CH
CH3 CH CH2 B
CH3 B
If boron is present on ring, then it moves across ring and if an alkyl side chain is present on ring, it ends on terminal carbon of side chain.
1500 diglyme
B B RCH CH2
B B H2O2 /OH
OH
BH3, THF
H BH2
1100C
H H
H2O2 / OH CH2BH2
H H CH2OH
J.Neber rearrangement:
Neber rearrangement is a reaction in which a ketoxime tosylate is converted to -amino ketone upon treatment with base.
NH2 R' R NOTs base R O R'
R' R N OTs
R'
H 2O
Base first abstracts proton to ketoxime group. This carbanion then displace tosylate group in nucleophilic displacement and forms azirine which on hydrolysis gives -aminoketone. The reaction is sometimes assisted by Beckmann rearrangement though it generally occurs in acidic conditions.
F NHBz Ph NOTs 1. 50% Toluene / KOH 2. BzCl, Py / DCM, 6N HCl Ph O F
NO2
O2N
CH2
O2N
CH NH2
C O
Cl
CH2
C NOTs
Cl
H2O , NaHCO3
NH2 Cl CH C O Cl
Ph
Ph
Ph
Ph
H2N N OTs O
A.Hofmann rearrangement:
When an unsubstituted amide is treated with sodium hypobromite, it gives corresponding primary amine with one carbon less. This reaction is known as Hofmann rearrangement.
O R C NH2 + NaOBr R N C O hydrolysis RNH2 + CO2
In the first step, base removes proton from amide. This conjugate base of amide then reacts with bromine to give N-bromoamide.
NH2
NH2
NH2
O OCH2Ph
R O C9H19 Bn R :- PhMe2Si O
1. Pb(OAc)4, BnOH, DMF 1000, 15h NH2 2. TsOH, C9H19 acetone, H2O, reflux, 2.5h
R H N Bn 75% O OB n
OPMP OR O O HO H2N O
OMe O O
OPMP OR
OMe
NH O 93%
When optically active -phenylpropionamide undergoes Hofmann degradation, -phenylethylamine of same configuration and optical purity is obtained i.e. rearrangement proceeds with retention of
configuration.
Ph H C CONH2 NaOH H Ph C NH2
B.Curtius rearrangement: In Curtius rearrangement, acyl azide are pyrolysed into isocynate which can be hydrolyzed to corresponding amines.
O R R N3 N C O
However, there is no evidence of existence of free nitrene. These two steps may be concerted.
O R R N N N N C O + N2
R may be alkyl, aryl or hydrogen. In case of tert.alkyl azides, there is evidence of existence of nitrene. Cycloalkyl azides give ring expansion.
R R H N3 80% 20% N + NR
If the reaction is carried out in di-tert.butyldicarbonate, product will be Boc protected amine.
O EtOOC OH Boc2O, NaN3 Bu4NBr Zn(OTf)2 THF, 500C EtOOC NHBoc
Ph
Ph
HOOC HOOC
COOH
H2N H2N
NH2
cis,cis-cyclohexan-1,3,5tricarboxylic acid
cis,cis-1,3,5-triaminocyclohexane (82%)
[ Bioorganic and Medicinal Chem. Lett., 9 April 1996, Vol.6, Issue 7, 807 ]
OH O O N3 N3 O tBuOH reflux NH O
NHBoc
O PMBO HO O H O H O OTBS Hunigs base iBuOCOCl 00C, NaN3 H2O, toluene 15 min, TMSCH2CH2OH 3h,
O O N H
OPMB O
TMS
HOOC O
C.Lossen rearrangement: O-acyl derivatives of hydroxamic acids on heating with base give isocynate, this reaction is known as Lossen rearrangement. Isocynate can be further hydrolyzed to corresponding amines.
O O R N H O R OH R N C O H2O RNH2
CNO H H2O
NH2 H
R1 : Et , R2 : (CH2) 3NMe2
CONHOH OH OH
Na2CO3 PhOSO2Cl O OH
NH O
D.Schmidt rearrangement :
Reaction of carboxylic acid or aldehyde or ketone with hydrazoic acid in presence of mineral or Lewis acid to give corresponding primary amine or amide respectively is known as Schmidt rearrangement.
RCOOH + HN3 H R N C O H2O RNH2
O R R
1
O + HN3 H R N H R1
Mechanism is similar to that of Curtius rearrangement, except that protonated azide undergo rearrangement.
O R O H R N N N H 2O R N H N N OH H -H2O R O O H N N N R N3 O
N H
RNH2 + CO2
OH HN3 R N
1
H R
1
N C OH
N R1
-H2O
N R
-N2
R1
H2O
O R1 C OH2 N R -H R1 C OH N R tautomerism R1 N H R
In reaction with ketone, ketone is activated by protonation for nucleophilic addition of azide group to it.
In case of alkyl aryl ketone, aryl group migrates preferentially except for bulky alkyl group. Intramolecular Schmidt reaction can be used for preparation of
bicyclic lactums.
O O N
MeAlCl2 / DCM
H N3
Ph 96%
N3 MeOOC O
81%
N3
Reaction of tert. alcohol and olefins with hydrazoic acid in acidic condition to give substituted imines is often termed as Schmidt rearrangement.
OH HN3 / H2SO4 R R R R R N R
R HN3 / H2SO4
OH H R R R R R
OH2 R
-H2O
HN3 R R
N R
N R
-N2
R C R N R
R H
RH
R HN3
RH
R H N N N -N2
R RH
R R -H
R R R
R R
R H
O H3C
O OEt CH3
ADA O N ADA
ADA
ADA :
E.Beckmann rearrangement : Oximes on treatment with Lewis acid or protic acid rearrange to give substituted amides. This reaction is called as Beckmann
rearrangement.
R N OH R' PCl3 R' N H O R
Generally group anti to hydroxyl migrates. However this is no hard and fast rule. R and R can be alkyl, aryl or hydrogen. Hydrogen does not migrate under conditions of reaction but it migrates when reaction is carried out with nickel acetate under neutral conditions.
enlargement.
NOH NH O
Mechanism of reaction usually goes through alkyl migration with expulsion of hydroxyl group followed by reaction similar to Schmidt rearrangement.
OH N R R1 R1 H2O R1 C OH N R R1 C C N N R H R N
OH2
-H2O
R1
R1
R1 R
C OH2
R -H
O R
1
R N H
Other reagents convert hydroxyl to an ester leaving group. Course of mechanism is supported by detection of nitrillium ion by NMR and UV spectroscopy.
HO N
O HN
N N OH
N O N
Cl
N OH
N Cl N
I H N O
F.Stieglitz rearrangement :
Stieglitz rearrangement is a general term applied for rearrangement reaction of trityl-N-haloamines and hydroxylamines to trityl imine.
Ar3C Ar 3C NHOH NHX PCl5 base Ar2C Ar2C NAr NAr
Mechanism is as follows,
Ph NH Ph Ph Ph Ph NPh Cl + Cl P Cl Cl Cl Ph NH Ph Ph Cl O Cl P Cl Cl
OH
Ar3CNH2
Ar2C
NAr
Pb(OAc)4
Ph2C
N +
OCH3 ~98%
PhN
C Ph
OCH3 ~2%
When methanolic solution of N-chloroisoquinudine was refluxed for 2h with AgNO3, AgCl was precipitated and 60% of 2-methoxy-1-azabicyclo[3.2.1]octane was obtained.
AgNO3 MeOH N Cl
N MeO
A.Baeyer-Villiger rearrangement : In Baeyer-Villiger rearrangement, ketone on treatment with peracid gives ester by oxyinsertion. Reaction is catalyzed by presence of acid catalyst.
R O PhCO3H R1 R OR1 O
Mechanism is as follows,
O H R R1 R R1 O O -H RO R1 O O OH OH R2CO3H R C R1 R2
RO
C OH
First step is addition of peroxy acid to carbonyl forming tetrahedral intermediate. In next step concerted migration of migrating group and loss of carboxylic acid to give product. The mechanism is supported by fact that oxidation of Ph2C18O yields
only PhC18OOPh i.e. there is no scrambling of 18O label in product ester. Loss of carboxylates and migration of R is concerted is by fact that reaction is speeded up by electron withdrawing substituent in leaving group and electron donating substituent in migrating group. Carboxylates are as such not very good leaving group. But, O-O bond is very weak and monovalent O can not carry positive charge. So that once peracid is added loss of carboxylate is concerted with rearrangement driven. Synthetic usefulness is syntheses of L-Dopa drug used to treat Parkinson's disease.
O COOH NH2 HO L-tyrosine O O HO COOH H3O NH2 HO L-Dopa NH2 AlCl 3, AcCl HO COOH H2O2, NaOH NH2
HO
COOH
If the migrating group is chiral then its stereochemistry is retained. By looking at orbitals involved in reaction, this can be explained. The sp3 orbital of migrating carbon just slips from one orbital to next with minimum amount of structural reorganization.
Migratory aptitude in unsymmetrical ketones is as, H>30>cyclohexyl>20>benzyl>aryl>10>methyl. In case of aryl group, migrating ability is increased by electron donating groups present on ring.
F Ph O mCPBA / CHCl3 Ph NaHCO 3 Ph O 71% F O Ph + Ph F O 29% O Ph
Migration is favored when migrating group is antiperiplanar to the O-O bond of leaving group. This is known as primary stereoelectronic
In case of unsaturated ketones epoxidation is likely a competitive reaction. But, Baeyer-Villiger rearrangement is favored because ring
O H2O2, AcOH
H O O H
Chemoselective oxidation of -lactum aldehyde has been achieved with mCPBA in DCM where only formates are formed in better yields.
H C H CHO O mCPBA, DCM rt, 20h O H C H OCHO
OMe
OMe 70%
Aldehyde can be oxidized to carboxylic acid due to preferential migration of hydride. Group that can stabilize positive charge on oxygen migrates.
O H Br Cl O OH Br Cl
mCPBA, DCM
[ JOC,1962, 27, 24 ]
O cyclohexanone oxygenase O O
Cl Cl O BnO OBn O
HO
O HO mCPBA, DCM
O O
HO H O
HO H
Caro's reagent
O O
O cyclopentanone monooxygenase O
98% ee
O O H
N Cbz
H Cl
H Cbz 85%
Cl
COOMe
CbzHN H PhO O
COOMe
75%
60%
H3CO
O O
HO
O OAc 65%
97 : 3
O O N P O
75%
B.Rearrangement of hydroperoxide : Hydroperoxides can be cleaved in presence of protic or Lewis acid. Reaction goes through rearrangement.
R R C R O O H H R R O + ROH
Mechanism is as follows.
R R C R R R C OH2 OR R R O O H H R R C R O + ROH O H O H -H2O R R C OR H2O
Acid converts peroxide to protonated peroxide which loses water molecule. Simultaneously, shift of alkyl group to electron deficient oxygen gives rearranged carbocation, which reacts with water to give hemiketal which breaks down to give alcohol and ketone.
Ph OOH AcOH O + OH
Alkyl group must be showing some sort of anchimeric assistance and the rearrangement must be going through benzonium ion.
OH H2O / H OOH +
Benzonium ion :
S T
1,2-free radical rearrangements though less common are observed in some cases. The mechanism is similar. First a free radical is generated, which rearranges itself by one electron transfer. This is followed by stabilization of newly formed radical.
R A B A B R
product
Me
C Me
H2 C
Ph
H abstraction
Me
H C Me
Ph
50%
In this reaction no migration of methyl group is seen. Also, migration of hydrogen is not seen (seen to lesser extent ) in free radical
rearrangement. As phenyl group, groups like vinyl, acetoxy can also migrate. Also, migration for chloro group has been observed.
Cl Cl C Cl Cl Cl C Cl C H Br CH2 Br2 Cl CH CH2 Br Cl Cl C Cl Br C Cl Cl C H Br CH2 CH Br CH2
It is shown that migration of Cl takes place easily if migration origin is tertiary and migration terminus is primary.
Migration of chlorine and bromine might be taking place because they can accommodate an odd electron in vacant d-orbital. In summary, 1,2-free radical rearrangements are less common as compared to analogous carbocation process and direction of migration is usually towards more stable radical. Apart from usual 1,2 shifts, 1,3 and longer distance shifts are also known. 1,5 being most common. Transannular H shifts are also known.
Rearrangement is intramolecular is shown by cross over experiment. Also, retention of configuration was seen in product. Two mechanistic pathways are possible. One involving radical pair trapped in solvent cage. Presence of solvent cage is important in order to explain retention of configuration.
R3 N R1 Z N R3 R2 R2 base
R3 N R1 R2
R3 N R1 R2
R3 N R1 R2
R1
90%
When Z group is an aryl group, the rearrangement is known as Sommelet-Hauser rearrangement, in which reaction of tert.alkyl ammonium salt with NaNH2 gives N-dialkylbenzylamine with ortho substituted aromatic ring.
N NaNH2 / NH3 N
Another competing reaction is Hofmann elimination, when one of the alkyl group contains hydrogen atom. Sulfur yields in place of nitrogen yields also give similar reaction.
R1 Z H C Z S R
2
H C R1
SR2
Et N Et KOtBu / MeCN
Et2N
PhLi N
PhHCN
nBuLi in hexane Ph
EtOOC N
COOEt
EtOOC N
COOEt
O NC N HN base N
O NC HN
NC HN
N N N N N N
+
N N
Ph Ph base N R
1
R1 Ph Ph N
Wittig rearrangement : Ethers on reaction with alkyl lithium rearrange in similar manner to that of Stevens rearrangement to give alkoxy lithium. This reaction is called Wittig rearrangement.
H R
1
R3 OR
3
C R2
R4Li
R1
C R2
OLi + R4H
R may be alkyl, aryl or vinyl group. Migratory aptitude are allylic, benzyl>ethyl>methyl>phenyl. Mechanism follows radical pair pathway.
R1
C R2
O R3
R1
Li
R2 R3
i.Reaction is largely intramolecular ii.Migratory aptitude of group is analogs to free radical mechanism.
BuLi Ph O Ph OLi
H Ph OH
O O tBuLi
OH 58%
NOMe
OH
CH2Ph O tBu SePh OH tBu OCH2Ph + tBu OH CH2Ph Naphthyllithium THF, -780C, 20 min tBu
HO O
OMe
OMe
When R2 is a good leaving group and electron withdrawing functional group like CN, then this group is eliminated and ketone is formed.
H R1 C CN OR R2Li R1 O + R2H + LiCN R
H R
1
Li OR R2Li R
1
R O R R
1
C CN O
C CN
R C OLi CN
R1
C CN
OLi
R1
Bt LDA Ph O OCH3
Ph O 61%
OCH3
Bt : benzotriazol-1-yl
HO O TBSO O Ph nBuLi, THF -780C-00C TBSO OTBS HO O Ph
TBSO
OTBS
F 3C
OH Ph N O
+ OH
Ph
N O
PhH2C
H2 C
OH MeLi Ph C H H2 C
OH Ph Li O Ph nBuLi Ph Ph + Ph OH Ph
O O N
O 29% N
The purpose of crossover experiment is to determine whether reaction takes place intermolecularly or intramolecularly i.e. whether reactant
together and are reacted in same reaction condition and the product
obtained is analyzed. Consider, a simple reaction in which A-B reacts to give C-D.
A A B + A* B + A* B* B* C C D + C* D + C* D* D* + C* D + C D*
There are two possibilities of outcome of reaction. One in which no crossover of substituent is seen. This is possible if reaction is intramolecular. And other possibility is that mixture of products obtained is by crossover reaction. This is possible in case of intermolecular reaction.
When I and II are mixed together and product is analyzed, V and VI, along with II and IV are obtained.
Cl OH OH Ph O V VI O