The [2,3]-Wittig rearrangement is a special class of [2,3]-sigma tropic rearrangement which involves an α-oxy carbanions as the migrating terminus to afford various types of homoallylic alcohols.

1. Dr. K. RAJENDER REDDY
D-206, Discovery Laboratory,
Organic Chemistry Division III
IICT, HYDERABAD
1

2. Contents
2
1. Introduction
2. [1,2] vs [2,3]-shifts
3. Scope and limitations
4. [2,3]-Wittig Rearrangement: Olefinic Stereoselection
5. Diastereoselectivity of the [2,3]-Wittig Rearrangement
6. Asymmetric [2,3]-Wittig Rearrangement
7. Variants of the [2,3]-Wittig rearrangement
8. Summary and conclusions

3. Introduction
• The [2,3]-Wittig rearrangement is a special class of [2,3]-sigma tropic rearrangement which
involves an α-oxy carbanions as the migrating terminus to afford various types of homoallylic
alcohols.
• This type of carbanion rearrangement possesses synthetically valuble features. (a) the
regiopecific carbon-carbon bond formation with allylic transposition of the oxygen function,
(b) the stereoselective formation of a new olefinic bond, and (c) the stereoselective creation of
vicinal centers.
2
R2R1
O
G
R2R1
O
G
_
R1 R2
GHO *
*
Takeshi Nakai.; Katsuhiko Tomooka. Pure & Appl. Chem.,1997, 69, 595-600

4. Mechanism
• After carbanion formation, the [2,3]-Wittig rearrangement is rapid and selective at low
temperature .
• [2,3]-Sigma tropic rearrangement – general scheme
• Y: anion, hetero atom with lone pairs, ylide
• Bases: LDA, n-BuLi, PhLi, ROLi, NaNH2/NH3
• R should be a carbanion-stabilizing group
• Driving force is commonly to quench a charge or to transfer charge to a more stabilizing atom
4
O
R
O
R
O
R
HO
R
allyl ether homoallylic
alcohol
work-upbase [2,3]
X Y X Y
X
Y
base

5. Initial Discovery
• Wittig (1949) and Stevens (1960):
Wittig, g., Doser, H., Lorenz, I. Leibigs
Ann. Chem. 1949, 562, 192.
Cast, J., Stevens, T. S., Holmes, J. J. Chem.
Soc., Abstracts 1960, 9, 763.
• [2,3] and [1,2] – Wittig rearrangement often compete
• [1,2]- Wittig Rearrangement: Wittig and Löhmann (1942)
5
HO
R2R1
HO
R1R2
HO
R2R1
and/or
[1,2] - rearranged product
(minor)
[2,3] - rearranged product
(major)
Ph
Me
O
Ph
Me
O
Ph OLi + Ph Me
OH
CH3
PhLi
Wittig, G., Lohmann, L. Ann. Chem. 1942, 550, 260.

6. [1,2] vs [2,3]-shifts
• [1,2]/[2,3] rearranged product ratio depends on structural environment and reaction
temperature
• Lower temperatures typically minimize contamination by the [1,2] – product, if the reaction
mixture is allowed to reach temperatures above -60 oC, [1,2]-rearrangement becomes
competitive.
6
Ph O Ph
Me Me
OH
+ Ph
OH
n-BuLi
[2,3] - product [1,2] - product
[2,3] / [1,2]
-25 o
C 7.5:1.0
23 o
C 6:1
Rautenstrach, V., J. Chem. Soc., Chem. Commum. 1970, 4

7. Scope and Limitations
• The fundamental requirement for the Wittig rearrangement is, the ability to generate the
appropriate carbanion in the substrate
• Conflicting results have been reported – rationale not completely
7
O
O X
O
O X
M
O
OM
X
MO
X
X
OM
O
Wittig
Claisen
X = alkyl, OR, etc
Me O
O
Ph
Me
O
Me
Me
O
Me
OM
Ph
O
Me
OH
Me
Me
KOt
Bu
KH or NaH
Wittig product only
Claisen product only
Still;, C., Mitra, A. J. Am. Chem. Soc. 1978, 100, 1927.

8. [2,3]-Wittig Rearrangement: Olefinic Stereo selection
• In general there is a strong preference for the (E) isomer
8
O
Me
R
RLi or LDA/THF
-85 to -50 o
C
Me
R
HO
R group % E isomer
HC(R')=CH2 (R' = H, Me)
HC CR' (R' = H, Me, TMS)
Ph
CO2H
CO2Me
98
93-98
100
74
78
Mikami, K.; Nakai, T. Chem. Rev. 1986, 86, 885.

9. Mechanism
• TS analysis: The group attached to the carbanion can occupy either a psuedoequatorial or
pseudoaxial position although the former is preferred
9
H H
O
R2
R1
R2 H
O
H
R1
H H
OH
R2
R1
R2 H
OH
H
R1
exo TS favored
endo TS disfavored
(E) isomer
(Z) isomer
baseO
R2
R1

10. Olefinic stereo selection
• Still variant of the [2,3] – Wittig Rearrangement
• Useful for synthesizing Z – trisubstituted homoallylic alcohol
• Differs in method of anion preparation
10
Bu
Me
OH
O SnBu3
OH
Me
1. KH, Bu3SnCH2I
2. BuLi
3. work-up
Bu
Bu
Me
O Li
Bu
Me
Me
O
Bu
BuLi
KH, Bu3SnCH2I
work-up
[2,3]
> 95 % yield
96 % Z - isomer
Still;, C., Mitra, A. J. Am. Chem. Soc. 1978, 100, 1927.

11. [2,3]-Wittig-Still Rearrangement
 Z-selectivity only applicable to tetra substituted olefin product
• There is a dramatic decrease in preference for TS A when the vinyl methyl group replaced
with a hydrogen atom
TS analysis of Z-selectivity
11
O SnBu3
R1
R2
R1 R2
OH
1. BuLi
2. work-up
R1 = n-C4H9, R2 = Me E/Z = 3:97
R1 = n-C7H15, R2 = H E/Z = 40:60
O
Me
H
Bu
A
favored
O
Me
Bu
H
B
Bu
OHMe
Me OH
Bu
Z - isomer
E - isomer
Still, C., Mitra, A. J. Am. Chem. Soc. 1978, 100, 1927.

12. 12
Diastereoselectivity of the [2,3]-Wittig rearrangement
Mikami, k., Azuma, K., Nakai, t. Chem. Lett. 1983, 1379.
Degree of diastereoselectivity depends on substituents R
Ally propargyl ethers have illustrated remarkable levels of diastereoselectivity
General trends
H
R
O
favored
Me
H
vs
R
H
O
Me
H
H
R
O
H
Me
R
H
O
H
Me
favored
vs
HO
HO
R
R
Me
Me
threo - homoallylic alcohol
R = C CH 99 % threo
R = C CMe 99 % threo
R = C CTMS 100 % erythro
R = C CMe 100 % erythro
erythro - homoallylic alcohol
O
R
Me
(E) - isomer
O Me
R
(Z) - isomer

13. Asymmetric [2,3]-Wittig Rearrangements
• Chirality transfer with high E selectivity
• (Z)-olefins are typically more stereoselective due to A-1,3 strain
13
Y
X
X
Y
R2
H
H
R2
R1
H
R1H
favoured
slightly
disfavored
Y
X
X
Y
R2
H
H
R2
R1
H
R1H
favoured
highly
disfavored
Y
R1 R2
X
Y
R2
R1
X
Y
R1 R2
X
Y
R2
R1
X
R1
X Y
R2
R1
R2X
Y
E olefin
Z olefin

14. Asymmetric [2,3]- Rearrangements
• First example of an asymmetric [2,3]- Wittig rearrangement:
14
O
OTBS
TBSO
TMS
OTBS
TBSO
H
TMS
HO
n-BuLi, THF
-78 o
C, 1 h
90 % yield
single stereoisomer
O
OH
TBSO
Stork's prostaglandin
intermediate
Nakai, T. et al. Tet. Lett. 1993, 34, 5923.

15. Asymmetric [2,3]-Wittig Rearrangements
15
 Synthetic applications:
 1. Astrophylline synthesis
15
O
N
Boc
SnBu3 O
N
Boc
Li
N
Boc
HO
N
H
N Ph
O
H
H
astrophylline
n-BuLi, THF
-78 o
C-rt
[2,3]
69 %yield
Blechhert. J. Org. Chem. 2003, 68, 2913.

16. Asymmetric [2,3]-Wittig Rearrangement
• 2. Stereo controlled formation of two chiral centers and one diastereomeric centre in the
product based on the chiral centre and double bond geometries of the starting material.
16Sayo, kithara, Nakai, Chem. Lett. 1984, 259.
O
HO Ph
CH3n-BuLi
-85 oC
O
HO Ph
CH3
precursor to L-ephedrinerearrangement

17. Asymmetric [2,3]-Wittig Rearrangements
CON(i
Pr)2
H
OH
CON(i
Pr)2
H
O
Br
O O
O
N
O
Me Me
OR
N
O
O
Me
O
O
90 %(93 %ee)
rearrangement
(+)-Eldanolide
LDA
17
Y.-J. Li et al. Tetrahedron: Asymmetry 2009, 20, 1854-1863.
 3. Synthesis of (+)-Eldanolide

18. Asymmetric [2,3]-Wittig Rearrangement
• 4. Synthesis' of a versatile anti, anti stereotriad building block
• The building block was converted to the “B-2” intermediate in Miyashita’s synthesis of
scytophycin C.
18
CHO
BrZn
lithium
(+)-N-methyl-
ephedrate
ether/toluene
0 o
C
OH
(81%, 90%ee )
O
H
CH3
1. NaH
2.
Br
THF, reflux
n-BuLi
THF
-78 to > 0 o
C
[2,3]-wittig rearrangement
OH
H
(93% syn:anti = 96:4)
OTBS
OMe
H OTBS
O OMe
Miyashita's "B2"
O3, CH2Cl2
-78 o
C
then DMS
-78 o
C
Kathyln A. Parker and Qiuzhe Xie. Org. Lett. 2008, 10, 1349-1352.

19. 5. synthesis of functionalized taxane skeleton
19J. S. Yadav. et al. Tet. Lett. 1991, 32, 2629-2632.
Br
+
OH
OH
O
H
H
OTBDMS
H
H
OTBDMS
HO
H
H
n-BuLi, THF
-78 o
C
O
Asymmetric [2,3]-Wittig Rearrangement

20. Variants of the [2,3]-Wittig Rearrangement
• Replacement of the allyl migrating group by a propargyl group affords allenic alcohols
20
O
RR R R
OH
50-64 % yield
n-BuLi, -85 o
C
R1 O
R2
CN
n-BuLi, -85 o
C R1
R2
O
49-69 % yield
Huche, M.; Cresson, P. Tet. Lett. 1975, 367.
Cazes, B.; Julia, S. Synth. Commum. 1977, 7, 273.

21. Variants of the [2,3]-Wittig Rearrangement
 Aza-[2,3]-Wittig rearrangement:
• Reaction is slower than the oxygen variant because the N-anion is less stable than the O-anion
(less thermodynamic driving force)
• Lewis acids can sometimes facilitate the rearrangement
21
N
R1
R3
R2
N
R1
R3
R2
N
R1
R3
R2
R3
NH
R2
R1
homoallylic 2o
amine
work-upbase [2,3]
N Me
Me
NH
Me
Me
BF3OEt2
n-BuLi
Kessar, S. etal. Tet. Lett. 1995, 36, 8481.

22. Variants of the [2,3]-Wittig Rearrangement
• Release of ring strain can be used to accelerate the reaction
• Formation a N-ylide has been shown to effect the rearrangement
22
N
i
Pr
t
BuO2C Ph
O
Ph3PMeBr(2 eq)
BuLi, DME, rt
tandem Wittig reaction /
[2,3]-Wittig rearrangement
N
H
Ph
CO2
t
Bui
Pr
66 % yield
single isomer
PhN
i
Pr
H
O
Li Ot
Bu
Coldham, I. et al. Tet. Lett. 1995, 36, 3557.
N
Me
Ph
CO2Me
N-alkyl-N-allyl-
2-amino ester
MeI
DMF, K2CO3
DBU, 40 o
C
N
Me
CO2Me
Me
CO2Me
Me
N-alkyl-C-allyl
glycine ester
[2,3]
spontaneous
63 % yield
N PhMePh
Coldham, I. et al. J. Chem. Soc., Perkin Trans. I, 1998, 2817.

23. Variants of the [2,3]-Wittig Reaarrangement
• Oxonium ylide rearrangements
• TS analysis:
23
O
CO2Me
Me
O
CO2Me
Me
TMS HO CO2Me
Me
93 % yield
E/Z 31:69
TMSOTf, TEA
O
OMe
TMS E
TMSO
Me
O
TMSO
OMe
Me
TMS
favored
Z
dis favored
Marshall, J. Comp. Org. Syn., 6, 873.

24. SUMMARRY AND CONCLUSIONS
substient, (Z)- olefinic ethers predominantly give syn-homoallylic alcohols, while
the (E) substrates afford anti products.
The [2,3]- Wittig rearrangement currently enjoys widespread application in many
facets of organic synthesis, particularly in the context of acyclic stereocontrol and
natural product synthesis.
`
24

25. Acknowledgments
25
 Dr. G. V. M. Sharma
 Dr. P. Radha krishna
 Scientists, Organic Division-III
 Director, IICT
 UGC
 Friends.

26. 26
THANK YOU