Witting Rearrangement

1. BY
Dr. Gurumeet.C.Wadhawa
DEPARTMENT OF CHEMISTRY
K. B. P. College,Vashi,Navimumbai
Witting Rearrangement

2. WITTIG-[1,2]- AND [2,3]-REARRANGEMENT
In 1942, G. Wittig and L. Löhmann reported that the deprotonation of
benzyl methyl ether with phenyllithium afforded 1-phenylethanol upon
work-up.1 Subsequent studies showed that the transformation was
general for α-lithiated aryl alkyl ethers that undergo a facile
rearrangement to give lithio alkoxides in an overall [1,2]-alkyl shift.
The rearrangement of aryl alkyl ethers to the corresponding secondary
or tertiary alcohols in the presence of stoichiometric amount of a
strong base is known as the [1,2]-Wittig rearrangement

3. The base catalysed rearrangement of an ether to an alcohol
via 1,2-shift is known as wittig rearrangement

5. The migratory aptitudes in the 1,2-rearrangement are in the order of allyl =
benzyl > alkyl > methyl > aryl with electron withdrawing substituents
increasing aryl migratory aptitude.

7. [1,2]-Wittig rearrangement. The most important features
are:
1) the R1 substituent has to be able to stabilize the carbanion;
2) the chiral center in the migrating group retainsits configuration;
3) yields are usually moderate due to the harsh reaction conditions and
the competing [1,4]- pathway;
4) at low temperatures, the formation of the [1,4]-product is favored,
while at higher temperatures the [1,2]- product dominates.

8. During the course of early mechanistic studies of this process, the
research groups of G. Wittig and T.S. Stevens found that upon
deprotonation, allylic ethers mainly underwent a [2,3]-sigmatropic shift to
afford homoallylic alcohols, a process that is now referred to as the [2,3]-
Wittig rearrangement.2,4 The general features of
the [2,3]-rearrangement are: 1) it proceeds under milder conditions and
gives higher yields than the [1,2]- rearrangement;
2) virtually any α-(allyloxy)carbanion can udergo the rearrangement; the
only limitation lies with the chemist's ability to generate a particular anion
with currently available methods;
3) the R4 substituent should be a carbanion-stabilizing group;
4) the [1,2]- and [2,3]-shifts often compete, and the amount of each
product depends strongly on the structure of the substrate and the
reaction temperature;
5) by carefully optimizing the reaction temperature, the formation of the
[1,2]-rearranged product can be avoided;
6) for acyclic and cyclic substrates, the anions can be generated by a
variety of different methods: with a strong base (e.g., LDA, n-BuLi) at -60
to -85 °C, via
a tin-lithium exchange reaction (Still variant)21 and by reductive lithiation
of O,S-acetals;
7) because of the highly ordered cyclic transition state, the rearrangement
is stereoselective with respect to the stereochemistry of the new

9. 8) in acyclic substrates, the chirality of the C1 stereocenter of the
substrate gets transferred to the product in a predictable fashion,
consistent with the orbital symmetry conservation rules;
9) the newly formed double bond generally has the (E)-
stereochemistry, but the Still variant (R4=SnR3) gives predominantly
(Z)-olefins;
10) the highest (E)-selectivity is achieved when the allylic moiety is
only monosubstituted (R5=alkyl and R6=H);
11) the diastereoselectivity with respect to the newly created vicinal
chiral
centers is high: (Z)-substrates give erythro products with high levels of
selectivity, while (E)-substrates afford threo products with lower
selectivity, but the nature of the R4 substituent also has a profound
effect on the level of
diastereoselectivity;and
12) five different asymmetric versions of the rearrangement have been
identified

16. References
1 Wittig, G.; Löhmann, L. Ann. 1942, 550, 260–268.
2 Peterson, D. J.; Ward, J. F. J. Organomet. Chem. 1974, 66,
209–217.
3 Tsubuki, M.; Okita, H.; Honda, T. J. Chem. Soc., Chem.
Commun. 1995, 2135–2136.
4 Tomooka, K.; Yamamoto, H.; Nakai, T. J. Am. Chem. Soc. 1996,
118, 3317–3318.
5 Maleczka, R. E., Jr.; Geng, F. J. Am. Chem. Soc. 1998, 120,
8551–8552.
6 Miyata, O.; Asai, H.; Naito, T. Synlett 1999, 1915–1916.
7 Katritzky, A. R.; Fang, Y. Heterocycles 2000, 53, 1783–1788.
8 Tomooka, K.; Kikuchi, M.; Igawa, K.; Suzuki, M.; Keong, P.-H.;
Nakai, T. Angew.
Chem. Int. Ed. 2000, 39, 4502–4505.
9 Miyata, O.; Asai, H.; Naito, T. Chem. Pharm. Bull. 2005, 53,
355–360.
10 Wolfe, J. P.; Guthrie, N. J. [1,2]-Wittig Rearrangement. In
Name Reactions for Homologations-
Part II; Li, J. J., Ed.; Wiley: Hoboken, NJ, 2009, pp 226􀀐240.
(Review).
11 Onyeozili, E. N.; Mori-Quiroz, L. M.; Maleczka, R. E., Jr.
Tetrahedron 2013, 69, 849–