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Related Reactions
Claisen Rearrangement
[1,2]-Wittig Rearrangement
Synthesis of homoallylic alcohols

[2,3]-Wittig Rearrangement

The [2,3]-Wittig Rearrangement allows the synthesis of homoallylic alcohols by the base-induced rearrangement of allyl ethers at low temperatures.

Mechanism of the [2,3]-Wittig Rearrangement

The [2,3]-Wittig Rearrangement is a [2,3]-sigmatropic reaction, a thermal isomerization that proceeds through a six-electron, five-membered cyclic transition state. A general scheme for [2,3]-sigmatropic reactions is given here:

[2,3]-Sigmatropic reactions encompass a vast number of synthetically useful variants in terms of both the atom pair involved (X, Y) and the electronic state (Y: anions, non-bonding electron pairs, ylides).

The transformation of deprotonated allyl ethers into homoallylic alcohols is the [2,3]-sigmatropic version of the [1,2]-Wittig Rearrangement, and is therefore termed [2,3]-Wittig Rearrangement:

These [2,3]-rearrangements feature regioselective carbon-carbon bond formation with allylic transposition of the oxygen, generation of specific olefin geometries and transfer of chirality. A discussion of the mechanism, scope and limitations, stereochemical control and synthetic applications can be found in the review by Nakai and Mikami (Chem. Rev., 1986, 86, 885-902).

The concerted [2,3]-shift competes with the [1,2]-shift in many cases:

The product ratio varies as a function of the temperature and structural environment (see also [1,2]-Wittig Rearrangement). The [2,3]-Wittig Rearrangement should be conducted at a low temperature to avoid contamination by the [1,2]-product.

The reaction rate depends on the energy gap between HOMO (anion) and LUMO (allyl). Roughly speaking, the less stable the carbanion, the faster the rearrangement.

For the Thio-[2,3]-Wittig Rearrangement, Nakai reported the following relative reaction rates: R = Ph > CO2Li > CN > CO2Et > COMe, and for R' = Ph > H > CH3. Reactions in this series were conducted at temperatures of from -80 C to +60 C.

The scope of the [2,3]-Wittig Rearrangement is mainly defined by the availability of methods for generating carbanions at temperatures low enough to minimize the occurrence of the [1,2]-rearrangement. Tin-lithium exchange, for example, allows the selective preparation of extremely unstable carbanions in a reaction known as the [2,3]-Wittig-Still rearrangement:

[2,3]-Wittig Rearrangements of propargyl ethers can afford allenic alcohols, but the scope is relatively limited and the process is not general.

Terminal alkynyl groups, for example, are deprotonated; the use of a second equivalent of base allows the generation of 1,2-rearrangement products via dianion intermediates.

Many diastereoselective rearrangements have been reported and chirality transfer with the generation of new stereocenters can be explained by models for the transition state based on an envelope conformation. The two putative pathways are shown below:

A strong preference for E products has been confirmed by numerous experiments.

An originally chiral carbon becomes a planar sp2 center in the course of the rearrangement of some asymmetric substrates, while simultaneously new chiral centers are generated at an originally sp2 center and the anionic carbon:

Properly designed strategies based on the [2,3]-Wittig Rearrangement are powerful tools for asymmetric synthesis as exemplified by the many examples presented in the review by Nakai and Mikami (Chem. Rev., 1986, 86, 885-902).

Recent Literature

Organocatalytic Sigmatropic Reactions: Development of a [2,3] Wittig Rearrangement through Secondary Amine Catalysis
A. McNally, B. Evans, M. J. Gaunt, Angew. Chem. Int. Ed., 2006, 45, 2116-2119.

Synthesis and Fluoride-Promoted Wittig Rearrangements of α-Alkoxysilanes
R. E. Maleczka, Jr., F. Geng, Org. Lett., 1999, 1, 1111-1113.