Applications of the Wittig–Still Rearrangement in Organic Synthesis

Abstract

This Review traces the discovery of the Wittig-Still rearrangement and its applications in organic synthesis. Its relationship to Wittig rearrangements is discussed along with detailed analysis of E/Z- and diastereoselectivity. Modifications of the products arising from the Wittig-Still rearrangement are reviewed in the context of increased complexity in intermediates potentially useful in target-oriented synthesis. Early applications of the Wittig-Still rearrangement to modifications of steroids are reviewed as are applications to various terpene and alkaloid natural product targets and miscellaneous compounds. To the best of our knowledge, the literature is covered through December 2016.

1,5‐Allyl Shift by a Sequential Achmatowicz/Oxonia‐Cope/Retro‐Achmatowicz Rearrangement

“…Unexpectedly, we isolated a minor product that was confirmed through careful analysis of NMR data to be a furan-derived compound 3 a (< 10 % yield). While puzzled about the mechanism accounting for this minor product, we recognized that this two-step sequence realized an unprecedented 1,5-allyl shift, which cannot be achieved by Woodward-Hoffmann forbidden [3,5]-sigmatropic rearrangement. Our attempts on direct pericyclic reaction of 1 a under thermal or basic condition failed to effect the similar 1,5-allyl shift (1 a!3a), which further demonstrated the experimental difficulty of [3,5]-sigmatropic rearrangement.…”

Basicity-Tuned Reactivity: diaza-[1,2]-Wittig versus diaza-[1,3]-Wittig Rearrangements of 3,4-Dihydro-2H-1,2,3-benzothiadiazine 1,1-Dioxides

“…This latter reaction can be considered as a nonclassical Stevens rearrangement, since here the reactant is a neutral species. While Wittig reactions including their variants 5 are well investigated, likewise the Stevens reaction, the aza- [1,2]-Wittig transformation is rare 6−8 and is often a side reaction, competing with aza- [2,3]-Wittig rearrangement. 9,10 In the case of tetrasubstituted hydrazines, the N−N bond is breaking and the terminal amino unit is shifting, resulting in a diaza- [1,2]-Wittig rearrangement (Scheme 1D).…”

“…This latter reaction can be considered as a nonclassical Stevens rearrangement, since here the reactant is a neutral species. While Wittig reactions including their variants are well investigated, likewise the Stevens reaction, the aza -[1,2]-Wittig transformation is rare − and is often a side reaction, competing with aza -[2,3]-Wittig rearrangement. , In the case of tetrasubstituted hydrazines, the N–N bond is breaking and the terminal amino unit is shifting, resulting in a diaza -[1,2]-Wittig rearrangement (Scheme D). − Exposure of these derivatives to bases can also result in imines and amines as possible intermediates, , indicating that with the breaking of the N–N bond during the reaction, the formation of new N–H bonds becomes also feasible. Diaza -1,4-Wittig rearrangement is also precedented; nonetheless, the diaza -[1,3]-Wittig reaction is a missing link.…”

[2,3]-Wittig Rearrangement as a Formal Asymmetric Alkylation of α-Branched Ketones

“…9 The Wittig rearrangement has been applied as a key step for the synthesis of many natural products. 10 On the other hand, formed rearranged products are substituted α-hydroxy ketones, also known as acyloins. Acyloins are compounds of great synthetic importance, and can be found in natural products and biologically active compounds.…”

“…The [2,3]-Wittig rearrangement is a transformation of allylic or propargylic ethers to homoallyl alcohols that makes it possible to generate a new C–C bond and to insert stereocomplexity into a structure . The Wittig rearrangement has been applied as a key step for the synthesis of many natural products . On the other hand, formed rearranged products are substituted α-hydroxy ketones, also known as acyloins.…”