Chiral sulfoxides: advances in asymmetric synthesis and problems with the accurate determination of the stereochemical outcome

Abstract

Chiral sulfoxides are in extremely high demand in nearly every sector of the chemical industry concerned with the design and development of new synthetic reagents, drugs, and functional materials. The primary objective of this review is to update readers on the latest developments from the past five years (2011–2016) in the preparation of optically active sulfoxides. Methodologies covered include catalytic asymmetric sulfoxidation using either chemical, enzymatic, or hybrid biocatalytic means; kinetic resolution involving oxidation to sulfones, reduction to sulfides, modification of side chains, and imidation to sulfoximines; as well as various other methods including nucleophilic displacement at the sulfur atom for the desymmetrization of achiral sulfoxides, enantioselective recognition and separation based on either metal–organic frameworks (MOF's) or host–guest chemistry, and the Horner–Wadsworth–Emmons reaction. A second goal of this work concerns a critical discussion of the problem of the accurate determination of the stereochemical outcome of a reaction due to the self-disproportionation of enantiomers (SDE) phenomenon, particularly as it relates to chiral sulfoxides. The SDE is a little-appreciated phenomenon that can readily and spontaneously occur for scalemic samples when subjected to practically any physicochemical process. It has now been unequivocally demonstrated that ignorance in the SDE phenomenon inevitably leads to erroneous interpretation of the stereochemical outcome of catalytic enantioselective reactions, in particular, for the synthesis of chiral sulfoxides. It is hoped that this two-pronged approach to covering the chemistry of chiral sulfoxides will be appealing, engaging, and motivating for current research-active authors to respond to in their future publications in this exciting area of current research.