Stereoselective Horner-Wittig synthesis of (Z)-1-chlorovinyl sulfoxides

Abstract

This paper describes the synthesis of (Z)-1-chlorovinyl sulfoxides 1 by the Horner-Wittig reaction. The required [(α-chloro)sulfinylmethyl]diphenylphosphine oxides 2 (R1=Me, c-Hex, Ph, p-Tol, p-(CF3)Ph), were prepared in high yields by selective monochlorination and subsequent monooxidation of (thiomethyl)diphenylphosphine oxides 3. The stable lithiated anions of 2 gave an efficient reaction with all structural types of aldehydes. Aromatic and α,β-unsaturated aldehydes gave 1 with excellent Z-selectivity (> 98%), irrespective of the nature of the substituent R1 at sulfur. With straight chain aliphatic aldehydes, an aromatic substituent at sulfur was required to obtain high Z-selectivity. A mechanistic explanation for these observations is presented. An X-ray analysis of 1, R1=Me, R2=4-MeOC6H4 confirmed the Z-disposition of the chloro and aryl substituents.