Mechanistic investigation on the remote stereocontrol in the chiral Lewis base-catalyzed, SiCl4-promoted kinetic resolution of chlorinated cis-vinyl epoxides

Abstract

It has been known that the enantioselectivity of the chiral Lewis base-catalyzed, SiCl4-promoted kinetic resolution of α,β-dichloro cis-vinyl epoxide is highly influenced by the configuration of the distal β-chlorine-bearing stereocenter. In this report, the precise nature of this unusual remote stereocontrol was investigated both experimentally and theoretically. Upon examination of a substrate that has an alkyl group in place of the β-chlorine substituent, the spatial location of major catalyst-substrate interaction was determined. Subsequently, through computational analysis of transition states, the steric repulsion by the β-substituents as well as the additional C–H/π hydrogen bond by the alkyl substituent were proposed as the crucial stereo-determining factors. © 2020 Elsevier Ltd