Insights into the chiral sulfide/selenide-catalyzed electrophilic carbothiolation of alkynes: mechanism and origin of axial chirality

Abstract

Although chiral sulfide/selenide-catalyzed electrophilic carbothiolation reaction to construct axially chiral compounds has achieved a breakthrough, understanding the possible mechanism and origin of stereoselectivity is still a challenging issue in this field. Herein, density functional theory (DFT) calculations were performed for systematically studying the bifunctional sulfide/selenide-catalyzed construction of an axially chiral amino sulfide vinyl arene with ortho-alkynylaryl amine and electrophilic sulfur reagent as substrates. The calculated results show that a thiiranium ion intermediate is preferentially generated and then transformed into a chiral aza-vinylidene quinone methide (aza-VQM) intermediate, which involves a pair of diastereoselective pathways. The S-configurational pathway is more energetically favorable, and the atoms-in-molecules (AIM) analysis demonstrates that the hydrogen bond interaction should be the key for controlling axial chirality. For the first time, frontier molecular orbital (FMO) and electron localization function (ELF) analyses along the intrinsic reaction coordinate (IRC) results afford the exact pictures for FMO overlap modes and electronic structural changes in the key process. Further investigations demonstrate that the volume of the substituents can be responsible for avoiding the racemization of the products. The obtained insights are of great significance to understand and develop a novel chiral sulfide/selenide catalytic reaction with high axial chirality.