Enantioselective synthesis of unsymmetrical α,α-diarylacetates via organocatalyzed formal C–H insertion reactions of sulfoxonium ylides with indoles and pyrroles

Abstract

The chiral unsymmetrical α,α-diarylmethine skeleton is widely found in natural products and synthetic pharmaceuticals. The catalytic asymmetric C–H insertion reaction of simple, unprotected indoles and pyrroles with α-aryl sulfur ylides provides a direct route to their stereoselective preparation. Nevertheless, controlling the reactivity and stereoselectivity of this reaction has presented a significant challenge. In this study, we present the highly enantioselective asymmetric formal C–H insertion reactions of N–H free indoles and pyrroles with sulfoxonium ylides, yielding chiral gem-heterodiarylmethine frameworks with good to excellent yields and enantioselectivities. Importantly, experimental mechanistic studies and DFT calculations indicate that the stereoselectivity originates from dynamic kinetic resolution, where multiple noncovalent interactions play a pivotal role, with C–C bond formation as the rate-determining step. The findings in this study may pave the way for the development of catalytic asymmetric C–H insertion reactions of sulfur ylides with other carbon nucleophiles.