Pd-Catalyzed Asymmetric Amination of Enamines: Expedient Synthesis of Structurally Diverse N–C Atropisomers

Abstract

The transition-metal-catalyzed cross-coupling of enamines is an attractive method for producing compounds with an N–C chiral axis; however, it faces considerable challenges that remain unresolved. Herein, a palladium-catalyzed amination method was developed to construct structurally diverse five–six biaryl and six–six nonbiaryl N–C atropisomers. The reaction mechanism was explained using density functional theory calculations, which showed that the mechanism involved the Curtin–Hammett control. N–C rotation occurred along the reaction coordinate until an enantio-determining three-centered reductive elimination transition structure established the stereochemistry. The developed method is highly attractive because of its broad substrate scope, high stereoselectivity, simple catalytic system, good functional group tolerance, and dynamic kinetic resolution.