Copper-catalyzed enantioselective desymmetrizing C(sp2)–H functionalization of azide-ynamides via α-imino copper carbenes

Abstract

α-Imino metal carbenes are versatile intermediates in organic synthesis, and have broad applications in the assembly of divergent N-heterocycles. However, the catalytic enantioselective desymmetrization based on α-imino metal carbenes has not been developed to date. Herein, we disclose an enantioselective desymmetrizing C(sp²)–H functionalization of azide-ynamides via α-imino copper carbenes, leading to the efficient assembly of divergent chiral indoloazepines in generally moderate to excellent yields with high enantioselectivities. Notably, this reaction represents the first enantioselective desymmetrization based on α-imino metal carbenes. Further synthetic transformations and biological tests show the potential utility of this method. Moreover, computational studies are employed to elucidate the reaction mechanism and the origin of enantioselectivity.