Silver(I)/Dirhodium(II) Catalytic Platform for Asymmetric N-H Insertion Reaction of Heteroaromatics.

Abstract

Transition-metal-catalyzed enantioselective N-H insertion reactions of carbene species offer a powerful and straightforward strategy to produce chiral nitrogen-containing compounds. Developing highly selective insertion reactions using indole variants can meet synthetic demand. Herein we present an asymmetric insertion reaction into N-H bonds of the aromatic heterocycles using donor/acceptor-substituted diazo compounds based on a heteronuclear catalytic platform. Although a previously developed catalysis comprising chiral silver catalyst or dirhodium(II,II) paddlewheel complexes with and without chiral phosphoric acid showed modest performance, a unique combination of widely available Rh2(OAc)4 and silver(I) phosphate dimer [(S)-TRIP-Ag]2 enabled asymmetric carbene insertion reactions (up to 98% ee). Moreover, the Ag/Rh catalytic system facilitated regioselective and enantioselective C-H functionalization of protic indoles. Mechanistic investigation based on density functional theory indicated that an in situ-generated Ag-Rh trimetallic enolate is protonated in a chiral environment.