Silver(I)/Dirhodium(II) Catalytic Platform for Asymmetric N–H Insertion Reaction of Heteroaromatics
Shingo Harada, Shumpei Hirose, Mizuki Takamura, Maika Furutani, Yuna Hayashi, Tetsuhiro Nemoto
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 Rh 2 (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.