Rhodium(I)‐Catalyzed Enantioselective C(sp3)—H Functionalization viaCarbene‐Induced Asymmetric Intermolecular C—H Insertion†

Abstract

Main observation and conclusionTransition‐metal‐catalyzed C—H insertion of metal‐carbene represents an excellent and powerful approach for C—H functionalization. However, despite remarkable advances in metal‐carbene chemistry, transition metal catalysts that are capable of enantioselective intermolecular carbene C—H insertion are mainly constrained to dirhodium(II) and iridium(III)‐based complexes. Herein, we disclose a new version of asymmetric carbene C—H insertion reaction with rhodium(I) catalyst. A highly enantioselective rhodium(I) complex‐catalyzed C(sp3)—H functionalization of 1,4‐cyclohexadienes with α‐aryl‐α‐diazoacetates was successfully developed. By using chiral bicyclo[2.2.2]‐octadiene as ligand, rhodium(I)‐carbene‐induced asymmetric intermolecular C—H insertion proceeds smoothly at room temperature, allowing access to a diverse variety of α‐aryl‐α‐cyclohexadienyl acetates and gem‐diaryl‐containing acetates in good yields with good to excellent enantioselectivities (up to 99% ee). Furthermore, the synthetic utility of the reaction was highlighted by facile synthesis of a novel cannabinoid CB1 receptor ligand. This method may offer a new opportunity for the development of therapeutically exploitable cannabinoid receptor type ligands in medicinal chemistry.