Enantioselective Radical Addition of Carboxylic Acids to Imines through Cooperative Copper/Acridine Catalysis
Haihui Huang, Guoqin Xia
Abstract
Amino acids and their derivatives are indispensable as both synthetic building blocks and functional entities in the chemical industry and life sciences. Herein, we report a modular strategy for the asymmetric synthesis of chiral α-amino acids and amines through the decarboxylative radical addition to imines. This protocol leverages readily available, cost-effective carboxylic acids, aldehydes, and anilines as starting materials, enabled by the synergistic catalysis of acridine and copper. The reaction operates under ambient conditions, exhibits excellent functional group compatibility, and delivers high stereocontrol across a diverse substrate scope. Notably, it allows for the stereodivergent installation of multiple chiral centers into amino acid derivatives. Preliminary mechanistic investigations support a pathway involving the direct radical addition to the imine. This method thus provides a robust and reliable platform for accessing chiral amino acids and amines.