Cobalt-Catalyzed Enantioconvergent Decarboxylative N-Alkylation
Siwen Huang, Ramon Trevino, Dishun Zuo, Xin Tian, Wenhan Yang, William B. Hughes, Seth O. Fremin, Arka Porey, Vy T. Nguyen, Bo Gao, Xiyuan Xu, Babu Raj Dhungana, Yingqian Jiang, Yao Sun, Chao Huang, Min He, Chandan Kumar Giri, Shree Krishna Dhakal, Bin Qin, Yongxiang Liu, Maosheng Cheng, Oleg V. Larionov, Shengfei Jin
Abstract
Introduction of alkyl substituents onto nucleophilic nitrogen atoms in amines is a central synthetic strategy for increasing molecular complexity and structural diversity in medicinal chemistry, organic synthesis, and materials science. Although the direct transfer of a stereogenic alkyl group onto a nitrogen atom by N-alkylation is one of the most efficient approaches to asymmetric C( sp 3 )–N bond formation, few methods are available for the enantioconvergent N-alkylation of amines with racemic alkyl transfer reagents. We report herein a previously unexplored enantioconvergent decarboxylative N-alkylation of aromatic amines with racemic carboxylic acids. The reaction is enabled by a merger of acridine photocatalysis with Co(salen)-catalyzed asymmetric radical–polar crossover (RPC). The study provides a simple synthetic segue to medicinally and synthetically valuable α-chiral benzylic amines and unravels the structural, electronic, and bonding effects that govern the stereocontrol imparted by the privileged Co(salen)-based asymmetric RPC catalytic system.