Cobalt-Catalyzed Enantioselective and Diastereodivergent Construction of C–N Atropisomers
Abir Das, Subramani Kumaran, Pritam Maity, J. Richard Premkumar, Basker Sundararaju
Abstract
Herein, we report an efficient method for the synthesis of atropisomers with distal 1,3-C-N diaxes using the cobalt/Salox system via C-H and N-H annulation with benzamide and sterically hindered alkynes. This one-step, step-economical process operates at room temperature with oxygen from air as the sole oxidant, removing the need for metal oxidants, photocatalysts, or electricity. The reaction is compatible with a broad range of arylamides and alkynes, providing high yields and excellent enantioselectivity (up to >99% ee). Experimental and DFT studies indicate that the migratory insertion is the rate-determining step, while C-H activation is the enantio-determining step. Additionally, we showcase a traceless bidentate directing group strategy for the synthesis of C-N atropisomers with high enantioselectivity, where the directing group is cleaved in situ and does not remain in the final product.