Cobalt-Catalyzed Enantioselective and Diastereodivergent Construction of C-N Atropisomers

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.