Synthesis of Remote C–N Diaxially Chiral Compounds via Cobalt-Catalyzed Atroposelective C–H Activation

The construction of atropisomers bearing multiple stereogenic elements has attracted considerable interest, given their broad utility in asymmetric catalysis, pharmaceuticas, and functional materials. Herein, we report a highly efficient cobalt-catalyzed atroposelective C-H activation-annulation reaction that simultaneously establishes two remote C-N chiral axes in a single operation. This approach proceeds under oxygen conditions by using a commercially available cobalt(II) catalyst in conjunction with a chiral salicyloxazoline (Salox) ligand. A wide range of benzamides and indole-based alkynes with various functional groups are well tolerated, yielding desired products in good yields with a high level of enantio- and diastereoselectivities. The resulting C-N diaxially chiral products demonstrate exceptional configurational stability at both C-N axes. The synthetic practicality is further highlighted by scalable synthesis, versatile derivatizations, and remarkable optical performance of the target molecules.