Enantioselective Synthesis of Spirocyclic γ-Lactams Featuring Dual Central and N–N Axial Chirality via Cobalt-Catalyzed Stereochemical Induction

Abstract

Co/salicyloxazoline (Salox)-catalyzed asymmetric C–H activation/spiro annulation is reported for the synthesis of spirocyclic γ-lactams with dual N–N axial and spiro-central chirality. Through an enantioselective desymmetrization protocol of the prochiral maleimide, products are obtained in yields of 34–62% with up to 95% ee and >20:1 dr. Axial chirality established during C–H activation directs subsequent enantioselective spiro-center formation. This protocol accommodates bioactive scaffolds, providing streamlined access to complex chiral N-heterocycles.