Cobalt-catalyzed construction of spiro scaffolds bearing central and axial chirality via enantioselective (4+1) C–H spiroannulation

Abstract

Abstract The construction of structurally complex, stereochemically rich spirocyclic frameworks remains a formidable challenge in organic synthesis, particularly when multiple stereoelements installed with precision in a single operation. Herein, we disclose a cobalt/Salicyloxazoline (Salox) catalyzed (4 + 1) spiroannulation between readily available aryl amides and diazaphenanthrenones, serving as carbene precursors, to afford isoindole-based spirocyclic scaffolds bearing central and atrop stereocenters. This transformation proceeds under mild conditions with remarkable regio-, diastereo-, and enantioselectivity, demonstrating broad substrate scope and high functional group tolerance. Preliminary mechanistic studies, including isotope labeling experiments, DFT studies decode the plausible mechanism. This work not only introduces a powerful synthetic platform for accessing multiple, stereochemically dense scaffolds but also highlights the command of cobalt catalysis in asymmetric C–H functionalization.