Cobalt-Catalyzed Construction of Spiro Scaffolds bearing Central and Axial Chirality via Enantioselective [4+1] C–H Spiroannulation

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. Mechanistic studies, including isotope labelling and kinetic isotope effect (KIE) experiments, DFT studies identify C–H activation as the enantio- and rate-determining step, and reductive elimination as diastereodetermining step mediated via a cobaltacycle intermediate stabilized by the salox ligand. 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.