Mechanistic Insights of Electroreductive Cobalt-Catalyzed Asymmetric Radical Addition

Abstract Transition-metal-catalyzed asymmetric electroreduction has emerged as a compelling platform for enantioselective C–C bond formation, with notable advances in electroreductive cross-coupling. Translating this success to stereocontrolled radical additions across unsaturated bonds remains a formidable challenge, particularly for the construction of fully substituted stereogenic carbon centers. Herein, we report an electroreductive, cobalt-catalyzed asymmetric radical addition of diverse organohalides to α-imino esters. This protocol delivers enantioenriched α-quaternary amino acid derivatives in up to 95% ee, completely circumventing the need for stoichiometric metal reductants. Beyond its synthetic utility, the electrochemical platform uniquely enables the direct interrogation of the operative electron-transfer events. A comprehensive mechanistic study─encompassing cyclic voltammetry, in situ electrochemical EPR spectroscopy, DFT calculations, stoichiometric experiments, and radical-trapping experiments─elucidates a highly orchestrated catalytic manifold. Crucially, we demonstrate that the α-imino ester serves a dual role, acting as both a radical acceptor and a redox-active ligand for the chiral cobalt catalyst. Subsequent cathodic reduction of the resulting cobalt–imine complex generates a key low-valent species that engages the alkyl halide via a turnover-limiting single-electron transfer (SET) to produce the requisite alkyl radical. Overall, this work establishes a robust electrochemical framework that synergizes reaction innovation with fundamental mechanistic elucidation in asymmetric radical catalysis.