Enantioconvergent Radical-Radical Cross-Coupling via Magnesium-Mediated Charge-Transfer Photocatalysis

Radical asymmetric reactions represent a crucial strategy in asymmetric synthesis, which is characterized by their high reaction efficiency and unique reactivity profiles. Despite significant progress in radical-based asymmetric transformations, the formation of C-N bonds using nonredox metal complexes via the inner-sphere stereocontrol mechanism remains a formidable challenge in the development of novel asymmetric catalytic strategies. This study introduces an innovative and highly efficient asymmetric photochemical bifunctional catalysis that utilizes a combination of magnesium salts and chiral PyBOX-type (pyridine-bisoxazoline) C₂-symmetric ligands under visible light irradiation. This approach enables the selective α-amidation of β-keto esters via an N-centered radical mechanism, facilitating the synthesis of substituted β-keto amino acid derivatives with a fully substituted stereocenter. The reaction proceeds in good yields (up to 79%) and excellent enantioselectivity (up to 94%). The catalysis proceeds through the in situ formation of prochiral quaternary charge-transfer complexes, which promote the Lewis acid-supported generation of radicals, thereby mediating the subsequent enantioconvergent radical-radical cross-coupling. Notably, the β-keto ester serves a trifunctional role as a sensitizer, reductant, and radical precursor, while the N-protected iminopyridinium ylide functions as both the oxidant and N-centered radical precursor. Experimental and computational mechanistic studies corroborate the enantioconvergent radical-radical cross-coupling process.