Metal-free decarboxylative C(sp3)–C(sp3) bond formation for the synthesis of unnatural amino acids and peptides via convergent paired electrolysis enabled radical–radical cross-coupling†

Herein, we present the first metal-free decarboxylative C(sp³)–C(sp³) cross-coupling of glycine derivatives with redox-active esters through highly atom and energy economical convergent paired electrolysis enabled radical–radical cross-coupling. Under mild and scalable conditions, various α-alkylated unnatural α-amino acids were prepared efficiently from readily available starting materials. The key point for the successful implementation of this strategy is minimizing the interelectrode distance to permit the rapid diffusion of radical species and outpace radical decomposition. Mechanistic investigations showed a radical–radical coupling pathway generated from anode and cathode simultaneously in the same electrolysis system. This novel protocol was successfully applied for the late-stage modification of pharmaceuticals, amino acids and peptides.