Visible-Light-Driven Photocatalyst-Free Synthesis of N-Aryl Amino Acids

Abstract

A visible-light-driven, three-component coupling for the synthesis of N-aryl amino acids and unnatural peptides is described, which proceeds under mild, catalyst-and photocatalyst-free conditions-even under natural sunlight. Glyoxylates, anilines, and 4-alkyl 1,4-dihydropyridines are efficiently assembled under mild conditions. This transformation exploits the intrinsic photoreactivity of 4-alkyl dihydropyridines, which directly generate alkyl radicals without external photocatalysts or electron-donor-acceptor (EDA) complexes. The reaction displays broad substrate scope, good functional-group tolerance, and excellent scalability, and enables late-stage modification of complex bioactive molecules. Mechanistic studies support radical addition to an imine followed by a kinetically relevant single-electron reduction step.