Visible‐Light‐Driven α‐C(sp 3 )−H Carboxylation of Primary Benzylamines with CO 2 to Access α‐Amino Acids

Abstract α‐Amino acid motifs, serving as essential building blocks, are ubiquitous in natural products, bioactive molecules and drugs. Despite significant advances in the synthesis of α‐amino acids (α‐AAs) using CO 2 as carboxyl source, the direct α‐C(sp 3 )−H carboxylation of primary amines, which are important organic chemical feedstocks, remains an attractive yet formidable challenge. Herein, we report the first visible‐light‐driven direct α‐C(sp 3 )−H carboxylation of primary benzylamines with CO 2 , wherein CO 2 acts dually as a transient protecting group and as the carboxyl source. This strategy enables efficient synthesis of diverse α‐AAs under mild reaction conditions with a broad substrate scope and good functional group compatibility. Mechanistic studies indicate that an intermolecular hydrogen atom transfer (HAT) between the external HAT reagent and the carbamate intermediate, in situ‐generated from primary amine and CO 2 , is followed by reduction and carboxylation to furnish α‐AAs. Moreover, a complementary protocol for carboxylation of α‐C(sp 3 )─H bonds in amides through an intramolecular 1,2‐HAT pathway is also developed, obviating the need for an external HAT reagent and further expanding the synthetic utility of this methodology. These advances represent a versatile and practical platform for the synthesis of α‐AAs from amine precursors using CO 2 .