Photoredox-Catalyzed Difluoromethylation of Dehydroalanine and Dehydroalanine-Containing Dipeptides: A Proof-of-Concept Enantioselective Variant

A photoredox-catalyzed difluoromethylation of dehydroalanine (Dha) derivatives and protected Dha-containing dipeptides is described. The reaction enables direct installation of the CF2H group to access β-difluoromethyl α-amino acid derivatives under mild conditions using difluoromethyl sulfone as the radical precursor. A proof-of-concept CPA-enabled enantioselective variant furnished the model product in 55% isolated yield and 73% ee. Mechanistic experiments support a radical–polar crossover pathway and suggest that reversible product deprotonation may contribute to stereochemical erosion.