Photoinduced Decarboxylative Radical Addition Reactions for Late Stage Functionalization of Peptide Substrates

Photoredox chemistry has greatly stimulated the application of radical based transformations in medicinal chemistry and early drug discovery in recent years. Carboxylate groups have been identified as traceless leaving groups that can be converted into radical intermediates capable of undergoing 1,4‐conjugate addition reactions to Michael acceptors. Herein, we show the successful C‐terminal derivatization of small peptide substrates by using this methodology in a parallel synthesis setting. Finally, we outline a general strategy for the γ‐homologation of several drugs derived from α‐amino acids in a late stage functionalization (LSF) approach.