Site-Selective Aryne-Mediated N-Arylation of Oligopeptides

Abstract We report herein an efficient transition-metal-free method for late-stage N-arylation at the C-terminus of oligopeptides. Exploiting intermediate O-benzyl hydroxamic acid derivatives, the transformation employs a range of aryne derivatives and is applicable to di-, tri-, and tetrapeptides, with subsequent selective N–O bond cleavage revealing the arylated parent oligopeptide. The method shows good tolerance of common protecting groups used in peptide synthesis and affords exclusive site-selectivity despite the presence of multiple N–H bonds.