Macrocyclization of Biaryl-Bridged Peptides through Late-Stage Palladium-Catalyzed C(sp2)–H Arylation

Macrocyclic peptides are promising scaffolds of bioactive compounds and clinical therapeutics. Herein, we develop a strategy for the macrocyclization of biaryl-bridged peptides through late-stage Pd-catalyzed C­(sp2)–H arylation. This method displays broad substrate scope and high efficiency in the synthesis of peptide conjugates with various bioactive molecules. Furthermore, we applied this method to prepare peptide macrocycles with aryl–aryl cross-links. Our results show the effectiveness of backbone amide groups as directing groups in Pd-catalyzed C–H functionalization of peptides.