Macrocyclic peptides (MP) and related molecules have attracted considerable interest as probe molecules and drug leads, particularly for addressing difficult protein targets. 1 Macrocyclization of peptides imparts many favorable properties, including increased resistance to proteases, decreased conformational flexibility and, in certain special cases, increased cell permeability by promoting intramolecular hydrogen bonds that mask otherwise highly hydrated amide N-H moieties. Moreover, powerful methods exist for the synthesis and screening of huge libraries of genetically-encoded MPs, such as phage display and mRNA display 4 . Split and pool synthesis of DNA-encoded libraries (DELs) of macrocycles is another route to access large numbers of these molecules. For such applications, there continues to be a need for new macrocyclization reactions that proceed with high efficiency under gentle reaction conditions, allow the introduction of novel functional groups, and suffers from little or no competitive intermolecular coupling. Here we report a new method for the macrocyclization of peptides that meets all of these criteria and confers on the products favorable pharmacological properties.