Palladium-Mediated Arylation of Lysine in Unprotected Peptides
Published: 16 Feb 2017
Authors: Dr. Hong Geun Lee, Dr. Guillaume Lautrette, Prof. Bradley L. Pentelute, Prof. Stephen L. Buchwald
A mild method for the arylation of lysine in an unprotected peptide is presented. In the presence of a preformed biarylphosphine-supported palladium(II)–aryl complex and a weak base, lysine amino groups underwent C−N bond formation at room temperature. The process generally exhibited high selectivity for lysine over other amino acids containing nucleophilic side chains and was applicable to the conjugation of a variety of organic compounds, including complex drug molecules, with an array of peptides. Finally, this method was also successfully applied to the formation of cyclic peptides by macrocyclization.