Cu-catalysed three-component C–H trifluoroalkylation of glycine derivatives: access to diverse CF3-containing amino acids

Abstract

A Cu-catalysed method that selectively incorporates a trifluoromethyl group and an alkene moiety onto the α carbon of glycine derivatives has been developed using commercialized Togni II reagent. In this three-component reaction, both the N-protecting group of glycinates and the Cu ligand played critical roles in controlling the catalytic activity and chemo-selectivity. Under the optimized conditions, a variety of unactivated alkenes were successively trifluoromethylated and coupled with N-PMP glycine derivatives, providing facile access to structurally diverse CF₃-containing amino acids, as well as functionalized peptides. In addition, this protocol also demonstrated potential application in the ligation between an alkene-tagged functional molecule and a peptide with a glycine N-terminus.