Metal-free approach for hindered amide-bond formation with hypervalent iodine(iii) reagents: application to hindered peptide synthesis

Abstract

A new bio-inspired approach is reported for amide and peptide synthesis using α-amino esters that possess a potential activating group (PAG) at the ester residue. To activate the ester functionality under mild metal-free conditions, we exploited the facile dearomatization of phenols with hypervalent iodine(III) reagents. Using a pyridine–hydrogen fluoride complex, highly reactive acyl fluoride intermediates can be successfully generated, thereby allowing for the smooth formation of sterically hindered amides and peptides from bulky amines and α-amino esters, respectively.