The Uronium/Guanidinium Peptide Coupling Reagents: Finally the True Uronium Salts

The strict exclusion of tertiary amines during the otherwise standard synthetic approach to the synthesis of the guanidinium-type peptide coupling reagents HBTU (X = CH, see scheme) and HATU (X = N) allows the synthesis of the uronium-type isomers of these guanidinium compounds, whose existence was until now pure speculation. These O isomers (O-HBTU and O-HATU) are more efficient coupling reagents than the N isomers.