Direct/Reversible Amidation of Troponyl Alkylglycinates via Cationic Troponyl Lactones and Mechanistic Insights.

The conversion of troponyl alkylglycinate acid/ester/amide derivatives ( acid/ester/amide) into cationic troponyl lactones () in the presence of trifluoroacetic acid and their amidation with amines is described. The reversible amidation of amides, that is, the cleavage and reformation of the amide bond via is demonstrated. The direct amidation of esters with the amino group of amino acid esters/peptide esters via is achieved. The direct amidation of the amine group of hydroxyl amino acid esters is selective over esterification. The amide bond is stable under basic ester hydrolysis and Fmoc removal conditions. Hence, the troponyl alkylglycinates could be applicable as protecting groups for amine functionality of amino acids and peptides. The reaction mechanism was investigated by using a deuterium probe and studied by NMR and electrospray ionisation mass spectrometry techniques. Deuterium incorporation at α-CH strongly supported the formation of via ketene intermediates.