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

[Image: see text] The conversion of troponyl alkylglycinate acid/ester/amide derivatives (Trag acid/ester/amide) into cationic troponyl lactones (CTLs) in the presence of trifluoroacetic acid and their amidation with amines is described. The reversible amidation of Trag amides, that is, the cleavage and reformation of the Trag amide bond via CTLs is demonstrated. The direct amidation of Trag esters with the amino group of amino acid esters/peptide esters via CTLs is achieved. The direct amidation of the amine group of hydroxyl amino acid esters is selective over esterification. The Trag 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(2) strongly supported the formation of CTLs via ketene intermediates.