6-spiro-1,4-diazepane-2,5-diones by head-to-tail N1/C2 amide bond formation
L.W.A. van Berkom, R. de Gelder, H.W. Scheeren.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 2005, 5, 907-916

Abstract:
The synthesis of a series of 6-spiro-1,4-diazepane-2,5-diones containing an arylpropylamide moiety via head-to-tail cyclisation of a terminal amine and a terminal carboxylate ester is described. To induce ring closure of the dipeptide precursor, both lactamisation of the N4/C5 amide bond and N1/C2 amide bond were investigated. Whereas ring closure of the N4/C5 amide bond proved unsuccessful, ring closure of the N1/C2 amide bond was more viable. Furthermore, it was discovered that incorporation of a N,N-disubstituted amide bond in the peptide sequence was essential for cyclisation to occur.