Nucleophilic reactivity of amines with an α-formylglycyl enol-tosylate fragment

The E-enol-tosylate of S-3-benzyl-6-formylpiperazine-2,5-dione reacts with 1°- and 2°-amines to yield its respective 3S-benzyl-6E-endiamine products while a 3°-amine, DABCO, exclusively yields a bis-3,6-ylidenepiperazine-2,5-dione product. These competitive reaction pathways with amine electron donors are shown to arise mechanistically via the same intermediate, or its tautomers, with an H-bond assisted nucleophilic substitution process being operative in the former case and an elimination reaction pathway in the latter instance.

Graphical abstractThe competitive reaction of an amine in aprotic polar solvent with 1 selectively yields 3 or 4 via intermediate [2] dependent on the protic or aprotic nature of the electron donor.Download full-size image