Large rate enhancement for the hydrolysis of a four-membered ring phosphonamidate

Abstract

Unlike β-lactams a four-membered cyclic 1,2-azaphosphetidine shows enhanced hydrolytic reactivity compared with an acyclic analogue; the cyclic phosphonamidate 3 undergoes hydroxide-ion catalysed hydrolysis in water with endocyclic P–N fission; a corresponding acyclic derivative hydrolyses with P–O fission in basic solution, the rate difference between the cyclic and acyclic structures for P–N fission is greater than 5 × 10⁸.