The reactivity of phosphate esters. Multiple structure–reactivity correlations for the reactions of triesters with nucleophiles

Abstract

The reactivities of a wide range of nucleophiles towards the phosphorus centre of a series of dialkyl substitutedphenyl phosphate esters are sensitive to changes in both the nucleophile and the leaving group. The sensitivity parameters, obtained from linear free-energy relationship equations, are themselves sensitive to the reactivity of the system and a single equation, correlating changes in both the nucleophile and the leaving group, is derived for the reactions of oxyanion nucleophiles. The sensitivity to the leaving group of the rate constant for nucleophilic attack is lower for more basic nucleophiles, and reaches a lower limit for nucleophiles much more basic than the leaving group. This and other observations favour, but do not require, an interpretation in terms of a two-step mechanism involving a quinquecovalent addition intermediate. Among several close similarities to the corresponding reactions of carboxylate esters is a change in mechanism from nucleophilic to general base catalysis of hydrolysis as the nucleophile becomes markedly less basic than the leaving group. Neutral hydrolysis involves general base catalysis in this way, and is an unexpectedly slow reaction.