A Revised Mechanism for the Mitsunobu Reaction

Article abstract of DOI:10.1021/jo00228a016

In contrast to previous studies, a 31P NMR examination of the Mitsunobu reaction using a poorly nucleophilic acid (CF3COOH) to retard intermediate reactions reveals a dual mechanism.Depending on the order of addition of the reactants, the reaction proceeds (a) exclusively by slow conversion of a protonated betaine to an alkoxyphosphonium salt or (b) by rapid conversion of a dialkoxyphosphorane to the same alkoxyphosphonium salt, with recycling of the liberated 1/2 equiv of alcohol by pathway (a).Sodium benzoate dramatically accelerated the reaction, resulting in trifluoroacetate esters in high yields.This latter result provides the basis for an unusually mild procedure for the inversion of certain secondary alcohols.