posted on 1999-06-06, 00:00authored byTarek Sammakia, T. Brian Hurley
This paper describes the mechanism of action of 2-formyl-4-pyrrolidinopyridine (FPP, 1a) which is
a catalyst for the hydroxyl-directed methanolysis of α-hydroxy esters. This species was initially
designed to act as a nucleophilic catalyst; however, we have ruled out a nucleophilic mechanism
by examining the activity of 6-substituted-FPP derivatives. These compounds are more hindered
in the vicinity of the pyridine nitrogen than FPP itself but are also more active catalysts.
Furthermore, the presence of p-nitrophenol, a mild acid, was found to accelerate the catalytic
reaction. These results are inconsistent with a nucleophilic catalysis mechanism. We provide
evidence that the reaction instead proceeds via dioxolanone intermediate 10. Dioxolanone 10 can
be obtained by treating either the p-nitrophenyl ester or the pentafluorophenyl ester of glycolic
acid with FPP in chloroform in the absence of methanol. It has been isolated, characterized, and
shown to be kinetically competent when subjected to the conditions of the catalytic reaction.