Sammakia Tarek, Hurley T. Brian
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215.
J Org Chem. 1999 Jun 25;64(13):4652-4664. doi: 10.1021/jo982281n.
This paper describes the mechanism of action of 2-formyl-4-pyrrolidinopyridine (FPP, 1a) which is a catalyst for the hydroxyl-directed methanolysis of alpha-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.
本文描述了2-甲酰基-4-吡咯烷吡啶（FPP，1a）的作用机制，它是α-羟基酯羟基导向甲醇解反应的催化剂。该物质最初被设计为亲核催化剂；然而，通过研究6-取代-FPP衍生物的活性，我们排除了亲核机制。这些化合物在吡啶氮附近比FPP本身受到的位阻更大，但也是活性更高的催化剂。此外，发现弱酸对硝基苯酚的存在会加速催化反应。这些结果与亲核催化机制不一致。我们提供的证据表明，反应是通过二氧杂环戊酮中间体10进行的。在没有甲醇的情况下，用FPP在氯仿中处理乙醇酸的对硝基苯酯或五氟苯酯，可以得到二氧杂环戊酮10。它已被分离、表征，并在催化反应条件下显示出动力学活性。
