Density-Functional Theory Calculation of acetal hydrolysis under mild conditions

Abstract

Protection of the hydroxyl group is essential for multi-step syntheses of structurally-complex chemicals such as natural products. Moreover, the protective group removal in those molecules under mild conditions is significant especially when the molecules are not so stable. We have reported mild deprotection method of methoxymethyl ether using the combination of TMSOTf and pyridine derivatives in dichloromethane. The reaction has two steps; the first step is the formation of a pyridinium salt from the reaction of pyridine derivatives and TMSOTf, and the second step is the hydrolysis between the pyridinium salt and water molecule. In the second step, we found that the reaction rate and the yield depended on the pyridine derivatives. For example, although the reaction was succeeded in the case of 2,2'-bipyridyl, 2,4,6-collidinium salt made it fail. In order to reveal the major reasons of the variation, we successfully carried out DFT computations in order to find the transition state structures of the hydrolysis reactions. In this study, B3LYP was used as a functional and 6-311G* basis set was adopted.