Conformational and solvation aspects of the chorismate–prephenate rearrangement studied by ab initio electronic structure and simulation methods

Abstract

The effect of water on the energetics of the Claisen rearrangement of chorismate to prephenate has been investigated with both a continuum model (PCM) and explicit solvation within a Monte Carlo (MC) free energy perturbation (FEP) treatment. Both models are surprisingly similar in their quantitative predictions. Solvation is shown to increase the conformational flexibility in the reactant by reducing the energy difference between the diequatorial and diaxial structures, and to lead to a considerable reduction in the barrier to the reaction. The estimate of the activation barrier, 22 kcal mol^-1, is very close to the experimental value of 24.5 kcal mol^-1. The implications of the various possible conformers on kinetic isotope effects are discussed.