Theoretical Simulations of Heavy-Atom Kinetic Isotope Effects in Aliphatic Claisen Rearrangement.

The aliphatic Claisen rearrangement of allyl vinyl ether has attracted great interest for its broad applications in chemical synthesis and biosynthesis. Although it is well agreed that this reaction proceeds via a concerted, "chair-like" transition state, certain inconsistencies of kinetic isotope effect (KIE) data between experimental measurements and theoretical simulations or between independent experiments indicate that the nature and mechanism of this important reaction need to be investigated in more detail. In order to verify two independent sets of experimental data, we present theoretical calculations on heavy-atom KIE values of alipahtic Claisen rearrangement, using our recently developed path-integral method with the second-order Kleinert's variational perturbation theory, which goes beyond the traditional method for computing KIE values by employing the Bigeleisen equation. Amazingly, the results demonstrate that both sets of experimental measurements are correct, while the inconsistency originates from the fact that the aliphatic Claisen rearrangement undergoes similar but different mechanisms in gas and solution phases. Different experimental conditions will alter the actual reactant state by tuning the population distribution of reactant conformers. According to the comparison between experimental and theoretical results, a more clear reaction mechanism of aliphatic Claisen rearrangement is revealed.