Role of carbocation's flexibility in sesquiterpene biosynthesis: computational study of the formation mechanism of terrecyclene.

Two mechanisms have been proposed in the literature to explain the formation of the skeleton of terrecyclic acid from farnesyl diphosphate. Both mechanisms satisfy the experimental data obtained using isotopic labeling, but computational results at the mPW1B95/6-31+G(d,p) level of theory allow the differentiation between them. While one of the mechanisms is basically a carbocation cascade, the other one requires several steps that imply high energetic demands. Specifically, there is a [1,3] hydride shift that requires approximately 100 kcal/mol making this mechanisms unlikely. The other mechanism is more plausible, and it suggests the participation of two secondary carbocation as intermediates, but these were not observed as minimums on the potential energy surface analyzed; they only appear as a point near the transition state in the intrinsic reaction coordinate. Both mechanisms proposed a [1,3] hydride shift, but in the less likely mechanism, the rigidity of the intermediate that undergoes the hydride shift greatly increases the energy of the corresponding transition state.