The regioselectivity in the gold-catalyzed cycloisomerization of alcohols: A full DFT study on carbene versus non-carbene mechanisms

The mechanistic study of in the gold-catalyzed cycloisomerization of alcohols or amine tethered-vinylidenecyclopropanes has been performed using high-level DFT calculations to find the reasons of the observed selectivity of the products. Two possible pathways were observed, which in the first product, during the cyclization process, the vinylidenecyclopropane moiety converts to methylidenecyclopropane-containing product (P1) via an ionic (non-carbene) intermediate and in the second product, converts to cyclobutene-containing product (P2) via a carbene intermediates. In all six examined derivatives (containing different alkyl group at C1 allenic carbon) P2 was the major product by both thermodynamic (the more stability of P1 than P2) and kinetic (the smaller barrier for producing P2 versus P1) criteria in both gas phase and solvent (THF, using PCM model) media. However, in the derivatives with low-strain allenic group (R), I1 (which leads to P1) is more stable than I3 intermediates (which leads to P2) by 0.6–4.2 kcal/mol in the gas phase and 1.0-3.1 kcal/mol in the solvent and the derivatives with high-strain allenic group, I3 is more stable than I1 by 2.1–2.5 kcal/mol in the gas phase and 3.5–4.2 kcal/mol in the solvent. Therefore, both gas phase and solvent data show that because of the different hinderance between alkyl group and gold cation complex, the selectivity of the reaction is yielded by the favorability of I1 or I3 intermediates. Interestingly, another evidence was provided by atomic charges in the reactants using NBO calculations. These calculations showed that when the atomic charge of C1 allenic carbon was higher than C3, the gold cation prefers to produce I1, leading to P1, and when the atomic charge of C3 allenic carbon was higher than C1, the gold cation prefers to produce I2, leading to P2.