Metal-controlled regioselective 1,2-methyl migration in Pt(IV)- and Au(I)-catalyzed cyclizations of indole-derived alkynyl alcohols

Density functional theory calculations were used to investigate the catalyst-controlled regioselective 1,2-migration occurring during the cyclization of indole-derived alkynyl alcohols catalyzed by PtCl4 and the cationic Au(I) species generated in situ from AuCl(PPh3) and AgBF4. Both catalytic systems proceed through metal-assisted 6-endo-dig cyclization, followed by proton transfer and dehydration, and then by 1,2-methyl migration. For PtCl4, an explicit water molecule acts as a proton shuttle and substantially lowers the barrier for dehydration relative to the intramolecular pathway. In the Au(I)-catalyzed reaction, water-assisted proton transfer and dehydration provide the most favorable route to the key migration intermediate. The two catalysts generate electronically distinct migration intermediates, leading to preferential methyl migration toward different carbon centers and accounting for the experimentally observed regioselectivity. Average local ionization energy analysis supports the different reactive-site preferences of the key Pt- and Au-containing intermediates.