Mechanism of AuCl₃-catalyzed cyclization of 1-(indol-2-yl)-3-alkyn-1-ols: a DFT study.

A computational study with the B3LYP functional was carried out to elucidate the mechanisms of AuCl₃- and AgOTf-catalyzed cyclization of 1-(indol-2-yl)-3-alkyn-1-ols. The theoretical studies suggested that the two main processes, cycloaddition and hydrogen-transfer, are included in all possible reaction pathways. Calculations revealed that AuCl₃ is more effective in catalytic ability than AgOTf to catalyze the cyclization of 1-(indol-2-yl)-3-alkyn-1-ols into carbazole derivatives. More importantly, we found that the ligands of catalysts, Cl⁻ and OTf⁻, are critical in a stepwise proton-transport process involved in intramolecular nucleophilic addition because they act as a proton shuttle to lower the activation free energy barrier of the rate-determining step. The theoretical discovery of the role of ligands of catalysts in hydrogen shift process suggests that AuCl₃- and AgOTf-catalyzed cyclization of 1-(indol-2-yl)-3-alkyn-1-ols can be accelerated when ligands with the property of nucleophile are used. Our theoretical calculations reproduced the experimental results very well. The present study is expected to help understand other transition metal-catalyzed reactions and to give guidance for future design of new catalysts.