Computational Study on Gold-Catalyzed Cascade Reactions of 1,4-Diynes and Pyrroles: Mechanism, Regioselectivity, Role of Catalyst, and Effects of Substituent and Solvent

This study is devoted to a theoretical investigation of the mechanism, regioselectivity, role of catalyst, and effect of substituent and solvent in the Au-catalyzed cascade reaction between 1,4-diynes and pyrroles. Density functional theory (DFT) calculations indicate that this reaction comprises four principal stages: (1) formation of different intermediates through the first intermolecular hydroarylation, (2) 1,3-H transfer to give the enyne intermediates, (3) a second intermolecular hydroarylation, and (4) a second proton transfer along with Au­(I) catalyst regeneration and final product formation. In addition, the computational results suggest that the first regioselectivity is determined by the electronic effects of the reagents. However, the torsional strains within the transition structures (intramolecular cyclization) and electronic effects of enyne intermediates would account for the second regioselectivity. A global reactivity index (GRI) analysis for different gold catalysts (namely, IPrAu⁺, PPh₃Au⁺, BrettPhosAu⁺, and JohnPhosAu⁺) shows the important role of the catalyst in enhancing the electrophilicity of 1,4-diynes, thus making possible a nucleophilic attack between the 2-position of pyrrole and the C¹ or C² position of the 1,4-diyne substrate. In addition, the effects of substituent and solvent were also analyzed in detail and discussed. Apart from being in good agreement with experimental data, the obtained DFT results also provide a notable contribution toward an understanding of the reaction mechanism