Gold-catalyzed domino cyclization to diverse polyheterocyclic frameworks: mechanism, origin of the cooperative hydrogen bond, and role of π-stacking interactions

Abstract

The detailed mechanism and origins of gold-catalyzed domino cyclization to diverse fused polyheterocyclic frameworks by cooperative catalysis and cascade catalysis were studied systematically. Specifically, different from cascade catalysis mechanisms proposed previously, the gold-counterion dual catalysis mechanism was the most plausible mechanism for domino cyclization because of its cooperative hydrogen bond, low activation energy, and favorable π-stacking stabilization interactions in transition states (TSs) and intermediates. Based on the Curtin–Hammett principle, the calculated activation energy of 33.3 kcal mol⁻¹ was the rate-determining step for the overall reaction. Besides, the energy profiles for three different models (i.e. catalysts without the OTf⁻ counterion or BF4⁻ counterion; use of (benzo)furans and pyrroles as substrates; modification of the substrate's phenol group by a substituent) were investigated to confirm the interplay of cooperative hydrogen bonds and π-stacking stabilization interactions in a cooperative dual catalysis mechanism. Thus, the obtained theoretical results not only rationalized the experimental results, but also provided insights into the details of the domino cyclization.