Exploring the role of ligands in gold(i)-catalyzed cyclizations: insights from density functional theory

This study uses density functional theory (DFT) to examine the gold(I)-catalyzed cascade cyclization of 1,4-dienyl-tethered 2-alkynylbenzaldehydes. It focuses on how different ligands influence regioselectivity and chemoselectivity. A consistent 6-endo-dig cyclization pathway is found, leading to a metal-bound benzopyran intermediate, regardless of the ligand. The BrettPhos ligand encourages a [3 + 2] cycloaddition with the internal olefin, followed by cyclopropanation to form a polycyclic bridged pyrrolidine. In contrast, SIMes promotes a [3 + 2] cycloaddition with the terminal olefin, resulting in a seven-membered azepine intermediate, which undergoes C(sp³)-H bond insertion to create polycyclic bridged azepines. Distortion/interaction energy analyses, IGMH, and surface distance projections show how these energies affect chemoselectivity. This study not only supports experimental data but also provides useful insights into ligand effects in gold(I)-catalyzed reactions. The calculation results contribute significantly to inorganic and coordination chemistry, offering a theoretical framework for designing gold(I)-catalyzed transformations and expanding our understanding of ligand effects on catalytic selectivity.