Cu-Catalyzed Regioselective and Enantioselective Allylation of Ketones with Allenylsilanes: Mechanistic Insights and Selectivity Origins via Density Functional Theory Analysis

Comprehensive density functional theory investigations were conducted to elucidate the mechanism and ligand-regulated regio- and enantioselectivity in the Cu-catalyzed asymmetric allylation of ketones with allenylsilanes. Reaction pathways involving two distinct ligands were explored, specifically Josiphos-type bidentate phosphine ligand L1 (reaction 1) and P-stereogenic ligand BenzP* L2 (reaction 2). For both catalytic systems, the catalytic cycle comprises catalyst activation, C-C bond formation accompanied by [Cu] migration, turnover-limiting σ-bond metathesis, and desilication. The 1,3-copper shift constitutes the key elementary step governing regioselectivity. Distortion-interaction analysis revealed that deformation energies of both the ligand and substrate constitute the primary determinants of enantioselectivity. With sterically demanding ligand L1, the linear C-C addition transition state exhibits severe substrate distortion, thereby favoring the branched product. Conversely, compact ligand L2 generates stronger noncovalent interactions in the linear transition state, rendering the linear product dominant. Additionally, the high Z-selectivity observed with L2 arises from a combination of reduced structural deformation and enhanced stabilizing interactions. This favorable balance is attributed to the stable synclinal conformation characterized by a dihedral angle of -49.5°. These mechanistic insights establish a predictive framework for the rational design of Cu-catalyzed asymmetric allylation reactions.