Mechanistic Insights into Palladium-Catalyzed 1,4-Hydrofunctionalization of 1,3-Enynes through a Coordination-Induced Orbital Polarization Framework

Abstract Palladium-catalyzed 1,4-hydrofunctionalization of 1,3-enynes provides a powerful and atom-economical approach to multisubstituted allenes. Despite extensive synthetic developments, the fundamental origin of activation mode selection and regioselectivity in these transformations remains elusive. Herein, we propose a coordination-induced orbital polarization (CIOP) framework that describes how established metal–substrate orbital interactions associated within different Pd coordination environments generate distinct site-dependent redistributions of frontier-orbital character across the conjugated enyne π-system. These electronic responses provide a common basis for rationalizing activation mode selection and regioselectivity. The applicability of the CIOP framework was examined through density functional theory investigations of Pd-catalyzed hydroboration, hydroamination, and hydrosilylation. Across all three reaction classes, the calculated orbital polarization patterns were consistent with the experimentally observed activation pathways and site selectivities. These findings support CIOP as a unified interpretative framework for relating metal coordination, enyne electronic structure, and catalytic divergence across the Pd-catalyzed hydrofunctionalization reactions examined in this study.