Dynamic Coordination Modulation Governs Enantioselectivity in Rhodium-Catalyzed Hydrogenation with Mono- and Bidentate Phosphine Ligands.

The enantioselective hydrogenation of enamides is a fundamental transformation in chiral synthesis. Although mono- and bidentate phosphine ligands have been widely employed in this reaction, the origin and differences in their enantiomeric induction abilities remain incompletely understood, representing a long-standing gap in mechanistic knowledge. In this work, the catalytic mechanisms of rhodium-phosphine (Rh-P) catalysts are systematically investigated to elucidate the enantioselectivity differences between mono- and bidentate phosphine ligands. The results reveal that the dynamic modulation of the relative strengths of the two Rh-P bonds during the reaction is critical for achieving catalytic asymmetry. While the phosphine bridge facilitates electron transfer, its structural constraints reduce the flexibility of this modulation; consequently, mono(phosphine) ligands, which lack such a bridge, exhibit enhanced enantioselectivity. These findings are consistent with experimental observations and offer new insight into how the electronic and structural features of ligands govern enantioselectivity. This study advances the fundamental understanding of asymmetric hydrogenation and informs the rational design of next-generation chiral phosphine catalysts.