Chiral Phosphine-Aminophosphine Ligands for Copper-Catalyzed Asymmetric Hydrogenation

New chiral bidentate phosphine-aminophosphine ligands based on a pentane-2,4-diyl backbone, with the general formula Ph2PCH(CH3)CH2CH(CH3)N(R1)PR22 (R1 = Me, Et, nPr, nBu, iPr; R2 = Ph, Cy), have been developed and applied in the copper-catalyzed asymmetric hydrogenation of simple ketones. The addition of achiral monodentate phosphines as co-ligands significantly enhanced both catalytic turnover and enantioselectivity. It was observed that the steric properties of the ligands predominantly influence catalytic activity and enantioinduction, whereas their electronic characteristics play a secondary role. Comprehensive screening of reaction conditions, including variation of the metal source and careful selection of both chiral and achiral ligands with appropriately tuned stereochemistry, enabled the hydrogenation to proceed with low catalyst loadings (0.5 mol%) while maintaining high yields and enantioselectivities (up to 92% ee) across a broad substrate scope. Based on experimental findings and relevant literature precedents, a mechanistic proposal is presented to explain the observed reactivity trends.