Role of Chiral Skeleton in Chiral Phosphoric Acids Catalyzed Asymmetric Transfer Hydrogenation: A DFT Study

Chiral phosphoric acids (CPAs) have received considerable attention due to their high activity for enantioselective transformations. However, the role of various chiral skeletons of CPAs in regulating the mechanism and enantioselectivity of asymmetric transfer hydrogenation has remained unclear. Density functional theory (DFT) calculations are performed to elucidate the role of chiral skeletons on the acidity, mechanism, enantioselectivity, and kinetic stabilities of transition states (TSs) in Asymmetric Transfer Hydrogen (ATH) reaction catalyzed by five CPAs. We found that the acidity of CPAs is strongly dependent on the chiral skeleton. The origin of enantioselectivity of ATH reaction arises from the differential noncovalent interactions between TSs and CPAs. Moreover, the shape and size of the catalyst pocket depending on chiral skeletons play key roles in the stability of TSs and the enantioselectivity of ATH. This study might facilitate to design and computationally screening of CPAs and guide the strategic choice of CPA skeletons to reduce the experimental workload.