Fundamental insights into the enantioselectivity of hydrogenations on cinchona-modified platinum and palladium

The influence of the configuration at the C8 and C9 positions of cinchona alkaloids was investigated by comparing the efficiency of cinchonidine, cinchonine, and 9-epi-cinchonidine as chiral modifiers. In the hydrogenation of ketones (methyl benzoylformate, ketopantolactone, methylglyoxal dimethylacetal, 2,2,2-trifluoroacetophenone) on Pt, a change in the configuration at C9 did not affect the absolute configuration of the main products; however, the ees and rates dropped significantly. In the hydrogenation of α-functionalized olefins (E-2-methyl-2-hexenoic acid, 2-phenylcinnamic acid, and 4-methoxy-6-methyl-2H-pyran-2-one) on Pd, replacement of cinchonidine or cinchonine by epi-cinchonidine diminished the rates and almost eliminated the enantioselection, indicating that a subtle combination of C8 and C9 configurations is required on Pd. DFT calculations of the adsorption of the modifiers and the nonlinear behavior of modifier mixtures revealed that the lower reaction rates observed for 9-epi-cinchonidine-modified surfaces cannot be related to different adsorption strength of this modifier. Additionally, substrate–modifier docking interactions are presented. A comparison between cinchonidine, cinchonine, and 9-epi-cinchonidine (or 8-epi-cinchonine) as chiral modifiers in seven different hydrogenation reactions revealed the importance of both C8 and C9 configurations on Pt, and the critical role of their appropriate combination on Pd. View high quality image (130K) ⺠The role of C8 and C9 configurations of cinchona modifiers was studied. ⺠9-Epi-cinchonidine (or 8-epi-cinchonine) was synthesized. ⺠The C9OH group of cinchona alkaloids is involved in the enantioselection on Pt. ⺠Induction of rate enhancement is not a requirement for an efficient modifier of Pt. ⺠The right combination of C8 and C9 configurations is required on Pd.