Enantioselective hydrogenation of ethyl pyruvate catalyzed by α- and β-isocinchonine-modified Pt/Al2O3 in acetic acid

The enantioselective hydrogenation of ethyl pyruvate (EtPy) was studied on Pt-alumina catalysts modified by high-purity α-isocinchonine (α-ICN) and β-isocinchonine (β-ICN) in AcOH. The effect of the modifier concentration, temperature, and hydrogen pressure on the reaction rate and the enantioselectivity was examined. Using the Engelhard 4759 catalyst under medium experimental conditions (273 K, hydrogen pressure of 25 bar, α-ICN concentration of 1 mmol/L) an optical yield of 93–94% can be achieved. In the case of β-ICN, maximum ee is 70–72% (297 K, 20 bar, β-ICN concentration of 1 mmol/L); at the same time, the rate of EtPy hydrogenation is higher than in the case of dihydrocinchonine (DHCN) or α-ICN. Chiral modifiers themselves are converted under the conditions of hydrogenation. The results of ESI-MS, ESI-MS-MS, HPLC-MS, and desorption measurements strongly suggest that α-ICN and β-ICN compounds with a rigid structure are responsible for chiral induction, since DHCN and hydrogenated products of DHCN were not identifiable among the reaction products. These experimental results support the earlier assumption that it is cinchona alkaloids in the “open 3” (in another terminology “antiopen”) conformation that participate in enantioselection. However, based on other experimental observations of this work, the participation of other, so far unknown factors in enantioselection may not be excluded either.