Enantioselective hydrogenation of ethyl pyruvate catalyzed by α- and β-isocinchonine-modified Pt/Al 2O 3 in toluene: inversion of enantioselectivity

Abstract

The enantioselective hydrogenation of ethyl pyruvate (EtPy) in toluene was studied on a Pt-alumina catalyst modified with α-isocinchonine ( α-ICN) and β-isocinchonine ( β-ICN). The effects of the modifier concentration, temperature, and hydrogen pressure on the reaction rate and the enantioselectivity were examined. Using the Engelhard 4759 catalyst under mild experimental conditions, we observed the formation of an excess of ( S)-ethyl lactate (EtLt) in the presence of α-ICN formed (ee max: 27%). In the case of β-ICN, an inversion of enantioselectivity was observed and ( R)-EtLt formed in excess (ee max: 50%). α-ICN mainly undergoes hydrogenation during the reaction, followed by desorption, whereas β-ICN works as a chiral modifier, and the hydrogenation of EtPy is the main transformation. The results of ESI-MS-MS, HPLC-ESI-ion-trap-MS, NMR, UV–vis measurements, and experiments with modifier mixtures strongly suggest that β-ICN, with a rigid, open conformation, is responsible for enantioselection and inversion. The proposed structure of the intermediate responsible for the inversion of enantioselectivity is a 1:1 β-ICN–EtPy surface complex in which the β-ICN acts as a nucleophile and binds EtPy.