Heterogeneous enantioselective hydrogenation of ethyl pyruvate catalyzed by cinchona-modified Pt catalysts: Effect of modifier structure

The effect of the structure of chiral modifiers derived from natural cinchona alkaloids on the enantioselectivity and rate of the Pt/Al2O3-catalyzed hydrogenation of ethyl pyruvate was investigated. The influence of the following structural elements was studied: the cinchonidine versus the cinchonine backbone; effect of the nature and the size of substituents attached to C-9; effect of partial hydrogenation of the quinoline ring; effects of changes of the substituent at the quinuclidine moiety. The strongest effects on ee and somewhat less on rate were observed for changes in the O-C-9-C-8-N part of the cinchona alkaloid and for partial or total hydrogenation of the quinoline rings. The nature of the substituents in the quinuclidine part had a comparably minor influence. The solvent was found to have a significant effect on enantioselectivity and rate. In acetic acid, the best results were obtained with O-methyl-10,11-diydroeinchonidine tee's up to 93%), whereas dihydrocinchonidine was the most effective modifier in toluene. In agreement with a basic model proposed by Pfaltz, it was concluded that the minimal requirements for an efficient modifier for the hydrogenation of a-keto esters is the presence of a basic nitrogen:center close to one or more stereogenic centers and connected to an aromatic system. The results are in qualitative agreement with mechanistic models based on hydrogen-bonding interactions between an adsorbed modifier molecule and adsorbed ethyl pyruvate or its half-hydrogenated intermediate.