Methylethers of cinchona alkaloids in Pt-catalyzed hydrogenation of methyl benzoylformate and pyruvaldehyde dimethyl acetal -: Part 2:: Effect of stereochemical factors on the enantioselectivity

The enantioselective hydrogenation of methyl benzoylformate (MBF) and pyruvaldehyde dimethyl acetal (PA) was investigated under mild experimental conditions on Pt-alumina catalyst modified with MeOCD, MeOCN, MeOQN and MeOQD alkaloid derivatives in acetic acid (AcOH) and in toluene (T). Besides low rate high ee's were achieved (> 90%) in the case of PA using MeOCD and MeOQN modifiers in AcOH. Under similar experimental conditions in the case of MBF the highest ee's (50-80%) were obtained in T. Hydrogenation in the presence of MeOCN and MeOQD proceeded with low ee's, namely 4-8% for MBF in AcOH and 40-50% for PA in T. Studies on the hydrogenation of MBF and PA suggested that the low ee are attributable to repulsive interactions of OMe and ethyl groups of the modifiers with the substrates and with Pt surface. The formation of the complex responsible for enantioselection and, as a consequence, for high ee may be presumed to necessitate a two-point interaction between the cinchona alkaloid and the substrate. The two-point interaction requires a closer geometrical fit as compared to a one-point interaction, while the cinchona alkaloid and the substrate are bound to active sites of the catalyst through the quinoline skeleton and the oxo group to be hydrogenated, respectively. These new experimental results can be interpreted on the basis of adsorbed 1: 1 interaction model not only of electrophilic mechanism but also in toluene by the nucleophilic mechanism, too. (c) 2008 Elsevier B.V. All rights reserved.