Enantioselective hydrogenation of N-acetyl dehydrophenylalanine methyl ester using cinchonine-modified Pd/TiO₂ catalysts

The enantioselective hydrogenation of N-acetyl dehydrophenylalanine methyl ester (NADPME) to N-acetyl phenylalanine methyl ester is investigated using cinchonine-modified Pd/TiO2 catalysts. The catalysts were prepared using deposition-reduction and wet impregnation methods and were evaluated for reaction using methanol as solvent with various cinchonine/NADPME molar ratios. Enantioselectivity was sensitive to this ratio and comparison with Pd/gamma-Al2O3 showed that the Pd/TiO2 gave marginally higher enantioselectivity when tested under comparable conditions. The effect of Pd loading and dispersion was investigated and the maximum enantiomeric excess observed was dependent on the dispersion: the role of the Pd particle size is discussed in the context of cinchonine adsorption. The reactions were carried out in solvents (methanol and dimethyl formamide) and mixed solvents (methanol-water and dimethyl formamide-water); the enantionteric excess was significantly enhanced using dimethyl formamide. The addition of water does not have a significant effect for the Pd/TiO2 catalysts. In this paper we report the highest enantiomeric excess for the hydrogenation of a prochiral ester using an iminobilised catalyst. (c) 2006 Elsevier B.V. All rights reserved.