Unexpected inversion in enantioselectivity in the hydrogenation N-acetyl dehydrophenylalanine methyl ester using cinchona-modified Pd/Al₂O₃ catalyst

The enantioselective hydrogenation of N-acetyl dehydrophenylalanine methyl ester (NADPME) to N-acetyl phenylalanine methyl ester is investigated using cinchona-modified Pd/Al2O3 catalysts. The catalyst was prepared using deposition-reduction and was evaluated for the reaction using methanol as solvent with various cinchonine alkaloid/NADPME molar ratios. Enantioselectivity was sensitive to this ratio. For cinchonine at low cinchonine:NADPME molar ratios the S-N-acetyl phenylalanine methyl ester was formed with low enantioselection, and as the cinchonine:NADPME ratio was increased the reaction became less enantioselective. In the extreme the solubility of cinchonine limited the extent of the experimental conditions that could be explored. As expected cinchonidine modified Pd/Al2O3 initially gave R-N-acetyl phenylalanine methyl ester, again with low enantioselection. However, as the cinchonidine:NADPME molar ratio was increased the reaction initially became racemic and then was selective to the formation of S-N-acetyl phenylalanine methyl ester. This unexpected inversion in the sense of enantioselection was observed in a range of solvents.