Heterogeneous asymmetric reactions: Part 17. Asymmetric hydrogenation of 2-methyl-2-pentenoic acid over cinchona modified Pd/Al2O3 catalysts Original Research Article

The enantioselective hydrogenation of 2-methyl-2-pentenoic acid (MPA) over a cinchona modified 5% Pd/Al2O3 catalysts is described. The main experimental variables studied were the MPA/catalyst and the cinchonidine (CD)/MPA ratios, the effect of ultrasonic irradiation and the modifier structure. Low MPA/catalyst ratio was found to be advantageous for obtaining enhanced enantioselectivity, while higher CD/MPA ratios resulted in increasing enantioselectivities according to a saturation type curve. The ultrasonic pretreatment (similarly to α-ketoesters) also slightly increased the enantiomeric excesses. These modifications of the CD–Pd/Al2O3 system, resulted in enantioselectivities up to 66% ee (0°C, 10 min sonication, CD/MPA=0.5, 50 bar H2 pressure) for (S)-2-methyl-pentanoic acid. The variation of the modifier structure provided unique information about the nature of the cinchona–substrate interaction. It has been revealed that the OH group of the alkaloid should be involved in the substrate–modifier interaction which more likely occurs in the liquid phase. An intermediate with refined structure is proposed and the mechanism is suggested to be of stoichiometric nature.