New data to the origin of rate enhancement on the Pt-cinchona catalyzed enantioselective hydrogenation of activated ketones using continuous-flow fixed-bed reactor system

Abstract

A study on the origin of rate enhancement (RE) in the enantioselective heterogeneous catalytic hydrogenation of methyl benzoylformate (MBF), ketopantolactone (KPL) and pyruvic aldehyde dimethyl acetal (PA) under the Orito reaction conditions over Pt catalyst modified with parent cinchona alkaloids, as compared to the unmodified catalyst is presented. The hydrogenations were carried out in continuous-flow fixed-bed reactor system over 20–100 mg Pt/Al 2O 3 catalyst in 1 mL min −1 flow of toluene/acetic acid 9/1 solvent mixture under 40–80 bar H 2 pressure, at 283 or 293 K using 0.044–2 mM modifier concentration and 45 mM substrate concentration. Our results obtained using racemic hydrogenations followed by three changes of the chiral modifier (on the same catalyst) supported the so-called “ligand acceleration” phenomenon in the enantioselective hydrogenation of activated ketones such as MBF, KPL and PA. In our opinion, RE produced by the first modifier added after racemic hydrogenation can also be explained by the purifying effect of the cinchona. REs observed following further exchanges of modifiers are indicative of the intrinsic character of the phenomenon. This research suggested that the origin of enantiodifferentiation and rate enhancement is the same, namely, both may be traced back—probably in different ways—to the role of the intermediate complexes of the hydrogenation, to its formation and transformation, which in turn depends on numerous factors.