The scope of the asymmetric hydrogenation of functionalized ketones over cinchona-modified platinum was extended to achiral α-hydroxyketones. Cinchonidine showed by far the best catalytic performance affording an enantiomeric excess between 57 and 82% depending on the substrate. O-methoxy-cinchonidine showed poor enantioselection. O-phenoxy-cinchonidine favoured the opposite enantiomer compared to cinchonidine. Solvents with empirical solvent parameters E_T ^N – ranging from 0.10 to 0.65 were tested. Tert-butylmethylether proved to be the most suitable. The highest ratio of substrate/cinchonidine where no loss in e.e. was observed was at around 540, independent of the structure of the α-hydroxyketone. The oxygen in α-position to the ketone seems to play an important role in the enantioselection as well as a phenyl ring or a rigid cis-conformation. The dependence of the enantiomeric excess on the modifier structure and the inversion of the sense of enantiodifferentiation is interpreted in terms of repulsive interactions, which become more evident as the steric demand of the functional group (OH, O-Me, O-Ph) of the modifier increases. The findings indicate that a hydrogen bond in the modifier reactant complex involving the hydroxyl functionality of cinchonidine is not crucial in order to achieve high enantioselectivity.

Alumina-supported rhodium modified with cinchonidine has been investigated with regard to its applicability in the enantioselective hydrogenation of various aromatic ketones possessing an α-hydroxy or α-methoxy group. The study revealed that depending on the substrate, rhodium can outperform the catalytic behavior of platinum. With one of the substrates, 2-hydroxy-1-(4-methoxy-phenyl)-ethanone (4), an enantiomeric excess (ee) of 80% at 89% conversion was reached, which is the highest ee reported so far for chirally modified rhodium. However, completely different conditions are required to achieve optimal catalytic performance with rhodium, compared with platinum. Rhodium requires a much higher modifier concentration, and high hydrogen pressure is favorable. The higher modifier concentration required is traced to the much higher activity of rhodium for the hydrogenation of the quinoline ring, which is assumed to be the anchoring moiety of the cinchona modifiers on the platinum group metals. Changing the modifier from cinchonidine to O-phenoxy-cinchonidine resulted in a switch of the major enantiomer of the product, as exemplified for 2-hydroxyacetophenone (1), which showed a switch from 73% ee in favor of the (R)-product to 68% ee for the (S)-product when the modifier was changed from cinchonidine to O-phenoxy-cinchonidine.