Asymmetric hydrogenation of 1-phenylpropane-1,2-dione over cinchona-modified Pt: Role of the C-9 OH group of cinchonidine

1-Phenylpropane-1,2-dione was hydrogenated over chirally modified 5% Pt/Al2O3 catalyst at 10 bar H2 and 15 °C using toluene and acetic acid as solvents. The highest enantiomeric excess for the major product (R)-1-hydroxy-1-phenyl-2-propanone (image) was obtained using cinchonidine as the chiral modifier. The presence of the hydroxyl group in the C-9 position of the modifier was important for achieving high enantioselectivity. When the C-9 hydroxyl group of cinchonidine was replaced by a methoxy group enantioselectivity was lost and a small 2% excess of (S)-1-hydroxy-1-phenyl-2-propanone enantiomer was observed. In acetic acid the reaction with cinchonidine proceeded yielding a 7% excess of the (R)-product. Hydrogenation of the intermediate hydroxyketones in acetic acid using cinchonidine or 9-methoxy-10,11-dihydrocinchonidine as chiral modifiers gave the corresponding (1S,2R)-diol in 67 and 78% enantiomeric excesses, respectively. By changing the solvent from acetic acid to toluene, an inversion of enantioselectivity took place yielding the (1R,2S)-diol as the main product in 38% ee. A mechanism was proposed involving a two-step cycle (reactant–modifier) and a three-step cycle (reactant-modified acetic acid) in order to account for the observed enantioselectivities.