Rhodium-catalyzed enantioselective hydrogenation of ketopantolactone

Hydrogenation of ketopantolactone was investigated on a 5 wt.% Rh/Al2O3 catalyst modified by cinchonidine (CD) and its O-methyl (MeOCD) and O-phenyl (PhOCD) derivatives. Weakly polar solvents, moderate pressure, and relatively high modifier/substrate ratios were advantageous for enantioselection. Chiral modification resulted in significant rate acceleration. The major enantiomer was (R)-pantolactone in the presence of CID and MeOCD, while an inversion was observed when using the bulky PhOCD. The similar ees measured with CD and MeOCD indicated that the OH function of CD is not involved in the enantioselection. The nonlinear behaviour of CD-PhOCD mixtures is probably due to the weaker adsorption of the latter modifier on rhodium. The highest ee achieved in this study with CD was 40%, less than half of that reported for CD-modified platinum. The lower efficiency of the rhodium-cinchona system is attributed partly to the weaker adsorption of the modifier and the faster hydrogenation of the quinoline ring of the alkaloid resulting in a gradual loss of enantioselectivity at high pressures. (c) 2005 Elsevier B.V. All rights reserved.