Nature of proline-induced enantiodifferentiation in asymmetric Pd catalyzed hydrogenations:: Is the catalyst really indifferent?

The mode of enantioselection in the proline modified asymmetric hydrogenation of isophorone (3,5,5-trimethyl-2-cyclohexenone) on supported Pd catalysts has been studied. It is shown that several experimental factors, such as modifier structure and chemical nature of the catalyst support, strongly affect the outcome of the hydrogenations. Secondary kinetic resolution was found to be the major reason for obtaining high enantioselectivities on most catalysts. Extensive studies have been carried out to clarify the importance of the interaction of the proline-dihydroisophorone complex with the catalyst. The secondary kinetic resolution of dihydroisophorone was investigated under different conditions. First, racemic-dihydroisophorone was studied using several (S)-proline modified supported Pd catalysts, then the individual enantiomers were subjected to a similar reaction on Pd/BaCO3 catalyst in the presence of (S)-proline. Our results provide convincing support for the heterogeneous enantioselection model under the current experimental conditions.