The diastereoselective hydrogenation of N-(2-methylbenzoyl)-(S)-proline methyl ester 1 into optically active 2-methylcyclohexane carboxylic acids was studied on rhodium catalysts supported on active carbon, graphite and alumina. The diastereoselectivity was highly dependent upon the nature of the support. Without modification of the catalysts by EDCA, a 40% d.e. was measured over Rh/Al(2)O(3), in contrast to Rh/C or Rh/G catalysts which were unselective. The adsorption of the aromatic substrate via a specific face on Rh/Al(2)O, was interpreted in terms of electronic and/or steric factors on the basis of TEM and XPS studies. EDCA addition had comparatively little effect on the initial rates and d.e. of Rh/Al(2)O(3), because the amine was preferentially adsorbed on the acidic sites of the alumina support. In contrast, the d.e. of carbon-supported catalysts increased from 0 to ca. 50% upon EDCA addition. The diastereoselectivity of Rh/Al(2)O(3) catalyst was higher after thermal treatments under hydrogen prior to hydrogenation reaction. The optimization of rhodium-based catalysts (support and thermal pretreatment) and of reaction conditions (solvent, addition of amine) led to a final d.e. of 68%.
