| Abstract
| - We have studied the proline-directed, Pd-catalyzed enantioselective hydrogenation of isophoronein the liquid state using a variety of methods. Our results unambiguously reveal the true reaction pathwayand demonstrate that all earlier mechanistic hypotheses are wrong: although a proline/isophoronecondensation product is formed, it is merely a spectator and not a key reaction intermediate in subsequentheterogeneous hydrogenation. Enantioselectivity is the result of kinetic resolutiona process that occurshomogeneously in solution and not at the metal surface. Racemic 3,3,5-trimethylcyclohexanone (TMCH)is produced by initial heterogeneous hydrogenation of isophorone; proline then reacts homogeneously,preferentially with one enantiomer of TMCH, leaving an excess of the other. Thus in complete contrast tothe case of ketoester asymmetric hydrogenation, the metal surface is not involved in the crucial enantio-differentiation step. The mechanism we propose also explains why the maximum attainable yield ofenantiopure TMCH cannot exceed 50%.
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