Asymmetric synthesis of 2-methyl cyclohexane carboxylic acids by heterogeneous catalysis: Mechanistic aspects

The catalytic hydrogenation of (S)-alkyl-N-(2-methylbenzoyl)pyroglutamates was studied over supported rhodium and ruthenium catalysts at room temperat ure and a pressure of 5 MPa. The reaction was diastereoselective with the p redominant formation of (1S,2R)-2-methylcyclohexane carboxylic acid with a diastereomeric excess (de) of up to 96%. The most stable conformation was d etermined by means of a combination of modelling calculations, NMR spectros copy and X-ray structural determination. In this conformation, the carbonyl group of the pyroglutamate auxiliary shields one face of the aromatic ring . The observed selectivity may thus be explained by a preferential adsorpti on at the unshielded face which avoids steric repulsion by the C=O group to result in a cis hydrogenation. The addition of an amine, the nature of the support (alumina or active carbon) or of the metal (Rh or Ru) were shown t o give additional stabilisation of the adsorption at the unshielded face to increase the diastereoisomeric excess.