Diastereoselective Hydrogenation of Substituted Aromatics on Supported Metal Catalysts

Abstract

The purpose of this work was to hydrogenate disubstituted aromatic compounds on supported metal catalysts to produce enantiomers of the corresponding cyclohexane derivatives using a diastereoselective approach, i.e., associating the organic substrates with chiral auxiliaries. The diastereoselective catalytic hydrogenation of N -(2-methylbenzoyl)-( S )-proline methyl ester was performed on carbon-supported metal catalysts, optionally modified by the adsorption of EDCA (ethyldicyclohexylamine). The formation of cis -diastereoisomers predominated and a cyclohexenic compound was formed transiently. After cleavage of the proline ester auxiliary, optically active 2-methylcyclohexane carboxylic acids were obtained. The influence on reaction kinetics and diastereoselectivity of various factors were investigated on Rh/C catalysts; these factors were pressure, substrate concentration, particle size, and thermal pretreatments of the rhodium catalysts modified with an amine. The reaction rate and the diastereoisomeric excess were found to be very sensitive to these parameters as well as to the presence of water on the catalyst. The importance of the nature of the metal (Rh, Ru, Pt, Pd) was clearly demonstrated. Pt and Pd showed very low activity. Without addition of amine, unmodified rhodium catalysts were nonselective as long as the aromatic substrate was present, whereas the ruthenium catalysts produced moderate selectivity. In the latter case, the carbonyl and carboxyl groups of the molecule could interact with the surface, thus determining which face of the aromatic ring would be preferentially adsorbed. Then, because of the consecutive hydrogenation of the cyclohexenic compound, diastereoselective excesses (d.e.) of 17 and 32%, respectively, were observed in favor of the (1R,2S,2S) isomer. In the presence of an achiral amine (e.g., EDCA) on rhodium catalysts, d.e. attaining ca. 50% were measured in favor of the (1S,2R,2′S) isomer. No inversion of configuration was observed with modified ruthenium, probably because the aromatic substrate is more strongly bonded to the surface than in the case of rhodium and thus displaces the amine. In contrast, the aromatic substrate is weakly bonded to platinum and palladium compared to the EDCA molecules which block the surface. In the absence of amine, the weaker adsorption of the aromatic substrate is responsible for the formation of trans products.