Diastereoselective heterogeneous catalytic hydrogenation of N-heterocycles. Part I. Hydrogenation of pyridines

Abstract

High diastereoselectivities were obtained in the heterogeneous catalytic hydrogenation of chiral picolinic and nicotinic acid derivatives with complete conversion, in non-acidic medium. The effects of catalytic metals, solvents, temperature and pressure on the conversion and the diastereomeric excess (d.e.) were investigated. The hydrogenation of N-picolinoyl-( S)-proline methyl ester ( 1) resulted in 79% d.e. over 10% Pd/C, in methanol, at moderate pressure and temperature (50 bar, 50°C). Very high d.e. (94%) was achieved in the saturation of N-nicotinoyl-( S)-proline methyl ester ( 2) under similar conditions. The hydrogenation of quaternized 1 took place already at room temperature (RT) and 20 bar with almost complete diastereoselectivity (98%), over palladium on carbon, in methanol. These are successful examples of a diastereoselection in the hydrogenation of prochiral pyridines.