Diastereoselective Hydrogenation of Pyrazine Derivatives: An Alternative Method of Preparing Piperazine-(2S)-Carboxylic Acid

The diastereoselective hydrogenation of a chiral pyrazine derivative was used for the stereoselective preparation of piperazine-2-carboxylic acid, which is an important chiral building block. The study was focused on the diastereoselective hydrogenation with various noble metal catalysts (Pd, Pt, Rh, Ru) on different supports. It was found that intramolecular cyclization of the substrate takes place during the hydrogenation, forming an unsaturated diketopiperazine derivative. This intermediate was further hydrogenated to a mixture of saturated heterocyclic diastereomers. The influence of the reaction conditions (temperature, pressure of hydrogen, and type of solvent) on the diastereoselectivity was also studied. The highest diastereoselectivity (79%) was reached with 10% Pd/C and with water as solvent. The desired molecule of piperazine-2-carboxylic acid was finally obtained by acidic hydrolysis of the diastereomeric diketopiperazine adduct.