Diastereoselective Synthesis of an Argatroban Intermediate, Ethyl (2R,4R)-4-methylpipecolate, by means of a Mandyphos/Rhodium Complex-catalyzed Hydrogenation

The synthetic antithrombotic argatroban is a dipeptide between the nonproteogenic (2R,4R)-4-methyl-2-piperidine carboxylic acid and L-arginine, in turn bonded to a methyltetrahydroquinoline sulfonyl group. An extensive screening of transition metal-based complexes with different ligands was performed in order to identify the best catalyst for the diastereoselective hydrogenation of the suitable 4,5-dehydropiperidine aimed towards the synthesis of the (2R,4R)-4-methyl piperidine moiety.