Diastereoselective hydrogenation of a tricyclic α,β-dehydrodipeptide

An unsaturated diketopiperazine derivative with a tricyclic α,β-dehydrodipeptide structure was isolated as a reaction intermediate in the hydrogenation of pyrazine-2-(methyl-(S)-prolinecarboxamide). The diastereoselective hydrogenation of this dehydrodipeptide was studied using various noble metals (Pd, Pt, Rh, and Ru) supported on charcoal. The hydrogenation over Pd, Rh, and Ru catalysts proceeded with a high diastereoselectivity (71–79%), and the diastereomer with the (S)-configuration on both chiral carbon atoms was formed preferentially. The reaction rates and diastereoselectivities of the hydrogenation over the Pd, Rh, and Ru catalysts were similar, while the platinum catalyst was much less active and selective (48% d.e.). The obtained results were compared with those of the hydrogenation of pyrazine-2-(methyl-(S)-prolinecarboxamide); two different pathways for the hydrogenation of this molecule were suggested. In one path, cyclization already occurs after hydrogenation to the tetrahydropyrazine molecule, and in the other path cyclization occurs after full hydrogenation of the pyrazine molecule.