Synthesis of Chiral Dipeptides by means of Asymmetric Hydrogenation of Dehydro Dipeptides

Asymmetric hydrogenation of various dehydro dipeptides was carried out by using rhodium complex catalysts with a variety of chiral diphosphine ligands. The efficiency of chiral diphosphine ligands as well as the effect of the chiral center in the substrate on the catalytic asymmetric induction was studied. It was found that extremely high stereoselectivities for producing the S,S, R,S, S,R, or R,R isomer were achieved with the proper choice of chiral ligands although a considerably large double asymmetric induction was observed in some cases. Pyrrolidinodiphosphines, e.g., Ph-CAPP, p-BrPh-CAPP, BPPM, CBZ-Phe-PPM, and diPAMP, exhibited excellent stereoselectivities, whereas chiraphos, prophos, and BPPFA only gave poor results especially for the reaction of N-acyldehydro dipeptide which had a free carboxylic acid terminus. Stereoselective dideuteration was also successfully performed.