The Noyori asymmetric hydrogenation of ketones is an excellent example of dynamic kinetic resolution at work. The enantiomeric β-ketoesters can undergo epimerization, and the choice of chiral catalyst, typically of the form Ru[(R)-BINAP]X, where X is a halogen, leads to one of the enantiomers reacting preferentially faster. The relative free energy for a representative reaction is shown below. As can be seen, the epimerization intermediate is lower in free energy than the transition states for hydrogenation, resulting in rapid racemization and high yields of a single enantiomer of the product.
The enantiomers interconvert through their common enol, which is the energetic minimum located between the enantiomers. The shown reaction yields a 93% ee sample of the anti product shown above. Solvent choice appears to have a major influence on the diastereoselectivity, as dichloromethane and methanol both show effectiveness for certain substrates. Noyori and others have also developed newer catalysts which have improved on both ee and diastereomeric ratio (dr).
Genêt and coworkers developed SYNPHOS, a BINAP analogue which forms ruthenium complexes, which perform highly selective asymmetric hydrogenations. Enantiopure Ru[SYNPHOS]Br was shown to selectively hydrogenate racemic α-amino-β-ketoesters to enantiopure aminoalcohols, as shown below utilizing (R)-SYNPHOS. 1,2-syn amino alcohols were prepared from benzoyl protected amino compounds, whereas anti products were prepared from hydrochloride salts of the amine.