Noyori asymmetric hydrogenation

In chemistry, the Noyori asymmetric hydrogenation of ketones is a chemical reaction for the enantioselective hydrogenation of ketones, aldehydes, and imines. This reaction exploits using chiral ruthenium catalysts introduced by Ryoji Noyori. He shared half of the Nobel Prize in Chemistry in 2001 with William S. Knowles for the study of the asymmetric hydrogenation.The stoichiometric asymmetric reduction of ketones has long been known, but a practical catalytic version was introduced by Noyori et al. While the BINAP-Ru dicarboxylate could only efficiently catalyze the hydrogenation of olefins, the BINAP-Ru dihalide could catalyze both the hydrogenation of olefins and the hydrogenation of functionalized C=O bond.(A) The BINAP-Ru dihalide precatalyst gets hydride from H2 and forms Ru-monohydride Reaction intermediate while giving off HCl. (B) The ruthenium center of the catalyst coordinates to the oxygen atoms in the ester compound. Because of the chirality of the BINAP ligand, one of the two possible diastereomeric transition states is favored (The transition state on the left is favored over the other because of the large R1/ Ph steric hindrance). (C) Ester gets proton, and hydride transfers from the catalyst to the carbonyl carbon. (D) Hydrogenated ester compound leaves the catalyst and solvent coordinate back to the catalyst. The (R)-BINAP-Ru catalyze the synthesis the (R)-Product, and the (S)-BINAP Ru catalyze the synthesis the (S)-product with high ee. (E) Again, the dehydrated BINAP-Ru catalyst is utilized by the addition of another hydride from H2. The newly activated Ru-monohydride re-participates in the catalytic cycle.Further developed from previously introduced BINAP-Ru dicarboxylate catalyst, the BINAP-Ru dihalide catalyzes the asymmetric hydrogenation of various α-,β- functionalized ketones. The reaction is limited to ketones that are functionalized with nearby nitrogen, oxygen or halide substituents.An antibacterial levofloxacin is synthesized using (R)-1,2-propandiol, which is synthesized from hydroxyacetone using Noyori asymmetric hydrogenation (Takasago Co./Daiichi Pharmaceutical Co.).