Asymmetric Hydrogenation of 3,5-Bistrifluoromethyl Acetophenone in Pilot Scale with Industrially Viable Ru/Diphosphine-Benzimidazole Complexes

A novel efficient asymmetric hydrogenation (AH) process was developed for the preparation of (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethanol (3), using a catalyst Ru/(4R,5R)-(+)-4,5-bis(diphenylphosphinomethyl)2,2-dimethyl-1,3-dioxoane-(R,R-Diop)-2R-(alpha-methylmethanamine)-4,7-dimethyl-1H-benzo[d]imidazole (R-D-Me-BIMAH) in toluene in the presence of potassium t-butoxide. Various hydrogenation parameters, such as ligand, solvent, and substrate-to-catalyst (S/C) ratio, were investigated. The hydrogenation was carried out for four times on a S kg scale at 30 atm and 25 degrees C with S/C of 20 000 with an enantiomeric excess of >89%.