Use of the Trost Ligand in the Ruthenium-Catalyzed Asymmetric Hydrogenation of Ketones

The Trost ligand, (1S,2S)-1,2-diaminocyclohexane-N,N'-bis(2'-diphenylphosphinobenzoyl) (L), is reported for the first time as a ligand for the asymmetric hydrogenation (AH) of ketones. Ligand (S,S)-L was screened in the presence of several metal salts and was found to form active catalysts if combined with ruthenium sources in the presence of hydrogen and a base. Reaction optimization was performed by screening different Ru sources, solvents, and bases. Under the optimized conditions, the complex formed by the combination of (S,S)-L with RuCl3(H2O)(x) in the presence of Na2CO3 was able to promote the AH of several ketones at room temperature in good yields with up to 96% ee. The reaction kinetics measured under the optimized conditions revealed the presence of a long induction period, during which the initially formed Ru species was transformed into the catalytically active complex by reaction with hydrogen. Remarkably, a ketone that is a precursor of the antiemetic drug aprepitant was hydrogenated in excellent yield with a good ee value.