Use of the Trost Ligand in 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 ligand in the asymmetric hydrogenation (AH) of ketones. Ligand (S,S)-L was screened in the presence of several metal salts and found to form active catalysts when combined with ruthenium sources in the presence of hydrogen and a base. Reaction optimization was carried out by screening different Ru sources, solvents and bases. Under the optimized conditions, the complex formed by combination of (S,S)-L with RuCl3(H2O)x in the presence of Na2CO3, is able to promote the AH of several ketones at r.t. with good yields and 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 is transformed into the catalytically active complex by reaction with hydrogen. Remarkably, ketone S8, precursor of the antiemetic drug Aprepitant, was hydrogenated with excellent yield and good ee.