Catalytic Asymmetric Hydrogenation and Cyanation Using Chiral Ruthenium Complexes

The development of catalytic asymmetric reactions with high reactivity and stereoselectivity is a central issue in the synthetic organic chemistry. The precise and rational design of catalysts is key to achieving this goal. We have studied catalytic asymmetric hydrogenation and cyanation using our original chiral ruthenium (Ru) complexes. These Ru complexes, each bearing a chiral diphosphine ligand and an amine-based ligand, exhibit excellent catalytic activity and enantioselectivity for the hydrogenation of ketones under neutral to slightly basic conditions. Mechanistic studies suggest that this high catalytic performance is attributed to a six-membered pericyclic-type transition state (metal-ligand cooperative transition state). The chiral environment can be readily tuned by changing the combination of these two ligands. As a result, a wide variety of simple and functionalized ketones were successfully subjected to the asymmetric hydrogenation. Imino compounds and several chiral esters were also smoothly converted to the corresponding amines and primary alcohols, respectively, in a highly stereoselective fashion. The resulting Ru complexes also showed excellent catalytic performance in the enantioselective isomerization of primary allylic alcohols, affording the aldehydes in nearly optically pure form. Combined systems consisting of amino acidate/diphosphine-Ru complexes and lithium compounds acted as effective catalysts for the asymmetric cyanosilylation of various aldehydes and both simple and functionalized ketones. The Ru·Li bimetallic complexes were isolated as crystalline compounds, and these efficiently catalyzed the asymmetric hydrocyanation of aldehydes. These combined catalytic systems were also successfully applied to the asymmetric conjugate cyanation of α,β-unsaturated ketones and acylpyrroles. The Strecker-type reaction of N-alkoxycarbonyl aldimines and α-ketimino esters with the combined catalysts afforded the corresponding aminonitriles in high enantioselectivity. This article provides an overview of the catalyst-design concepts and the catalytic performance achieved in asymmetric hydrogenation and cyanation.