Asymmetric Catalytic Hydrogenation. Design of New Ru Catalysts and Chiral Ligands: From Laboratory to Industrial Applications

This Account covers the design of Ru catalysts and ligands. Two classes of chiral phosphine ligands are prepared: the electron-rich trans-2,4-substituted phosphetanes, readily available from optically pure 1,3-diol cyclic sulfates, and atropoisomeric ligands (SYNPHOS, MeO-NAPhePHOS, bearing heterotopic biaryl moieties, and a chiral water-soluble diguanidinium binaphthyl diphosphine, Digm-BINAP). Applications of these ligands to rhodium- and rutheniummediated hydrogenation of ketones and olefins have been reported with high enantioselectivities. The recognition abilities of RuSYNPHOS for a wide range ofketones is superior to those observed with BINAP, MeO-NAPhePHOS, and MeO-BIPHEP. Several biologically active compounds have been prepared through dynamic kinetic resolution. This work gives access to a number of highly active catalysts of the type [Ru(biphosphane)(H)((eta)6-cot))BF4. These catalysts have demonstrated their utility in the enantioselective hydrogenation of the tetrasubstituted cyclopentenone "dehydrodione", which leads to the commercially important perfume component Paradisone (Firmenich).