Recent Developments in Asymmetric Hydrogenation with Chiral Ru(II) Catalysts and Synthetic Applications to Biologically Active Molecules

Abstract

Among all the possible methods of creating optically active compounds, enantioselective catalysis using chiral transition metal complexes is the most effective methods since a small amount of chiral material can, in principle, produce a large amount of optically active product. The enantioselective hydrogenation of prochiral C=C and C=X (X=N,O) double bonds constitutes a powerful technology to establish chirality at stereogenic carbon atoms. This tool has enabled the chemist to compete successfully with nature in the creation of enantiomerically pure compounds. The Rh(I) complexes bearing chiral tertiary phosphines are remarkable catalysts in the hydrogenation of dehydroamino acids1,2,3,4. Optimisation of the conditions made it possible for the industrial production of several amino acids5. In spite of such impressive achievments and improvments in the design of new ligands for rhodium(I) catalysts , the scope of asymmetric hydrogenation is not so wide. A breakthrough came by the discovery of hexacoordinated ruthenium catalysts containing the highly effective axially symmetric BINAP ligand 7,8 . A disguishing feature of theses catalysts is their universality, they are suitable for enantioselective hydrogenation of wide range of substrates9. In the application of such technology to the synthesis optically active compounds in perfumery, food industry and drugs research, chemists are facing the task of designing broad libraries of chiral catalysts. Therefore developments of chemistry which allows preparation of wide range of chiral ruthenium catalysts is highly desirable for a rapid screening. As part of our research programm we have initiated and developed a novel and general route for the preparation of chiral ruthenium (II) catalysts. Such chemistry and the usefulness of these catalysts will be briefly presented with the successful development of enantioselective hydrogenation of prochiral substrates including olefins and functionalized ketones. Moreover, several applications in the synthesis of various complex biologically active molecules will be reported.