New Developments in Chiral Ruthenium (II) Catalysts for Asymmetric Hydrogenation and Synthetic Applications

Abstract

This chapter covers catalytic asymmetric synthesis effected by chiral ruthenium (II) complexes. New general and useful methods for the synthesis of diphosphine ruthenium (II) complexes : (P*P)RuX2 (X = carboxylato, 2-methylallyl, halide), P*P =, BIPHEMP, MeO-BIPHEP, BINAP DIPAMP, DIOP, CHIRAPHOS, DUPHOS etc., as well as hydrido and dinuclear chiral ruthenium complexes are reviewed. These catalysts were evaluated in asymmetric hydrogenation reactions of prochiral substrates. Allylic alcohols, α- and β- acylamino acrylic acids, enamides, α- and β-keto esters, diketones were easily reduced to give the corresponding saturated products in good yields. High efficiency is displayed by Ru catalysts having atropisomeric ligands and C2 symmetric bis phospholanes (e.g. Me-DUPHOS, Et-DUPHOS and iPr-BPE). Chirally labile compounds capable of undergoing in situ racemization were hydrogenated with high diastereoselectivity (syn or anti) and high enantioselectivity. This reaction provides a powerful tool, dynamic kinetic resolution, for the synthesis of chiral compounds. Applications of these processes, particularly significant in the preparation of synthetic intermediates and pharmaceuticals, are summarized.