Transition metal catalysts particularly those based on chiral ruthenium (Ru) phosphine complexes are known to be effective for the asymmetric hydrogenation of ketones. EP-B-0718265 describes the use of chiral Ru-bis(phosphine)-1,2-diamine complexes for the hydrogenation of ketones to produce chiral alcohols. Similarly, WO 01/74829 describes a chiral Ru-Phanephos-1,2-diamine complex for the asymmetric hydrogenation of ketones.
Although it is accepted that the combination of bis(phosphine) and the chiral diamine ligands are important for achieving a high enantiomeric excess (ee) and a wide range of phosphine ligands has been described, only 1,2-diamine ligands have been widely used heretofore. By the term “1,2-diamines” we mean diamines wherein the carbon atoms to which the amine functionalities are bound are directly linked. Such diamines include chiral substituted ethylenediamine compounds such as (S,S)-diphenylethylenediamine ((S,S)-Dpen). Without wishing to be bound by any theory we believe that this is due to the perceived need for the resulting conformationally-stable 5-membered ring structure that forms when 1,2-diamines co-ordinate to the metal atom. Larger ring structures, for example those formed using 1,3- or 1,4-diamines can be less conformationally-stable and therefore may be expected to provide catalysts that give lower enantiomeric excesses than the corresponding catalysts prepared using 1,2-diamines.
Accordingly the chiral catalysts used heretofore comprise 1,2-diamines and have relied principally upon variation of the structure of the phosphine ligand to improve their enantioselectivity. Although effective for some substrates such as acetophenone, a range of ketone and imine substrates remain unreactive to the existing catalysts or are obtained with undesirably low enantiomeric excesses.