Biaryl diphosphine ligands and their ruthenium complexes: preparation and use for catalytic hydrogenation of ketones

Abstract Procedures for the preparation of the nucleophilic diphosphine ligands (R)-(4,4',6,6'-tetramethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) ((R)-Ph-Garphos, 2a) and (S)-(4,4',6,6'-tetramethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) ((S)-Ph-Garphos, 2b) were described. The ligands were used to prepare the ruthenium(II) Ph-Garphos complexes, chloro(p-cymene)(R)-(4,4',6,6'-tetraamethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine)ruthenium(II) chloride ([RuCl(p-cymene)(R)-Ph-Garphos]Cl (3)) and chloro(p-cymene)(S)-(4,4',6,6'-tetraamethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine)ruthenium(II) chloride ([RuCl(p-cymene)(S)-Ph-Garphos]Cl (4)). In the presence of the chiral diamine co-ligands (1R,2R)-1,2-diphenylethane-1,2-diamine (R,R-DPEN) and (1S,2S)-1,2-diphenylethane-1,2-diamine (S,S-DPEN), complexes 3 and 4 were found to be active catalyst precursors for the enantioselective reduction of aryl ketones under mild conditions (room temperature and 3-4 atm of H2). The chiral alcohols were isolated in moderate to good yields and with enantioselectivities of up to 93%. The ruthenium complexes, chloro(p-cymene)(R)-(4,4',6,6'-tetramethoxybiphenyl-2,2'-diyl)bis(bis(3,5-dimethylphenyl)-phosphine)ruthenium(II) chloride ([RuCl(p-cymene)(R)-Xyl-Garphos]Cl (5)) and chloro(p-cymene)(S)-(4,4',6,6'-tetramethoxybiphenyl-2,2'-diyl)bis(bis(3,5-dimethylphenyl)-phosphine)ruthenium(II) chloride ([RuCl(p-cymene)(S)-Xyl-Garphos]Cl (6)), were also prepared and used as catalyst precursors for the hydrogenation of aryl ketones in the presence of (R,R)-DPEN and (S,S)-DPEN. Significant improvements in the enantioselectivities of the alcohols (up to 98% ee.) were afforded. A combination of 6 and (S,S)-DPEN afforded (R)-1-(3-methoxyphenyl)ethanol in 89% yield and with 95% ee which was shown to be a suitable precursor for the preparation of (S)-rivastigmine.