Abstract:
The invention relates to a novel class of ruthenium complexes containing phosphine and hybrid amine ligands, their preparation and use as catalysts in the reduction of simple ketones to alcohols by molecular hydrogenation. The reactivity and enantioselectivity of such complexes in the asymmetric hydrogenation of simple ketones could be enchanced by the addition of some selective additives.

Description:
THE FIELD OF INVENTION 
       [0001]    The invention relates to a novel class of ruthenium complexes containing phosphine and hybrid amine ligands, their preparation and use as catalysts in the reduction of simple ketones to alcohols by molecular hydrogenation. The reactivity and enantioselectivity of such complexes in the asymmetric hydrogenation of simple ketones can be enchanced by the addition of some additives. 
       BACKGROUND ART 
       [0002]    Asymmetric catalytic hydrogenation is an area of intensive research within asymmetric synthesis. [Ohkuma, T.; Kitamura, M.; Noryori, R. (1999) Asymmetric Hydrogenation. In:  Catalytic Asymmetric Synthesis,  2 nd Ed . (Ed.: Ojima, I.). Wiley-VCH, New York, 2000], [ The Handbook of Homogeneous Hydrogenation  (Ed.: de Vries, J. G, Elsevier, C. J.). Wiley-VCH: Weinheim, 2007; Vol. 1-3.]. The efficiency and usefulness of the process is examplified by several industrial applications so far developed. [ Asymmetric Catalysis on Industrial Scale  (Ed.: Blaser, H.-U.; Schmidt). Wiley-VCH, Weinheim, 2004]. 
         [0003]    Chiral alcohols are one of the important chiral compounds in the pharmaceutical, agrochemical and fine chemical industries, with asymmetric hydrogenation of ketone substrates the most effective way for the preparation of chiral alcohols. Noyori&#39;s research group have achieved the asymmetric hydrogenation of ketones by applying the concept of bifunctional catalysis in designing complexes of the type trans-RuCl 2 (diphosphane)(1,2-diamine). In the presence of bases like t-BuOK or KOH, these type of complexes can catalyse the asymmetric hydrogenation of simple ketone substrates with excellent enantioselectivity and catalytic efficiency. [Noyori, R.; Takeshi, 0.; Hirohito, O. Shohei, H.; Takao, I.  J. Am. Chem. Soc.  1995, 117, 2675], [Noyori, R.; Ohkuma, T.; Douce, H.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England, A. F.; Ikariya, T.,  Angew. Chem. Int. Ed.  1998, 37, 1703]. With various combinations of new design bidentate ligands, such complexes have been successfully used in the asymmetric hydrogenation of a wide range of ketone substrates. [Jing, W.; Hua, C.; Waihim, K.; Rongwei, G; Zhongyuan, Z.; Chihung, Y.; Chan, A. S. C.,  J. Chem. Soc.  2002, 67, 7908], [Jing, W.; Jian, X.; Rongwei, G; Chihung, Y.; Chan, S. C.,  Chem. Eur J.  2003, 9, 2963], [Jian, H. X.; Xin, L. W.; Fu, Y.; Shuo, F. Z.; Bao, M. F.; Hai, F. D.; Zhou, Q. L.  J. Am. Chem. Soc.  2003. 125, 4404], [Mark, J.; William, H.; Daniela, H.; Christophe, M.; Antonio, Z. G  Org. Lett.  2000, 26, 4173]. 
         [0004]    Recently Noyori&#39;s group has devised a new catalyst, RuCl 2 (phosphane)(α-picolylamine). By changing the diamine ligand to a hybrid amine ligand having structural motif of NH 2 —N(sp 2 ), they can reduce ketones having a sterically bulky tert-butyl group on the α-position to the corresponding chiral secondary alcohol. This type of catalyst is by far the most active hydrogenation catalyst toward these particularly difficult ketone substrates. It is worth noting that the chiral tert-butyl alcohols are important for the preparation of some useful chiral surfactants. The common Ru complex of diphosphine-diamine type can only result in low conversion and low enantioselectivity (&lt;20% e.e and conversion) in the reduction of these particular class of ketone substrates. [Ohkuma, T.; Sandoval, C. A.; Srinivasan, R.; Lin, Q.; Wei, Y; Muniz, K.; Noyori R.  J. Am. Chem. Soc.  2005, 127, 8288.]. 
         [0005]    The major drawback for all aforementioned NH 2 -ligand containing catalyst systems is the necessary use of protonic solvents and basic conditions during the hydrogenation reaction. The employment of protonic solvents may limit the scope of ketone substrates being applied in this catalytic hydrogenation methodology due to solubility issues, and also unfavorably interact with additional functionalities when more elaborate substrates are involved. Furthermore the difficulties on accessing a wide range of vicinal chiral diamine ligands are another limitation for the preparation of such catalyst systems. After our systematic study on the mechanism of this ketone reduction using RuCl 2 (phosphane)(α-picolylamine or 1,2-diamine) as hydrogenation catalyst, we are able to design a new class of ruthenium complexes having a new hybrid NH 2 —N(sp 2 ) structural motif as bidentate amine ligand that can catalyse the hydrogenation of simple aryl ketone in both aprotonic (e.g. toluene, THF) and protonic solvents, in contrast to current catalyst system that only work in protonic solvents. 
       SUMMARY OF THE INVENTION 
       [0006]    One of the objects for this invention is to provide a new class of ruthenium complexes, which contain both phosphine and hybrid amine ligands featuring the NH 2 —N(sp 2 ) structural motif. 
         [0007]    Another aspect of the invention is to provide a preparation process of the aforementioned ruthenium complexes by using the readily available hybrid chiral amine ligands. 
         [0008]    A further aspect of the invention is the use of the said complexes in the catalytic asymmetric hydrogenation of simple ketone substrates, particular the catalytic asymmetric hydrogenation of simple ketones with aryl or unsaturated alkyl group on a-position, diaryl ketones and their analogues, ketones having bulky alkyl group on a-position, ketones having heteroaromatic group on a-position, α-phenyl-β-N,N-dimethylalkyl ketones and their analogues, and other simple aryl-alkyl ketone substrates. 
         [0009]    A further aspect of the invention is the use of the said ruthenium complexes in the catalytic hydrogenation of simple ketones in both protonic and aprotonic solvents. 
         [0010]    A further aspect of the invention is the use of additives with the said ruthenium complexes in the catalytic hydrogenation of ketones. The use of some additives can improve the rate of the hydrogenation or the enantioselectivity in the reaction. The additives can be selected from the group of monodentate tertiary phosphines or monodentate tertiary amines, such as triphenylphosphine, tri(4-methoxyphenyl)phosphine, tri(3,5-dimethylphenyl)phosphine, tri(3-methylphenyl)phosphine, diphenyl-2-naphthyl phosphine, triethylamine. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0011]    The invention therefore provides the ruthenium complexes with a general formula (I) [RuLmL′XY] in which, 
         [0012]    X and Y can be equal or different, X can be a halogen (Cl, Br, I) or hydrogen, Y can be a halogen (Cl, Br, I) or BH 4  correspondingly. 
         [0013]    L is the ligand selected from the following groups: 
         [0014]    a) monophosphine having general formula PR 1 R 2 R 3 , wherein R 1 , R 2 , R 3  can be equal or different and be aliphatic alkyl groups or aromatic groups having from 1 to 6 carbon atoms; 
         [0015]    b) bidentate phosphine with general formula R 5 R 6 P—R 4 —PR 7 R 8 , wherein R 4  represented an organic hydrocarbon backbone that can be chiral or achiral; R 5 , R 6 , R 7  and R 8  can be equal or different, and be aliphatic alkyl group or aromatic groups having from 1 to 10 carbons; 
         [0016]    with m become 2 in the case of equal monodentate phosphine ligands selected from a), and m become 1 in case of a bisphosphine selected from b). 
         [0017]    L′ is the bidentate hybrid amine ligand selected from the following groups (II to V): 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 9  can independently be hydrogen, alkyl groups having 1 to 6 carbon atoms, when R 9  is not a hydrogen, the aforementioned hybrid amine ligands (II to V) are chiral ligands having either R or S configuration; the alkyl group for R9 is selected from the groups comprising methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary-butyl, isopentyl, cyclopentyl, isohexyl, cyclohexyl, phenyl. 
         [0018]    R 10 , R 11 , R 12  can be independently hydrogen or alkyl groups, aryl groups, arylalkyl groups, each having up to 12 carbon atoms; the alkyl groups can be selected from the group comprising methyl, ethyl, propyl, butyl, isobutyl, tertiary-butyl, pentyl, hexyl, isopentyl, cyclopentyl, cyclohexyl; the aryl groups can be selected from phenyl, substituted phenyls, the arylalkyl group can be selected from benzyl, alkyl-substituted benzyl. 
         [0019]    A can be independently alkyl, alkoxy, aryl, each having from 1 to 8 carbon atoms; A can also be independently hydrogen, halogen, nitro, amino, sulfonic acid; n is an integer from 1 to 4 equal to the number of unsubstituted aromatic ring carbons; the alkyl group for A is selected from the groups comprising methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary-butyl, isopentyl, cyclopentyl, cyclohexyl, fluoromethyl, trifluoromethyl; alkoxy group for A can be methoxy, ethoxy, tertiary-butoxy; aryl group for A can be phenyl, substituted phenyl, benzyl and substituted benzyl. 
         [0020]    The aforementioned hybrid amine ligands can be conveniently prepared with methods known in the art of organic synthesis. 
         [0021]    The said Ru complexes represented by the general formula (I) can be further illustrated by the following general structures as: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0022]    The complexes can be trans or cis configuration, in which P represents the phosphine ligands that coordinate to the ruthenium as defined above (vide supra); the phosphine ligands used in this invention include but not limit to the following: triphenyl phosphine, BINAP and its analogue bisphosphine having binaphthyl or substituted binaphthyl backbone, BIPHEP and its analogue bisphosphines having biphenyl or substituted biphenyl backbone, JOSIPHOS and similar bisphosphine with a ferrocene or substituted ferrocene backbone, DIOP, chiraphos, skewphos, norphos, segphos, phanephos etc. 
         [0023]    The structure 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    represents the bidentate hybrid amine ligands that can be selected from the groups represented by formula II, III, IV and V as above; X can be hydrogen, halogen, Y can be hydrogen, halogen or BH 4 . 
         [0024]    The complexes representing by formula I can be prepared by ligand replacement methods known in the art. Usually the said complexes can be prepared by mixing the ruthenium compounds, the hybrid amine ligands, bidentate or monodentate phosphine ligands in organic solvents under 20˜120° C. for 0.5˜20 hours. The reaction molar ratio for the ruthenium compound, amine ligand and phosphine ligand can be 1:1˜3:1˜5, the phosphine ligand is represented by structure P, bidentate amine ligand is represented by structure formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    in which P and R 9  are denoted as above. When monodentate phosphines are employed, the molar ratio for rethenium compound, amine ligand and monodentate phosphine ligand is 1:1˜3:3˜5, the recommended ratio is 1:2:4; when bidentate phosphines are employed, the molar ratio become 1:1˜3:1˜3, the recommended ratio is 1:2:2. The ruthenium metal compounds can be the halogenide of Ru complexes or their derivatives, such as [RuX 2 (C 6 H 6 ) 2 ] 2 , RuX2(PPh 3 ) 3 , RuX 3 , wherein X is the halogen (Cl, Br, I). 
         [0025]    Their preparation can be illustrated by the following reaction scheme using the ruthenium complexes as example: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0026]    When the Y is BH 4  in the complex of the said general formula, its preparation can be described here: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0027]    In the reaction scheme, P represents the phosphine ligand as defined above. 
         [0028]    The solvents used in all above synthetic schemes can be organic solvents selected from benzene, dimethyl benzene, trimethyl benzene, acetonitrile, diethyl ether, THF, dimethyl ethylene ether, chloroform, dichloromethane, methanol, ethanol, isopropanol, N—N-dimethylformamide, N—N-dimethylacetamide, DMSO, N-methylpyrrole etc. 
         [0029]    The preparation of the said Ru complexes and chiral amine ligands of this invention is simple to operate. The said Ru complexes are useful as catalyst in the hydrogenation of simple ketones, particularly the asymmetric hydrogenation of ketones having aryl or unsaturated alkyl group on α-position, ketones having bulky alkyl group on α-position, diaryl ketones and its derivatives, ketones having heteroaromatic group on α-position, β-N—N-dimethylamino-α-phenyl ketones and its derivatives, and other simple alkyl-aryl ketones. When the said Ru complexes are being used in the hydrogenation of simple ketones, the said Ru complexes can be prepared in situ for the hydrogenation reaction. 
         [0030]    The catalytic reactivity of the said ruthenium complexes can be enhanced with the use of some additives, the additives can be selected from the groups of monodentate tertiary phosphines or monodentate tertiary amines, such as triphenylphosphines, tri(4-methylphenyl)phosphines, tri(4-methoxyphenyl)phosphine, tri(3,5-dimethylphenyl)phosphine, triethylamine etc. It is also found that such type of additives can also increase the enantioseletivity of the said ruthenium complexes in the asymmetric hydrogenation of simple ketones when the said ruthenium complexes are chiral. The molar ratio for the additives against the ruthenium metal is in the range of 3˜1:1 (additive:Ru). 
         [0031]    The invention can be illustrated by the following examples, and these examples are not intended to limit the scope of the invention. 
       A. Synthesis of Ruthenium Complexes 
       [0032]    Synthesis of Complexes using C 2  symmetric bis-P ligands (DIOP, BINAP, Cl-MeO-BIPHEP, SEGPHOS, PhanePHOS, DIPAMP, DuPHOS, BDPP, CHIRAPHOS, PPM, PYRPHOS) uses the compound [RuCl 2 (benzene)], RuCl 2 (PPh 3 ) 3  and trans-RuCl 2 (NBD)(py) 2  as the starting material, while the complexes were prepared in accordance with the procedure published in the literature (Noyori, R.; Takeshi, O.; Hirohito, O. Shohei, H.; Takao, I.  J. Am. Chem. Soc.  1995, 117, 2675; Akotsi, O. M.; Metera, K.; Reid, R. D.; McDonald, R.; Bergens, S. H.  Chirality  2000, 12, 514-522; BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, DIOP=4,5-Bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxolane, Cl-MeO-BIPHEP=5,5′-Dichloro-6,6′-dimethoxy-2,2′-bis(diphenylphosphino)-1,1′-biphenyl, SEGPHOS=5,5′-Bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole, PhanePHO S=4,12-Bis(diphenylphosphino)-[2.2]-paracyclophane,DIPAMP=1,2-Bis[(2-methoxyphe-nyl)(phenyl)phosphino]ethane, Me-DuPHOS=1,2-Bis((2S,5S)-2,5-dimethylphospholano)benzene,BDPP=2,4-Bis(diphenylphosphino)pentane, CHIRAP HO S=Bis(diphenylphosphino)butane, PYRPHO S=3,4-bis(diphenylphosphino)-Pyrrolidine, PPM=4-(diphenylphosphino)-2-[(diphenylphosphino)methyl]-Pyrrolidine. Synthesis of Complexes using C 1  symmetric bis-P ligand (JosiPHOS, WalPHOS, MandyPHOS) uses the compound RuCl 2 (PPh 3 ) 3  as the starting material which can be obtained easily from hydrated RuCl 3  and PPh 3  (Steohenson, T. A.; Wilkinson, G.  J. Inorg. Nucl. Chem.  1966, 28, 945-956; Josiphos=1-[Diarylphosphano]-2[1-(dicyclohexylphosphano) ethyl]ferrocene.), while the complexes and RuCl 2 [(R,S)-Josiphos](PPh 3 ) were prepared in accordance with the procedure published in the literature (Baratta, W.; Ballico, M.; Chelucci, G.; Siega, K.; Rigo, P.  Angew. Chem. Int. Ed.  2008, 47, 4362-4365). The monochloride complex (11) was prepared from (10) by reacting with Et 3 N. The pre-catalysts used for in situ hydrogenation were [RuCl 2 BINAP(pyridine) 2 , RuCl 2 DIOP-(pyridine) 2 , RuCl 2 (Josiphos)(pyridine) 2 ]. As non-limiting examples of the present invention the synthesis and the characteristics of the complexes (8-25) are described in detail. All the syntheses were carried out under argon atmosphere, using freshly distilled solvents. 
       Example 1 
     Synthesis of C 1  Symmetric Complex RuCl 2 [(R,S)-Josiphos][(S)-Me-bimaH][(RS,S)-8] 
       [0033]    
       
                 
         
             
             
         
       
     
         [0034]    RuCl 2 (PPh 3 ) 3  (250 mg, 0.26 mmol) or trans-RuCl 2 (NBD)(py) 2  (110 mg, 0.26 mmol) and (R,S)-Josiphos (165 mg, 0.26 mmol) were dissolved in CH 2 Cl 2  (5 mL) and placed in a 20-mL Schlenk under an Ar atmosphere. Ar was bubbled through the solution for 5 min and the solution was stirred for 12 h. Following solvent removal under vacuum, (S)-Me-BimaH [(S)-Me-7] (42 mg, 0.26 mmol) was added together with degassed toluene (2 mL). The suspension was then heated at 100° C. for 4 h. Reduction of the volume to ca. 0.5 mL and addition of ether (5 mL) yielded a yellow precipitate. The supernatant was removed by filtration and the resulting powder was dried in vacuo to give 8 as a mixture of isomers. 
         [0035]    Yield 190 mg (79%); MS (MALDI) m/z: 892 [M-Cl] + ; Elemental analysis, calcd. (%) for C 45 H 55 Cl 2 N 3 P 2 FeRu.H 2 O: C, 57.15; H, 6.07; N, 4.44. Found: C, 58.01; H, 6.06; N, 4.34. Major isomer (ca 61%):  1 H NMR (300 MHz, DMSO-d 6 , 21° C.): δ 14.26 (br, 1H, imidazole-NH), 7.88-7.28 (m, 14H, aromatic protons), 5.03 (m, 1H, PCH), 4.75-4.68 (m, 2H), 3.92-3.51 (m, 7H, C 5 H 5  and CHMe), 2.31-0.86 (m, 30H, C 6 H 11 , NH 2  and CH 3 );  13 C NMR (100 MHz, DMSO-d 6 , 21° C.): d 157.3 (s, NCCMe), 143.5-123.3 (m, aromatic carbons), 111.7 (d, J(C,P)=7.5 Hz, FeC 5 H 3 ), 96.5 (d, J(C,P)=3.6 Hz, FeC 5 H 3 ), 72.5 (d, J(C,P)=3.1 Hz, FeC 5 H 3 ), 71.0 (s, FeC 5 H 3 ), 70.3 (s, FeC 5 H 5 ), 68.8 (d, J(C,P)=4.8 Hz, FeC 5 H 3 ), 51.2 (s, NCMe), 36.0 (d, J(C,P)=21.1 Hz, PCMe), 35.2-25.0 (m, CH 2  of Cy), 21.0 (s, NCMe), 14.9 (d, J(C,P)=7.2 Hz, PCMe);  31 P NMR (121 MHz, DMSO-d 6 ): δ 57.8 (d,  2 J(P,P)=41.1 Hz), 41.8 (d,  2 J(P,P)=41.1 Hz); 
       Example 2 
     Synthesis of the Complex Trans-RuCl 2 [(S,S)-DIOP][(S)-Me-bimaH][(SS,S)-9] 
       [0036]    
       
                 
         
             
             
         
       
     
         [0037]    The complex [RuCl 2 (benzene)] 2  (4.8 mg, 0.019 mmol) and (S,S)-DIOP (9.7 mg, 0.019 mmol) were suspended in 3 ml of degassed DMF. After stirring for 1 hour at 100° C., the solvent was removed under high vacuum at 50° C. for 2 hours. After (S)-Me-bimaH (3.1 mg, 0.019 mmol) and 3 ml of degassed CH 2 Cl 2  were added following 5-hours stirring at room temperature, the volume of the solution was redued to about 0.5 ml and the complex was precipitated by adding 6 ml of hexane. The solid obtained was filtered off, washed twice with 3 ml of ethyl ether and dried under vacuum. 
         [0038]    Yield 12.3 mg (76%).  31 P{ 1 H} NMR (162 MHz, CDCl 3 , 20° C.) δ 40.7 (d,  2 J(P,P)=42.6 Hz), 28.6 (d,  2 J(P,P)=42.6 Hz); MS (MALDI) m/z: 796.0 [M-Cl] + . 
       Example 3 
     Synthesis of the Complex cis-RuCl 2 [(S,S)-DIOP][(S)-Me-bimaH][(SS,S)-10] 
       [0039]    
       
                 
         
             
             
         
       
     
         [0040]    The complex (9) (20 mg, 0.024 mmol) was suspended in 3 ml of degassed toluene. After stirring for 2 hour at 110° C., the volume of the solution was redued to about 0.5 ml and the complex was precipitated by adding 6 ml of hexane. The solid obtained was filtered off, washed twice with 3 ml of ethyl ether and dried under vacuum. 
         [0041]    Yield 17.3 mg (86%).  31 P{ 1 H} NMR (162 MHz, CDCl 3 , 20° C.) δ 48.8 (d,  2 J(P,P)=37.9 Hz), 29.8 (d,  2 J(P,P)=37.3 Hz). 
       Example 4 
     Synthesis of the Monochloride Complex RuCl[(S,S)-DIONRS)-Me-bima][(SS,S)-11] 
       [0042]    The complex (10) (20 mg, 0.024 mmol) and Et 3 N (5.2 μl, 0.036 mmol) was suspended in 3 ml of degassed toluene. After stirring for 2 hour at 60° C., the solvent was removed under high vacuum. After dissolving in 5 ml of CH 2 Cl 2  and filtration, the volume was reduced to about 0.5 ml and the complex was precipitated by adding 6 ml of hexane. The solid obtained was filtered off, washed twice with 3 ml of ethyl ether and dried under vacuum. 
         [0043]    Yield 18.2 mg (94%).  31 P{ 1 H} NMR (162 MHz, CDCl 3 , 20° C.) δ 39.6 (d,  2 J(P,P)=39.0 Hz), 23.8 (d,  2 J(P,P)=39.0 Hz). 
       Example 5 
     Synthesis of the Complex Trans-RuCl 2 [(S)-BINAP][(S)-Me-bimaH][(S,S)-12] 
       [0044]    
       
                 
         
             
             
         
       
     
         [0045]    The complex [RuCl 2 (benzene)] 2  (6.6 mg, 0.013 mmol) and (S)-BINAP (16.4 mg, 0.026 mmol) were suspended in 3 ml of degassed DMF. After stirring for 1 hour at 100° C., the solvent was removed under high vacuum at 50° C. for 2 hours. After (S)-Me-bimaH (4.3 mg, 0.026 mmol) and 3 ml of degassed CH 2 Cl 2  were added following 5-hours stirring at room temperature, the volume of the solution was redued to about 0.5 ml and the complex was precipitated by adding 5 ml of hexane. The solid was obtained by filtration following with dryness under vacuum. 
         [0046]    Yield 19 mg (71%).  31 P{ 1 H} NMR (121 MHz, CDCl 3 , 20° C.) δ (ppm) 49.58 (d, J=38.7 Hz), 47.32 (d, J=38.7 Hz); MS (MALDI) m/z: 884 [M-71] + . 
       Example 6 
     Synthesis of the Complex Trans-RuCl 2 [(S)-PhanePHOS][(S)-Me-bimaH][(S,S)-13] 
       [0047]    The complex [RuCl 2 (benzene)] 2  (5.8 mg, 0.023 mmol) and (S)-PhanePHOS (13.5 mg, 0.023 mmol) were suspended in 3 ml of degassed DMF. After stirring for 1 hour at 100° C., the solvent was removed under high vacuum at 50° C. for 2 hours. After (S)-Me-bimaH (3.7 mg, 0.023 mmol) and 3 ml of degassed CH 2 Cl 2  were added following 5-hours stirring at room temperature, the volume of the solution was redued to about 0.5 ml and the complex was precipitated by adding 6 ml of hexane. The solid obtained was filtered off, washed twice with 3 ml of ethyl ether and dried under vacuum. 
         [0048]    Yield 17.6 mg (84%).  31 P{ 1 H} NMR (162 MHz, CDCl 3 , 20° C.) δ 47.26 (d, J=31.0 Hz), 42.71 (d, J=31.0 Hz). 
       Example 7 
     Synthesis of the Complex Trans-RuCl 2 [(S)-SEGPHOS][(S)-Me-bimaH][(S,S)-14] 
       [0049]    The complex [RuCl 2 (benzene)] 2  (5.8 mg, 0.011 mmol) and (S)-SEGPHOS (14.1 mg, 0.023 mmol) were suspended in 3 ml of degassed DMF. After stirring for 1 hour at 100° C., the solvent was removed under high vacuum at 50° C. for 2 hours. After (S)-Me-bimaH (3.7 mg, 0.023 mmol) and 3 ml of degassed CH 2 Cl 2  were added following 5-hours stirring at room temperature, the volume of the solution was redued to about 0.5 ml and the complex was precipitated by adding 6 ml of hexane. The solid obtained was filtered off, washed twice with 3 ml of ethyl ether and dried under vacuum. 
         [0050]    Yield 15.4 mg (71%).  31 P{ 1 H} NMR (162 MHz, CDCl 3 , 20° C.) δ 46.90 (d, 36.3 Hz), 32.75 (d, J=36.3 Hz). 
       Example 8 
     Synthesis of the Complex Trans-RuCl 2 [(S)-Cl-MeO-BIPHEP][(S)-Me-bimaH] [(S,S)-15] 
       [0051]    The complex [RuCl 2 (benzene)] 2  (3.3 mg, 7 μmol) and (S)-Cl-MeO-BIPHEP (8.5 mg, 0.013 mmol) were suspended in 3 ml of degassed DMF. After stirring for 1 hour at 100° C., the solvent was removed under high vacuum at 50° C. for 2 hours. After (S)-Me-bimaH (2.1 mg, 0.013 mmol) and 3 ml of degassed CH 2 Cl 2  were added following 5-hours stirring at room temperature, the volume of the solution was redued to about 0.5 ml and the complex was precipitated by adding 6 ml of hexane. The solid obtained was filtered off, washed twice with 3 ml of ethyl ether and dried under vacuum. 
         [0052]    Yield 11.7 mg (91%).  31 P{ 1 H} NMR (162 MHz, CDCl 3 , 20° C.) δ 48.42 (d, J=29.7 Hz), 46.18 (d, J=29.7 Hz). 
       Example 9 
     Synthesis of the Mono-Phosphine Complex RuCl 2 (PPh 3 ) 2 [(S)-Me-bimaH][(S,S)-16] 
       [0053]    The complex RuCl 2 (PPh 3 ) 3  (153 mg, 0.16 mmol) was suspended in 3 ml of degassed toluene. After stirring for 1 hour at room temperature, (S)-Me-bimaH (26 mg, 0.16 mmol) was added following with refluxing for 2 hour. The solvent was then reduced to about 0.5 ml and the complex was precipitated by adding 5 ml of hexane. The solid was obtained by filtration followed by removal of volatiles under vacuum. 
         [0054]    Yield 101 mg (71%).  31 P{ 1 H} NMR (121 MHz, CDCl 3 , 20° C.) δ 43.72, 45.34 ppm. 
       Example 10 
     Synthesis of the Tetrazole Complex RuCl 2 (PPh 3 ) 2 [(S)-Me-temaH][(S,S)-17] 
       [0055]    
       
                 
         
             
             
         
       
     
         [0056]    Using the same method as described in example 9. 
         [0057]    Yield 74%.  31 P{ 1 H} NMR (121 MHz, CDCl 3 , 20° C.) δ42.80, 44.62 ppm. 
       Example 11 
     Synthesis of the Complex RuCl 2 [(S)-BINAP][(S)-Me-temaH] [(S,S)-18] 
       [0058]    The complex [RuCl 2 (benzene)] 2  (6.6 mg, 0.013 mmol) and (S)-BINAP (16.4 mg, 0.026 mmol) were suspended in 3 ml of degassed DMF. After stirring for 1 hour at 100° C., the solvent was removed under high vacuum at 50° C. for 2 hours. After (S)-Me-temaH (4.3 mg, 0.026 mmol) and 3 ml of degassed CH 2 Cl 2  were added following 5-hours stirring at room temperature, the volume of the solution was reduced to about 0.5 ml and the complex was precipitated by adding 5 ml of hexane. The solid was obtained by filtration following with dryness under vacuum. 
         [0059]    Yield 19 mg (86%).  31 P{ 1 H} NMR (121 MHz, CDCl 3 , 20° C.) δ (ppm) 47.61, 49.15. 
       Example 12 
     Synthesis of the Complex RuCl 2 [(S)-BINAP][trimaH] [(S)-19] 
       [0060]    
       
                 
         
             
             
         
       
     
         [0061]    The complex [RuCl 2 (benzene)] 2  (9.3 mg, 0.018 mmol) and (S)-BINAP (23.0 mg, 0.036 mmol) were suspended in 3 ml of degassed DMF. After stirring for 1 hour at 100° C., the solvent was removed under high vacuum at 50° C. for 2 hours. Following addition of trimaH (4.7 mg, 0.036 mmol) and 3 ml of degassed CH 2 Cl 2 , the solution was stirred for 5-hours at room temperature. The volume of the solution was reduced to ca 0.5 ml and the complex was precipitated by adding 5 ml of hexane. The final solid was obtained by filtration followed by removal of volatiles under vacuum. 
         [0062]    Yield 23.6 mg (71%).  31 P{ 1 H} NMR (121 MHz, CDCl 3 , 20° C.) δ (ppm) 47.5, 49.2. 
       Example 13 
     Synthesis of the Complex RuCl 2 [(S)-BINAP][dimaH] [(S)-20] 
       [0063]    
       
                 
         
             
             
         
       
     
         [0064]    The complex [RuCl 2 (benzene)] 2  (7.9 mg, 0.016 mmol) and (S)-BINAP (19.7 mg, 0.032 mmol) were suspended in 3 ml of degassed DMF. After stirring for 1 hour at 100° C., the solvent was removed under high vacuum at 50° C. for 2 hours. Following addition of dimaH (4.2 mg, 0.032 mmol) and 3 ml of degassed CH 2 Cl 2 , the solution was stirred for 5-hours at room temperature. The volume of the solution was reduced to ca 0.5 ml and the complex was precipitated by adding 5 ml of hexane. The final solid was obtained by filtration followed by removal of volatiles under vacuum. 
         [0065]    Yield 19.2 mg (65%).  31 P{ 1 H} NMR (121 MHz, CDCl 3 , 20° C.) δ (ppm) 46.2, 48.6. 
       Example 14 
     Synthesis of Complex RuCl 2 [(R,S)-Josiphos](bimaH) [(R,S)-21] 
       [0066]    Using the same method as example 1. 
         [0067]    Yield 71%.  31 P{ 1 H} NMR (121 MHz, CDCl 3 , 20° C.) δ (ppm) 63.51, 41.81. 
       Example 15 
     Synthesis of RuCl 2 [(R,S)-Josiphos][(S)-iPr-bimaH] [(RS,S)-22] 
       [0068]    Using the same method as example 1. 
         [0069]    Yield 76%.  31 P{ 1 H} NMR (121 MHz, CDCl 3 , 20° C.) δ (ppm) 63.67, 40.04. 
       Example 16 
     Synthesis of the Complex Trans-RuCl 2 [(S,S)-DION][(S)-iPr-bimaH][(SS,S)-23] 
       [0070]    Using the same method as example 2. 
         [0071]    Yield 87%.  31 P{ 1 H} NMR (162 MHz, CDCl 3 , 20° C.) δ 39.8 (d, J=42.1 Hz), 26.3 (d, J=42.1 Hz). 
       Example 17 
     Synthesis of the Complex Trans-RuCl 2 [(S,S)-DIOP][(S)-tBu-bimaH][(SS,S)-24] 
       [0072]    Using the same method as example 2. 
         [0073]    Yield 82%.  31 P{ 1 H} NMR (162 MHz, CDCl 3 , 20° C.) δ 40.5 (d, J=41.8 Hz), 27.9 (d, J=41.8 Hz). 
       Example 18 
     Synthesis of the Complex Trans-RuCl 2 [(S,S)-DION][(S)-Bn-bimaH][(SS,S)-25] 
       [0074]    Using the same method as example 2. 
         [0075]    Yield 88%.  31 P{ 1 H} NMR (162 MHz, CDCl 3 , 20° C.) δ 39.9 (d, J=43.2 Hz), 28.6 (d, J=43.2 Hz). 
       B. Catalytic Tests in Asymmetric Hydrogenation 
     Example 19 
     A Typical In Situ Hydrogenation Using R-bimaH (7) 
       [0076]    Accurately weighed amounts of RuCl 2 -[(R,S)-Josiphos](PPh 3 ) (1.1 mg, 0.33 mM) or trans-RuCl 2 (NBD)(py) 2  (1 mg, 0.33 mM), and R-bimaH (7) (0.33 mM) were placed in a pre-oven-dried (120° C.) Schlenk. Freshly distilled toluene (2.8 mL) was added, the mixture degassed by running Ar through the solution (5 min), and the mixture stirred at 100° C. for 20 min. After quickly cooling to RT, acetophenone (0.12 mL, S/C=1000) was added. The mixture was then added under Ar to a pre-oven-dried (120° C.) 100-mL glass autoclave containing solid KO-t-C 4 H 9  (7.3 mg, 20 mM) and a magnetic stirring bar. H 2  was introduced under 4 atm pressure with several quick release-fill cycles before being set to the desired pressure. The solution was vigorously stirred at 25° C. and H 2  consumption monitored. Following designated reaction time, the H 2  was released, and a small aliquot of the crude product mixture was analyzed by chiral GC to determine conversion and ee of phenylethanol  1 H NMR (300 MHz, CDCl 3 ) δ 7.38-7.25 (m, aromatic protons, 5H), 4.87 (q, J=6.6 Hz, 1H), 2.03 (br, 1H), 1.48 (d, J=6.6 Hz, 3H); GC: BETA-DEX™ 120 fused silica capillary column (df=0.25 m, 0.25 mm i.d., 30 m, Supelco); P=100.3 kPa; T=125° C.; t R  of (R)-isomer=12.3 min; t R  of (9-isomer=12.9 min. The results were shown below in Table 1. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Asymmetric hydrogenation of acetophenone catalyzed by in situ generated 
               
               
                 catalysts comprised of RuCl 2 (binap)(dmf) n  (26) or trans-RuCl 2 [(R,S)- 
               
               
                 Josiphos](pyridine) 2  [(R,S)-27] and R-bimaH ligands (R-7). a   
               
             
          
           
               
                   
                 Catalyst components 
                   
                 Time 
                 Yield 
                 ee (%) b   
               
             
          
           
               
                 Entry 
                 complex 
                 ligand 
                 Solvent 
                 (h) 
                 (%) 
                 (config) 
               
               
                   
               
             
          
           
               
                 1 
                 (S)-24 
                 H-7 
                 Toluene 
                 8 
                 100 
                 77 
                 (S) 
               
               
                 2 
                 (S)- 24 
                 H-7 
                 i-PrOH 
                 8 
                 100 
                 25 
                 (S) 
               
               
                 3 
                 (S)-24 
                 (S)-Me-7 
                 Toluene 
                 8 
                 100 
                 91 
                 (S) 
               
               
                 4 
                 (R)-24 
                 (R)-Me-7 
                 Toluene 
                 8 
                 100 
                 91 
                 (R) 
               
               
                 5 
                 (S)-24 
                 (S)-Me-7 
                 i-PrOH 
                 8 
                 100 
                 28 
                 (S) 
               
               
                 6 
                 (S)-24 
                 (S)-iPr-7 
                 Toluene 
                 12 
                 100 
                 87 
                 (S) 
               
               
                 7 
                 (S)-24 
                 (S)-tBu-7 
                 Toluene 
                 10 
                 100 
                 91 
                 (S) 
               
               
                 9 
                 (R,S)-25 
                 (S)-Me-7 
                 Toluene 
                 9 
                 95 
                 91 
                 (S) 
               
               
                   
               
               
                   a Hydrogenation conditions: [ketone] = 0.33 M, [26 or 27] = 0.33 mM, [7] = 0.33 mM, P(H 2 ) = 8 atm, [KO-t-C 4 H 9 ] = 20 mM, t = 25° C. 
               
               
                   b Enantiomeric excess (ee) determined by GC analysis; absolute configuration (config) determined from [α] D  measurement. 
               
             
          
         
       
     
       Example 20 
     Additive Effect in In-Situ Hydrogenation Using R-bimaH and Additive 
       [0077]    Accurately weighed amounts of RuCl 2 [(R,S)-Josiphos](PPh 3 ) (1.1 mg, 0.33 mM) or trans-RuCl 2 (NBD)(py) 2  (1 mg, 0.33 mM), and R-bimaH (7) (0.33 mM) were placed in a pre-oven-dried (120° C.) Schlenk. Freshly distilled toluene (2.8 mL) was added, the mixture degassed by running Ar through the solution (5 min), and the mixture stirred at 100° C. for 20 min. After quickly cooling to RT, acetophenone (0.12 mL, S/C=1000) was added. The mixture was then added under Ar to a pre-oven-dried (120° C.) 100-mL glass autoclave containing solid KO-t-C 4 H 9  (7.3 mg, 20 mM), phosphine additive (e.g. 0.8 mg, 1 mM for PPh 3 ) and a magnetic stirring bar. H 2  was introduced under 4 atm pressure with several quick release-fill cycles before being set to the desired pressure. The solution was vigorously stirred at 25° C. and H 2  consumption monitored. Following designated reaction time, the H 2  was released, and a small aliquot of the crude product mixture was analyzed by chiral GC to determine conversion and ee of phenylethanol. The results were shown below in Table 2. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Phosphine addition effect in asymmetric hydrogenation of acetophenone catalyzed by in 
               
               
                 situ generated catalysts comprised of trans-RuCl 2 [(R,S)-Josiphos](pyridine) 2   
               
               
                 [(R,S)-27] and R-bimaH ligands (R-7). a   
               
             
          
           
               
                   
                 Catalyst components 
                   
                 Time 
                 Yield 
                 ee (%) b   
               
             
          
           
               
                 Entry 
                 complex 
                 ligand 
                 Additive 
                 Solvent 
                 (h) 
                 (%) 
                 (config) 
               
               
                   
               
             
          
           
               
                 8 
                 (R,S)-27 
                 H-7 
                 P(C 6 H 5 ) 3   
                 Toluene 
                 9 
                 100 
                 82 (S) 
               
               
                 10 
                 (R,S)-27 
                 (S)-Me-7 
                 P(C 6 H 5 ) 3   
                 Toluene 
                 9 
                 100 
                 96 (S) 
               
               
                 11 
                 (R,S)-27 
                 (S)-iPr-7 
                 P(C 6 H 5 ) 3   
                 Toluene 
                 9 
                 100 
                 96 (S) 
               
               
                 12 
                 (R,S)-27 
                 (S)-tBu-7 
                 P(C 6 H 5 ) 3   
                 Toluene 
                 9 
                 50 
                 93 (S) 
               
               
                 13 
                 (R,S)-27 
                 (S)-Me-7 
                 P(C 6 H 5 ) 3   
                 iPrOH 
                 9 
                 100 
                 78 (S) 
               
               
                 14 
                 (R,S)-27 
                 (S)-Me-7 
                 P(C 6 H 5 ) 3   
                 tBuOH 
                 8 
                 100 
                 93 (S) 
               
               
                 15 
                 (R,S)-27 
                 (S)-Me-7 
                 P(C 6 H 5 ) 3   
                 THF 
                 9 
                 100 
                 89 (S) 
               
               
                 16 
                 (R,S)-27 
                 (S)-Me-7 
                 P(C 6 H 5 ) 3   
                 Et 2 O 
                 9 
                 100 
                 92 (S) 
               
               
                 17 
                 (R,S)-27 
                 (S)-Me-7 
                 P(4-ClC 6 H 4 ) 3   
                 Toluene 
                 12 
                 100 
                 90 (S) 
               
               
                 18 
                 (R,S)-27 
                 (S)-Me-7 
                 P[3,5-(C 6 H 5 ) 2 C 6 H 3 ] 3   
                 Toluene 
                 12 
                 100 
                 82 (S) 
               
               
                 21 
                 (R,S)-27 
                 (S)-Me-7 
                 P(CH 2 CH 2 CH 2 CH 3 ) 3   
                 Toluene 
                 18 
                 52 
                 98 (S) 
               
               
                 21 
                 (R,S)-27 
                 (S)-Me-7 
                 H 2 O 
                 Toluene 
                 18 
                 100 
                 96 (S) 
               
               
                   
               
               
                   a Hydrogenation conditions: [ketone] = 0.33 M, [25] = 0.33 mM, [7] = 0.33 mM, P(H 2 ) = 8 atm, [KO-t-C 4 H 9 ] = 20 mM, [additive] = 1.0 mM (3 equiv), t = 25° C. 
               
               
                   b Enantiomeric excess (ee) determined by GC analysis; absolute configuration (config) determined from [α] D  measurement. 
               
             
          
         
       
     
       Example 21 
     AH of Aromatic Ketones Using Complex (RS,S)-8 with a S/C Equal to 50,000 
       [0078]    Accurately weighed amounts of (RS,S)-8 (2.5 mg, 0.038 mM), solid KO-t-C 4 H 9  (120 mg, 16.4 mM) and PPh 3  (60 mg, 3.4 mM) were placed in a pre-oven-dried (120° C.) 350-mL autoclave containing a magnetic stirring bar, and placed under high vacuum for at least 20 min before purging with argon. Freshly distilled solvent (toluene, 35 mL; t-BuOH, 15 mL) and purified acetophenone (15 mL, 1.9 M, S/C=50,000) were placed into a pre-dried Schlenk and degassed by 3 cycles of freeze-and-thaw and then added to the autoclave under an Ar atmosphere. H 2  was introduced under 20 atm pressure with several quick release-fill cycles before being set to 40 atm. The solution was vigorously stirred at 25° C. and H 2  consumption monitored. The H 2  was carefully released after 10 h, the solution passed through a short pad of silica gel and solvent removed under reduced pressure. The crude product mixture was analyzed by chiral GC to determine conversion and ee of (S)-phenylethanol. GC: BETA-DEX™ 120 fused silica capillary column (df=0.25 m, 0.25 mm i.d., 30 m, Supelco); P=100.3 kPa; T=125° C.; t R  of (R)-7a=12.3 min; t R  of (S)-7a=12.9 min(major). Conv.&gt;99%; ee=97%. 
       Example 22 
     AH of Aromatic Ketones Using Complex (RS,S)-8 
       [0079]    Several aromatic ketones were reduced using the same process described in Example 19. The hydrogenation conditions and results were shown in Table 3. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Asymmetric hydrogenation of simple aryl ketones catalyzed by 
               
               
                 RuCl 2 [(R,S)-Josiphos)][(S)-Me-bimaH)][(RS,S)-8] complex. a   
               
             
          
           
               
                   
                   
                   
                 P/H 2   
                   
                 Yield 
                 ee (%) b   
               
               
                 Entry 
                 Substrate 
                 S/C ratio 
                 (atm) 
                 Time (h) 
                 (%) b   
                 (config) c   
               
               
                   
               
             
          
           
               
                 1 
                 acetophenone 
                 1,000 
                 8 
                 2 
                 100 
                 96 (S) 
               
               
                 2 
                 acetophenone 
                 10,000 
                 20 
                 12 
                 100 
                 96 (S) 
               
               
                     3 d   
                 acetophenone 
                 50,000 
                 40 
                 10 
                 100 
                 97 (S) 
               
               
                 4 
                 4-MeO-acetophenone 
                 5,000 
                 20 
                 16 
                 95 
                 97 (S) 
               
               
                 5 
                 4-CF 3 -acetophenone 
                 5,000 
                 20 
                 8 
                 90 
                 82 (S) 
               
               
                 6 
                 2-Me-acetophenone 
                 5,000 
                 20 
                 8 
                 100 
                 95 (S) 
               
               
                 7 
                 3-Br-acetophenone 
                 5,000 
                 20 
                 6 
                 100 
                 92 (S) 
               
               
                   
               
               
                      8 e   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 5,000 
                 20 
                 24 
                 95 
                 99 (R) 
               
               
                   
               
               
                 9 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1,000 
                 8 
                 12 
                 92 
                 94 (S) 
               
               
                   
               
               
                 10  
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1,000 
                 8 
                 12 
                 100 
                 97 (S) 
               
               
                   
               
               
                   a Hydrogenation conditions: [ketone] = 0.3-1.9M, [(RS,S)-8] = 0.04-0.3 mM, [KO-t-C 4 H 9 ] = 15-20 mM, [PPh 3 ] = 1.0-3.4 mM, t = 25° C., solvent = toluene/t-BuOH (9/1). 
               
               
                   b Determined by GC. 
               
               
                   c Absolute configuration (config) determined from [α] D . 
               
               
                   d Toluene/t-BuOH (7/3). 
               
               
                   e Yield determined by  1 H NMR; ee determined by HPLC. 
               
             
          
         
       
     
       Example 23 
     Screening of Diphosphane Ligands in Asymmetric Hydrogenation of Acetophenone 
       [0080]    The acetophenone reduction results using different phosphines and (S)-Me-bimaH are given in Table 4. The hydrogenation procedure was the same as described in Example 19. The H 2  pressure is always 8 atm. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 AH of acetophenone using different chiral diphosphanes and 
               
               
                 (S)—Me-bimaH within a 1 h hydrogenation period. a   
               
             
          
           
               
                 Entry 
                 Bis-P Ligand 
                 S/C 
                 Conv. % 
                 Ee % (S) 
               
               
                   
               
             
          
           
               
                 1 
                 (S)-PhanePHOS 
                 1000 
                 100 
                 78 
               
               
                 2 
                 (S)-SEGPHOS 
                 1000 
                 100 
                 89 
               
               
                 3 
                 (S,S)-DIOP 
                 1000 
                 100 
                 96 
               
               
                 4 
                 (S)—Cl—MeO-BIPHEP 
                 1000 
                 100 
                 86 
               
               
                 5 
                 (S,S)-DIPAMP 
                 1000 
                 NR 
                 \ 
               
               
                 6 
                 (S)-BINAP 
                 1000 
                 90 
                 88 
               
               
                 7 
                 (S,S)-DuPHOS 
                 1000 
                 1 
                  0 
               
               
                 8 
                 (S,S)-WalPHOS 
                 1000 
                 62 
                 13 
               
               
                 9 
                 (R,S)-Josiphos 
                 1000 
                 13 
                 71 
               
               
                   
               
               
                   a Conditions: 
               
               
                 Substrate/Catalyst/Base ratio = 1000/1/50; 
               
               
                 V T  = 3 ml; 
               
               
                 t = 1 h; 
               
               
                 25° C. 
               
             
          
         
       
     
       Example 24 
     AH of Aromatic Ketones Using Complex (Ss,S)-9 
       [0081]    Accurately weighed amounts of (SS,S)-9 (0.9 mg, 1 μmol), solid KO-t-C 4 H 9  (6 mg, 0.05 mmol) and sometimes derivatives [e.g. PPh 3  (0.3 mg, 1 μmol)] were placed in a pre-oven-dried (120° C.) 350-mL autoclave containing a magnetic stirring bar, and placed under high vacuum for at least 20 min before purging with argon. Freshly distilled solvent (toluene, 2.7 mL; t-BuOH, 0.3 mL) and purified ketones (1 mmol, S/C=1,000) were placed into a pre-dried Schlenk and degassed by 3 cycles of freeze-and-thaw and then added to the autoclave under an Ar atmosphere. H 2  was introduced under 20 atm pressure with several quick release-fill cycles before being set to 8 atm. The solution was vigorously stirred at 25° C. and H 2  consumption monitored. The H 2  was carefully released after a period of time, the solution passed through a short pad of silica gel and solvent removed under reduced pressure. The crude product mixture was analyzed by  1 H NMR to determine conversion and chiral GC or HPLC to determine ee of the chiral alcohol products. The hydrogenation results are given in Table 5. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Screening of aromatic substrates using complex (SS,S)-9 a   
               
             
          
           
               
                 Entry 
                 sub 
                 PPh 3   b   
                 t/h 
                 Conv. % 
                 Ee % (S) 
               
               
                   
               
             
          
           
               
                  1 
                 acetophenone 
                 \ 
                 1 
                 100 
                 96 
               
               
                  2 
                 acetophenone 
                 3eq 
                 1 
                 62 
                 98 
               
               
                  3 
                 acetophenone 
                 1eq 
                 1 
                 100 
                 98 
               
               
                  4 
                 2-Me-acetophenone 
                 \ 
                 13.5 
                 87 
                 90 
               
               
                  5 
                 2-Me-acetophenone 
                 1eq 
                 8.5 
                 74 
                 97 
               
               
                  6 
                 4-MeO-acetophenone 
                 \ 
                 5 
                 99 
                 97 
               
               
                  7 
                 4-MeO-acetophenone 
                 1eq 
                 3 
                 99 
                 99.6 
               
               
                  8 
                 4-Br-acetophenone 
                 \ 
                 15 
                 100 
                 93 
               
               
                  9 
                 4-Br-acetophenone 
                 1eq 
                 6 
                 99 
                 98 
               
               
                 10 
                 4-F-acetophenone 
                 1eq 
                 9.5 
                 100 
                 98 
               
               
                 11 
                 4-Me-acetophenone 
                 1eq 
                 12 
                 99 
                 98 
               
               
                 12 
                 3-Br-acetophenone 
                 1eq 
                 1.5 
                 99 
                 98 
               
               
                 13 
                 3,5-CF 3 -acetophenone 
                 1eq 
                 3 
                 100 
                 92 
               
               
                   
               
               
                 14 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1eq 
                 5 
                 100 
                 99 
               
               
                   
               
               
                 15 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1eq 
                 2 
                 99 
                 99 
               
               
                   
               
               
                 16 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1eq 
                 10 
                 90 
                 98 
               
               
                   
               
               
                 17 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1eq 
                 3 
                 97 
                 91 
               
               
                   
               
               
                 18 c   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1eq 
                 8 
                 99 
                 99 
               
               
                   
               
               
                   a Conditions: Substrate/Catalyst/Base = 1000/1/50; V T  = 3 mL, 25-30° C. 
               
               
                   b Compared to catalyst; 
               
               
                   c The H 2  pressure was 20 atm and the configuration of the product was R. 
               
             
          
         
       
     
       Example 25 
     Asymmetric Hydrogenation of Dialkyl Ketone Using (S,S)-18 
       [0082]    Accurately weighed amounts of (S,S)-18 (2.9 mg, 3.0 μmol), solid KO-t-C 4 H 9  (6 mg, 0.05 mmol) were placed in a pre-oven-dried (120° C.) 350-mL autoclave containing a magnetic stirring bar, and placed under high vacuum for at least 20 min before purging with argon. Freshly distilled solvent (2-PrOH, 3 mL) and purified pinacolone (0.62 g, 6.0 mmol, S/C=2,000) were placed into a pre-dried Schlenk and degassed by 3 cycles of freeze-and-thaw and then added to the autoclave under an Ar atmosphere. H 2  was introduced under 20 atm pressure with several quick release-fill cycles before being set to 8 atm. The solution was vigorously stirred at 25° C. and H 2  consumption monitored. The H 2  was carefully released after a period of time (12 h), the solution passed through a short pad of silica gel and solvent carefully removed under reduced pressure. The crude product mixture was analyzed by chiral GC: CP-Chirasil-DEX CB column, P=41 kPa, T(column)=60° C., T(injection)=200° C., T(detector)=200° C., t R  of (R)-isomer=17.2 min, t R  of (S)-isomer=17.9 min. Cony., 100%; ee, 75%. 
       C. Catalytic Tests in Asymmetric Transfer Hydrogenation 
     Example 26 
     Asymmetric Transfer Hydrogenation of Acetophenone Using (RS,S)-8 
       [0083]    Accurately weighed amounts of (RS,S)-8 (1.0 mg, 1 μmol) and solid KO-t-C 4 H 9  (4.5 mg, 0.04 mmol) were placed in a pre-oven-dried (120° C.) 30-mL Schlenk tube containing a magnetic stirring bar, and placed under high vacuum for at least 20 min before purging with argon. Freshly distilled solvent (i-PrOH, 3 mL) and purified acetophenone (0.12 mL, 1 mmol, S/C=1,000) were placed into a pre-dried Schlenk and degassed by bubbling for 5 min and then added to the Schlenk tube above under an Ar atmosphere. The solution was vigorously stirred at 80° C. for 12 h, then the solution was passed through a short pad of silica gel and solvent removed under reduced pressure. The crude product mixture was analyzed by chiral GC to determine conversion and ee of (S)-phenylethanol. GC: BETA-DEX™ 120 fused silica capillary column (df=0.25 m, 0.25 mm i.d., 30 m, Supelco); P=100.3 kPa; T=125° C.; t R  of (R)-isomer=12.3 min; t R  of (9-isomer=12.9 min(major). Conv.=95%; ee=15%. 
       D. Asymmetric Hydrogenation Reaction Profile Using (RS,S)-8. 
       [0084]    Hydrogenations were conducted in a glass autoclave equipped with a sampling needle connected to a three-way stop valve. An accurately measured mass of (RS,S)-8, KO-t-C 4 H 9  and (where applicable) PPh 3  were placed into a pre-dried (120° C.) glass autoclave containing a magnetic stirring bar, which was then maintained under high vacuum for at least 5 min prior to purging with argon. Into a pre-dried Schlenk tube were placed accurately measured amounts of acetophenone and a solvent such that the desired [(RS,S)-8], [acetophenone], S/C ratio, [PPh 3 ] and [KO-t-C 4 H 9 ] were obtained. The reaction mixture was degassed by three freeze-thaw cycles and added under Ar to the autoclave. If needed, the autoclave was placed in a pre-warmed oil-bath set at the desired reaction temperature. H 2  was introduced under 4 atm pressure with several quick release-fill cycles before being set to the desired pressure. Stirring and timing (t=0 min) were immediately commenced. Reaction samples were obtained (2 drops into an ether-filled GC sample tube) at specified time-intervals (t), and the extent of substrate consumption and ee of phenylethanol determined by GC. 
       Example 27 
       [0085]    Effects of added PPh 3  for toluene systems. Conditions: [(RS,S)-8]=0.33 mM; [acetophenone]=0.33 M; P(H 2 )=4 atm; [KO-t-C 4 H 9 ]=15 mM; [PPh 3 ]=0 or 1 mM; S/C=1000; T=25° C.; V T =3 mL, solvent=toluene. 

 
       Example 28 
       [0086]    Hydrogenation in t-BuOH solvent. Conditions: [(RS,S)-8]=0.33 mM; [acetophenone]=0.33 M; P(H 2 )=4 atm; [KO-t-C 4 H 9 ]=15 mM; [PPh 3 ]=0 or 1 mM; S/C=1000; T=30° C.; V T =3 mL, solvent=(CH 3 ) 3 COH. 

 
         [0087]    Extra statements about the Hydrogenation reactions above:
       The solvents used can be at least one of those shown below: benzene, toluene, xylene, methylxylene, THF, CH 2 Cl 2 , Et 2 O, CH 3 OH, EtOH, iPrOH, nPrOH, nBuOH, iBuOH, tBuOH, MeCN, ethylene glycol dimethyl ether, CHCl 3 , DMSO, DMF etc.   The base used can be tBuOK, tBuONa, tBuOLi, tBuOCs, NaOH, KOH, Cs 2 CO 3 , Na 2 CO 3 , K 2 CO 3 , NaHCO 3 , KHCO 3 , K 3 PO 4 , K 2 HPO 3 , KH 2 PO 3 , KF, NaH, KH, CaH 2 , Et 3 N, TMEDA, DABCO, DBU, pyridine etc.   The reaction is tolerant to small amount of water.   The reaction is tolerant to substrates with functional groups: e.g. ester [—C(═O)O—], amine (NH 2 ).   The substrates can be heteroaromatic ketones.   The reaction time can be 0.1-48 hours, the H 2  pressure can be 1-80 atm.