Abstract:
The invention relates to an asymmetric hydrogenation method for ketone compounds, comprising the step of: under hydrogen atmosphere, in the presence of an in situ catalyst derived from a chiral ligand and a ruthenium salt, adding a ketone compound and a base into a second solvent to carry out an asymmetric hydrogenation for the ketone compound. The invention can obtain a conversion of 100% and a highest asymmetric inducement effect of 99.7% for the ketone compound. The invention has the advantages including simple procedure, high conversion and selectivity, good atom economy and good prospect of industrial application.

Description:
TECHNICAL FIELD 
     The invention relates to organic chemistry and drug synthesis chemistry, and in particular, relates to an asymmetric hydrogenation method for ketone compounds. The invention can provide a method for reducing a prochiral ketone to a chiral alcohol. 
     BACKGROUNDS 
     Enantiomerically pure alcohols are widely used in fine chemical industries such as pharmaceuticals, pesticides, perfumes, etc., and thus the studies on the various synthesis methods thereof have been increasing recently. The asymmetric hydrogenation of a prochiral ketone is one of the most important methods in preparing an enantiomerically pure alcohol. This method has gained much attention because of high catalytic activity, quick reaction time, good atom economy, simple product separation, simple post-processing, and less side reactions. 
     Based on the reasons above, numerous chiral ligands have been developed for the asymmetric hydrogenation of prochiral ketones. Among these ligands, the most representative one is BINAP-based ligands invented by Noyori, a Japanese chemist (EP0901997A1), which achieved good selectivity in the asymmetric hydrogenation of various ketone compounds. However, it is not easy to synthesize such ligand, and the costs are relatively high. In addition, the ligand cannot be stably stored. Further, many other chiral ligands have been applied to asymmetric hydrogenation of ketones. For example, Xumu Zhang et al. have mentioned that the asymmetric hydrogenation of ketones is realized by using a complex of a chiral ligand PennPhos with rhodium (Xumu Zhang et al., Highly Enantioselective Hydrogenation of Simple Ketones Catalyzed by a Rh-PennPhos Complex. Angew. Chem., Int. Ed. 1998, 37, 1100-1103). However, the selectivity of such system is not good, and the ligand is hard to be synthesized and has poor stability. In this respect, it is hard to apply this system in industrial productions. In addition, the use of metal rhodium leads to an increase of the costs. 
     SUMMARY OF THE INVENTION 
     The invention has been made through numerous researches to overcome the above-mentioned defects which existed in the prior art. 
     The object of the invention is to provide an asymmetric hydrogenation method for ketone compounds, which can conveniently and effectively synthesize enantiomerically pure alcohols so as to be used in various fields, such as medicine and health, fine chemical industry, and the like. 
     The invention overcomes the disadvantages in the prior art described above by using C 2 -symmetric metallocenyl planar chiral ligands. The outstanding advantages of this invention are mainly as follows: (1) simple synthesis: the ligand can be obtained through only 3-4 steps with high yield; (2) stable ligand: the ligand is insensitive to water and oxygen, and thus can be stored and used easily; (3) good atom economy: since the C 2 -symmetric planar chiral ligand has a two-center structure, one ligand molecule can coordinate with two ruthenium molecules to form two reaction centers; (4) good catalytic effect: 100% conversion with the highest stereoselectivity of 99.7% can be achieved in most ketone substrates. In view of the above, it will have an excellent industrial prospect if the C 2 -symmetric planar chiral ligand of the invention is used in the asymmetric reduction method for ketone. 
     The invention has a bright prospect of industrial application, as it has the advantages including simple procedure, high conversion and selectivity, low cost, high atom economy, environment friendly, and the like. 
     The invention is accomplished by the following technical solutions. 
     The asymmetric hydrogenation method for ketone compounds of the invention comprises the step of: under hydrogen atmosphere, in the presence of an in situ catalyst derived from a chiral ligand and a ruthenium salt, adding a ketone compound and a base into a second solvent to carry out an asymmetric hydrogenation for the ketone compound. 
     The in situ catalyst of the invention is obtained by reacting the chiral ligand with a ruthenium salt in a first solvent. 
     In addition, the chiral ligand of the invention is preferably a compound of formula (IV): 
     
       
                 
         
             
             
         
      
     
     In formula (IV), M represents Fe (iron) or Ru (ruthenium); R represents methyl, C 2 -C 8  saturated aliphatic group, phenyl or benzyl; Ar represents phenyl or substituted phenyl. Preferably, in formula (IV), M represents Fe or Ru; R represents methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, pentyl, phenyl or benzyl; Ar represents phenyl, p-methylphenyl, p-methoxyphenyl, 3,5-dimethylphenyl, 3,5-di-t-butylphenyl, 3,5-di(trifluoromethyl)phenyl. 
     Additionally, the ruthenium salt is preferably any one selected from tris(triphenylphosphine)ruthenium(II) chloride, benzeneruthenium(II) chloride dimer, or dichloro(p-cymene)ruthenium (II) dimer. 
     Further, the molar ratio of Ru from ruthenium salt to the chiral ligand is preferably 1:0.5˜0.7 when reacting the chiral ligand with the metal ruthenium in the first solvent to produce the in situ catalyst. 
     The first solvent is preferably any one selected from methanol, ethanol, i-propanol, dichloromethane, 1,4-dioxane, tetrahydrofuran, diethyl ether, toluene, or xylene. 
     When the chiral ligand reacts with the metal ruthenium in the first solvent to obtain the in situ catalyst, the reaction temperature is preferably 30° C.˜140° C. and the reaction time is preferably 0.5 h˜3 h. 
     The second solvent of the invention is preferably any one selected from methanol, ethanol, i-propanol, dichloromethane, 1,4-dioxane, tetrahydrofuran, diethyl ether, toluene, or xylene. 
     The ketone compound of the invention is preferably a compound represented by formulae (I), (II) or (III): 
     
       
                 
         
             
             
         
      
     
     In formula (I), R 1  is C 1 -C 15  linear or branched alkyl or alkenyl, or C 3 -C 1s  saturated cyclic hydrocarbyl; R 2  is C 4 -C 20  substituted or unsubstituted aromatic group or aromatic heterocyclic group, or C 1 -C 15  linear or branched alkyl or alkenyl, or C 3 -C 15  saturated cyclic hydrocarbyl. 
     In formula (II) R 3  is —OR 5 , —NHR 6 , —F, —Cl, —Br, —I, —NO 2 , —OH, or C 1 -C 5  linear or branched alkyl or alkenyl, or C 3 -C 15  saturated cyclic hydrocarbyl; n 1  is 0˜4; R 5  and R 6  independently represent C 1 -C 15  linear or branched alkyl or alkenyl, or C 3 -C 15  saturated cyclic hydrocarbyl. 
     In formula (III), R 4  is OR 7 —NHR B , —F, —Cl, —Br, —I, —NO 2 , —OH, C 1 -C 15  linear or branched alkyl or alkenyl, or C 3 -C 15  saturated cyclic hydrocarbyl; n 2  is 0˜4; R 7  and R 8  independently represent C 1 -C 15  linear or branched alkyl or alkenyl, or C 3 -C 15  saturated cyclic hydrocarbyl. 
     The base of the invention is preferably any one selected from potassium t-butoxide, sodium t-butoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, potassium bicarbonate, or sodium bicarbonate. 
     The molar ratio of the base to the ketone compound is preferably 0.2˜0.02:1. 
     When the ketone compound undergoes an asymmetric hydrogenation, the reaction temperature is preferably −20˜50° C., the hydrogen pressure is preferably 3˜50 atm, and the reaction time is preferably 6˜72 h. 
     Further, the invention preferably comprises the following first and second steps: in the first step, the chiral ligand reacts with ruthenium in the first solvent to obtain the in situ catalyst; in the second step, under hydrogen atmosphere, in the presence of the in situ catalyst, the ketone compound and the base are added into the second solvent to carry out the asymmetric hydrogenation for the ketone compound; and the first and second steps are continuously performed without additional separation of the in situ catalyst obtained in the first step. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     As described above, an asymmetric hydrogenation for ketone compounds is performed in the presence of an in situ catalyst. The in situ catalyst is a complex of ruthenium salt and chiral ligand, and the chiral ligand is a C 2 -symmetric planar chiral ferrocenyl or ruthenoceyl ligand represented by the above formula (IV). 
     In formula (IV), M represents Fe or Ru; R represents methyl, C 2 -C 8  saturated aliphatic group, phenyl or benzyl, and R is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, pentyl, phenyl or benzyl; Ar represents C 4 -C 10  substituted or unsubstituted aromatic group in which the substituent group on the aromatic group can be, for example, C 1 -C 4  alkyl or alkoxy or halogenated alkyl, and Ar is preferably phenyl, p-methylphenyl, p-methoxyphenyl, 3,5-dimethylphenyl, 3,5-di-t-butylphenyl, 3,5-di(trifluoromethyl)phenyl. 
     The ruthenium salt of the invention is preferably any one selected from tris(triphenylphosphine)ruthenium(II) chloride, benzeneruthenium(II) chloride dimer, or dichloro(p-cymene)ruthenium(II) dimer. 
     In the invention, when the chiral ligand reacts with ruthenium in the first solvent to obtain the in situ catalyst, the molar ratio of Ru derived from the ruthenium salt to the chiral ligand is 1:0.5˜0.7, preferably 1:0.5˜0.65, more preferably 1:0.5˜0.6, further preferably 1:0.5˜0.55. 
     In the invention, when the chiral ligand reacts with ruthenium in the first solvent to obtain the in situ catalyst, the reaction temperature can be set as required. However, in view of the reaction efficiency and the safety of operation, the reaction temperature is preferably 30˜140° C., more preferably 40˜120° C., further preferably 40˜105° C., even more preferably 65˜85° C. 
     In the invention, when the chiral ligand reacts with ruthenium in the first solvent to obtain the in situ catalyst, in view of the reaction efficiency, stirring is preferably performed. In addition, in view of both the reaction efficiency and the safety of operation, the stirring rate is preferably 200˜800 rpm, more preferably 300˜600 rpm, further preferably 400˜500 rpm. The way of stirring can be selected arbitrarily, for example, stirring equipments with stirring paddles or magnetic stirring with a stirring bar can be employed. 
     In the invention, when the chiral ligand reacts with ruthenium in the first solvent to obtain the in situ catalyst, the reaction time is preferably 0.5˜3 h, more preferably 1˜2 h, and further preferably 1˜1.5 h, in view of the yield. 
     Obviously, in the invention, when the chiral ligand reacts with ruthenium in the first solvent to obtain the in situ catalyst, any combination of the above-mentioned reaction temperature, stirring rate and reaction time can be employed. 
     In addition, the ketone compound which undergoes the asymmetric hydrogenation in the invention is a compound of formulae (I), (II) or (III) as described above. In formula (I), it is preferably that R 1  is methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, n-pentyl, n-hexyl, n-heptyl, or the like; R 2  is C 4 -C 20  substituted or unsubstituted aromatic group or aromatic heterocyclic group, wherein the aromatic group can be for example, phenyl, naphthyl, anthryl, or the like; the aromatic heterocyclic group can be for example, pyridyl, furyl, thienyl, or the like; the substituent group on the aromatic group can be for example, fluoro, chloro, bromo, iodo, amine, hydroxyl, methoxy, methyl, phenyl, or the like; the aromatic group can be monosubstituted, disubstituted, or trisubstituted, and the position(s) to be substituted on the aromatic group is/are not specially limited. More specifically, the examples of the compound of formula (I) can be acetophenone, m-methylacetophenone, o-methylacetophenone, p-methylacetophenone, m-chloroacetophenone, o-chloroacetophenone, p-chloroacetophenone, m-methoxyacetophenone, o-methoxyacetophenone, p-methoxyacetophenone, p-bromoacetophenone, p-fluoroacetophenone, 3,4-dichloroacetophenone, 2,4-difluoroacetophenone, m-hydroxylacetophenone, o-hydroxylacetophenone, p-aminoacetophenone, p-phenylacetophenone, 1-acetonaphthone, 2-acetonaphthone, 3,4-dimethoxyacetophenone, 3,4,5-trimethoxyacetophenone, propiophenone, butyrophenone, i-butyrophenone, p-methyloctanophenone, 3-acetylpyridine, 2-acetylfuran, or the like. 
     In formula (II), it is preferably that R 3  is —OCH 3 , —NHCH 3 , —F, —Cl, —Br, —I, NO 2 , OH, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, or the like; n 1  is 1, 2, 3, or 4. More specifically, the examples of the compound of formula (II) can be 1-tetralone, 1-indanone, 5-methoxy-1-tetralone, or the like. 
     In formula (III), it is preferably that R 4  is —OCH 3 , —NHCH 3 , —F, —Cl, —Br, —I, NO 2 , OH, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, n-pentyl, or the like; n 2  is 0, 1, 2, 3, or 4. More specifically, the examples of the compound of formula (III) can be 1-methylcyclopentanone, 2-fluorocyclohexanone, 2-methoxycycloheptanone, or the like. 
     The base used in the invention can be an organic or inorganic base. For example, it can be alkali metal alkoxides, alkali metal hydroxides, alkali metal carbonates, or the like. More specifically, the examples of the base can be potassium t-butoxide, sodium t-butoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, potassium hydroxide, sodium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate, potassium bicarbonate or sodium bicarbonate. 
     In the invention, when the ketone compound undergoes the asymmetric hydrogenation, the molar ratio of the base and the ketone compound can be 0.2˜0.02:1, preferably 0.15˜0.03:1, more preferably 0.15˜0.04:1, further preferably 0.1˜0.06:1, and even more preferably 0.1˜0.08:1. 
     In the invention, when the ketone compound undergoes the asymmetric hydrogenation, the molar ratio of the ketone compound to the in situ catalyst can be 100˜5000:1. Actually, there is no limitation to the molar ratio of the ketone to the in situ catalyst, because the in situ catalyst has such a high catalytic efficiency that the asymmetric hydrogenation for ketone can be performed even with little amount of in situ catalyst, and a very high conversion and very good inducement effect can be obtained. This can also be confirmed by the Examples below. 
     In the invention, when the ketone compound undergoes the asymmetric hydrogenation, the reaction temperature can be set as required. However, in view of the reaction efficiency and the safety of operation, the reaction temperature is −20˜50° C., preferably −10˜40° C., more preferably −10˜25° C., further preferably 0˜20° C., and even more preferably 10˜20° C. 
     In the invention, when the ketone compound undergoes the asymmetric hydrogenation, in view of the reaction efficiency, stirring is preferably performed. In addition, in view of both the reaction efficiency and the safety of operation, the stirring rate is preferably 200˜800 rpm, more preferably 300˜600 rpm, further preferably 400˜500 rpm. The way of stirring can be selected arbitrarily, for example, stirring equipments with stirring paddles or magnetic stirring with a stirring bar can be employed. 
     In the invention, when the ketone compound undergoes the asymmetric hydrogenation, there is no limitation to the reaction time. However, the reaction time is preferably 6˜72 h, more preferably 12˜48 h, further preferably 12˜24 h, and even more preferably 18˜24 h, in view of the yield. 
     In the invention when the ketone compound undergoes the asymmetric hydrogenation, there is no limitation to the hydrogen pressure. However, in view of the yield, the pressure is preferably 3˜50 atm, more preferably 5˜40 atm, further preferably 10˜20 atm, and even more preferably 10˜15 atm. 
     Obviously, when the ketone compound undergoes the asymmetric hydrogenation in the invention, any combination of the above-mentioned reaction temperature, stirring rate, reaction time and hydrogen pressure can be employed 
     Further, in the invention, when the chiral ligand reacts with ruthenium in the first solvent to obtain the in situ catalyst and when the ketone compound undergoes the asymmetric hydrogenation, stirring under heat is preferred to reduce the reaction time and improve the reaction efficiency. 
     The first and second solvents in the invention can be the same or different. However, the first and second solvents are preferred to be the same in view of simple operation. 
     The invention preferably comprises the following first and second steps. In the first step, the chiral ligand reacts with the ruthenium salt in the first solvent to obtain the in situ catalyst; in the second step, under hydrogen atmosphere, in the presence of the in situ catalyst obtained from the chiral ligand and ruthenium, the ketone compound and the base are added into the second solvent to carry out the asymmetric hydrogenation for the ketone compound; and the first and second steps are continuously performed without additional separation of the in situ catalyst obtained in the first step. 
     EXAMPLES 
     The examples of the invention will be described in detail hereinafter. It is noted that the examples are carried out based on the technical solutions of the invention. Although detailed embodiments and specific procedures are provided, the invention is not limited to these examples. 
     The “mol %” used in the following examples refers to the molar percentage of a substance relative to a ketone compound. 
     Example 1 
     Preparation of 1-phenethanol from acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=4-MeC 6 H 4 —, 2.6 μmol, 0.65 mol %) were dissolved in methanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 65° C. After the mixture was cooled to room temperature, acetophenone (0.4 mmol), methane (2 mL), and a solution of sodium hydroxide in methane (0.4 mL, 0.2 M) were added thereto. The reaction system was placed in an autoclave, and stirred for 12 h under H 2  (10 atm) at 10° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-phenethanol was obtained and the ee value (ee=97%) was measured by GC analysis. 
     Example 2 
     Preparation of 1-phenethanol from acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=s-Bu, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in ethanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 80° C. After the mixture was cooled to room temperature, acetophenone (0.4 mmol), ethanol (2 mL), and a solution of sodium hydroxide in ethane (0.4 mL, 0.2 M) were added thereto. The reaction system was placed in an autoclave, and stirred for 12 h under H 2  (20 atm) at 10° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-phenethanol was obtained and the ee value (ee=99.0%) was measured by GC analysis. 
     Example 3 
     Preparation of 1-phenethanol from acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Fe, R=Me, Ar=3,5-(CF 3 ) 2 C 6 H 3 —, 2.6 μmol, 0.65 mol %) were dissolved in toluene (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 120° C. After the mixture was cooled to room temperature, acetophenone (0.4 mmol), toluene (2 mL), and an aqueous solution of potassium hydroxide (0.4 mL, 0.2 M) were added thereto. The reaction system was placed in an autoclave, and stirred for 12 h under H 2  (20 atm) at 10° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-phenethanol was obtained and the ee value (ee=99.3%) was measured by GC analysis. 
     Example 4 
     Preparation of 1-phenethanol from acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (1.9 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Fe, R=n-Pr, Ar=3,5-t-Bu 2 C 6 H 3 —, 1.3 μmol, 0.33 mol %) were dissolved in tetrahydrofuran (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 65° C. After the mixture was cooled to room temperature, acetophenone (0.4 mmol), tetrahydrofuran (2 mL), an aqueous solution of potassium carbonate (0.2 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 48 h under H 2  (20 atm) at 0° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-phenethanol was obtained and the ee value (ee=97%) was measured by GC analysis. 
     Example 5 
     Preparation of 1-phenethanol from acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Fe, R=Bn, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 85° C. After the mixture was cooled to room temperature, acetophenone (0.4 mmol), i-propanol (2 mL) and a solution of potassium t-butoxide in i-propanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (20 atm) at 10° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-phenethanol was obtained and the ee value (ee=99.1%) was measured by GC analysis. 
     Example 6 
     Preparation of 1-phenethanol from acetophenone 
     
       
                 
         
             
             
         
      
     
     Benzeneruthenium(II) chloride dimer (0.5 mg, 1 μmol, 0.25 mol %) and a chiral ligand (M=Fe, R=Ph, Ar=4-MeOC 6 H 4 —, 2.6 μmol, 0.33 mol %) were dissolved in ether (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 40° C. After the mixture was cooled to room temperature, acetophenone (0.8 mmol), ether (2 mL) and an aqueous solution of sodium carbonate (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 6 h under H 2  (40 atm) at 50° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-phenethanol was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 7 
     Preparation of 1-phenethanol from acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in tetrahydrofuran (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 65° C. After the mixture was cooled to room temperature, acetophenone (0.4 mmol), tetrahydrofuran (2 mL) and a solution of sodium ethoxide in tetrahydrofuran (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (10 atm) at 10° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-phenethanol was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 8 
     Preparation of 1-phenethanol from acetophenone 
     
       
                 
         
             
             
         
      
     
     Dichloro(p-cymene)ruthenium(II) dimer (1.2 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=3,5-Me 2 C 6 H 3 —, 2.6 μmol, 0.65 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 0.5 h at 85° C. After the mixture was cooled to room temperature, acetophenone (0.4 mmol), i-propanol (2 mL) and a solution of sodium ethoxide in i-propanol (0.8 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 6 h under H 2  (10 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-phenethanol was obtained and the ee value (ee=99.1%) was measured by GC analysis. 
     Example 9 
     Preparation of 1-(m-methylphenyl)ethanol from m-methyl acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in dichloromethane (3 mL) under nitrogen atmosphere, and then heated and stirred for 0.5 h at 40° C. After the mixture was cooled to room temperature, m-methylacetophenone (0.4 mmol), dichloromethane (2 mL) and an aqueous solution of lithium hydroxide (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (20 atm) at 0° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(m-methylphenyl)ethanol was obtained and the ee value (ee=99.0%) was measured by GC analysis. 
     Example 10 
     Preparation of 1-(o-methylphenyl)ethanol from o-methyl acetophenone 
     
       
                 
         
             
             
         
      
     
     Dichloro(p-cymene)ruthenium(II) dimer (1.2 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Fe, R=i-Pr, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in toluene (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 120° C. After the mixture was cooled to room temperature, o-methylacetophenone (0.4 mmol), toluene (2 mL) and an aqueous solution of potassium hydroxide (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (10 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(o-methylphenyl)ethanol was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 11 
     Preparation of 1-(p-methylphenyl)ethanol from p-methyl acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=C 6 H 5 —, 2.6 μmol, 0.33 mol %) were dissolved in ether (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 40° C. After the mixture was cooled to room temperature, p-methylacetophenone (0.8 mmol), ether (2 mL) and a solution of potassium ethoxide in i-propanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (10 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(p-methylphenyl)ethanol was obtained and the ee value (ee=99.3%) was measured by GC analysis. 
     Example 12 
     Preparation of 1-(m-chlorophenyl)ethanol from m-chloro acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium (II) chloride (3.8 mg, 4 μmol, 0.5 mol %) and a chiral ligand (M=Fe, R=t-Bu, Ar=C 6 H 5 —, 2.6 μmol, 0.33 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 85° C. After the mixture was cooled to room temperature, m-chloroacetophenone (0.8 mmol), i-propanol (2 mL) and a solution of potassium methoxide in i-propanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (50 atm) at 10° C. The solvent was removed under reduced pressure, the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(m-chlorophenyl)ethanol was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 13 
     Preparation of 1-(o-chlorophenyl)ethanol from o-chloro acetophenone 
     
       
                 
         
             
             
         
      
     
     Benzeneruthenium(II) chloride dimer (0.5 mg, 1 μmol, 0.25 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=C 6 H 5 —, 2.6 μmol, 0.33 mol %) were dissolved in methanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 65° C. After the mixture was cooled to room temperature, o-chloroacetophenone (0.8 mmol), methanol (2 mL) and a solution of sodium t-butoxide in methanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 6 h under H 2  (40 atm) at 50° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(o-chlorophenyl)ethanol was obtained and the ee value (ee=97%) was measured by GC analysis. 
     Example 14 
     Preparation of 1-(p-chlorophenyl)ethanol from p-chloro acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Fe, R=n-Pr, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in ethanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 80° C. After the mixture was cooled to room temperature, p-chloroacetophenone (0.4 mmol), ethanol (2 mL) and a solution of sodium ethoxide in ethanol (0.2 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (5 atm) at 0° C. The solvent was removed under reduced pressure, the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(p-chlorophenyl)ethanol was obtained and the ee value (ee=97%) was measured by GC analysis. 
     Example 15 
     Preparation of m-methoxyphenylethanol from m-methoxyacetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 0.5 h at 85° C. After the mixture was cooled to room temperature, m-methoxyacetophenone (0.4 mmol), i-propanol (2 mL) and a solution of sodium methoxide in i-propanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 6 h under H 2  (5 atm) at 40° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure m-methoxyphenylethanol was obtained and the ee value (ee=99.2%) was measured by GC analysis. 
     Example 16 
     Preparation of 1-(o-methoxyphenyl)ethanol from o-methoxyacetophenone 
     
       
                 
         
             
             
         
      
     
     Benzeneruthenium(II) chloride dimer (1.0 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in xylene (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 140° C. After the mixture was cooled to room temperature, o-methoxyacetophenone (0.4 mmol), xylene (2 mL) and an aqueous solution of potassium hydroxide (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (3 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure (o-methoxyphenyl)ethanol was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 17 
     Preparation of 1-(p-methoxyphenyl)ethanol from p-methoxyacetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (1.9 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Fe, R=i-Pr, Ar=3,5-Me 2 C 6 H 3 —, 1.3 μmol, 0.33 mol %) were dissolved in tetrahydrofuran (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 65° C. After the mixture was cooled to room temperature, p-methoxyacetophenone (0.4 mmol), tetrahydrofuran (2 mL) and an aqueous solution of sodium bicarbonate (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (20 atm) at 40° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(p-methoxyphenyl)ethanol was obtained and the ee value (ee=99.1%) was measured by GC analysis. 
     Example 18 
     Preparation of 1-(p-bromophenyl)ethanol from p-bromoacetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=n-Pr, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in ethanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 80° C. After the mixture was cooled to room temperature, p-bromoacetophenone (0.4 mmol), ethanol (2 mL) and a solution of sodium methoxide in ethanol (0.8 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (10 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(p-bromophenyl)ethanol was obtained and the ee value (ee=97%) was measured by GC analysis. 
     Example 19 
     Preparation of 1-(p-fluorophenyl)ethanol from p-fluoroacetophenone 
     
       
                 
         
             
             
         
      
     
     Dichloro(p-cymene)ruthenium(II) dimer (1.2 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in 1,4-dioxane (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 105° C. After the mixture was cooled to room temperature, p-fluoroacetophenone (0.4 mmol), 1,4-dioxane (2 mL) and a solution of sodium carbonate in 1,4-dioxane (0.8 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (5 atm) at 10° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(p-fluorophenyl)ethanol was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 20 
     Preparation of 1-(3,4-dichlorophenyl)ethanol from 3,4-dichloroacetophenone 
     
       
                 
         
             
             
         
      
     
     Benzeneruthenium(II) chloride dimer (1.0 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Fe, R=s-Bu, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 0.5 h at 85° C. After the mixture was cooled to room temperature, 3,4-dichloroacetophenone (0.4 mmol), i-propanol (3 mL) and a solution of potassium t-butoxide in i-propanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 72 h under H 2  (3 atm) at −20° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(3,4-dichlorophenyl)ethanol was obtained and the ee value (ee=95%) was measured by GC analysis. 
     Example 21 
     Preparation of 1-(2,4-difluorophenyl)ethanol from 2,4-difluoroacetophenone 
     
       
                 
         
             
             
         
      
     
     Dichloro(p-cymene)ruthenium(II) dimer (1.2 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 85° C. After the mixture was cooled to room temperature, 2,4-difluoroacetophenone (0.4 mmol), i-propanol (2 mL) and an aqueous solution of sodium hydroxide (1.0 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (20 atm) at 0° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(2,4-difluorophenyl)ethanol was obtained and the ee value (ee=93%) was measured by GC analysis. 
     Example 22 
     Preparation of 1-(m-hydroxylphenyl)ethanol from m-hydroxyacetophenone 
     
       
                 
         
             
             
         
      
     
     Dichloro(p-cymene)ruthenium(II) dimer (1.2 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=Bn, Ar=3,5-Me 2 C 6 H 3 —, 2.6 μmol, 0.65 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 0.5 h at 85° C. After the mixture was cooled to room temperature, m-hydroxyacetophenone (0.4 mmol), i-propanol (2 mL) and a solution of sodium ethoxide in i-propanol (0.4 mL, 0.2M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 6 h under H 2  (50 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/2). Accordingly, pure 1-(m-hydroxylphenyl)ethanol was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 23 
     Preparation of 1-(o-hydroxylphenyl)ethanol from o-hydroxyacetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium (II) chloride (1.9 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=Ph, Ar=C 6 H 5 —, 1.3 μmol, 0.33 mol %) were dissolved in xylene (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 140° C. After the mixture was cooled to room temperature, o-hydroxyacetophenone (0.4 mmol), xylene (2 mL) and an aqueous solution of sodium hydroxide (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (10 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/2). Accordingly, pure 1-(o-hydroxylphenyl)ethanol was obtained and the ee value (ee=97%) was measured by GC analysis. 
     Example 24 
     Preparation of 1-(p-aminophenyl)ethanol from p-amino-acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (1.9 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Fe, R=t-Bu, Ar=3,5-(CF 3 ) 2 C 6 H 3 —, 1.3 μmol, 0.33 mol %) were dissolved in tetrahydrofuran (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 65° C. After the mixture was cooled to room temperature, p-amino-acetophenone (0.4 mmol), tetrahydrofuran (2 mL) and an aqueous solution of sodium carbonate (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 48 h under H 2  (20 atm) at 0° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/1). Accordingly, pure 1-(p-aminophenyl)ethanol was obtained and the ee value (ee=97%) was measured by GC analysis. 
     Example 25 
     Preparation of 1-(p-phenylphenyl)ethanol from p-phenyl-acetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium (II) chloride (1.9 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=C 6 H 5 —, 1.3 μmol, 0.33 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 85° C. After the mixture was cooled to room temperature, p-phenyl-acetophenone (0.8 mmol), i-propanol (2 mL) and a solution of potassium carbonate in i-propanol (0.8 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (10 atm) at −20° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(p-phenylphenyl)ethanol was obtained and the ee value (ee=99.2%) was measured by GC analysis. 
     Example 26 
     Preparation of 1-(1-naphthyl)ethanol from 1-acetonaphthone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Fe, R=Me, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in 1,4-dioxane (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 105° C. After the mixture was cooled to room temperature, 1-acetonaphthone (0.4 mmol), 1,4-dioxane (2 mL) and a solution of potassium t-butoxide in 1,4-dioxane (0.4 mL, 0.4 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (40 atm) at 0° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(1-naphthyl)ethanol was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 27 
     Preparation of 1-(2-naphthyl)ethanol from 2-acetonaphthone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=3,5-t-Bu 2 C 6 H 3 —, 2.6 μmol, 0.65 mol %) were dissolved in dichloromethane (3 mL) under nitrogen atmosphere, and then heated and stirred for 0.5 h at 40° C. After the mixture was cooled to room temperature, 2-acetonaphthone (0.4 mmol), dichloromethane (2 mL) and an aqueous solution of potassium hydroxide (0.2 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (10 atm) at 50° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(2-naphthyl)ethanol was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 28 
     Preparation of 1-(3,4-dimethoxyphenyl)ethanol from 3,4-dimethoxyacetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (0.38 mg, 0.4 μmol, 0.1 mol %) and a chiral ligand (M=Fe, R=t-Bu, Ar=C 6 H 5 —, 0.26 μmol, 0.065 mol %) were dissolved in toluene (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 120° C. After the mixture was cooled to room temperature, 3,4-dimethoxyacetophenone (0.4 mmol), toluene (2 mL) and an aqueous solution of sodium carbonate (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (10 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(3,4-dimethoxyphenyl)ethanol was obtained and the ee value (ee=96%) was measured by GC analysis. 
     Example 29 
     Preparation of 1-(3,4,5-trimethoxyphenyl)ethanol from 3,4,5-trimethoxyacetophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in ethanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 80° C. After the mixture was cooled to room temperature, 3,4,5-trimethoxyacetophenone (0.4 mmol), ethanol (2 mL) and a solution of sodium t-butoxide in ethanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 48 h under H 2  (10 atm) at 0° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(3,4,5-trimethoxyphenyl)ethanol was obtained and the ee value (ee=97%) was measured by GC analysis. 
     Example 30 
     Preparation of 1-phenylpropanol from propiophenone 
     
       
                 
         
             
             
         
      
     
     Dichloro(p-cymene)ruthenium(II) dimer (1.2 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 85° C. After the mixture was cooled to room temperature, propiophenone (0.4 mmol), i-propanol (2 mL) and a solution of sodium carbonate in i-propanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 24 h under H 2  (5 atm) at 10° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/8). Accordingly, pure 1-phenylpropanol was obtained and the ee value (ee=99.2%) was measured by GC analysis. 
     Example 31 
     Preparation of 1-phenylbutynol from 1-phenylbutan-1-one 
     
       
                 
         
             
             
         
      
     
     Benzeneruthenium(II) chloride dimer (1.0 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=3,5-t-Bu 2 C 6 H 3 —, 2.6 μmol, 0.65 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 85° C. After the mixture was cooled to room temperature, 1-phenylbutan-1-one (0.4 mmol), i-propanol (2 mL) and a solution of sodium hydroxide in i-propanol (0.4 mL, 0.4 M) were added thereto. Thereafter, the reaction system were placed in an autoclave, and stirred for 12 h under H 2  (10 atm) at 40° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/8). Accordingly, pure 1-phenylbutynol was obtained and the ee value (ee=99.2%) was measured by GC analysis. 
     Example 32 
     Preparation of 2-methyl-1-phenyl-1-propanol from i-butyrophenone 
     
       
                 
         
             
             
         
      
     
     Benzeneruthenium(II) chloride dimer (1.0 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Fe, R=i-Pr, Ar=4-MeC 6 H 4 —, 2.6 μmol, 0.65 mol %) were dissolved in xylene (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 140° C. After the mixture was cooled to room temperature, i-butyrophenone (0.4 mmol), xylene (2 mL) and a solution of sodium carbonate in i-propanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (5 atm) at 40° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 2-methyl-1-phenyl-1-propanol was obtained and the ee value (ee=99.3%) was measured by GC analysis. 
     Example 33 
     Preparation of 1-phenylpentanol from pentanophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium (II) chloride (1.9 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=C 6 H 5 —, 1.3 μmol, 0.33 mol %) were dissolved in xylene (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 140° C. After the mixture was cooled to room temperature, pentanophenone (0.4 mmol), xylene (2 mL) and a solution of potassium hydroxide in methanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (10 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/8). Accordingly, pure 1-phenylpentanol was obtained and the ee value (ee=99.6%) was measured by GC analysis. 
     Example 34 
     Preparation of 1-(p-methylphenyl)octanol from p-methyloctanophenone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium (II) chloride (1.9 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=C 6 H 5 —, 1.3 μmol, 0.33 mol %) were dissolved in xylene (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 140° C. After the mixture was cooled to room temperature, p-methyloctanophenone (0.8 mmol), xylene (2 mL) and a solution of potassium hydroxide in methanol (0.8 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 6 h under H 2  (10 atm) at 50° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(p-methylphenyl) octanol was obtained and the ee value (ee=99.0%) was measured by GC analysis. 
     Example 35 
     Preparation of 3-(1-hydroxyethyl)pyridine from 3-acetylpyridine 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=C 6 H 5 —, 2.6 μmol, 0.65 mol %) were dissolved in tetrahydrofuran (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 65° C. After the mixture was cooled to room temperature, 3-acetylpyridine (0.4 mmol), tetrahydrofuran (2 mL) and a solution of potassium ethoxide in ethanol (0.1 mL, 0.2M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 6 h under H 2  (50 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/1). Accordingly, pure 3-(1-hydroxyethyl)pyridine was obtained and the ee value (ee=93%) was measured by GC analysis. 
     Example 36 
     Preparation of 2-(1-hydroxyethyl)furan from 2-acetylfuran 
     
       
                 
         
             
             
         
      
     
     Benzeneruthenium(II) chloride dimer (1.0 mg, 2 μmol, 0.1 mol %) and a chiral ligand (M=Fe, R=t-Bu, Ar=4-MeOC 6 H 4 —, 2.6 μmol, 0.13 mol %) were dissolved in i-propanol (15 mL) under nitrogen atmosphere, and then heated and stirred for 0.5 h at 85° C. After the mixture was cooled to room temperature, 2-acetylfuran (2.0 mmol), i-propanol (15 mL) and a solution of potassium methoxide in i-propanol (2.0 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 48 h under H 2  (40 atm) at −20° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 2-(1-hydroxyethyl)furan was obtained and the ee value (ee=98%) was measured by GC analysis. 
     Example 37 
     Preparation of 1,2,3,4-tetrahydro-1-naphthol from 1-tetralone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium (II) chloride (1.9 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=C 6 H 5 —, 1.3 μmol, 0.33 mol %) were dissolved in ethanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 80° C. After the mixture was cooled to room temperature, 1-tetralone (0.4 mmol), ethanol (2 mL) and a solution of potassium hydroxide in ethanol (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 48 h under H 2  (10 atm) at 0° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1,2,3,4-tetrahydro-1-naphthol was obtained and the ee value (ee=99.7%) was measured by GC analysis. 
     Example 38 
     Preparation of 1-hydroxylhydrindene from 1-indanone 
     
       
                 
         
             
             
         
      
     
     Tris(triphenylphosphine)ruthenium (II) chloride (0.76 mg, 0.8 μmol, 0.2 mol %) and a chiral ligand (M=Ru, R=i-Pr, Ar=C 6 H 5 —, 0.52 μmol, 0.13 mol %) were dissolved in ether (3 mL) under nitrogen atmosphere, and then heated and stirred for 2 h at 40° C. After the mixture was cooled to room temperature, 1-indanone (0.4 mmol), ether (2 mL) and an aqueous solution of potassium carbonate (0.2 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H 2  (5 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent: ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-hydroxylhydrindene was obtained and the ee value (ee=99.5%) was measured by GC analysis.