Title of Invention

METHOD FOR PRODUCING OPTICALLY ACTIVE ALCOHOL

Abstract

An industrially advantageous method for, producing optically-active alcohols, which is also applicable to the production of acid-unstable compounds, or the method ia which hydrogen is allowed to react in the presence of an inorganic salt and an optically-active hydrogenation complex catalyst with a compound expressed by Formula (I) [R1 denotes an alkyl group and others which may have a substituent group, R2 denotes a hydrogen atom and others, and R3 denotes a hydroxyl group and others] thereby producing an optically-active alcohol compound expressed by Formula (II) [R1, R2 and R3 have the same meanings as those given in Formula (I) and the asterisk (*) denotes an optically-active carbon atom].

Full Text

DESCRIPTION ETHOD FOR PRODUCING OPTICALLY-ACTIVE ALCOHOLS TECHNICAL FIELD [0001] The present invention provides an industrially advantageous method for producing optically-active alcohols. BACKGROUND ART [0002] Optically-active alcohols are useful as intermediates of agricultural chemicals and/or medical drugs. Various methods for producing optically-active alcohols are known, such as a resolution method, eazymatic/microbial method and asymmetric synthesis method. Methods for inducing ketone to corresponding optically-active alcohols by a catalytic asymmetric hydrogenation reaction is used have been extensively studied, since the reaction produces a smaller quantity of industrial waste and inexpensive hydrogen is used as a reducing agent. Industrially, among these methods, an asymmetric hydrogenation reaction of carbonyl compounds having a functional group in which an optically-active homogenous ruthenium catalyst is used is one of the effective techniques (for example, refer to "Asymmetric Catalysis in Organic Synthesis" written by R. Noyori, (U.S.A.), p. 56-82, 1994, Japanese Published Examined Patent Application No. H5-12353, Japanese Published Examined Patent Application No. H4-81596, Japanese Published Unexamined Patent Application No. H9-294932, Japanese Published Unexamined Patent Application No. H10-59992, Japanese Published Examined Patent Application No. 117-57758). However, the complex catalyst used in the above-described reaction is extremely expensive, which requires the catalyst quantity used in producing optically-active alcohols to be decreased to an industrially advantageous cost. [0003] It is known that in order to decrease the catalyst quantity, the addition of a strong acid such as hydrogen chloride results in improvement in catalyst activities in a reduction reaction similar to the above-described reaction (for example, "Journal of Organic Chemistry" (U.S.A.), Vol. 57, p. (5689, 1992, and "Tetrahedron Asymmetry" (UK), Vol. 8, p. 4041, 1997). However, substrates unstable to acid such as carbonyl compounds having a functional group may result in a drastic reduction in yield by addition of an acid. Therefore, in an industrial production of optically-active alcohols, there has been demanded a method which will not affect a substrate or pose any problems in terms of operation and cost. DISCLOSURE OF INVENTION [0004] An object of the present invention is to provide an industrially advantageous method for producing optically-active alcohols, which is applicable to an acid-unstable compound in an asymmetric hydrogenation reaction of carbonyl compounds. [0005] The present inventors have actively studied a method for producing optically-active alcohols and found a method for decreasing a catalyst quantity, which has led to completion of the present invention. More specifically, the present invention is a method for producing an optically-active alcohol compound, comprising reacting hydrogen in the presence of an inorganic salt and an optically-active hydrogenation complex catalyst with a compound expressed by Formula (I) [wherein R denotes an alkyl group which may have a substituent group, an aryl group which may have a substituent group, a hetero-aryl group which may have a substituent group or an aralkyl group which may have a substituent group, R2 denotes a hydrogen atom, an alkyl group which may have a substituent group, an aryl group which may have a substituent group, or an aralkyl group which may have a substituent group, R2 may be combined with another counterpart to form a ring, and R3 denotes a hydroxyl group, an alkoxy group which may have a substituent group, a thiol group or an alkylthio group], wherein the optically-active alcohol compound is a compound expressed by Formula (II) [wherein R1, R2 and R3 have the same meanings as those given in Formula (I) and the asterisk (*) denotes an optically-active carbon atom]. [0011] The present invention is able to provide an efficient method for decreasing a quantity of catalyst, without decomposition of raw materials or products, thereby producing optically-active alcohols at a low cost. Furthermore, the present invention relates to an industrially advantageous method for producing optically-active alcohols. which is also applicable to acid-unstable compounds. BEST MODE FOR CARRYING OUT THE INVENTION [0012] In the present invention, there is no restriction on an additive agent, as long as it is an inorganic salt. However, alkaline metal salts or alkaline earth metal salts are preferable. More preferable are lithium salt, sodium salt, potassium salt, and particularly preferable are lithium chloride, lithium bromide, sodium chloride, potassium chloride, etc. These salts may be added directly as commercial product at the time of reaction, or an inorganic base is allowed to react with an acid in a reaction solvent, for example, sodium hydroxide with hydrogen chloride, lithiium hydroxide with hydrogen chloride or potassium hydroxide with hydrogen chloride, which may be used as an inorganic base. [0013] R1 given in the formulae (!) and (II) denotes an alkyl group which may have a substituent group, an aryl group which may have a substituent group, a hetero-aryl group which may have a substituent group or an aralkyl group which may have a substituent group. Base alkyl groups of alkyl groups which may have a substituent group include those of methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopentyl, cyclohexyl, octyl and eicosanyl; base aryl groups of aryl groups which may have a substituent group include those of phenyl, 1-naphthyl, and 2-naphthyl; and base aralkyl groups of aralkyl groups which may have a substituent group include those of benzyl,phenethyl, 3-phenylpropyl, and diphenyl methyl. Base aryl groups of aryl groups which may have a substituent group include those of phenyl, 1 -naphthyl, and 2-naphthyl; and base hetero-aryl groups of hetero-aryl groups which may have a substituent group include those of 2-pyridyl, 3-pyridy], 4-pyridyl, 2-imidazoyl, 4-imidazoyl, 3-pyrazoyl, 4-pyrazoyl, 5-pyrazoyl, 2-indolyl, 3-indoyl, and quinolyl. [0014] The above-described alkyl groups, aryl groups, aralkyl groups, aryl groups, and hetero-aryl groups may have one or a plurality of substituent groups which are the same or mutually different. These substituent groups include halogen atoms such as fluorine, chlorine, bromine and iodine; alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, pentyl and hexyl; and alkoxy groups such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, t-butoxy and pentoxy. [0015] R2denotes a hydrogen atom, an alkyl group which may have a substituent group, an aryl group which may have a substituent group, or an aralkyl group which may have a substituent group. R2 may be combined with another counterpart to form a ring. Base alkyl groups of alkyl groups which may have a substituent group include those of methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopentyl, cyclohexyl, octyl, and eicosanyl; and base aryl groups of aryl groups which may have a substituent group include those of phenyl, 1 -naphthyl, and 2-naphthyl. Base aralkyl groups of aralkyl groups which may have a substituent group include those of benzyl, phenethyl, 3-phenylpropyl, and diphenyl methyl. [0016] The above-described alkyl groups, aryl groups and aralkyl groups may have one or a plurality of substituent groups which are the same or mutually different. These substituent groups include halogen atoms such as fluorine, chlorine, bromine and iodine; alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, pentyl and hexyl; and alkoxy groups such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, t-butoxy and pentoxy. [0017] R3 denotes a hydroxy! group, an alkoxy group which may have a substituent group, a thiol group or an alkylthio group. Base alkoxy groups of alkoxy groups which may have a substituent group include those of methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy and t-butoxy; and base alkylthio groups of alkylthio groups which may have a substituent group include those of methylthio, ethylthio. n-propyllhio, iso-propylthio, n-butylthio, iso-butylthio. sec-butyithio, and t-butylthio. [0018] The above-described alkoxy groups or alkylthio groups may have one or a plurality of substituent groups which are the same or mutually different. These substituent groups include halogen atoms such as fluorine, chlorine, bromine and iodine; alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, pentyl and hexyl; and alkoxy groups such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, t-butoxy and pentoxy. [0019] Among compounds having the above substituent groups, preferably applicable to the present invention is a reaction for obtaining a compound expressed by Formula (IV) [wherein, R1, and R2 have the same meanings as those given in the formula (III) and the asterisk (*) denotes an optically-active carbon atom] by reacting a compound expressed by Formula (111) as a raw material [wherein R1 denotes an alkyl group which may have a substituent group, an aryl group which may have a substituent group, a hetero-aryl group which may have a substituent group or an aralkyl group which may have a substituent group, R2 denotes a hydrogen atom, an alkyl group which may have a substituent group or an aralkyl group which may have a substituent group, and R may be combined with another counterpart to form a ring]. [0020] In an asymmetric hydrogenation complex catalyst expressed by Composition Formula (V) of the present invention [wherein, m, n and p individually and independently denote 1 or 2 and q denotes a real number from 0 to 2], there are no restrictions as long as a bidentate tertiary phosphorus ligand expressed by L as long as it is optically-active. More specifically, tertiary phosphines of bidentate ligands in which a phosphorus atom is optically-active , include bis (methyl tBu phosphino) methane (MiniPHOS), 1, 2-bis (methyl tBu phosphino) ethane (Bis P*); tertiary phosphines of optically-active bidentate ligands having the same two substituent groups on a phosphorus atom includes, for example, BPPFA: 1-[1', 2-bis (diphenyl phosphino) ferroccnyl] ethyl diamine, BICHEP: 2, 2-bis (dicylco-hexylphosphino)-6, 6-dimethyl-l, l'-biphenyl, CHfRAPHOS: 2, 3-bis-(diphenyl phosphino) butane, CYCPHOS: 1-cyclohexyl-l, 2-bis-(diphenyI phosphino) ethane, DEGPHOS: 1 -substitution-3,4-bis (diphenyl phosphino) pyrrolidine, DIOP: 2, 3-0-isopropylidene-2, 3-dihydroxy-l, 4-bis (diphenyl phosphino) butane, DIPAMP: 1, 2-bis [(O-methoxy phenyl) phenyl phosphino] ethane, DuPHOS: (substitution-1, 2-bis (phosphorano) benzene), NORPIIOS: 5, 6-bis-(diphenyl phosphino) -2-norbornene, PNNP:N, N'-bis- (diphenyl phosphino) -N, N'-bis [1-phenyl ethyl] ethylene diamine, PROPHOS: 1, 2-bis- (diphenyl phosphino) propane, SKEWPHOS: 2, 4-bis-(diphenyl phosphino) pentane; tertiary phosphines of axially asymmetric bidentate ligands include, for example, MeO-BIPHEP: (6,6'-dimethoxybiphenyl-2, 2'-diyl)-bis-(drphenjl phosphine), Cl-MeO-BIPHEP: (5, 5'-dichloro-6, 6'-dimethoxy 2, 2'-bis- (diphenyl phosphino) -1,l'-biphenyl. BIPHMP: (6, 6'-dimethylbiphenyl-2, 2'-bis- (diphenyl phosphino)-!, 1 '-biphenyl; TUNEPHOS (CI to C6) include, for example, C3-TUNEPH0S: 1, 13-bis (diphenyl phosphmo)-7, 8-dihydro-6PI-dibenzo [f,h] [1,5] dioxyoncne, SYNPHOS: 6,6'-bis (diphenyl phosphino)-2, 2'-3, 3'-telrdhydro-5, 5"-bi-l, 4-benzodioxyine, P-PHOS: 2, 2'-6, 6-tetramethoxy-4, 4'-bis (diphenyl phosphino)-3, 3'-bipyridine, BINAP: 2, 2'-bis-(diphenyl phosphino)-l, l'-binaphthyl; BINAP derivatives having substituent groups such as an alkyl group and an aryl group on a naphthyl ring of BINAP: BINAP derivatives having a fluorine substituent group; BINAP derivatives, etc., having 1 to 5 substituent groups of alkyl, alkoxy, etc., respectively on the same two benzene rings on a phosphorus atom include, for example, Tol-BINAP: 2, 2'-bis-(di-p-toly] phosphino)-l, 1'-binaphthyl, Xylyl-BINAP: 2, 2'-bis [bis (3, 5-dimethylphenyl)phosphino]-l, 1 '-binaphthyl; those in which a substituent group on a phosphorus atom is an alkyl group include, for example, 2. 2'-bis- (dicylco-hexyl phosphino) -l, 1'-binaphthyl, SEGPHOS: [(5, 6), (5', 6') -bis (methylene dioxy) biphenyl 2. 2'-diyl] bis (diphenyl phosphine). [0021] Halogen atoms expressed by X are chlorine, bromine and iodine, which are counter anions of divalent ruthenium complexes available ns a raw material. [0022] Y denotes a ligand compound expressed by Formula (A), (B) or (C) [wherein, Ra, Rb and Rc denote individually and independently denote a hydrogen atom and an alkyl Jjroup, Rb may join with Re to form alkylene chains of C2 to C7, and k denotes an integral number from 1 to 4]. More specifically, preferable compounds expressed by Formula (A) include N, N-dimethyl formamide (DMF), N, N-dimethyl acetoamide and N, N-diethyl formamide, compounds expressed by Formula (B) include N-methyl-2-pyrrolidinone, N-isoprapy)-2-pyrrolidinone and N-methyl-2-piperidone, and compounds expressed by Formula (C) include N, N'-dimcthyl-2-imidazolidinone, l,3-drmethyl-3, 4, 5, 6-tetraliydro-2 (lH)-pyrimidinone. [0023] The above catalysts can be synthesized in accordance with the method described in Tetrahedron Lett., Vol.. 32, p. 4163, 1991. More specifically, an optically-active bidentate tertiary phosphorus ligand expressed by bivalent ruthenium complexes such as [RuCl2(l, 5-CgH12)]„(nithcnium chloride (II) I, 5-cyclooctadienc complex) is heated together with a coordinate compound expressed by Y such as DMF at temperatures from 50 to 200°C, preferably from 100 to 160°C, to obtain the catalysts. The molar ratio of a divalent ruthenium complex to an optically-active bidentate tertiary phosphorus ligand expressed by L is 1 : 0.5 to 1 : 5. preferably from 1 : 1 to 1 : 1.5. Since the previously described compounds which can be used as a ligand such as DMF are used as a reaction solvent, they arc not restricted in particular in usage amount relative to the divalent ruthenium complexes. However, these compounds are usually used in a quantity from 2 to 10,000 times (on w/w basis), preferably from 5 to 300 limes. Furthermore, after the synthesis of a ruthenium compound expressed by General Composition Formula (V), the compound (V) may be used in the reaction solution as it is. It is, however, preferable that the compound be used as a powder obtained by removing a substance (Y) from the reaction solution thereof. [0024] The above reaction can be carried out either in the presence or absence of a solvent. Any solvents can be used as long as they are inactive in the reaction, and preferable solvents include, for example, hydrocarbon-based solvents such as pentane, hexane, heptane, benzene, toluene and xylene; halogen-based solvents such as dichloromethane, 1, 2-dichloroelhane, chloroform and carbon tetrachloride; alcohols such as methanol and ethanol; nitrile-based solvents such as acetonitrlie, propione nitrile; emer-based solvents such as diethyl ether, dioxane, tetrahydrofuran; non-protonic polar solvents such as DMF and dimethyl sulfoxide; water; and mixed solvents in which two or more of the above-described solvents are mixed. Of these solvents, alcohols are in particular preferable. Inactive solvents may be used in any quantity. However, a practical volume ratio(a compound expressed by Formula (I) to an inactive solvent) is from 0 to 100, and a preferable ratio is from 0 to 10. [0025] An optically-active alcohol (II) of the present invention can be produced by mixing a compound expressed by Formula (I), an optically-active hydrogenation complex catalyst expressed by Composition Formula (V) and an inorganic salt in the presence or absence of a solvent and applying hydrogen pressure thereto. Addition of an inorganic salt, which is a feature of the present invention, makes it possible to attain favorable optical and chemical yields, while the molar ratio (a compound expressed by Formula (1) / an optically-active hydrogenated catalyst expressed by Composition Formula (V),hereinafter, abbreviated as S/C) is kept high. [0026] The molar ratio of (an inorganic salt) / (an optically-active hydrogenation complex catalyst expressed by Composition Formula (V)) is from 50 to 1,000, preferably from 3 to 400. An inorganic salt may be used as it is or may be used after being dissolved in any of the above-desciibed solvents. In this case, the S/C is from 5,000 to 100, 000, preferably from 10,000 to 3C,000. Where the inorganic salt is used in the above-described quantity and S/C range, an appropriate reaction can be carried out, with the pressure, the temperature and the time being subjected to practical restrictions. More specifically, the reaction can be carried out at any pressure above a normal pressure, if there are no apparatus restrictions and at temperatures higher than a melting point of a reaction solution but lower than a decomposition point of a substrate. Furthermore, the reaction will be completed in a shorter time under high pressure and high temperature conditions and in a longer time under low pressure and low temperature conditions. In a practical point of view, a preferable reaction pressure is from 3 to 10 MPa, and a preferable reaction temperature is from 5 to 100°C. In this case, the reaction will be completed within 1 to 48 hours. Since favorable optical and chemical yields can be attained, an optically-active alcohol, which is a reaction product after the reaction, can be purified by a known method such as distillation. [0027] Next, a further detailed description will be made of the present invention by referring to reference examples and embodiments. It is to be understood that the present invention is not restricted thereto. [Embodiments] [0028] Embodiment 1: Synthesis of optically-active 1, 3-butanediol A stirrer and an optically-active hydrogenation complex catalyst synthesized in Reference Example 1 (4.8 mg: 0.0051 mmol; S/C = 19,600) were placed into an autoclave (100 ml) and subjected io argon substitution. 3-Oxo-l-butanol (8.8 g: 99.9 mmol) and methanol (7.0 ml) were placed into a Schlenk flask and subjected to argon substitution. Thereafter, a syringe was used to transfer the resultant to the autoclave. Furthermore, a syringe was used to add 0.01N lithium chloride methanol solution (2.4 ml: 0.024 mmol) to the autoclave, and the reaction was carried out at a hydrogen pressure of 6 MPa at 60°C for 7 hours. Thereafter, the autoclave was cooled to reduce the pressure to a normal level, and the reaction solution was subjected to gas chromatography (CP-Chirasil DEX-CB: 0.25 mm *25 m, In]: 200°C. Column: 100°C, DET: 200°C) to analyze the same. The target compound was 96.7%ee in optical purity, 100% in conversion rate and 91.5% in yield. [0029] Embodiment 2: Synthesis of optically-active 2-methyl 2,4-pentanediol A stirrer and an optically-active hydrogenation complex catalyst synthesized in Reference Example 1 (4.8 mg: 0.0051 mmol; S/C = 19,600) were placed into an autoclave (100ml) and subjected to argon substitution. 2-Methyl-4-oxo-2-pentanol (11.5 g: 100 mmol) and methanol (11.6 ml) were placed into a Schlenk flask and subjected to argon substitution. Thereafter, a syringe was used to transfer the resultant to the autoclave. Furthermore, lithium chloride (60 mg: 1.4 mmol) was added to the autoclave, and the reaction was canied out at a hydrogen pressure of 9 MPa at 60°C for 12 hours. Thereafter, the autoclave was cooled to reduce the pressure to a normal level, and the reaction solution was subjected to gas chromatography (CP-Chirasil DEX-CB: 0.25 mm *25 m, Inj: 200°C. Column: 100°C, DET: 200°C) to analyze the same. The target compound was 96.7%ee in optical purity, 100% in conversion rate and 99.1% in GC yield. [0030] Reference Example 1: Production of an optically-active hydrogenation complex catalyst (In Formula V, [L] = (R) - BINAP, m =1, n =1, X=C1, p=2, Y= DMF, q= 1 to 2) expressed by Composition Formula [(R) - (binap) RuCfe (dm!) q] (R) - BINAP (65 mg: 0.1 mmol) and [RuCb(COD)] (28mg: 0.1 mmol) were placed into a Schlenk flask and subjected to argon substitution. Deaerated DMF (5 ml) was added thereto, and the resultant was heated for 20 minutes in an oil bath kept at 160°C, with agitation. Thereafter, the resultant was cooled to room temperature,and DMF was removed under a reduced pressure to obtain the target compound of 93 mg (yield: quantitative). [0031] Reference Example 2: Production of optically-active 1. 3-butanediol (addition of methanol hydrochloride solution) A stirrer and an optically-active hydrogenation complex catalyst synthesized in Reference Example 1 (4.8 mg: 0.0051 mmol; S;'C = 19,600) were placed into an autoclave (lOOml) and subjected to argon substitution. 3-Oxo-l-butanol (8.8 g: 99.9 mmol) and methanol (7.3 ml) were placed into a Schlenk flask and subjected to argon substitution. Thereafter, a syringe was used to transfer the resultant to the autoclave. Furthermore, a syringe was used to add 0.012N hydrochloride methanol solution (2.0 ml: 0.024 mmol) to the autoclave, and die reaction was carried out at a hydrogen pressure of 6 MPa at 60°C for 24 hours. Thereafter, the autoclave was cooled to reduce the pressure to a normal level, and the reaction solution was subjected to gas chromatography (CP-Chirasil DEX-CB; 0.25 nun *25 m, Inj: 200°C. Column: 100°C, DET: 200°C) to analyze the same. The target compound was 95.9%ee in optical purity, 100% in conversion rate and 77.5% in yield. [0032] Reference Example 3: Production of optically-active 1, 3-butanediol (free of inorganic salt) 3-Oxo-l-butanol (9.2 g: 0.105 mol) and an optically-active hydrogenation complex catalyst (5.2 mg: 0.0055 mmol; S/C = 19,000) synthesized similarly to Reference Example 1 were pi iced into a Schleivk flask and subjected to argon substitution. After a stirrer was placed into an autoclave (100 ml), a syringe was used to transfer the resultant to the autoclave (100 ml) which had been subjected to argon substitution. The reaction was carried out at a hydrogen pressure of 10 MPQ at 70°C for 19 hours. Thereafter, the autoclave was cooled to reduce the pressure to a normal level, and the reaction solution was analyzed, it was found that the thus obtained target compound was 96.0%ee in optical purity and 43% in conversion rale. INDUSTRIAL APPLICABILITY [0033] The present invention is able to decrease a quantity of catalyst without causing degradation of raw materials or products and also effectively produce optically-active alcohols at a lower cost. t WE CLAIM: 1. A method for producing an optically-active alcohol compound, comprising reacting hydrogen in the presence of an inorganic salt and an optically-active hydrogenstion complex catalyst with a compound expressed by Formula (T) [wherein R1 denotes an alkyl group which may have a substituent group, an aryl group which may have a snbstituent group, a hetero-aryl group which may have a snbstituent group or an aralkyl group which may have asubstituent group, R2 denotes a hydrogen atom, an alkyl group which may have a substituent group, an aryl group which may have a snbstituent group, or an aralkyl group which may have a substitaent group, R2 may be combined with another counterpart to form a ring,, R denotes a hydroxyl group, an alkoxy group which may have a snbstituent group, a thiol group ot an alkylthio group], and wherein the substituent group is one selected from the group consisting of a halogen atom, an alkyl group and an alkoxy group, such as herein described], wherein the optically-active alcohol compound is a compound expressed by Formula (II) [wherein R1, R2 and R3 have the same meanings as those given ir and the asterisk (*) denotes an optically-active carbon atom]. wherein the optically-active hydrogenation complex catalyst is a ruthenium compound expressed by Composition Formula (V) [wherein, L denotes an optically-active bidentate tertiary phosphorus ligand, X denotes a halogen atom, and Y denotes a coordinate compound expressed by Formula (A), (B) or (C) (wherein,Ra, Rb and Re individually and independently denote a hydrogen atom or an alklyl group, Rb may join with Rc to form alkylene chains, and k denotes an integral number from 1 to 4), m, n and p independently denote 1 or 2, and q denotes a real number from 0 to 2]. wherein the inorganic salt is an alkaline metal salt or alkaline earth metal salt. 2. A method for producing an optically-active alcohol compound, comprising reacting hydrogen in the presence of an inorganic salt and an optically-active hydrogenation complex catalyst with a compound expressed by Formula (III) [wherein R1 denotes an alkyl group which may have a substitucnt group, an aryl group -which may have a substituent group, a hetero-aryl group which may have a substituent group or an aralkyl group which may have a substituent group, R2 denotes a hydrogen atom, an alkyl group which may have a substituent group or an aralkyl group which may have a substituent group, R2 may be combined with another counterpart to form a ring], and wherein the substituent group is one selected from the group consisting of a halogen atom, an alkyl group and an alkoxy group, such as herein described], wherein the optically-active alcohol compound is a compound expressed by Formula [wherein R1.and R2 have the same meanings as those given in Formula (I) and the asterisk (*) denotes an optically-active carbon atom], wherein the optically-active hydrogenation complex catalyst is a ruthenium compound expressed by Composition Formula (V) [L]mRunXp(Y)q CO [wherein, L denotes an optically-actrve bidentate tertiary phosphorus ligand, X denote? a halograa atom, and Y denotes a coordinate compound expressed by Formula (A), (B) or (C) (wherein,Ra, Rb and Rc individually and independently denote a hydrogen atom or an alkyl group, Rb may join with Rc to form alkylene chains, and k denotes an integral number from i to 4), m, n and p independently denote 1 or 2, and q denotes a real number from 0 to 2], wherein the inorganic salt is an alkaline metal salt or alkaline earth metal salt. 3. The method for producing an optically-active alcohol compound as claimed in any of claims 1 and 2, wherein the inorganic salt is added at molar ratio of 3 to 400 relative to the optically-active hydrogenation complex catalyst. 4. The method for producing an optically-active alcohol as claimed in any of claims 1 to 3, wherein the inorganic salt is a lithium salt, sodium salt or potassium salt. 5. The method for producing an optically-active alcohol as claimed in any of claims 1 to 3, wherein the inorganic salt is selected from any one of lithium chloride, lithium bromide, sodium chloride or potassium chloride. An industrially advantageous method for, producing optically-active alcohols, which is also applicable to the production of acid-unstable compounds, or the method ia which hydrogen is allowed to react in the presence of an inorganic salt and an optically-active hydrogenation complex catalyst with a compound expressed by Formula (I) [R1 denotes an alkyl group and others which may have a substituent group, R2 denotes a hydrogen atom and others, and R3 denotes a hydroxyl group and others] thereby producing an optically-active alcohol compound expressed by Formula (II) [R1, R2 and R3 have the same meanings as those given in Formula (I) and the asterisk (*) denotes an optically-active carbon atom].

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