JP5087395B2 - Sulfonate catalyst and method for producing alcohol compound using the same - Google Patents

Description

The present invention relates to a sulfonate catalyst and a method for producing an alcohol compound using the sulfonate catalyst.

  So far, various methods for producing optically active alcohols using metal complexes as catalysts have been reported. In particular, a method for synthesizing an optically active alcohol from a ketone compound by a reductive method using a ruthenium complex as a catalyst in the presence of a base has been studied very vigorously.

  Regarding asymmetric hydrogenation and a catalyst in which hydrogen is used as a reducing agent and a ketone is asymmetrically hydrogenated to obtain an optically active alcohol, for example, JP-A-8-225466 discloses BINAP (2,2′-bis (diphenyl). An example was reported in which an optically active alcohol was produced by hydrogenating a ketone compound in the presence of a base using a complex of phosphino) -1,1'-binaphthyl) and DMF coordinated to ruthenium and diphenylethylenediamine as a catalyst. Yes.

However, depending on the structure of the ketone compound, the hydrogenation reaction may not proceed efficiently, or the enantiomeric excess may be insufficient. In addition, in the above catalyst system, the reaction is carried out under basic conditions. Base labile ketone compounds and ketones with acidic hydrogen could not be hydrogenated. Several attempts have been made to solve such problems.

  For example, in JP 2003-104993 A, a base is added under pressure hydrogen using tetrahydroborate of an asymmetric ruthenium metal complex in which a diphosphine compound such as BINAP and a diamine compound are coordinated to ruthenium as a catalyst. Several examples have been reported in which an optically active alcohol is produced by hydrogenating a base-labile ketone compound in 2-propanol. Specifically, the corresponding optically active alcohol is produced from ethyl 4-acetylbenzoate, 3-nonen-2-one and the like.

  However, in the catalyst described in Japanese Patent Application Laid-Open No. 2003-104993, the yield and enantiomeric excess may be low depending on the reaction substrate, and the structure of applicable ketone compounds is limited.

For catalytic asymmetric hydrogenation, many methods using alcohol or formic acid as a reducing agent, that is, catalytic asymmetric reduction reaction, have been reported. In particular, the performance of an asymmetric ruthenium catalyst having an amine ligand having a sulfonylamide group as an anchor (Japanese Patent Laid-Open No. 11-322649) is notable. In addition, a similar catalyst system (Chem. Commun. 1996, 223. Organometallics 1996, 15, 1087.) having a ruthenium-amine complex as a basic skeleton has been reported. Similarly, rhodium and iridium catalysts having a metal-amine bond (J. Org. Chem. 1999, 64, 2186.) have also been reported. These asymmetric metal catalysts can asymmetrically reduce more types of ketone substrates than the hydrogenation catalysts, but have a low hydrogen activation ability, and the hydrogen source is organic such as 2-propanol or formic acid. Only compounds can be used. Compared to asymmetric hydrogenation using hydrogen, more catalyst is required. In addition, when formic acid is used, there are problems such as the problem of corrosion of the reaction kettle. Asymmetric reduction of phenacyl chloride using formic acid as a reducing agent in the presence of a catalyst having rhodium as a central metal has been reported (WO2002 / 051781). In this case, however, catalytic activity and corrosive formic acid are also reported. There is a problem such as using.
Therefore, it has been desired to perform asymmetric hydrogenation of various ketone substrates with hydrogen as a reducing agent with high enantioselectivity and high efficiency.

  As described above, in the conventional method using a hydrogenation catalyst, applicable structures of the ketone compound are limited, and although it is industrially useful, such as 2-chloro-1-phenylethanol and 4-chromanol. However, it has been a big problem because alcohol having such a structure and optically active alcohols thereof cannot be efficiently produced. On the other hand, although a method for asymmetric reduction of these ketones using formic acid or the like as a reducing agent is known, the amount of catalyst used is large, so that formic acid is used in terms of efficiency and corrosiveness. There was a problem such as.

  The present invention has been made to solve such a problem, and provides a hydrogenation catalyst useful in producing an alcohol compound that has been difficult to obtain, and an alcohol using the hydrogenation catalyst. It aims at providing the manufacturing method of a compound.

  In order to achieve such an object, the present inventors have made extensive studies, and as a result, group 8 or group 9 transition metal sulfonate complexes having amine ligands have been difficult to achieve with conventional hydrogenation catalysts. It has been found that hydrogenation of hydrogen, particularly high enantioselective hydrogenation, can proceed efficiently, and the present invention has been completed.

（一般式（１）中、Ｒ¹及びＲ²は、同一であっても互いに異なっていてもよく、置換基を有していてもよい、アルキル基、フェニル基、ナフチル基若しくはシクロアルキル基、又は互いに結合して脂環式環を形成したときの該環の一部であり、
Ｒ³は、置換基を有していてもよい、アルキル基、フェニル基、ナフチル基又はカンファーであり、
Ｒ⁴は、水素原子又はアルキル基であり、
Ｒ⁵は、置換基を有していてもよい、アルキル基、フェニル基、ナフチル基又はカンファーであり、
Ａｒは、M¹とπ結合を介して結合している、置換基を有していてもよいベンゼン又は置換基を有してもよいシクロペンタジエニル基であり、
M¹は、ルテニウム、ロジウム又はイリジウムであり、
＊は、キラル炭素を示す。）That is, the present invention provides a sulfonate catalyst represented by the general formula (1) and used for the hydrogenation reaction.
General formula (1)

(In the general formula (1), R ¹ and R ² may be the same or different from each other, and may have a substituent, an alkyl group, a phenyl group, a naphthyl group, or a cycloalkyl group, Or a part of the ring when bonded to each other to form an alicyclic ring,
R ³ is an alkyl group, a phenyl group, a naphthyl group or camphor, which may have a substituent,
R ⁴ is a hydrogen atom or an alkyl group,
R ⁵ is an alkyl group, a phenyl group, a naphthyl group or camphor, which may have a substituent,
Ar is an optionally substituted benzene or an optionally substituted cyclopentadienyl group bonded to M ¹ via a π bond;
M ¹ is ruthenium, rhodium or iridium;
* Indicates a chiral carbon. )

In the method for producing an alcohol compound of the present invention, a ketone compound is hydrogenated with the sulfonate catalyst to obtain an alcohol compound. And if the sulfonate catalyst of this invention is utilized, the alcohol compound which was hard to obtain until now can be manufactured.

Hereinafter, the present invention will be described in detail.
In the sulfonate catalyst of the present invention, R ¹ and R ² in the general formula (1) are, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, tert-butyl. C1-C10 alkyl groups, such as group, are mentioned. In addition, it has a halogen substituent such as a phenyl group having 1 to 5 carbon atoms such as a phenyl group, a 4-methylphenyl group or a 3,5-dimethylphenyl group, a 4-fluorophenyl group, or a 4-chlorophenyl group. Examples thereof include a phenyl group having an alkoxy group such as a phenyl group and a 4-methoxyphenyl group. Moreover, a naphthyl group, a 5,6,7,8-tetrahydro-1-naphthyl group, a 5,6,7,8-tetrahydro-2-naphthyl group and the like can be mentioned. Moreover, a cyclopentyl group, a cyclohexyl group, etc. are mentioned. Further, alicyclic ring having an unsubstituted or substituted group and R ¹ and R ² are bound to form a ring include, for example, R ¹ and cyclopentane ring Ya to which R ² and are joined to form a ring A cyclohexane ring etc. are mentioned. Among these, R ¹ and R ² are preferably both a phenyl group or a cyclohexane ring in which R ¹ and R ² are bonded to form a ring.

Examples of the alkyl group represented by R ³ in the general formula (1) include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, and a tert-butyl group. 10 alkyl groups are mentioned. These alkyl groups may have a substituent, for example, may have one or more fluorine atoms as a substituent. Examples of the alkyl group containing one or more fluorine atoms include a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, and a pentafluoroethyl group. Examples of the naphthyl group which may have a substituent include unsubstituted naphthyl group, 5,6,7,8-tetrahydro-1-naphthyl group, 5,6,7,8-tetrahydro-2- And a naphthyl group. Examples of the phenyl group which may have a substituent include an unsubstituted phenyl group, a 4-methylphenyl group, a 3,5-dimethylphenyl group, a 2,4,6-trimethylphenyl group, and 2,4. A phenyl group having an alkyl group such as 1,6-triisopropylphenyl group, a phenyl group having a halogen substituent such as 4-fluorophenyl group or 4-chlorophenyl group, a phenyl group having an alkoxy group such as 4-methoxyphenyl group, etc. Is mentioned.

Specific examples of R ^{4 in} the general formula (1) include a C 1-5 alkyl group such as a methyl group and an ethyl group, and a hydrogen atom, with hydrogen being preferred.

Examples of Ar in the general formula (1) include unsubstituted benzene, toluene, o-, m- and p-xylene, o-, m- and p-cymene, 1,2,3-, 1, Alkyl groups such as 2,4- and 1,3,5-trimethylbenzene, 1,2,4,5-tetramethylbenzene, 1,2,3,4-tetramethylbenzene, pentamethylbenzene, and hexamethylbenzene Benzene having Further, the cyclopentadienyl group which may have a substituent includes cyclopentadienyl group, methylcyclopentadienyl group, 1,2-dimethylcyclopentadienyl group, 1,3-dimethylcyclopentadiene. An enyl group, 1,2,3-trimethylcyclopentadienyl group, 1,2,4-trimethylcyclopentadienyl group, 1,2,3,4-tetramethylcyclopentadienyl group and 1,2,3 , 4,5-pentamethylcyclopentadienyl group (Cp ^* ) and the like.

M ¹ in the general formula (1) is any one of ruthenium, rhodium and iridium.

Examples of the alkyl group represented by R ⁵ in the general formula (1) include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, and a tert-butyl group. 10 alkyl groups are mentioned. These alkyl groups may have a substituent, for example, may have one or more fluorine atoms as a substituent. Examples of the alkyl group containing one or more fluorine atoms include a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, and a pentafluoroethyl group. Examples of the naphthyl group which may have a substituent include unsubstituted naphthyl group, 5,6,7,8-tetrahydro-1-naphthyl group, 5,6,7,8-tetrahydro-2- And a naphthyl group. Examples of the phenyl group which may have a substituent include an unsubstituted phenyl group, a 4-methylphenyl group, a 3,5-dimethylphenyl group, a 2,4,6-trimethylphenyl group, and 2,4. A phenyl group having an alkyl group such as 1,6-triisopropylphenyl group, a phenyl group having a halogen substituent such as 4-fluorophenyl group, a 4-chlorophenyl group, a phenyl group having an alkoxy group such as 4-methoxyphenyl group, etc. Is mentioned. Among these, an alkyl group containing one or more fluorine atoms is preferable, a perfluoroalkyl group is more preferable, and a trifluoromethyl group is particularly preferable.

The sulfonate catalyst represented by the general formula (1) can be regarded as a structure in which an ethylenediamine compound (R ³ SO ₂ NHCHR ¹ CHR ² NHR ⁴ ), which is a bidentate ligand, is bonded to a metal. In order to more specifically disclose the sulfonate catalyst represented by (1), specific examples of ethylenediamine compounds are listed as follows. That is, N- (p-toluenesulfonyl) -1,2-diphenylethylenediamine (TsDPEN), N-methanesulfonyl-1,2-diphenylethylenediamine (MsDPEN), N-methyl-N ′-(p-toluenesulfonyl)- 1,2-diphenylethylenediamine, N- (p-methoxyphenylsulfonyl) -1,2-diphenylethylenediamine, N- (p-chlorophenylsulfonyl) -1,2-diphenylethylenediamine, N-trifluoromethanesulfonyl-1,2- Diphenylethylenediamine, N- (2,4,6-trimethylbenzenesulfonyl) -1,2-diphenylethylenediamine, N- (2,4,6-triisopropylbenzenesulfonyl) -1,2-diphenylethylenediamine, N- (4 -Tert-butyl Nzensulfonyl) -1,2-diphenylethylenediamine, N- (2-naphthylsulfonyl) -1,2-diphenylethylenediamine, N- (3,5-dimethylbenzenesulfonyl) -1,2-diphenylethylenediamine, N-pentamethyl Examples include benzenesulfonyl-1,2-diphenylethylenediamine and 1,2-N-tosylcyclohexanediamine (TsCYDN). Of these, TsDPEN and TsCYDN are preferred.

The sulfonate catalyst represented by the general formula (1) can be prepared by a reaction between a metal amide complex and a sulfonic acid such as trifluoromethanesulfonic acid. It can also be prepared by reaction of a metal amide complex with a metal sulfonate such as ytterbium sulfonate. Alternatively, the metal has a ligand X ² (X ² is an anionic group, and examples thereof include a hydride group, a hydroxyl group, a bridged oxo group, a fluorine group, a chlorine group, a bromine group, and an iodine group). It can also be prepared by reacting a metal amine complex with a sulfonic acid such as trifluoromethanesulfonic acid. It can also be prepared by a reaction between a metal amine complex having a ligand X ² on a metal and a metal sulfonate such as yttrium sulfonate. When an amine complex is used as a starting material, the reaction may proceed well when a base is added.

  The preparation method of the metal amide complex as a raw material and the metal amine complex having an amine ligand is described in Angew. Chem., Int. Ed. Engl. Vol. 36, p285 (1997) and J. Org. Chem. Vol. , p2186 (1999). Specifically, it can be synthesized by a reaction of a transition metal complex such as a ruthenium arene complex, a pentamethylcyclopentadienylrhodium complex, or a pentamethylcyclopentadienyliridium complex with a sulfonyldiamine ligand.

  The alcohol production method in the present invention is performed, for example, by putting a sulfonate catalyst represented by the general formula (1) and a ketone compound in a solvent, mixing them in the presence of hydrogen, and hydrogenating the ketone compound. When the molar ratio of the ketone compound to the sulfonate catalyst is expressed as S / C (S is a substrate and C is a catalyst), the amount of the catalyst used at this time is not particularly limited. In consideration, it can be used in the range of 10 to 100,000, and preferably used in the range of 50 to 10,000.

Examples of the solvent for the hydrogenation reaction include alcohol solvents such as methanol, ethanol, 2-propanol, 2-methyl-2-propanol, and 2-methyl-2-butanol, and ether solvents such as tetrahydrofuran (THF) and diethyl ether. , DMSO, DMF, acetonitrile-containing heteroatom-containing solvents, toluene, xylene and other aromatic hydrocarbon solvents, pentane, hexane and other aliphatic hydrocarbon solvents, methylene chloride and other halogen-containing hydrocarbon solvents, water alone Or it can use together. Moreover, the mixed solvent of the solvent illustrated above and another solvent can also be used. Among these solvents, alcohol-based solvents are preferable and methanol and ethanol are more preferable in order to efficiently proceed the reaction. The amount of the solvent is determined by the solubility and economics of the reaction substrate. For example, in the case of methanol, the concentration of the hydrogenation reaction is as low as 1% by weight or less and as high as 99% by weight or more near the absence of solvent. The reaction can be carried out and is preferably carried out at a concentration of 5 to 80% by weight. Under such high concentration conditions, few examples of hydrogenation reactions proceeding with high reactivity are known, and the production amount per batch of the hydrogenation reaction can be increased. It is advantageous.

Although there is no restriction | limiting in particular in the pressure of hydrogen, It can implement in the range of 1-200 atmospheres, The range of 5-150 atmospheres is preferable when economical efficiency is considered. Although reaction temperature does not have a restriction | limiting in particular, when economical consideration is considered, it can carry out in the range of -50-100 degreeC, It is preferable to carry out in the range of -30-60 degreeC, and it carries out in the range of 20-60 degreeC. Is more preferable. The reaction time varies depending on the reaction conditions such as the type, concentration, S / C, temperature and pressure of the reaction substrate, and the type of the catalyst, so various conditions may be set so that the reaction can be completed within a few minutes to a few days. In particular, it is preferable to set various conditions so that the reaction is completed in 5 to 24 hours. Further, the reaction product can be purified arbitrarily by known methods such as column chromatography, distillation, recrystallization and the like.

Further, in the method for producing an alcohol compound in the present invention, it is not essential to add a base to the reaction system, so that the hydrogenation reaction of the ketone compound proceeds promptly without adding a base. However, this does not exclude the addition of a base. For example, a small amount of a base may be added depending on the structure of the reaction substrate and the purity of the reagent used.

  The two chiral carbons in the sulfonate complex represented by the general formula (1) of the present invention are either the (R) isomer or the (S) isomer in order to obtain an optically active alcohol. There must be. By selecting either of these (R) isomers or (S) isomers, an optically active alcohol having a desired absolute configuration can be obtained with high selectivity. In addition, when it is desired to produce a racemic alcohol or an achiral alcohol, both of these chiral carbons do not have to be (R) isomer or (S) isomer, and may be either independently.

As described above, since the method for producing an alcohol compound of the present invention hydrogenates a ketone compound without adding a base, even a ketone compound unstable to a base is hydrogenated and the corresponding alcohol compound. Can be obtained. Therefore, according to the method for producing an alcohol compound of the present invention, compared with a conventionally known method using a hydrogenation catalyst not containing a base, it can be applied to a ketone compound having a wider structure, and the hydrogenation reaction can be performed. It is difficult to be affected by impurities and proceeds with good reproducibility, and the target substance can be obtained with high optical purity and high yield. In addition, according to the sulfonate complex of the present invention, an optically active cyclic alcohol can be produced by hydrogenating a cyclic ketone, which has not been able to be reduced efficiently with conventional hydrogenation catalysts, or it has an olefin moiety or an acetylene moiety. Hydrogenation of ketones (especially ketones whose α, β-bonds are olefin or acetylene moieties) to produce optically active alcohols having olefinic or acetylene moieties, or hydrogenation of ketones having hydroxyl groups to optically active having hydroxyl groups Producing alcohols, hydrogenating ketones having halogen substituents (particularly ketones having halogen substituents at the α-position) to produce optically active alcohols having halogen substituents, and hydrogenating cyclic ketones such as chromanone derivatives To produce corresponding optically active alcohols or hydrogenate diketones Or to produce an optical active diol Te, or producing an optically active hydroxy ester by hydrogenating ketoester, can be produced optically active hydroxyamide by hydrogenating ketoamide, the process according to the invention is very useful. Typical examples of ketone compounds applicable to the process for producing the optically active alcohol of the present invention are listed below.

In the method for producing an alcohol compound of the present invention, a ketone compound having an oxygen functional group or a cyano group in the vicinity of the carbonyl carbon (for example, α-position or β-position) such as hydroxy ketones, keto esters, cyano ketones, etc. is used as a reaction substrate. In some cases, it is preferable to use an iridium catalyst because the iridium catalyst exhibits extremely high catalytic performance compared to the ruthenium catalyst.

  EXAMPLES Hereinafter, an Example is shown and this invention is demonstrated in detail. Of course, the present invention is not limited to the following examples. The hydrogenation reaction of the ketone compound in the present invention can be carried out in a batch type or a continuous type.

In the following examples, the solvent used for the reaction was dried and degassed. NMR was measured using JNM-LA400 (400 MHz, manufactured by JEOL Ltd.) and JNM-LA500 (500 MHz, manufactured by JEOL Ltd.). ^{In 1} HNMR and ¹³ CNMR, tetramethylsilane (TMS) was used as an internal standard substance, and its signal was δ = 0 (δ is a chemical shift). The optical purity was measured by gas chromatography (GC) or high performance liquid chromatography (HPLC). GC was measured using Chirazil-DEX CB (0.25 mm × 25 m, DF = 0.25 μm) (manufactured by CHROMPACK), and HPLC was CHIRALCEL OD (0.46 cm × 25 cm), CHIRALCEL OB (0.46 cm × 25 cm). ), CHIRALCEL OJ-H (0.46 cm × 25 cm) (manufactured by Daicel). Specific rotation was measured using DIP-370 (manufactured by JASCO Corporation).

[Example 1]
Preparation of Ru (OTf) [(S, S) -Tsdpen] (p-cymene) which is a sulfonate complex First, Ru [(S, S) -Tsdpen] (p-cymene) was placed in a 20 ml Schlenk type reaction tube substituted with argon. ) (200 mg, 0.34 mmol), TfOH (30 μl, 0.34 mmol) (manufactured by Kanto Chemical Co., Inc.), and 3 ml of THF were charged. Subsequently, the mixture was stirred at room temperature for 1 hour. The resulting precipitate was collected by filtration, washed with 5 ml of THF, and then dried under reduced pressure (1 mmHg) to obtain 200 mg of Ru (OTf) [(S, S) -Tsdpen] (p-cymene). The resulting spectral data sulfonate complex is as ^{follows: 1 HNMR (400MHz, THF-} d8) δ1.37,1.43 (each d, J = 7Hz, 3H, CH (C H 3) 2), 2. 18 (s, 3 H, C H ₃ ), 2.29 (s, 3 H, C H ₃ ), 2.98 (m, 1 H, C H (CH ₃ ) ₂ ), 3.55 (m, 1 H, C H NH), 3.85 (br.dd, J = 11Hz, 12Hz, 1H, CHN H H), 3.94 (d, J = 11Hz, 1H, C H NTs), 5.78 (d, J = 6 Hz, 1 H, aromatic H), 5.92-5.93 (m, 2 H, aromatic H), 6.15 (d, J = 6 Hz, 1 H, aromatic H), 6.53-7.13 (m, 14H, aromatic H), 7.16 (br.d, 1H, ^{HNH H); 13 CNMR (100.4MHz} , THF-d8) δ18.6,21.1,22.6,22.8,31.4,70.3,73.2,82.4,82.9 , 84.2, 84.3, 97.0, 101.2, 127.0, 127.8, 128.1, 128.6, 128.7, 128.8, 129.2, 130.0, 139 .7, 139.9, 140.3, 143.6.

Note that Ru [(S, S) -Tsdpen] (p-cymene) was synthesized according to the technique described in the above-mentioned publicly known document, and a specific procedure is shown below. First, [RuCl ₂ (p-cymene)] ₂ (310 mg, 0.5 mmol) (manufactured by Kanto Chemical Co., Inc.), (S, S) -TsDPEN (370 mg, 1 mmol), KOH ( 400 mg, 7 mmol) and 7 ml of methylene chloride were charged. Subsequently, the mixture was stirred at room temperature for 5 minutes. 7 ml of water was added and stirred at room temperature for 5 minutes. Thereafter, the layers were separated, and the methylene chloride layer was washed with 7 ml of water. After CaH ₂ was added and dried, CaH ₂ was removed by filtration. Methylene chloride was distilled off under reduced pressure (1 mmHg) and dried to obtain 520 mg of Ru [(S, S) -Tsdpen] (p-cymene).

[Example 2]
Preparation of Ru (OTf) [(S, S) -Tsdpen] (p-cymene) which is a sulfonate complex First, Ru [(S, S) -Tsdpen] (p-cymene) was placed in a 20 ml Schlenk type reaction tube substituted with argon. ) (180 mg, 0.3 mmol), Yb (OTf) ₃ (183 mg, 0.3 mmol) (manufactured by Aldrich), and ₃ ml of CH ₃ OH. Subsequently, after deaeration, the mixture was stirred at room temperature for 10 minutes. After CH ₃ OH was distilled off under reduced pressure (1 mmHg), 2 ml of THF was added and the resulting precipitate was collected by filtration. After washing with 1 ml of THF and then 5 ml of toluene, it was dried under reduced pressure (1 mmHg) to obtain 130 mg of Ru (OTf) [(S, S) -Tsdpen] (p-cymene).

[Example 3]
Preparation of sulfonate complex Ru (OTf) [(R, R) -Tsdpen] (mesitylene) First, RuCl [(R, R) -Tsdpen] (mestyrene) (210 mg, 210 mg, 0.34 mmol), KOH (27 mg, 0.48 mmol), 6 ml of methylene chloride, and 1 ml of water were charged. Stir at room temperature for 10 minutes. Na ₂ SO ₄ was added to the reaction solution and dried, and then Na ₂ SO ₄ was removed by filtration. CaH was added to the filtrate and stirred at room temperature for 30 minutes. After removing CaH by filtration, the solvent was distilled off under reduced pressure (1 mmHg). 6 ml of THF and TfOH (30 μl, 0.34 mmol) (manufactured by Kanto Chemical Co., Inc.) were added and stirred at room temperature for 20 minutes. The resulting precipitate was collected by filtration, washed with 2 ml of THF, and then dried under reduced pressure (1 mmHg) to obtain 140 mg of Ru (OTf) [(R, R) -Tsdpen] (mesitylene). The spectrum data of the resulting sulfonate complex are as follows: ¹ HNMR (400 MHz, CD ₃ OD) δ 2.22 (s, 3H, C H ₃ ), 2.38 (s, 9H, C H ₃ ), 3. 74 (d, J = 11 Hz, 1H, C H NH ₂ ), 4.06 (d, J = 11 Hz, 1 H, C H NTs), 5.74 (s, 3H, aromatic H), 6.63-7 .18 (m, 14H, aromatic H).

Note that RuCl [(R, R) -Tsdpen] (mesitylene) was synthesized according to the technique described in the above-mentioned publicly known document, and a specific procedure is shown below. First, [RuCl ₂ (mesitylene)] ₂ (1.5 g, 2.5 mmol), (R, R) -TsDPEN (1.8 g, 5 mmol), triethylamine (1.4 ml, 10 mmol) and 30 ml of 2-propanol were charged. Then, it stirred at 80 degreeC for 1 hour. The solution was concentrated under reduced pressure (1 mmHg), and the precipitated crystals were collected by filtration and washed with 5 ml of water. Drying under reduced pressure (1 mmHg) gave 3 g of RuCl [(R, R) -Tsdpen] (mesitylene).

[Example 4]
Preparation of Ru [OSO ₂ (p-NO ₂ Ph)] [(S, S) -Tsdpen] (p-cymene), a sulfonate complex First, Ru [(S, S ) -Tsdpen] (p-cymene) (251 mg, 0.42 mmol), (p-NO ₂ Ph) SO ₃ H (100 mg, 0.42 mmol) (manufactured by ACROS), and 4 ml of THF were charged. Subsequently, the mixture was stirred at room temperature for 2 hours. After THF was distilled off under reduced pressure (1 mmHg), 15 ml of toluene was added and the resulting precipitate was collected by filtration. After washing with 10 ml of toluene, it was dried under reduced pressure (1 mmHg) to obtain 230 mg of Ru (OSO ₂ (p-NO ₂ Ph)) [(S, S) -Tsdpen] (p-cymene). Spectral data of the resulting sulfonate complexes as _{^{follows: 1 HNMR (400MHz, CD 3}} OD) δ1.39,1.43 (each d, J = 7Hz, 3H, CH (C H 3) 2), 2. 23 (s, 3H, C H ₃ ), 2.36 (s, 3H, C H ₃ ), 3.02 (m, 1 H, C H (CH ₃ ) ₂ ), 3.65 (d, J = 11 Hz) , 1H, C H NH ₂ ), 4.00 (d, J = 11 Hz, 1H, C H NTs), 5.68 (d, J = 6 Hz, 1H, aromatic H), 6.03-6.07 ( m, 3H, aromatic H), 6.58-7.17 (m, 14H, aromatic H), 8.00 (d, J = 9 Hz, 2H, aromatic H), 8.26 (d, J = 9 Hz, 2H, aromatic H).

[Example 5]
Preparation of Ru (OSO ₂ CH ₃ ) [(S, S) -Tsdpen] (p-cymene) as a sulfonate catalyst First, Ru [(S, S) -Tsdpen] ( p-cymene) (180 mg, 0.3 mmol), CH ₃ SO ₃ H (20 μl, 0.3 mmol) (manufactured by Kanto Chemical Co., Inc.), and 3 ml of THF were charged. Subsequently, the mixture was stirred at room temperature for 1 hour. After distilling off THF under reduced pressure (1 mmHg), 5 ml of toluene was added. The mixture was concentrated under reduced pressure (1 mmHg) to a total volume of 2 ml, and the resulting precipitate was collected by filtration. After washing with 2 ml of toluene, it was dried under reduced pressure (1 mmHg) to obtain 130 mg of Ru (OSO ₂ CH ₃ ) [(S, S) -Tsdpen] (p-cymene). The spectral data of the resulting sulfonate complex are as follows: ¹ HNMR (400 MHz, CD ₃ OD) δ 1.39, 1.43 (each d, J = 7 Hz, 3H, CH (CH ₃ ) ₂ ), 2.24 (S, 3H, CH ₃ ), 2.35 (s, 3H, CH ₃ ), 2.70 (s, 3H, CH ₃ ), 3.02 (m, 1H, CH (CH ₃ ) ₂ ), 3 .62 (d, J = 11 Hz, 1H, CHNH ₂ ), 3.99 (d, J = 11 Hz, 1H, CHNTs), 5.68 (d, J = 6 Hz, 1H, aromatic H), 6.01− 6.04 (m, 3H, aromatic H), 6.59-7.18 (m, 14H, aromatic H).

[Example 6]
Preparation of Cp ^* Ir (OTf) [(S, S) -Tsdpen] as a sulfonate catalyst First, Cp ^* Ir [(S, S) -Tsdpen] (78 mg, 0. 11 mmol), TfOH (10 μl, 0.11 mmol) (manufactured by Kanto Chemical Co., Inc.), and THF 5 ml were charged. Subsequently, the mixture was stirred at room temperature for 1 hour. The THF was distilled off under reduced pressure (1 mmHg) and then dried to obtain 93 mg of Cp ^* Ir (OTf) [(S, S) -Tsdpen]. The spectrum data of the obtained sulfonate complex are as follows: ¹ HNMR (400 MHz, CD ₃ OD) δ 1.94 (s, 15 H, C H ₃ ), 2.29 (s, 3 H, C H ₃ ) 4.25 (Br, 1 H, C H NH ₂ ), 4.65 (br, 1 H, C H NTs), 6.92-7.39 (m, 14 H, aromatic H)

Cp ^* Ir [(S, S) -Tsdpen] was synthesized according to the method described in the above-mentioned publicly known document, and a specific procedure is shown below. First, [Cp ^* IrCl ₂ ] ₂ (660 mg, 1 mmol) (manufactured by Aldrich), (S, S) -TsDPEN (800 mg, 2.2 mmol), triethylamine (0.6 ml, 4 mmol) were placed in a Schlenk-type reaction tube purged with argon. .2 mmol) was charged with 30 ml of 2-propanol. Subsequently, the mixture was stirred at room temperature for 12 hours. The solution was concentrated to 10 ml under reduced pressure (1 mmHg), and the precipitated crystals were collected by filtration and washed with 2 ml of 2-propanol. Drying under reduced pressure (1 mmHg) gave 1.2 g of Cp ^* IrCl [(S, S) -Tsdpen]. Subsequently, Cp ^* IrCl [(S, S) -Tsdpen] (21 mg, 0.032 mmol), 0.1 M NaOHaq (32 μl, 0.032 mmol), and 5 ml of methylene chloride were charged into a Schlenk reaction tube purged with argon. Subsequently, the mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure (1 mmHg), followed by drying to obtain 22 mg of Cp ^* Ir [(S, S) -Tsdpen].

[Example 7]
Synthesis of (R) -2-chloro-1-phenylethanol by hydrogenation reaction of α-chloroacetophenone In a stainless steel autoclave, Ru (OTf) [(S, S) -Tsdpen] (p-cymene) (2.4 mg , 3.3 μmol) and α-chloroacetophenone (0.3 g, 2 mmol) were charged, and the atmosphere was replaced with argon. Subsequently, 4 ml of methanol was added, pressurized with hydrogen, and replaced 10 times. Hydrogen was charged to 20 atm to start the reaction. And after 30-hour stirring at 30 degreeC, the reaction pressure was returned to the normal pressure. From ¹ H NMR and GC analysis of the product, 95% ee (R) -2-chloro-1-phenylethanol was produced in 100% yield. The spectrum data of the obtained alcohol compound are as follows. ¹ H NMR (400 MHz, CDCl ₃ ) δ 2.61 (d, J = 3 Hz, 1 H, CHO H ), 3.65 (dd, J = 9 Hz, 11 Hz, 1 H, C H HCl), 3.75 (dd, J = 3 Hz, 11 Hz, 1 H, CH H Cl), 4.91 (ddd, J = 3 Hz, 3 Hz, 9 Hz, 1 H, C H OH), 7.27-7.39 (m, 5 H, aromatic H); GC (Chirasil-DEX CB; column temperature, 130 ° C .; injection temperature, 250 ° C .; detection temperature, 275 ° C .; helium pressure, 100 kPa); t _{R of} (R) -2-chloro-1-phenylethanol, 17.0 min; (S)-2-chloro-1-phenylethanol t _R, 15.7 min; alpha-chloroacetophenone of t _R, 9.0 min; specific rotation _{^{[α] 20 D -46 ° (}} c2 8, C ₆ H _12); literature _{^{value, [α] 20 D -48 °}} (c2.8, C 6 H 12), (R), Aldrich.

[Example 8-9]
(R) -2-Chloro-1-phenylethanol was synthesized by carrying out the reaction under the same conditions as in Example 7 except that the substrate catalyst ratio, the hydrogen pressure, and the type of solvent were changed. The results are summarized in Table 1.
Table 1

[Example 10-14]
(R) -2-Chloro-1-phenylethanol was synthesized by carrying out the reaction under the same conditions as in Example 7 except that the hydrogen pressure, the substrate catalyst ratio, and the substrate concentration were changed. The results are summarized in Table 2. In Example 14, it was shown that the hydrogenation reaction proceeds even at a high concentration where the substrate is not completely dissolved.
Table 2

[Example 15]
Synthesis of (S) -4-chromanol by hydrogenation of 4-chromanone In a stainless steel autoclave, Ru (OTf) [(S, S) -Tsdpen] (p-cymene) (2.4 mg, 3.3 μmol), 4-Chromanone (1.48 g, 10 mmol) was charged and purged with argon. After adding 0.5 ml of methanol and pressurizing with hydrogen, it was replaced 10 times. Hydrogen was charged to 15 atm to start the reaction. After stirring at 50 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 91% ee (S) -4-chromanol was produced in 100% yield. The spectrum data of the obtained alcohol compound are as follows. ¹ HNMR (400 MHz, CDCl ₃ ) δ 1.99 (m, 1 H, C H HCHOH), 2.08 (m, 1 H, CH H CHOH), 2.31 (br, 1 H, O H ), 4.23 ( m, 2H, C H ₂ OC), 4.74 (m, 1H, C H OH), 6.81-6.92 (m, 2H, aromatic H), 7.17-7.30 (m, 2H) , Aromatic H); HPLC (CHIRALCEL OJ-H; solvent, hexane / 2-propanol = 99/1; flow rate, 1.5 ml / min; temperature, 35 ° C .; UV wavelength, 220 nm); (S) -4-chromanol T _R , 26.7 min; (R) -4-chromanol t _R 30.8 min; 4-chromanone t _R 11.8 min; specific rotation [α] ²⁵ _D −72 ° (c 0 .5, C ₂ H ₅ OH); literature values, [α] ²⁵ _D +80 .4 ° (c 0.5, C ₂ H ₅ OH), 100% ee (R), J. Am. Chem. Soc. 1993, 115, 3318.

[Comparative Example 1]
A stainless steel autoclave was charged with Ru [(S, S) -Tsdpen] (p-cymene) (1.2 mg, 2 μmol), 4-chromanone (0.3 g, 2 mmol) and purged with argon. Subsequently, 2 ml of methanol was added and pressurized with hydrogen, followed by replacement 10 times. Thereafter, hydrogen was charged to 30 atm to start the reaction. After stirring at 50 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 86% ee (S) -4-chromanol was produced in 7% yield. Thus, it was found that the sulfonate catalyst of the present invention exhibits superior activity as compared with conventionally known ruthenium complexes.

[Example 16]
Synthesis of (S) -4-chromanol by hydrogenation of 4-chromanone In a stainless steel autoclave, Ru (OTf) [(S, S) -Tsdpen] (p-cymene) (2.4 mg, 3.3 μmol), 4-Chromanone (1.48 g, 10 mmol) was charged and purged with argon. Subsequently, 0.7 ml of methanol was added, pressurized with hydrogen, and replaced 10 times. Thereafter, hydrogen was charged to 15 atm to start the reaction. After stirring at 50 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 93% ee (S) -4-chromanol was produced in 100% yield.

[Example 17]
Synthesis of (S) -4-chromanol by hydrogenation of 4-chromanone In a stainless steel autoclave, Ru (OTf) [(S, S) -Tsdpen] (p-cymene) (2.4 mg, 3.3 μmol), Yb (OTf) ₃ (0.62 mg, 1 μmol) and 4-chromanone (1.48 g, 10 mmol) were charged and purged with argon. Subsequently, 0.7 ml of methanol was added, pressurized with hydrogen, and replaced 10 times. Thereafter, hydrogen was charged to 15 atm to start the reaction. After stirring at 50 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 97% ee (S) -4-chromanol was produced in 98% yield.

[Example 18-20]
(S) -4-chromanol was synthesized by carrying out the reaction under the same conditions as in Example 15 except that the substrate catalyst ratio and the hydrogen pressure were changed. The results are summarized in Table 3.
Table 3

[Example 21]
Synthesis of (R) -4-chromanol by hydrogenation of 4-chromanone In a stainless steel autoclave, Ru (OTf) [(R, R) -Tsdpen] (mesitylene) (2.4 mg, 3.3 μmol), 4- Chromanone (1.48 g, 10 mmol) was charged and purged with argon. Subsequently, 0.5 ml of methanol was added, pressurized with hydrogen, and replaced 10 times. Thereafter, hydrogen was charged to 15 atm to start the reaction. After stirring at 50 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 83% ee (R) -4-chromanol was produced in 54% yield.

[Example 22]
Synthesis of (S) -4-chromanol by hydrogenation of 4-chromanone In a stainless steel autoclave, Ru [OSO ₂ (p-NO ₂ Ph)] [(S, S) -Tsdpen] (p-cymene) (2 .6 mg, 3.3 μmol) and 4-chromanone (1.48 g, 10 mmol) were charged and purged with argon. Subsequently, 0.5 ml of methanol was added, pressurized with hydrogen, and replaced 10 times. Thereafter, hydrogen was charged to 15 atm to start the reaction. After stirring at 50 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 91% ee (S) -4-chromanol was produced in 77% yield.

[Example 23]
Synthesis of (S) -4-chromanol by hydrogenation reaction of 4-chromanone Ru (OSO ₂ CH ₃ ) [(S, S) -Tsdpen] (p-cymene) (1.4 mg, 2 μmol) in a stainless steel autoclave 4-Chromanone (300 mg, 2 mmol) was charged and purged with argon. Subsequently, 0.1 ml of methanol was added, and after pressurization with hydrogen, replacement was performed 10 times. Thereafter, hydrogen was charged to 15 atm to start the reaction. After stirring at 50 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 95% ee (S) -4-chromanol was produced in 98% yield.

[Example 24]
Synthesis of (S) -4-chromanol by hydrogenation reaction of 4-chromanone In a stainless steel autoclave, Cp ^* Ir (OTf) [(S, S) -Tsdpen] (1.6 mg, 2 μmol), 4-chromanone (300 mg) , 2 mmol) and purged with argon. Subsequently, 0.4 ml of methanol was added and pressurized with hydrogen, followed by replacement 10 times. Thereafter, hydrogen was charged to 30 atm to start the reaction. After stirring at 50 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 95% ee (S) -4-chromanol was produced in 95% yield.

[Example 25]
Synthesis of 2-chloro-1- (p-chlorophenyl) ethanol by hydrogenation of 2,4'-dichloroacetophenone In an autoclave, Ru (OTf) [(S, S) -Tsdpen] (p-cymene) (2. 4 mg, 3.3 μmol) and 2,4′-dichloroacetophenone (1.1 g, 6 mmol) were charged and purged with argon. Subsequently, 0.75 ml of methanol was added, and after pressurization with hydrogen, replacement was performed 10 times. Hydrogen was charged to 100 atm and the reaction was started. After stirring at 30 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and GC analysis of the product, 92% ee of 2-chloro-1- (p-chlorophenyl) ethanol was produced in 100% yield. The spectrum data of the obtained alcohol compound are as follows. _{^{1 HNMR (400MHz, CDCl 3)}} δ2.88 (br, 1H, O H), 3.58 (m, 1H, C H HCHOH), 3.68 (m, 1H, CH H CHOH), 4.85 ( m, 1H, C H OH), 7.26 (m, 4H, aromatic H); GC (Chirasil-DEX CB; column temperature, 140 ° C; injection temperature, 250 ° C; detection temperature, 275 ° C; helium pressure, 100 kPa); t _R of the optical isomer of 2-chloro-1- (p-chlorophenyl) ethanol, 31.4 min, 34.7 min; R, S not identified.

[Example 26]
Synthesis of 1- (m-hydroxyphenyl) ethanol by hydrogenation of m-hydroxyacetophenone In a stainless steel autoclave, Ru (OTf) [(S, S) -Tsdpen] (p-cymene) (2.4 mg, 3. 3 μmol) and m-hydroxyacetophenone (1.1 g, 8 mmol) were charged, and the atmosphere was replaced with argon. Subsequently, 1 ml of methanol was added, pressurized with hydrogen, and replaced 10 times. Thereafter, hydrogen was charged to 100 atm to start the reaction. After stirring at 30 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 94% ee 1- (m-hydroxyphenyl) ethanol was produced in 100% yield. The spectrum data of the obtained alcohol compound are as follows. ¹ HNMR (400 MHz, acetone-d6) δ 1.37 (d, J = 6 Hz, 3H, C H ₃ ), 4.07 (d, J = 4 Hz, 1H, CHO H ), 4.77 (m, 1H, C H OH), 6.67-7.13 (m , 4H, aromatic H), 8.15 (s, 1H, O H); HPLC (CHIRALCEL OB; solvent, hexane / 2-propanol = 95/5; Flow rate, 1.0 ml / min; temperature, 35 ° C .; UV wavelength, 254 nm); t _R , 17.2 min, 31.5 min of the optical isomer of 1- (m-hydroxyphenyl) ethanol; Not identified.

[Example 27]
Synthesis of 1-Indanol by Hydrogenation of 1-Indanone Ru (OTf) [(S, S) -Tsdpen] (p-cymene) (2.4 mg, 3.3 μmol), 1-Indanone ( 0.8 g, 6 mmol) was charged and replaced with argon. Subsequently, 0.75 ml of methanol was added, and after pressurization with hydrogen, replacement was performed 10 times. Thereafter, hydrogen was charged to 100 atm to start the reaction. After stirring at 30 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 97% ee 1-indanol was produced in 95% yield. The spectrum data of the obtained alcohol compound are as follows. ¹ H NMR (400 MHz, CDCl ₃ ) δ 1.92 (m, 1 H, C H HC), 2.40 (s, 1 H, O H ), 2.45 (m, 1 H, CH H C), 2.79 ( m, 1H, C H HCHOH), 3.03 (m, 1H, CH H CHOH), 5.20 (m, 1H, C H OH), 7.20-7.40 (m, 4H, aromatic H) HPLC (CHIRALCEL OB-H; solvent, hexane / 2-propanol = 9/1; flow rate, 0.5 ml / min; temperature, 35 ° C .; UV wavelength, 254 nm); t _R of the optical isomer of 1-indanol, 10.9 minutes, 16.0 minutes; R and S have not been identified.

[Example 28]
Synthesis of 2-chloro-1- (p-methoxyphenyl) ethanol by hydrogenation of 4-methoxyphenacyl chloride To a stainless steel autoclave, Ru (OTf) [(S, S) -Tsdpen] (p-cymene) ( 1.2 mg, 1.6 μmol), 4-methoxyphenacyl chloride (1.1 g, 6 mmol) was charged, and the atmosphere was replaced with argon. Subsequently, 0.75 ml of methanol was added, and after pressurization with hydrogen, replacement was performed 10 times. Thereafter, hydrogen was charged to 100 atm to start the reaction. After stirring at 30 ° C. for 15 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 94% ee of 2-chloro-1- (p-methoxyphenyl) ethanol was produced in 73% yield. The spectrum data of the obtained alcohol compound are as follows. ¹ HNMR (400 MHz, CDCl ₃ ) σ 3.36 (br, 1H, CHO H ), 3.57-3.66 (m, 2H, C H ₂ CHOH), 3.76 (s, 3H, OC H ₃ ) , 4.80 (m, 1H, C H OH), 6.86 (d, J = 9 Hz, 2H, aromatic H), 7.27 (d, J = 9 Hz, 2H, aromatic H); GC (Chirasil- DEX CB; column temperature, 140 ° C .; injection temperature, 250 ° C .; detection temperature, 275 ° C .; helium pressure, 100 kPa); t _R of the optical isomer of 2-chloro-1- (p-methoxyphenyl) ethanol, 30 1 minute, 31.7 minutes; R and S have not been identified.

[Example 29]
Preparation of sulfonate catalyst Cp ^* Ir (OTf) [(S, S) -Msdpen] First, Cp ^* Ir [(S, S) -Msdpen] (200 mg, 0. 325 mmol) and 10 ml of methylene chloride. TfOH (26 μl, 0.295 mmol) (manufactured by Kanto Chemical Co.) dissolved in 5 ml of methylene chloride was added dropwise thereto. Subsequently, the mixture was stirred at room temperature for 1 hour. Methylene chloride was distilled off under reduced pressure (1 mmHg). After washing with a mixed solvent of toluene and hexane, drying was performed to obtain 93 mg of Cp ^* Ir (OTf) [(S, S) -Msdpen]. The spectrum data of the obtained sulfonate complex are as follows: ¹ HNMR (400 MHz, CD ₃ OD) δ 1.89 (s, 15 H, C H ₃ ), 2.26 (s, 3 H, C H ₃ ) 4.37 (br, 1H, C H NH 2), 5.05 (br, 1H, C H NMs), 7.23-7.43 (m, 10H, aromatic H)

Cp ^* Ir [(S, S) -Msdpen] was synthesized according to the method described in the above-mentioned publicly known document, and the specific procedure is shown below. First, [Cp ^* IrCl ₂ ] ₂ (500 mg, 0.63 mmol), (S, S) -MsDPEN (364 mg, 1.26 mmol), potassium hydroxide (86% manufactured by Kanto Chemical Co., Inc.) Content) (409 mg, 6.28 mmol), 12 ml of methylene chloride, and 12 ml of water. Subsequently, after stirring for 1 hour at room temperature, the aqueous layer was extracted using a syringe. 5 ml of water was added, stirred and allowed to stand, and then the aqueous layer was extracted. This operation was performed 8 times and then dried with sodium sulfate. The solution part was extracted into another Schlenk flask, and the solvent was distilled off to obtain 696 mg of Cp ^* Ir [(S, S) -Msdpen].

[Example 30]
Synthesis of optically active 1-phenyl-1,2-ethanediol by hydrogenation reaction of α-hydroxyacetophenone In a stainless steel autoclave, Cp ^* Ir (OTf) [(S, S) -Tsdpen] (1.7 mg, 2. 0 μmol) and α-hydroxyacetophenone (0.136 g, 1.0 mmol) were charged, and the atmosphere was replaced with argon. Subsequently, 1 ml of methanol was added, pressurized with hydrogen, and replaced 10 times. Hydrogen was charged to 100 atm and the reaction was started. Then, after stirring at 50 ° C. for 16 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 82% ee of optically active 1-phenyl-1,2-ethanediol was produced in 100% yield. The spectrum data of the obtained alcohol compound are as follows. ¹ H NMR (400 MHz, CD ₃ COCD ₃ ) δ 3.53 (dd, J = 2 Hz, 4 Hz, 1 H, C H HOH), 3.64 (dd, J = 2 Hz, 10 Hz, 1 H, CH H OH), 4. 04 (br, 1H, O H ), 4.43 (br, 1H, O H), 4.73 (dd, J = 4Hz, 10Hz, 1H, C H OH), 7.21-7.40 (m , 5H, aromatic H); HPLC (CHIRALCEL OB; solvent, hexane / 2-propanol = 98/2; flow rate, 1.0 ml / min; temperature, 35 ° C .; UV wavelength, 220 nm); 1-phenyl-1, 2 - t _R of both optical isomers of ethanediol, 26.0 minutes, 36.2 minutes, in this reaction, an optical isomer which is detected in 26.0 minutes was the major component, R, S is Not identified.

In addition, when the hydrogenation reaction of α-hydroxyacetophenone was attempted in the same manner as in Example 30 except that the sulfonate catalyst was changed to Ru (OTf) [(S, S) -Tsdpen] (p-cymene), 67% Only 3% yield of optically active 1-phenyl-1,2-ethanediol of ee was produced.

[Example 31]
Synthesis of optically active 1-phenyl-1,2-ethanediol by hydrogenation reaction of α-hydroxyacetophenone In a stainless steel autoclave, Cp ^* Ir (OTf) [(S, S) -Msdpen] (1.5 mg, 2. 0 μmol) and α-hydroxyacetophenone (0.272 g, 2.0 mmol) were charged, and the atmosphere was replaced with argon. Subsequently, 2 ml of methanol was added and pressurized with hydrogen, followed by replacement 10 times. Hydrogen was charged to 100 atm and the reaction was started. Then, after stirring at 50 ° C. for 16 hours, the reaction pressure was returned to normal pressure. From ¹ HNMR and HPLC analysis of the product, 98% ee of optically active 1-phenyl-1,2-ethanediol was produced in 100% yield. The products R and S have not been identified.

[Example 32]
Synthesis of optically active 1-phenyl-1,2-ethanediol by hydrogenation of α-hydroxyacetophenone When α-hydroxyacetophenone was reacted in the same manner as in Example 3 except that the reaction was carried out at a hydrogen pressure of 10 atm. 97 % Ee optically active 1-phenyl-1,2-ethanediol was produced in 98% yield. The products R and S have not been identified.

[Example 33]
Synthesis of optically active 1-phenyl-1,2-ethanediol by hydrogenation reaction of α-hydroxyacetophenone In a stainless steel autoclave, Cp ^* Ir (OTf) [(S, S) -Msdpen] (1.5 mg, 2. 0 μmol) and α-hydroxyacetophenone (0.545 g, 4.0 mmol) were charged and purged with argon. Subsequently, 4 ml of methanol was added, pressurized with hydrogen, and replaced 10 times. Hydrogen was charged to 10 atm to start the reaction. Then, after stirring at 50 ° C. for 24 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 97% ee of optically active 1-phenyl-1,2-ethanediol was produced in 100% yield. The products R and S have not been identified.

[Example 34]
Synthesis of (R) -mandelic acid methyl ester by hydrogenation of benzoylformic acid methyl ester Cp ^* Ir (OTf) [(S, S) -Tsdpen] (1.7 mg, 2.0 μmol) was charged into a stainless steel autoclave. Argon substitution was performed. Subsequently, 1 ml of methanol and methyl benzoylformate (0.28 ml, 2.0 mmol) were charged. Subsequently, after pressurizing with hydrogen, it was replaced 10 times. Hydrogen was charged to 30 atm to start the reaction. And after stirring at 50 degreeC for 15 hours, the reaction pressure was returned to the normal pressure. From ¹ H NMR and HPLC analysis of the product, 66% ee (R) -mandelic acid methyl ester was quantitatively produced. The spectrum data of the obtained alcohol compound are as follows. ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.75 (s, 3 H, C H ₃ ), 5.18 (s, 1 H, C H OH), 7.26-7.43 (m, 5 H, aromatic H); HPLC (CHIRALCEL OJ-H; solvent, hexane / 2-propanol = 98/2; flow rate, 1.0 ml / min; temperature, 35 ° C .; UV wavelength, 254 nm); (R) -mandelic acid methyl ester t _R , 29.0 min, (S) -Mandelic acid methyl ester t _R , 30.8 min.

[Example 35]
Synthesis of (R) -mandelic acid methyl ester by hydrogenation reaction of benzoylformic acid methyl ester, except that Cp ^* Ir (OTf) [(S, S) -Msdpen] (1.5 mg, 2.0 μmol) was used as a catalyst When benzoylformic acid methyl ester was reacted in the same manner as in Example 34, 44% ee (R) -mandelic acid methyl ester was quantitatively produced.

[Example 36]
Synthesis of optically active 3-hydroxy-3-phenylpropionic acid ethyl ester by hydrogenation of benzoylacetic acid ethyl ester Cp ^* Ir (OTf) [(S, S) -Tsdpen] (1.7 mg, 2 0.0 μmol) was charged and the atmosphere was replaced with argon. Then, 1 ml of methanol and ethyl benzoyl acetate (0.34 ml, 2.0 mmol) were charged. Subsequently, after pressurizing with hydrogen, it was replaced 10 times. Hydrogen was charged to 30 atm to start the reaction. And after stirring at 50 degreeC for 15 hours, the reaction pressure was returned to the normal pressure. From ¹ H NMR and HPLC analysis of the product, 91% ee of optically active 3-hydroxy-3-phenylpropionic acid ethyl ester was produced in a yield of 36%. The spectrum data of the obtained alcohol compound are as follows. ¹ HNMR (400 MHz, CDCl ₃ ) δ 1.27 (t, J = 2 Hz, 3H, C H ₃ ), 2.73 (m, 2H, C HH ), 4.16 (m, 2H, C H ₂ CH ₃ ), 5.12 (m, 1H, C H OH), 7.26-7.39 (m, 5H, aromatic H); HPLC (CHIRALCEL OD-H; solvent, hexane / 2-propanol = 99/1; Flow rate, 1.0 ml / min; temperature, 35 ° C .; UV wavelength, 220 nm); t _R of both optical isomers of 3-hydroxy-3-phenylpropionic acid ethyl ester, 34.2 min, 45.3 min. In this reaction, the optical isomer detected at 34.2 minutes was the main component. The products R and S have not been identified.

[Example 37]
Synthesis of optically active 3-hydroxy-3-phenylpropionic acid ethyl ester by hydrogenation of benzoylacetic acid ethyl ester In a stainless steel autoclave, Cp ^* Ir (OTf) [(S, S) -Msdpen] (1.5 mg, 2 0.0 μmol) was charged and the atmosphere was replaced with argon. Subsequently, 0.5 ml of methanol and ethyl benzoyl acetate (0.17 ml, 1.0 mmol) were charged. Subsequently, after pressurizing with hydrogen, it was replaced 10 times. Hydrogen was charged to 30 atm to start the reaction. And after stirring at 50 degreeC for 15 hours, the reaction pressure was returned to the normal pressure. From ¹ H NMR and HPLC analysis of the product, 93% ee of optically active 3-hydroxy-3-phenylpropionic acid ethyl ester was produced in 92% yield. The products R and S have not been identified.

[Example 38]
Synthesis of (S) -lactic acid methyl ester by hydrogenation of pyruvic acid methyl ester Cp ^* Ir (OTf) [(S, S) -Tsdpen] (1.7 mg, 2.0 μmol) was charged into a stainless steel autoclave. Replaced. Next, 1 ml of methanol and methyl pyruvate (0.18 ml, 2.0 mmol) were charged. Subsequently, after pressurizing with hydrogen, it was replaced 10 times. Hydrogen was charged to 30 atm to start the reaction. And after stirring at 50 degreeC for 15 hours, the reaction pressure was returned to the normal pressure. From ¹ HNMR and GC analysis of the product, 76% ee (S) -lactic acid methyl ester was quantitatively produced. The spectrum data of the obtained alcohol compound are as follows. _{^{1 HNMR (400MHz, CDCl 3)}} δ1.42 (d, J = 7Hz, 3H, C H 3), 3.10 (br, 1H, O H), 3.79 (s, 3H, OC H 3), 4.30 (q, J = 7 Hz, 1 H, C H OH); GC (Chirasil-DEX CB; column temperature, 80 ° C .; injection temperature, 250 ° C .; detection temperature, 275 ° C .; helium pressure, 100 kPa); R) - t _R of methyl lactate ester, 3.11 min; (S) - methyl lactate ester t _R, 3.49 min.

  When hydrogenation reaction of pyruvic acid methyl ester was attempted in the same manner as in Example 38 except that the sulfonate catalyst was changed to Ru (OTf) [(S, S) -Tsdpen] (p-cymene), 33% Only the (S) -lactic acid methyl ester of ee was produced in 25% yield.

[Example 39]
Synthesis of (S) -lactic acid methyl ester by hydrogenation reaction of pyruvic acid methyl ester Example 10 except that Cp ^* Ir (OTf) [(S, S) -Msdpen] (1.5 mg, 2.0 μmol) was used When pyruvate methyl ester was reacted in the same manner as in Example 1, 78% ee (S) -lactic acid methyl ester was quantitatively produced.

[Example 40]
Synthesis of optically active 1- [3 ', 4'-bis (benzyloxy) phenyl] -2-chloroethanol by hydrogenation of 3', 4'-bis (benzyloxy) -2-chloroacetophenone In a stainless steel autoclave , Cp ^* Ir (OTf) [(S, S) -Tsdpen] (1.5 mg, 2.0 μmol), 3 ′, 4′-bis (benzyloxy) -2-chloroacetophenone (0.367 g, 1.0 mmol) ) And replaced with argon. Subsequently, 1.1 ml of methanol and 0.36 ml of dimethylformamide were added, and after pressurization with hydrogen, replacement was performed 10 times. Hydrogen was charged to 100 atm and the reaction was started. Then, after stirring at 50 ° C. for 18 hours, the reaction pressure was returned to normal pressure. From ¹ H NMR and HPLC analysis of the product, 82% ee of optically active 1- [3 ′, 4′-bis (benzyloxy) phenyl] -2-chloroethanol was produced in 100% yield. The spectrum data of the obtained alcohol compound are as follows. ¹ H NMR (400 MHz, CD ₃ Cl ₃ ) δ 3.55 (dd, J = 9 Hz, 11 Hz, 1 H, C H HCl), 3.64 (dd, J = 3 Hz, 11 Hz, 1 H, CH H Cl), 4. 78 (dd, J = 3 Hz, 9 Hz, 1 H, C H OH), 5.15 (s, 2 H, OC H ₂ Ph), 5.16 (s, 2 H, OC H ₂ Ph), 6.86-7 .45 (m, 13H, aromatic H); the optical purity of the alcohol obtained was reacted with 4N aqueous sodium hydroxide in 2-propanol at 0 ° C. for 1 hour and 1- [3 ′, 4′-bis ( After conversion to benzyloxy) phenyl] -ethane-1,2-oxide, it was analyzed by HPLC. HPLC (CHIRALPAK AS-H; solvent, hexane / 2-propanol = 98/2; flow rate, 0.5 ml / min; temperature, 35 ° C .; UV wavelength, 215 nm); 1- [3 ′, 4′-bis (benzyl Oxy) phenyl] -ethane-1,2-oxide, t _R of both optical isomers, 26.2 minutes, 30.0 minutes. In this reaction, the main component is the optical isomer detected at 26.2 minutes. Met. The products R and S have not been identified.

[Example 41]
Synthesis of 2-cyano-1-phenylethanol by hydrogenation reaction of α-cyanoacetophenone In a stainless steel autoclave, Cp ^* Ir (OTf) [(S, S) -Msdpen] (1.5 mg, 2.0 μmol), α -Cyanoacetophenone (0.15 g, 1.0 mmol) was charged and purged with argon. Then, 5 ml of methanol was charged. Subsequently, after pressurizing with hydrogen, it was replaced 10 times. Hydrogen was charged to 30 atm to start the reaction. And after stirring at 50 degreeC for 15 hours, the reaction pressure was returned to the normal pressure. From ¹ H NMR and HPLC analysis of the product, 96% ee (S) -2-cyano-1-phenylethanol was quantitatively produced.
The spectrum data of the obtained alcohol compound are as follows. _{^{1 HNMR (400MHz, CDCl 3)}} δ2.51 (brs, 1H, O H), 2.76 (m, 2H, C HH CN), 5.04 (t, J = 6.0Hz, H, C H OH ), 7.35-7.50 (m, 5H, aromatic H); HPLC (CHIRALCEL OJ-H; solvent, hexane / 2-propanol = 95/5; flow rate, 1.0 ml / min; temperature, 35 ° C .; UV wavelength, 254 nm); t _{R of} (S) -2-cyano-1-phenylethanol, 42.5. Min, t _R, 47.7 min (R)-2-cyano-1-phenylethanol.

The hydrogenation reaction of α-cyanoacetophenone was attempted in the same manner as in Example 41 except that the sulfonate catalyst was changed to Ru (OTf) [(S, S) -Tsdpen] (p-cymene). It did not progress.

Industrial applicability

The present invention is used to produce optically active alcohols as pharmaceuticals, agricultural chemicals, or synthetic intermediates of many general-purpose chemicals.

Claims (9)

A sulfonate catalyst represented by the general formula (1) and used in a hydrogenation reaction in which a ketone compound is hydrogenated to obtain an alcohol compound in the presence of hydrogen.

(In the general formula (1), R ¹ and R ² may be the same or different from each other, and may have a substituent, an alkyl group, a phenyl group, a naphthyl group, or a cycloalkyl group, Or a part of the ring when bonded to each other to form an alicyclic ring,
R ³ is an alkyl group, a phenyl group, a naphthyl group or camphor, which may have a substituent,
R ⁴ is a hydrogen atom or an alkyl group,
R ⁵ is an alkyl group, a phenyl group, a naphthyl group or camphor, which may have a substituent,
Ar is an optionally substituted benzene or an optionally substituted cyclopentadienyl group bonded to M ¹ via a π bond;
M ¹ is ruthenium, rhodium or iridium;
* Indicates a chiral carbon. ) In the general formula (1), R ¹ and R ^{2, which} may be the same or different from each other, are a phenyl group, a phenyl group having an alkyl group having 1 to 5 carbon atoms, or an alkoxy having 1 to 5 carbon atoms. The sulfonate catalyst according to claim 1, which is a phenyl group having a group, a phenyl group having a halogen substituent, or an alkyl group which may be bonded to each other to form a 5-membered ring or a 6-membered ring. The sulfonate catalyst according to claim 1 or 2, wherein R ⁵ in the general formula (1) is an alkyl group containing one or more fluorine atoms. The presence of hydrogen, to obtain the alcohol compound by hydrogenating a ketone compound sulfonates catalyst according to any one of claims 1 to 3, preparation of an alcohol compound. The presence of hydrogen, hydrogen ketone compound by using those chiral carbon of a sulfonate catalyst 2 places described are those or any S of any R-form to any one of claims 1 to 3 A process for producing an alcohol compound, wherein an optically active alcohol compound is obtained.   The method for producing an alcohol compound according to claim 4 or 5, wherein the ketone compound is hydrogenated using one or more selected from the group consisting of methanol, ethanol and 2-propanol as a solvent. The presence of hydrogen, the sulfonate catalyst according to any one of claims 1 to 3 M1 in the formula (1) is iridium, hydrogen ketone compounds having an oxygen functional group, or a cyano group in the vicinity of the carbonyl carbon A process for producing an alcohol compound, wherein an alcohol compound is obtained by conversion. The presence of hydrogen, the formula (1) M1 in is iridium any chiral carbon of a sulfonate catalyst 2 places according to any one of claims 1 to 3 none or one of R form S A method for producing an alcohol compound, in which an optically active alcohol compound is obtained by hydrogenating a ketone compound having an oxygen functional group or a cyano group in the vicinity of a carbonyl carbon.   The method for producing an alcohol compound according to claim 7 or 8, wherein the ketone compound is an α- or β-hydroxyketone, an α- or β-ketoester, or an α- or β-cyanoketone.