JP2008222611A - Method for producing optically active sulfoxide compound using aluminum salalen complex catalyst - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing an optically active sulfoxide compound useful as a synthetic intermediate or base material for a physiologically active substance such as a medicine, etc., in a high optical purity. <P>SOLUTION: The method for producing an optically active sulfoxide compound such as methyl phenyl sulfoxide, etc., comprises subjecting a sulfide compound represented by thioanisole to a liquid-phase oxidation in the presence of an aluminum salalen complex as an optically active metal complex catalyst by using an oxidizing agent such as hydrogen peroxide, etc., and a solvent such as methanol. The optically active metal complex is obtained. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a method for producing an optically active sulfoxide compound, which comprises asymmetrically oxidizing a sulfide compound in the presence of an optically active aluminum salalene complex catalyst.

  Optically active sulfoxide compounds are important intermediates as asymmetric auxiliary agents in asymmetric synthesis.

  An optically active sulfoxide compound is used as an asymmetric auxiliary for the synthesis of an optically active allyl alcohol derivative (see, for example, Patent Document 1). In addition, optically active sulfoxide compounds are used as asymmetric auxiliary agents for the synthesis of various optically active compounds (see, for example, Non-Patent Documents 1 and 2).

  Furthermore, many pharmaceuticals having an optically active sulfoxide compound site have been developed, and a technique for asymmetrically oxidizing a sulfide compound into an optically active sulfoxide compound is also useful as a pharmaceutical production method.

  As a method for producing an optically active sulfoxide compound from a sulfide compound, a reaction using titanium-tartaric acid ester as a catalyst (for example, see Non-Patent Documents 3 and 4), a reaction using titanium-optically active binaphthol as a catalyst. (For example, see Non-Patent Documents 5 and 6.), a reaction using a metalloporphyrin complex as a catalyst (for example, see Non-Patent Documents 7 and 8), a reaction using a metallosalen complex as a catalyst (for example, Non-Patent Document 9). 10 and 11) are known.

In recent years, methods using hydrogen peroxide as an oxidizing agent have been actively studied. For example, a reaction using a vanadium complex as a catalyst (see, for example, Non-Patent Documents 12, 13, 14, 15, and 16) and a reaction using an iron complex as a catalyst (see, for example, Non-Patent Documents 17, 18, and 19). ), A reaction using a tungsten complex as a catalyst (for example, see Non-Patent Document 20), and the like.
Japanese Unexamined Patent Publication No. 7-82195 Chem. Ind. 15, 636 (1994) Acc. Chem. Res. 20, 72 (1987) J. Am. Chem. Soc. 106, 8188 (1984) J. Org. Chem. 60, 8086 (1995) Tetrahedron Lett. 33, 5391 (1992) J. Org. Chem. 58, 4529 (1993) Tetrahedron Lett. 23, 1685 (1982) J. Org. Chem. 55, 3628 (1990) Chem. Lett. 1483 (1986) Tetrahedron Lett. 33, 7111 (1992) Tetrahedron Lett. 35, 1887 (1994) Synlett, 1055-1060 (2002) Synlett 161-163 (2002) Org. Lett. 5,1317-1320 (2003) J. Org. Chem, 69, 8500-8503 (2004) Angew. Chem. Int. Ed., 44, 7221-7223 (2005) Angew.Chem. Int, Ed., 42, 5487-5489 (2003) Angew.Chem. Int, Ed., 43, 4225-4228 (2004) Chem. Eur. J., 11, 1086-1092 (2005) Tetrahedron Asymmetry, 14, 407-410 (2003)

  All of the above methods are reactions using an optically active metal complex as a catalyst, and are very excellent methods. In particular, the reaction using hydrogen peroxide as an oxidizing agent is excellent in operability and safety, and can be said to be an excellent reaction from the viewpoint of atomic utilization rate (atom economy).

  However, a reaction system showing high stereoselectivity for a wide range of substrates is not yet known.

As a result of intensive studies on the asymmetric sulfide oxidation reaction, the present inventor proceeds the asymmetric oxidation reaction of sulfide in a high yield and high stereoselectivity by using an optically active aluminum salarene complex as a catalyst. As a result, the present invention has been completed. That is, the present invention
1. Formula (1), Formula (1 ′), Formula (2), or Formula (2 ′)

[R ¹ in Formula (1), Formula (1 ′), Formula (2), and Formula (2 ′) is a hydrogen atom, a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group, C _{A 6-12} aryloxy group or a C _6-22 aryl group (the aryl group is unsubstituted or a C _1-4 alkyl group (the alkyl group is unsubstituted or optionally substituted with a halogen atom); Substituted), or a C _1-4 alkoxy group (the alkoxy group is unsubstituted or substituted with a C _6-12 aryl group), and the aryl group is In the case of forming axial asymmetry with the aromatic ring in formula (2) and formula (2 ′), the axial asymmetry may be optically active or optically inactive), and R ² is a hydrogen atom, halogen _{atom, C 1-4 alkyl, C 1-4 alkoxy, C 6-12} aryloxy Or a _{C 6-12} aryl group, ^{R 3} _{is, C 1-4} alkyl _{group, C 6-18} aryl group or, in the _{C 3-5} two ^{R 3} together form a ring divalent Each of R ⁴ is independently a hydrogen atom, a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group, a nitro group or a cyano group, and R ⁵ is a hydrogen atom or C _{1- 4 is} an alkyl group, M is an aluminum atom, and X means an anion pair capable of forming an ion pair with M. In the presence of an optically active metal complex represented by
Formula (3)

(In the formula, R ⁶ and R ⁷ are different and each represents a C _6-12 aryl group, a C _6-12 arylmethyl group (the C _6-12 aryl group and the C _6-12 arylmethyl group are substituted). Or substituted by a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group, a C _2-5 alkylcarbonyloxy group, a C _2-5 alkoxycarbonyl group, a nitro group, or a cyano group ), A C _1-6 alkyl group (the C _1-6 alkyl group is unsubstituted or substituted by a halogen atom, a nitro group, a hydroxyl group, or a cyano group), or R ⁶ is When it is a C _6-12 aryl group and a C _1-4 alkyl group or a C _1-4 alkoxy group is substituted at the ortho position thereof, R ⁷ together with the substituent forms a ring. _It may be a _2-4 divalent group.)
Wherein the sulfide compound represented by formula (4) is asymmetrically oxidized with an oxidizing agent.

(In formula, R < ⁶ >, R < ⁷ > is the same as the above. The absolute coordination of the sulfur atom shown by * means R or S.)
The manufacturing method of the optically active sulfoxide compound represented by these.
2.
In the presence of the optically active metal complex represented by formula (1), formula (1 ′), formula (2), or formula (2 ′), formula (5)

(In the formula, R ⁶ and R ⁷ are the same as above.)
By selectively oxidizing one optical isomer of a racemic or low optical purity sulfoxide compound represented by formula (6) with an oxidizing agent.

(In the formula, R ⁶ and R ⁷ are the same as above.)
To the sulfone compound represented by formula (4)

(In formula, R < ⁶ >, R < ⁷ > is the same as the above. The absolute coordination of the sulfur atom shown by * means R or S.)
A process for producing an optically active sulfoxide compound, characterized in that:
3.
R ⁶ represents a C _6-12 aryl group or a C _6-12 arylmethyl group (the C _6-12 aryl group and the C _6-12 arylmethyl group are not substituted or are a halogen atom, C _1-4 An alkyl group, a C _1-4 alkoxy group, a C _2-5 alkylcarbonyloxy group, a C _2-5 alkoxycarbonyl group, a nitro group, or a cyano group), and R ⁷ is C _1-4 When R ⁶ is a C _6-12 aryl group and a C _1-4 alkyl group or a C _1-4 alkoxy group is substituted at the ortho position thereof, R ⁷ is combined with the substituent. A C _2-4 divalent group which forms a ring in the following manner: Or 2. The manufacturing method of the optically active sulfoxide compound of description.
4).
Use hydrogen peroxide as the oxidizing agent. To 3. The manufacturing method of the optically active sulfoxide compound of any one of these.
5.
Formula (2) or Formula (2 ′)
Wherein R ¹ is a C _6-22 aryl group (the aryl group is unsubstituted or a C _1-4 alkyl group (the alkyl group is unsubstituted or optionally substituted with a halogen atom) Substituted), or a C _1-4 alkoxy group (the alkoxy group is unsubstituted or substituted with a C _6-12 aryl group), and the aryl group is In the case of forming an axial asymmetry with the aromatic ring in formula (2) or formula (2 ′), the axial asymmetry may be optically active or optically inactive, and R ² is a hydrogen atom. R ³ is a tetramethylene group in which two R ³ together form a ring, R ⁴ is a hydrogen atom, R ⁵ is a hydrogen atom or a methyl group, and X is chlorine. 1. It reacts in presence of optically active metal complex represented. To 4. The manufacturing method of the optically active sulfoxide compound of any one of these.
6).
4. R ¹ forms an axial asymmetry with the aromatic ring in formula (2) or formula (2 ′), and the axial asymmetry is optically active. A process for producing the optically active sulfoxide compound described in 1.
7).
5. R ¹ is a 1-phenylnaphthyl group A process for producing the optically active sulfoxide compound described in 1.
8).
1. Addition of buffer or inorganic salt To 7. A process for producing the optically active sulfoxide compound according to any one of the above, and
9.
Formula (7)

(R ³ in the formula (7) is a C _1-4 alkyl group, a C _6-18 aryl group, or a C _3-5 divalent group in which two R ³ together form a ring. , R ⁵ represents a hydrogen atom or a C _1-4 alkyl group, M represents an aluminum atom, and X represents an anion pair capable of forming an ion pair with M). The present invention provides an optically active metal complex whose axial asymmetry is optically active or optically inactive, or an enantiomer thereof.

  According to the method of the present invention, the sulfide compound represented by the formula (3) is converted into the optically active aluminum complex represented by the formula (1), the formula (1 ′), the formula (2), or the formula (2 ′). In the presence of, an optically active sulfoxide compound represented by the formula (4) can be produced by oxidation using an oxidizing agent.

  Hereinafter, the present invention will be described in more detail. In the present invention, “n” is normal, “i” is iso, “s” or “sec” is secondary, “t” or “tert” is tertiary, “c” is cyclo, “o” means ortho, “m” means meta, “p” means para, and “Ph” means phenyl.

First, R ¹ , R ² , R ³ , R ^4, R ⁵ , R ⁶ , R ⁷ and X will be described.

_Examples of the C _1-4 alkyl group in the present invention include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a sec-butyl group, and a tert-butyl group. It is done. Preferably, they are a methyl group and an ethyl group.

As the C _1-6 alkyl group, methyl group, ethyl group, n-propyl group, c-propyl group, i-propyl group, c-propyl group, n-butyl group, i-butyl group, sec-butyl group, Examples thereof include a tert-butyl group, an n-pentyl group, an i-pentyl group, an n-hexyl group, and a c-hexyl group. Preferably, they are a methyl group and an ethyl group.

_{Examples of the} C _1-4 alkoxy group include a methoxy group, an ethoxy group, an n-propoxy group, an i-propoxy group, an n-butoxy group, an i-butoxy group, a sec-butoxy group, and a tert-butoxy group. Preferably, it is a methoxy group or an ethoxy group.

Examples of the C _2-5 alkylcarbonyloxy group include methylcarbonyloxy group, ethylcarbonyloxy group, n-propylcarbonyloxy group, i-propylcarbonyloxy group, n-butylcarbonyloxy group, i-butylcarbonyloxy group, sec -Butylcarbonyloxy group, tert-butylcarbonyloxy group, n-amylcarbonyloxy group, i-amylcarbonyloxy group, neopentylcarbonyloxy group and the like. A methylcarbonyloxy group and an ethylcarbonyloxy group are preferable.

As the C _2-5 alkoxycarbonyl group, a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an i-propoxycarbonyl group, an n-butoxycarbonyl group, an i-butoxycarbonyl group, a sec-butoxycarbonyl group, a tert- Examples include butoxycarbonyl group, n-amyloxycarbonyl group, i-amyloxycarbonyl group, neopentyloxycarbonyl group and the like. Preferably, they are a methoxycarbonyl group and an ethoxycarbonyl group.

The C _6-12 aryloxy group is an oxy group substituted by an aromatic hydrocarbon having 6 to 12 carbon atoms. Examples thereof include a phenyloxy group, a 2-methylphenyloxy group, a 1-naphthyloxy group, and 2-naphthyloxy. Group and 2-biphenylyloxy group. Of these, a phenyloxy group and a 1-naphthyloxy group are preferable.

The C _6-22 aryl group is an aromatic hydrocarbon having 6 to 22 carbon atoms, among which a phenyl group, a 2-methylphenyl group, a 2-ethylphenyl group, a 1-naphthyl group, a 2-naphthyl group, 2- Biphenylyl group, 2-phenyl-1-naphthyl group, 2- (m-biphenylyl) -1-naphthyl group, 2- (p-biphenylyl) -1-naphthyl group (the 2-phenyl-1-naphthyl group, 2- (M-biphenylyl) -1-naphthyl group or 2- (p-biphenylyl) -1-naphthyl group is optically active or optically inactive, and more preferably a phenyl group. , 2-methylphenyl group, 2-phenyl-1-naphthyl group.

The C _6-18 aryl group is an aromatic hydrocarbon having 6 to 18 carbon atoms, among which a phenyl group, a 2-methylphenyl group, a 3,5-dimethylphenyl group, a 2,4,6-trimethylphenyl group, A 1-naphthyl group and a 2-naphthyl group are preferable, and a phenyl group, a 3,5-dimethylphenyl group, and a 2,4,6-trimethylphenyl group are more preferable.

The C _6-12 aryl group is an aromatic hydrocarbon having 6 to 12 carbon atoms, and examples thereof include a phenyl group, a 2-methylphenyl group, a 1-naphthyl group, a 2-naphthyl group, and a 2-biphenylyl group. Preferably, they are a phenyl group and a 2-naphthyl group.

The C _6-12 arylmethyl group is a methyl group substituted by an aromatic hydrocarbon having 6 to 12 carbon atoms, and examples thereof include a benzyl group, 1′-methylphenylmethyl group, 1′-naphthylmethyl group, 2 ′ -Naphthylmethyl group, 2'-biphenylmethyl group.
A benzyl group and a 1′-naphthylmethyl group are preferable.

  A halogen atom is a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

_Examples of the C _3-5 divalent group in the case where two R ³ are combined to form a ring include a trimethylene group, a tetramethylene group, and a pentamethylene group. A tetramethylene group and a pentamethylene group are preferable, and a tetramethylene group is more preferable.

When R ⁶ is a C _6-12 aryl group and a C _1-4 alkyl group or a C _1-4 alkoxy group is substituted at the ortho position thereof, R ⁷ together with the substituent forms a ring. _Examples of the C _2-4 divalent group include a dimethylene group, a dimethyleneoxy group, a trimethylene group, a trimethyleneoxy group, a tetramethylene group, and a tetramethyleneoxy group. Preferably, they are a dimethylene group, a dimethyleneoxy group, and a trimethylene group.

Examples of the anion pair capable of forming a salt of X include OH ⁻ , F ⁻ , Cl ⁻ , Br ⁻ , I ⁻ , CH ₃ CO ₂ ⁻ , PF ₆ ⁻ , ClO ₄ ⁻ , BF ₄ ⁻ , CO ₃ ^2−. , SO ₄ ²⁻ , PO ₄ ^{3− and the} like.

  Next, the asymmetric sulfide oxidation reaction will be described.

Among the sulfide compounds represented by the formula (3), particularly preferred sulfide compounds based on the combination of substituents R ⁶ and R ⁷ include methyl phenyl sulfide, ethyl phenyl sulfide, methyl o-tolyl sulfide, methyl p-tolyl sulfide, Methyl o-nitrophenyl sulfide, methyl p-nitrophenyl sulfide, methyl o-chlorophenyl sulfide, methyl p-chlorophenyl sulfide, methyl o-bromophenyl sulfide, methyl p-bromophenyl sulfide, methyl o-methoxyphenyl sulfide, methyl p-methoxyphenyl sulfide, ethyl o-nitrophenyl sulfide, methyl 1-naphthyl sulfide, methyl 2-naphthyl sulfide, methyl 2-pyridyl sulfide, methyl And benzyl sulfide and ethyl benzyl sulfide.

  Examples of the oxidizing agent include iodosylbenzene, iodosylmesitylene, iodosobenzoic acid, sodium hypochlorite, calcium hypochlorite, hydrogen peroxide, and the like, and preferably hydrogen peroxide.

  The amount of the oxidizing agent used is in the range of 1 to 20 times mol, preferably in the range of 1 to 2 times mol, relative to the sulfide compound of formula (1).

  In the optically active metal complex represented by formula (1), formula (1 '), formula (2), or formula (2'), preferred examples of the catalyst include the following optically active iron complexes and their enantiomers.

  The amount of the optically active metal complex catalyst used is in the range of 0.01 to 50 mol%, preferably in the range of 0.1 to 10 mol% with respect to the sulfide compound of formula (3).

  The reaction solvent is not particularly limited as long as it does not participate in the reaction. For example, nitriles such as water, acetonitrile, propionitrile, butyronitrile, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, benzene, toluene, Aromatic hydrocarbons such as xylene, mesitylene, chlorobenzene, fluorobenzene, o-dichlorobenzene, aliphatic hydrocarbons such as n-hexane, cyclohexane, n-octane, n-decane, methyl acetate, ethyl acetate, Esters such as butyl acetate, halogenated hydrocarbons such as dichloromethane, dichloroethane, carbon tetrachloride, ethers such as tetrahydrofuran (THF), diethyl ether, t-butyl methyl ether, dimethoxyethane, methanol, ethanol, 1-propanol , 2- Examples include alcohols such as lopanol, 1-butanol, 2-butanol, isobutanol and cyclohexanol, preferably methanol, ethanol, ethyl acetate, tetrahydrofuran, methylene chloride, toluene, and more preferably methanol. Can be mentioned.

  Furthermore, these reaction solvents can be used alone or in combination.

  In addition, a reagent for adjusting pH can be added to improve the reactivity.

  The pH range to be adjusted is 4 to 11, preferably 6 to 9, and more preferably 7 to 8.

  As a reagent for pH adjustment, an inorganic salt or a buffer solution can be used. Examples of the salt include carbonates, sulfates, phosphates, borates, acetates, phthalates and the like, preferably phosphates.

  The concentration of the buffer solution is in the range of 0.1 mM to 1000 mM, preferably 10 mM to 100 mM.

  Examples of the method for adding the oxidizing agent include batch addition, divided addition, and continuous addition. Split addition is a method in which the oxidizing agent to be used is added in a plurality of times, and the split may be equally or unequal, and the number of splits is preferably in the range of 2 to 100.

  The oxidizing agent may be charged as a solid or may be charged after being dissolved in a solvent. When hydrogen peroxide is used as the oxidizing agent, it is desirable to add it as an aqueous solution. The concentration of the aqueous solution can be selected as necessary, but is preferably 0.1 to 70% by mass, preferably 3 to 60% by mass, and more preferably 10 to 40% by mass.

  The reaction temperature is usually in the range of −50 ° C. to 60 ° C., preferably in the range of −20 ° C. to 40 ° C.

    The reaction time depends on the type of the sulfide compound of formula (3) to be used, the optically active metal complex represented by formula (1), formula (1 ′), formula (2), and formula (2 ′) and the oxidizing agent. However, it is usually 0.1 to 1000 hours, more generally 0.1 to 96 hours.

  After completion of the reaction, the target optically active sulfoxide compound can be isolated by a known method. As an example of the isolation method, the target product is extracted from the mixture after the reaction with an appropriate solvent, the solvent is concentrated under reduced pressure, and the reaction is performed by an operation such as chromatography using silica gel or the like, distillation, or crystallization. The method of obtaining the optically active sulfoxide compound of 4) is mentioned.

  The optical purity of the obtained target product can be measured by an optically active chromatography column or optical rotation.

  In addition, racemic sulfoxide compounds can be selectively oxidized to sulfone compounds using similar metal complexes and reaction systems. That is, optically active sulfoxide can be obtained by dynamic kinetic resolution.

Hereinafter, although an Example demonstrates in more detail, this invention is not limited to these.
Example 1
To a solution of salalene ligand (5 ′) (84.5 mg, 0.10 mmol) and toluene (1.0 mL) was added 0.92 M diethylaluminum chloride hexane solution (100 μL) at room temperature, and the mixture was stirred for 3 hours. The yellow precipitate was collected by filtration and washed with n-hexane to obtain Complex (5) (79.5 mg, 87%).
Anal. Calcd C ₆₁ H ₄₈ N ₂ O ₂ AlCl ・ 1 / 2H ₂ O: C 79.20; H 5.49, N 3.03%. Found: C 79.10, H 5.36, N 3.03%.

Example 2
Thioanisol (24.8mg, 0.20mmol) was added to a solution of asymmetric aluminum oxide-saralene complex (5) (3.6mg, 4.0μmol) and methanol (2.0mL) of thioanisole using an aluminum-salalen complex catalyst. Acid buffer (20.0 μL, pH 7.4, 67 mmol / L) was added. 30% aqueous hydrogen peroxide (25.0 mg, 0.22 mmol) was added, and the mixture was stirred at room temperature for 24 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 4/1 to 1/1) to give optically active methylphenyl sulfoxide (24.1 mg, 86% yield). It was.
The optical purity was measured by liquid chromatography (optically active column DAICEL CHIRALCEL OB-H: hexane / 2-propanol = 4/1) and found to be 98% ee.

Example 3
To a solution of aluminum salalene complex (4.0 μmol) and methanol (2.0 mL), sulfide (0.20 mmol) was added, and phosphate buffer (20.0 μL, pH 7.4, 67 mmol / L) was added. 30% aqueous hydrogen peroxide (25.0 mg, 0.22 mmol) was added, and the mixture was stirred at room temperature for 24 hours. The reaction solution was concentrated under reduced pressure and then purified by silica gel column chromatography to obtain optically active sulfoxide. The results are shown in Tables 1 and 2.

Example 4
Production of optically active sulfoxides by dynamic kinetic resolution using aluminum-salalen complex catalyst

  Racemic methylphenyl sulfoxide (28.0 mg, 0.20 mmol) is added to a solution of aluminum-salalen complex (5) (3.6 mg, 4.0 μmol) and methanol (2.0 mL), and phosphate buffer (20.0 μL, pH 7.4, 67 mmol / L) was added. 30% aqueous hydrogen peroxide (25.0 mg, 0.22 mmol) was added, and the mixture was stirred at room temperature for 24 hours. The reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography (elution solvent: hexane / ethyl acetate = 4/1 to 1/1) to obtain methylphenyl sulfoxide (17.4 mg, 62% yield) and sulfone (11.8 mg , 38%).

  The optical purity of methylphenyl sulfoxide was measured by liquid chromatography (optically active column DAICEL CHIRALCEL OB-H: hexane / 2-propanol = 4/1).

Claims (9)

Formula (1), Formula (1 ′), Formula (2), or Formula (2 ′)

[R ¹ in Formula (1), Formula (1 ′), Formula (2), and Formula (2 ′) is a hydrogen atom, a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group, C _{A 6-12} aryloxy group or a C _6-22 aryl group (the aryl group is unsubstituted or a C _1-4 alkyl group (the alkyl group is unsubstituted or optionally substituted with a halogen atom); Substituted), or a C _1-4 alkoxy group (the alkoxy group is unsubstituted or substituted with a C _6-12 aryl group), and the aryl group is In the case of forming axial asymmetry with the aromatic ring in formula (2) and formula (2 ′), the axial asymmetry may be optically active or optically inactive), and R ² is a hydrogen atom, halogen _{atom, C 1-4 alkyl, C 1-4 alkoxy, C 6-12} aryloxy Or a _{C 6-12} aryl group, ^{R 3} _{is, C 1-4} alkyl _{group, C 6-18} aryl group or, in the _{C 3-5} two ^{R 3} together form a ring divalent Each of R ⁴ is independently a hydrogen atom, a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group, a nitro group or a cyano group, and R ⁵ is a hydrogen atom or C _{1- 4 is} an alkyl group, M is an aluminum atom, and X means an anion pair capable of forming an ion pair with M. In the presence of an optically active metal complex represented by
Formula (3)

(In the formula, R ⁶ and R ⁷ are different, and are each a C _6-12 aryl group, a C _6-12 arylmethyl group (the C _6-12 aryl group and the C _6-12 arylmethyl group are substituted). Or substituted by a halogen atom, a C _1-4 alkyl group, a C _1-4 alkoxy group, a C _2-5 alkylcarbonyloxy group, a C _2-5 alkoxycarbonyl group, a nitro group, or a cyano group) , A C _1-6 alkyl group (the C _1-6 alkyl group is unsubstituted or substituted by a halogen atom, a nitro group, a hydroxyl group, or a cyano group), or R ⁶ is C _{6. -12} If an aryl group, and _{the C 1-4} alkyl group or _{C 1-4} alkoxy groups on the ortho position is substituted, ^{R 7} form a ring together with the substituent _{C 2-} It may be a divalent group.)
Wherein the sulfide compound represented by formula (4) is asymmetrically oxidized with an oxidizing agent.

(In formula, R < ⁶ >, R < ⁷ > is the same as the above. The absolute coordination of the sulfur atom shown by * means R or S.)
The manufacturing method of the optically active sulfoxide compound represented by these. In the presence of the optically active metal complex represented by formula (1), formula (1 ′), formula (2), or formula (2 ′), formula (5)

(In the formula, R ⁶ and R ⁷ are the same as above.)
By selectively oxidizing one optical isomer of a racemic or low optical purity sulfoxide compound represented by formula (6) with an oxidizing agent.

(In the formula, R ⁶ and R ⁷ are the same as above.)
To the sulfone compound represented by formula (4)

(In formula, R < ⁶ >, R < ⁷ > is the same as the above. The absolute coordination of the sulfur atom shown by * means R or S.)
A process for producing an optically active sulfoxide compound, characterized in that: R ⁶ represents a C _6-12 aryl group or a C _6-12 arylmethyl group (the C _6-12 aryl group and the C _6-12 arylmethyl group are not substituted or are a halogen atom, C _1-4 An alkyl group, a C _1-4 alkoxy group, a C _2-5 alkylcarbonyloxy group, a C _2-5 alkoxycarbonyl group, a nitro group, or a cyano group), and R ⁷ is C _1-4 When R ⁶ is a C _6-12 aryl group and a C _1-4 alkyl group or a C _1-4 alkoxy group is substituted at the ortho position thereof, R ⁷ is combined with the substituent. The method for producing an optically active sulfoxide compound according to claim 1 or 2, which is a _C2-4 divalent group that forms a ring.   The method for producing an optically active sulfoxide compound according to claim 1 or 3, wherein hydrogen peroxide is used as an oxidizing agent. Formula (2) or Formula (2 ′)
Wherein R ¹ is a C _6-22 aryl group (the aryl group is unsubstituted or a C _1-4 alkyl group (the alkyl group is unsubstituted or optionally substituted with a halogen atom) Substituted), or a C _1-4 alkoxy group (the alkoxy group is unsubstituted or substituted with a C _6-12 aryl group), and the aryl group is In the case of forming an axial asymmetry with the aromatic ring in formula (2) or formula (2 ′), the axial asymmetry may be optically active or optically inactive, and R ² is a hydrogen atom. R ³ is a tetramethylene group in which two R ³ together form a ring, R ⁴ is a hydrogen atom, R ⁵ is a hydrogen atom or a methyl group, and X is chlorine. The reaction is carried out in the presence of the optically active metal complex represented. Process for producing an optically active sulfoxide compound according to any one of 4. The method for producing an optically active sulfoxide compound according to claim 5, wherein R ¹ forms an axial asymmetry with the aromatic ring in formula (2) or formula (2 '), and the axial asymmetry is optically active. . The method for producing an optically active sulfoxide compound according to claim 6, wherein R ¹ is a 1-phenylnaphthyl group.   The method for producing an optically active sulfoxide compound according to any one of claims 1 to 7, wherein a buffer solution or an inorganic salt is added. Formula (7)

(R ³ in the formula (7) is a C _1-4 alkyl group, a C _6-18 aryl group, or a C _3-5 divalent group in which two R ³ together form a ring. , R ⁵ represents a hydrogen atom or a C _1-4 alkyl group, M represents an aluminum atom, and X represents an anion pair capable of forming an ion pair with M). An optically active metal complex whose axial asymmetry is optically active or optically inactive, or an enantiomer thereof.