JP5211495B2 - Process for producing optically active alcohol compound and asymmetric complex used therefor - Google Patents

Description

  The present invention relates to a method for producing an optically active alcohol compound and an asymmetric complex used therefor.

  Optically active alcohol compounds represented by optically active 1- (4-phenoxyphenoxy) -2-propanol are useful as synthetic intermediates for pharmaceuticals, agricultural chemicals and the like (see, for example, Patent Documents 1 and 2). As a method for producing such an optically active alcohol compound, a reaction between a phenol and a cyclic ether compound using an optically active salen-type metal complex as a catalyst is known (for example, see Non-Patent Document 1). In addition, an optically active salen metal complex is reacted with a Lewis acid selected from the group consisting of aluminum halide, dialkylaluminum halide, trialkoxyaluminum, titanium halide, tetraalkoxytitanium, boron halide and zinc halide. A method of reacting a phenol compound and a cyclic ether compound using a complex catalyst is also known (see, for example, Patent Documents 3 and 4). These methods are excellent in that an alcohol compound having high optical activity can be obtained. However, since the optically active salen-type metal complex is expensive, further improvement in catalytic activity is required for industrial implementation. It was done.

JP-A-60-215671 Japanese Patent Publication No. 5-59718 JP 2003-2854 A JP 2004-285003 A J. Am. Che. Soc., 121, 6086-6087 (1999)

  Under such circumstances, the inventor of the present invention relates to a method for further improving the catalytic activity in a method for producing an optically active alcohol compound in which a phenol and a cyclic ether compound are reacted using an optically active salen metal complex as a catalyst. As a result of intensive studies, it has been found that a novel asymmetric complex obtained by reacting an optically active salen-type metal complex with zirconium alkoxide or hafnium alkoxide exhibits high catalytic activity, leading to the present invention.

（式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵、Ｒ⁶、Ｒ⁷およびＲ⁸はそれぞれ同一または相異なって、水素原子、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、アルコキシ基、ハロアルキル基、ハロアルコキシ基、置換されていてもよいアリール基、アラルキル基、水酸基、ニトロ基、アミノ基、カルバモイル基、カルボキシル基またはシリル基を表すか、またはＲ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵、Ｒ⁶、Ｒ⁷およびＲ⁸のうち、隣接する二つの基が結合して、それらが結合するベンゼン環とともに環を形成し、ナフタレン環を表す。Ｒ⁹およびＲ¹⁰は、そのいずれか一方が水素原子を表し、他方が、ハロゲン原子で置換されていてもよい炭素数１〜４のアルキル基、ハロゲン原子で置換されていてもよい炭素数１〜４のアルコキシ基およびハロゲン原子からなる群から選ばれる少なくとも一つで置換されていてもよいフェニル基またはナフチル基を表すか、または、異なる炭素原子に結合したＲ⁹とＲ¹⁰からなる対のうち、いずれか一対が結合してテトラメチレン基を形成し、他方の対がそれぞれ水素原子を表す。Ｑは、単結合もしくは炭素数１〜４のアルキレン基を表す。また、

で示される基で、２，２’−ビナフチル基を表してもよい。ここで、・は窒素原子との結合部位を示す。Ｍは金属イオンを表し、金属イオンのイオン価と配位子の配位数が同一のとき、Ａは存在せず、前記イオン価と配位数が相異なるとき、Ａは対イオンまたは配位子を表す。）
で示される光学活性な金属錯体とジルコニウムアルコキシドまたはハフニウムアルコキシドとを反応せしめてなる不斉錯体、および、その存在下に、環状エ−テル化合物とフェノ−ル類とを反応させることを特徴とする光学活性なアルコ−ル化合物の製造方法を提供するものである。 That is, the present invention provides the formula (1)

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, an alkynyl group, Represents an alkoxy group, a haloalkyl group, a haloalkoxy group, an optionally substituted aryl group, an aralkyl group, a hydroxyl group, a nitro group, an amino group, a carbamoyl group, a carboxyl group or a silyl group, or R ¹ , R ² , R ^3, R ^4, R ^5, R ^6, R ⁷ and of R ^8, by bonding two groups adjacent, together with the benzene ring to which they are attached form a ring, represents a naphthalene ring .R ⁹ and R ¹⁰ represents any one of them represents a hydrogen atom, and the other represents an alkyl group having 1 to 4 carbon atoms which may be substituted with a halogen atom, or an alkoxy having 1 to 4 carbon atoms which may be substituted with a halogen atom. Basic And a phenyl group or a naphthyl group which may be substituted with at least one selected from the group consisting of halogen atoms, or any pair of R ⁹ and R ¹⁰ bonded to different carbon atoms. Are bonded to form a tetramethylene group, and the other pair represents a hydrogen atom, and Q represents a single bond or an alkylene group having 1 to 4 carbon atoms.

May represent a 2,2′-binaphthyl group. Here, · indicates a binding site with a nitrogen atom. M represents a metal ion. When the ionic valence of the metal ion and the coordination number of the ligand are the same, A does not exist, and when the ionic valence and the coordination number are different, A is a counter ion or coordination. Represents a child. )
An asymmetric complex obtained by reacting an optically active metal complex represented by formula (II) with zirconium alkoxide or hafnium alkoxide, and a cyclic ether compound and phenols in the presence thereof. A method for producing an optically active alcohol compound is provided.

  According to the present invention, a novel asymmetric complex obtained by reacting an optically active salen-type metal complex with zirconium alkoxide or hafnium alkoxide exhibits high catalytic activity in the reaction between a cyclic ether compound and phenols. By reacting a cyclic ether compound and a phenol in the presence of an asymmetric complex, an optically active alcohol compound can be produced more advantageously industrially.

  First, an optically active metal complex represented by the above formula (1) (hereinafter abbreviated as optically active metal complex (1)) and a zirconium alkoxide or hafnium alkoxide (hereinafter abbreviated as metal alkoxide) are reacted. The novel asymmetric complex is described.

In the formula of the optically active metal complex (1), R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, halogen atom, alkyl A group, an alkenyl group, an alkynyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, an optionally substituted aryl group, an aralkyl group, a hydroxyl group, a nitro group, an amino group, a carbamoyl group, a carboxyl group or a silyl group.

  Examples of the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom.

  Examples of the alkyl group include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, tert. -A linear, branched or cyclic alkyl group having 1 to 6 carbon atoms such as a pentyl group, an n-hexyl group, a cyclopentyl group and a cyclohexyl group.

  Examples of the alkenyl group include straight chain having 2 to 6 carbon atoms such as vinyl group, propenyl group, 1-butenyl group, 2-butenyl group, 2-methyl-1-propenyl group, pentenyl group, hexenyl group, and cyclohexenyl group. , Branched or cyclic alkenyl groups.

  Examples of the alkynyl group include linear or branched alkynyl groups having 2 to 6 carbon atoms such as ethynyl group, propynyl group, 1-butynyl group, 2-butynyl group, and hexynyl group.

  Examples of the alkoxy group include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, an n-hexyloxy group, and a cyclohexyloxy group. Examples thereof include a linear, branched or cyclic alkoxy group having 1 to 6 carbon atoms.

  Examples of the haloalkyl group include those in which one or two or more hydrogen atoms of the alkyl group are substituted with the halogen atoms, and specifically include chloromethyl group, chloroethyl group, fluoromethyl group, trifluoromethyl group. Examples are groups.

  Examples of the haloalkoxy group include those obtained by substituting one or two or more hydrogen atoms of the alkoxy group with the halogen atom, specifically, a chloromethoxy group, a chloroethoxy group, a fluoromethoxy group, Examples include a fluoromethoxy group.

  As an aryl group, C6-C10 aryl groups, such as a phenyl group and a naphthyl group, are mentioned, for example. Examples of the substituent which may be present on these aryl groups include halogen atoms such as fluorine atom, chlorine atom and bromine atom; methyl group, ethyl group, n-propyl group, isopropyl group and n-butyl group. , Alkyl groups such as isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, tert-pentyl group, n-hexyl group, cyclopentyl group, cyclohexyl group; methoxy group, ethoxy group , N-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, n-hexyloxy group, cyclohexyloxy group and other alkoxy groups; nitro group; Specific examples of the aryl group substituted with such a substituent include a toluyl group, a xylyl group, a nitrophenyl group, and a methoxyphenyl group.

  Examples of the aralkyl group include those in which one or two or more hydrogen atoms of the alkyl group are substituted with the aryl group, and specifically include a benzyl group, a triphenylmethyl group, 1-methyl-1- Examples thereof include a phenylethyl group.

  Examples of the silyl group include groups in which the alkyl group, the aryl group, and the like are trisubstituted on a silicon atom. Specifically, a trimethylsilyl group, a triethylsilyl group, a triphenylsilyl group, a tert-butyldimethylsilyl group, and the like. Is exemplified.

Also, among R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ , two adjacent groups are bonded to form a naphthalene ring together with the benzene ring to which they are bonded. It may be.

One of R ⁹ and R ¹⁰ represents a hydrogen atom, and the other represents an alkyl group having 1 to 4 carbon atoms that may be substituted with a halogen atom, or 1 carbon atom that may be substituted with a halogen atom. Represents a phenyl group or a naphthyl group which may be substituted with at least one selected from the group consisting of an alkoxy group of ˜4 and a halogen atom, or a pair of R ⁹ and R ¹⁰ bonded to different carbon atoms Among them, any pair is bonded to form a tetramethylene group, and the other pair represents a hydrogen atom.

  Examples of the alkyl group having 1 to 4 carbon atoms include linear or branched alkyl groups such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, and tert-butyl group. It is done. Examples of the halogen atom that may be present on the alkyl group having 1 to 4 carbon atoms include a fluorine atom, a chlorine atom, and a bromine atom. Specific examples of the alkyl group having 1 to 4 carbon atoms substituted with the halogen atom include a chloromethyl group, a chloroethyl group, a fluoromethyl group, and a trifluoromethyl group.

  Examples of the alkoxy group having 1 to 4 carbon atoms include linear or branched alkoxy groups such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, and a tert-butoxy group. Can be mentioned. Examples of the halogen atom that may be present on the alkoxy group having 1 to 4 carbon atoms include a fluorine atom, a chlorine atom, and a bromine atom. Specific examples of the alkoxy group having 1 to 4 carbon atoms substituted with a halogen atom include a chloromethoxy group, a chloroethoxy group, a fluoromethoxy group, and a trifluoromethoxy group.

  Examples of the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom.

  Substitution with at least one selected from the group consisting of an alkyl group having 1 to 4 carbon atoms which may be substituted with such a halogen atom, an alkoxy group having 1 to 4 carbon atoms which may be substituted with a halogen atom, and a halogen atom Examples of the phenyl group or naphthyl group that may be used include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, and a 2-methoxyphenyl group. 3-methoxyphenyl group, 4-methoxyphenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 4-bromophenyl Group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoro B-methylphenyl group, 2-methyl-1-naphthyl group and the like.

で示される基で、２，２’−ビナフチル基を表してもよい。ここで、・は窒素原子との結合部位を示す。炭素数１〜４のアルキレン基としては、例えばメチレン基、エチレン基、トリメチレン基、テトラメチレン基等が挙げられる。 Q represents a single bond or an alkylene group having 1 to 4 carbon atoms. Also,

May represent a 2,2′-binaphthyl group. Here, · indicates a binding site with a nitrogen atom. Examples of the alkylene group having 1 to 4 carbon atoms include a methylene group, an ethylene group, a trimethylene group, and a tetramethylene group.

  M represents a metal ion. When the ionic valence of the metal ion and the coordination number of the ligand are the same, A does not exist, and when the ionic valence and the coordination number are different, A is a counter ion or coordination. Represents a child.

  Examples of metal ions include cobalt ions, chromium ions, manganese ions, and the like. Examples of the counter ion or the ligand include halide ions such as chloride ion, bromide ion and iodide ion; perfluoroalkoxide ions such as nonafluoro-tert-butoxide ion; acetate ligand; Halide ions are preferable in terms of easy preparation, and iodide ions are more preferable.

  Examples of the optically active metal complex (1) include iodinated (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexane. Diaminocobalt (III), chloride (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (III), odor (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (III), (R, R)-( -)-N, N'-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (III) acetate, (R, R)-(-)-N, N ' -Bis (3,5-di-tert-butylsalicylidene) -1,2-cyclo Xanthodiaminocobalt (III) nonafluoro-tert-butoxide, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (III) hexafluoroisopropoxide, iodide (R, R)-(-)-N, N'-bis (salicylidene) -1,2-cyclohexanediaminocobalt (III), chloride (R, R)-( -)-N, N'-bis (salicylidene) -1,2-cyclohexanediaminocobalt (III), bromide (R, R)-(-)-N, N'-bis (salicylidene) -1,2- Cyclohexanediaminocobalt (III), (R, R)-(-)-N, N'-bis (salicylidene) -1,2-cyclohexanediaminocobalt (III) acetate, (R, R)-(-)-N , N ' Bis (salicylidene) -1,2-cyclohexane-diamino cobalt (III) nonafluoro -tert- butoxide,

Iodinated (R, R)-(-)-N, N'-bis (3-tert-butyl-5-methylsalicylidene) -1,2-cyclohexanediaminocobalt (III), chloride (R, R) -(-)-N, N'-bis (3-tert-butyl-5-methylsalicylidene) -1,2-cyclohexanediaminocobalt (III), bromide (R, R)-(-)-N , N′-bis (3-tert-butyl-5-methylsalicylidene) -1,2-cyclohexanediaminocobalt (III), (R, R)-(−)-N, N′-bis (3- tert-butyl-5-methylsalicylidene) -1,2-cyclohexanediaminocobalt (III) acetate, (R, R)-(−)-N, N′-bis (3-tert-butyl-5-methyl) Salicylidene) -1,2-cyclohexanediaminocobalt III) Nonafluoro-tert-butoxide, iodide (R, R)-(−)-N, N′-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminocobalt (III ), Chloride (R, R)-(−)-N, N′-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminocobalt (III), bromide (R, R)-(-)-N, N'-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminocobalt (III), (R, R)-(-)-N , N′-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminocobalt (III) acetate, (R, R)-(−)-N, N′-bis (3 -Tert-butyl-5-nitrosalicylidene 1,2-cyclohexane-diamino cobalt (III) nonafluoro -tert- butoxide,

Iodinated (R, R)-(−)-N, N′-bis (3-tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminocobalt (III), chloride (R, R) -(-)-N, N'-bis (3-tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminocobalt (III), bromide (R, R)-(-)-N , N′-bis (3-tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminocobalt (III), (R, R)-(−)-N, N′-bis (3- tert-Butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminocobalt (III) acetate, (R, R)-(−)-N, N′-bis (3-tert-butyl-5-methoxy) Salicylidene) -1,2-cyclohexanediamy Cobalt (III) nonafluoro-tert-butoxide, iodide (R, R)-(−)-N, N′-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminocobalt (III), chloride (R, R)-(−)-N, N′-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminocobalt (III), bromide ( R, R)-(−)-N, N′-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminocobalt (III), (R, R)-(−) -N, N'-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminocobalt (III) acetate, (R, R)-(-)-N, N'-bis (3-tert-butyl-5-chlorosa Chiriden) -1,2-cyclohexane-diamino cobalt (III) nonafluoro -tert- butoxide,

Iodinated (R, R)-(-)-N, N'-bis (3-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (III), chloride (R, R)-(-) -N, N'-bis (3-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (III), bromide (R, R)-(-)-N, N'-bis (3- tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (III), (R, R)-(−)-N, N′-bis (3-tert-butylsalicylidene) -1,2- Cyclohexanediaminocobalt (III) acetate, (R, R)-(-)-N, N'-bis (3-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (III) nonafluoro-tert-butoxide , Iodination (R, R)- -)-N, N'-bis [(5-methyl-3- (1-methyl-1-phenylethyl) salicylidene) -1,2-cyclohexanediaminocobalt (III), chloride (R, R)-(- ) -N, N'-bis [(5-methyl-3- (1-methyl-1-phenylethyl) salicylidene) -1,2-cyclohexanediaminocobalt (III), bromide (R, R)-(- ) -N, N'-bis [(5-methyl-3- (1-methyl-1-phenylethyl) salicylidene) -1,2-cyclohexanediaminocobalt (III), (R, R)-(-)- N, N′-bis [(5-methyl-3- (1-methyl-1-phenylethyl) salicylidene) -1,2-cyclohexanediaminocobalt (III) acetate, (R, R)-(−) — N , N′-bis [(5-methyl-3- (1-me -1-phenylethyl) salicylidene) -1,2-cyclohexane-diamino cobalt (III) nonafluoro -tert- butoxide,

Iodinated (R, R)-(−)-N, N′-bis (3-tert-butyl-5-triphenylmethylsalicylidene) -1,2-cyclohexanediaminocobalt (III), chloride (R, R)-(−)-N, N′-bis (3-tert-butyl-5-triphenylmethylsalicylidene) -1,2-cyclohexanediaminocobalt (III), bromide (R, R)-( -)-N, N'-bis (3-tert-butyl-5-triphenylmethylsalicylidene) -1,2-cyclohexanediaminocobalt (III), (R, R)-(-)-N, N '-Bis (3-tert-butyl-5-triphenylmethylsalicylidene) -1,2-cyclohexanediaminocobalt (III) acetate, (R, R)-(-)-N, N'-bis (3 -Tert-butyl-5-triphenyl Tyrsalicylidene) -1,2-cyclohexanediaminocobalt (III) nonafluoro-tert-butoxide, iodide (R, R)-(−)-N, N′-bis [5-tert-butyl-3- (1-methyl) -1-phenylethyl) salicylidene] -1,2-cyclohexanediaminocobalt (III), chloride (R, R)-(-)-N, N′-bis [5-tert-butyl-3- (1-methyl) -1-phenylethyl) salicylidene] -1,2-cyclohexanediaminocobalt (III), (R, R)-(−)-N, N′-bis [5-tert-butyl-3- (1- Methyl-1-phenylethyl) salicylidene] -1,2-cyclohexanediaminocobalt (III), (R, R)-(−)-N, N′-bis [5-tert-butyl-3- (1-methyl) − -Phenylethyl) salicylidene] -1,2-cyclohexanediaminocobalt (III) acetate, (R, R)-(-)-N, N'-bis [5-tert-butyl-3- (1-methyl-1) -Phenylethyl) salicylidene] -1,2-cyclohexanediaminocobalt (III) nonafluoro-tert-butoxide,

Iodinated (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-diphenylethylenediaminocobalt (III), chloride (R, R )-(-)-N, N'-bis (3,5-di-tert-butylsalicylidene) -1,2-diphenylethylenediaminocobalt (III), bromide (R, R)-(-) -N, N'-bis (3,5-di-tert-butylsalicylidene) -1,2-diphenylethylenediaminocobalt (III), (R, R)-(-)-N, N'-bis (3,5-di-tert-butylsalicylidene) -1,2-diphenylethylenediaminocobalt (III) acetate, (R, R)-(−)-N, N′-bis (3,5-di -Tert-butylsalicylidene) -1,2-diphenylethylenediaminocobalt III) Nonafluoro-tert-butoxide, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-diphenylethylenediaminocobalt (III) Hexafluoroisopropoxide, iodinated (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminochromium (III), Chloride (R, R)-(-)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminochromium (III), bromide (R, R) -(-)-N, N'-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminochromium (III), (R, R)-(-)-N, N '-Bis (3,5-di-tert-butylsalicylidene) -1 2-cyclohexanediaminochromium (III) acetate, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminochrome (III ) Nonafluoro-tert-butoxide,

Iodinated (R, R)-(-)-N, N'-bis (salicylidene) -1,2-cyclohexanediaminochromium (III), chloride (R, R)-(-)-N, N'-bis (Salicylidene) -1,2-cyclohexanediaminochromium (III), (R, R)-(−)-N, N′-bis (salicylidene) -1,2-cyclohexanediaminochromium (III), (R , R)-(−)-N, N′-bis (salicylidene) -1,2-cyclohexanediaminochrome (III) acetate, (R, R)-(−)-N, N′-bis (salicylidene)- 1,2-cyclohexanediaminochrome (III) nonafluoro-tert-butoxide, chloride (R, R)-(−)-N, N′-bis (3-tert-butyl-5-methylsalicylidene) -1, 2-cyclohexanediaminochrome (III , (R, R)-(−)-N, N′-bis (3-tert-butyl-5-methylsalicylidene) -1,2-cyclohexanediaminochromium (III), (R, R) -(-)-N, N'-bis (3-tert-butyl-5-methylsalicylidene) -1,2-cyclohexanediaminochromium (III) acetate, iodide (R, R)-(-)- N, N'-bis (3-tert-butyl-5-methylsalicylidene) -1,2-cyclohexanediaminochrome (III), (R, R)-(-)-N, N'-bis (3 -Tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminochromium (III) acetate, iodide (R, R)-(-)-N, N'-bis (3-tert-butyl- 5-Nitrosalicylidene) -1,2-cyclohexanediamino Rom (III), chloride (R, R)-(−)-N, N′-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminochromium (III), bromide (R, R)-(−)-N, N′-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminochromium (III), iodide (R, R) — (-)-N, N'-bis (3-tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminochromium (III), chloride (R, R)-(-)-N, N '-Bis (3-tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminochromium (III), bromide (R, R)-(-)-N, N'-bis (3- tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediamino Chromium (III), (R, R)-(−)-N, N′-bis (3-tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminochrome (III) acetate,

Iodinated (R, R)-(−)-N, N′-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminochromium (III), chloride (R, R) -(-)-N, N'-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminochromium (III), bromide (R, R)-(-)-N , N′-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminochrome (III), (R, R)-(−)-N, N′-bis (3- tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminochromium (III) acetate, iodide (R, R)-(-)-N, N'-bis (3-tert-butylsalicylide) Den) -1,2-cyclohexanediaminochrome (III), chloride (R R)-(-)-N, N'-bis (3-tert-butylsalicylidene) -1,2-cyclohexanediaminochromium (III), bromide (R, R)-(-)-N, N '-Bis (3-tert-butylsalicylidene) -1,2-cyclohexanediaminochromium (III), (R, R)-(-)-N, N'-bis (3-tert-butylsalicylidene) ) -1,2-cyclohexanediaminochrome (III) acetate, iodide (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2 -Diphenylethylenediaminochromium (III), chloride (R, R)-(-)-N, N'-bis (3,5-di-tert-butylsalicylidene) -1,2-diphenylethylenediaminochrome ( III), bromide (R, R)-(−)-N, N′-bis (3 5-Di-tert-butylsalicylidene) -1,2-diphenylethylenediaminochromium (III), (R, R)-(−)-N, N′-bis (3,5-di-tert-butyl Salicylidene) -1,2-diphenylethylenediaminochromium (III) acetate, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1 , 2-diphenylethylenediaminochrome (III) nonafluoro-tert-butoxide,

Iodinated (R, R)-(-)-N, N'-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminomanganese (III), chloride (R, R) -(-)-N, N'-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminomanganese (III), bromide (R, R)-(-)-N , N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminomanganese (III), (R, R)-(−)-N, N′-bis (3 5-Di-tert-butylsalicylidene) -1,2-cyclohexanediaminomanganese (III) acetate, (R, R)-(−)-N, N′-bis (3,5-di-tert-butyl Salicylidene) -1,2-cyclohexanediaminomanganese (III) nonafluoro- ert-butoxide, iodide (R, R)-(−)-N, N′-bis (salicylidene) -1,2-cyclohexanediaminomanganese (III), chloride (R, R)-(−) — N, N′-bis (salicylidene) -1,2-cyclohexanediaminomanganese (III), bromide (R, R)-(−)-N, N′-bis (salicylidene) -1,2-cyclohexanediaminomanganese (III ), (R, R)-(−)-N, N′-bis (salicylidene) -1,2-cyclohexanediaminomanganese (III) acetate,

Iodinated (R, R)-(−)-N, N′-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminomanganese (III), chloride (R, R) -(-)-N, N'-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminomanganese (III), bromide (R, R)-(-)-N , N′-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminomanganese (III), (R, R)-(−)-N, N′-bis (3- tert-Butyl-5-methylsalicylidene) -1,2-cyclohexanediaminomanganese (III) acetate, (R, R)-(−)-N, N′-bis (3-tert-butyl-5-methyl) Salicylidene) -1,2-cyclohexanediaminomanganese III) Nonafluoro-tert-butoxide, (R, R)-(−)-N, N′-bis (3-tert-butyl-5-nitrosalicylidene) -1,2-cyclohexanediaminomanganese (III) acetate , Iodide (R, R)-(-)-N, N'-bis (3-tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminomanganese (III), chloride (R, R )-(−)-N, N′-bis (3-tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminomanganese (III), bromide (R, R)-(−) — N, N′-bis (3-tert-butyl-5-methoxysalicylidene) -1,2-cyclohexanediaminomanganese (III), (R, R)-(−)-N, N′-bis (3 -Tert-butyl-5-methoxysali Isopropylidene) -1,2-cyclohexane-diamino-manganese (III) acetate,

Iodinated (R, R)-(−)-N, N′-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminomanganese (III), chloride (R, R) -(-)-N, N'-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminomanganese (III), bromide (R, R)-(-)-N , N′-bis (3-tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminomanganese (III), (R, R)-(−)-N, N′-bis (3- tert-butyl-5-chlorosalicylidene) -1,2-cyclohexanediaminomanganese (III) acetate, iodide (R, R)-(-)-N, N'-bis (3-tert-butylsalicylide) Den) -1,2-cyclohexanediaminomanganese (III) Chloride (R, R)-(-)-N, N'-bis (3-tert-butylsalicylidene) -1,2-cyclohexanediaminomanganese (III), bromide (R, R)-(-) -N, N'-bis (3-tert-butylsalicylidene) -1,2-cyclohexanediaminomanganese (III), (R, R)-(-)-N, N'-bis (3-tert- Butylsalicylidene) -1,2-cyclohexanediaminomanganese (III) acetate, iodide (R, R)-(−)-N, N′-bis [5-methyl-3- (1-methyl-1- Phenylethyl) salicylidene] -1,2-cyclohexanediaminomanganese (III), chloride (R, R)-(−)-N, N′-bis [5-methyl-3- (1-methyl-1-phenylethyl) ) Salicylidene] -1,2-cyclohexanediaminomer Cancer (III), bromide (R, R)-(−)-N, N′-bis [5-methyl-3- (1-methyl-1-phenylethyl) salicylidene] -1,2-cyclohexanediaminomanganese (III), (R, R)-(−)-N, N′-bis [5-methyl-3- (1-methyl-1-phenylethyl) salicylidene] -1,2-cyclohexanediaminomanganese (III) Acetate, (R, R)-(−)-N, N′-bis (3-tert-butyl-5-triphenylmethylsalicylidene) -1,2-cyclohexanediaminomanganese (III), chloride ( R, R)-(−)-N, N′-bis (3-tert-butyl-5-triphenylmethylsalicylidene) -1,2-cyclohexanediaminomanganese (III), bromide (R, R) -(-)-N, N'-bis (3-ter t-butyl-5-triphenylmethylsalicylidene) -1,2-cyclohexanediaminomanganese (III), (R, R)-(−)-N, N′-bis (3-tert-butyl-5- Triphenylmethylsalicylidene) -1,2-cyclohexanediaminomanganese (III) acetate,

Iodinated (R, R)-(-)-N, N'-bis [5-tert-butyl-3- (1-methyl-1-phenylethyl) salicylidene] -1,2-cyclohexanediaminomanganese (III) (R, R)-(−)-N, N′-bis [5-tert-butyl-3- (1-methyl-1-phenylethyl) salicylidene] -1,2-cyclohexanediaminomanganese (III) , (R, R)-(−)-N, N′-bis [5-tert-butyl-3- (1-methyl-1-phenylethyl) salicylidene] -1,2-cyclohexanediaminomanganese (III ), (R, R)-(−)-N, N′-bis [5-tert-butyl-3- (1-methyl-1-phenylethyl) salicylidene] -1,2-cyclohexanediaminomanganese (III) Acetate, iodide (R R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-diphenylethylenediaminomanganese (III), chloride (R, R)-(−) -N, N'-bis (3,5-di-tert-butylsalicylidene) -1,2-diphenylethylenediaminomanganese (III), bromide (R, R)-(-)-N, N ' -Bis (3,5-di-tert-butylsalicylidene) -1,2-diphenylethylenediaminomanganese (III), (R, R)-(-)-N, N'-bis (3,5- Di-tert-butylsalicylidene) -1,2-diphenylethylenediaminomanganese (III) acetate, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsali Tylidene) -1,2-diphenylethylenediaminomanganese (III) nona Ruoro -tert- butoxide, and the configuration of the optically active metal complex as described above (R, R) - (-) is (S, S) - (+) optically active metal complex or the like instead of the like.

As this optically active metal complex (1), a commercially available product may be used. Am. Chem. Soc. , 121 , 6086 (1999), J. Am. Am. Chem. Soc. 113 , 6703 (1991), J. Am. Org. Chem. , 56 , 2296 (1991), Japanese Patent Application Laid-Open No. 2004-285003, etc. may be used.

  Among metal alkoxides, zirconium alkoxides include, for example, tetramethoxyzirconium, tetraethoxyzirconium, tetra (n-propoxy) zirconium, tetraisopropoxyzirconium, tetra (n-butoxy) zirconium, tetra (sec-butoxy) zirconium, tetra ( tert-butoxy) zirconium and the like. Examples of the hafnium alkoxide include tetramethoxyhafnium, tetraethoxyhafnium, tetra (n-propoxy) hafnium, tetraisopropoxyhafnium, tetra (n-butoxy) hafnium, tetra (sec-butoxy) hafnium, tetra (tert-butoxy). ) Hafnium and the like. In terms of availability, zirconium alkoxide is preferable.

  A commercially available metal alkoxide may be used, or a metal alkoxide prepared according to a known method such as a method of reacting zirconium halide or hafnium halide with a corresponding alcohol compound may be used. . The metal alkoxide may be used as it is or as a solution in an organic solvent. Since metal alkoxide is usually unstable with respect to air and moisture, it is preferably used as a solution of an organic solvent. Examples of the organic solvent include aliphatic hydrocarbon solvents such as hexane and heptane; ether solvents such as diethyl ether and tert-butyl methyl ether;

  Although the usage-amount of a metal alkoxide is not restrict | limited especially, it is 0.2-10 mol times normally with respect to an optically active metal complex (1), Preferably it is the range of 0.5-5 mol times.

  The reaction between the optically active metal complex (1) and the metal alkoxide is usually carried out in an organic solvent by contacting and mixing them. When both are contacted and mixed, a reaction occurs and a new asymmetric complex is formed.

  The reaction temperature between the optically active metal complex (1) and the metal alkoxide is usually in the range of −50 ° C. to the reflux temperature of the reaction mixture, preferably −25 to 50 ° C.

  Examples of the organic solvent include ether solvents such as diethyl ether and tert-butyl methyl ether; aromatic hydrocarbon solvents such as toluene; halogenated hydrocarbon solvents such as chlorobenzene and chloroform; aliphatic hydrocarbon solvents such as hexane; The amount used is not particularly limited.

  For example, if water is present in the reaction system, the metal alkoxide is likely to be decomposed. Therefore, the reagents and solvents to be used may be dehydrated in advance, or a dehydrating agent such as molecular sieves may be allowed to coexist in the reaction system. preferable.

  In addition, when the optically active metal complex (1) and the metal alkoxide are reacted in an organic solvent, a solution containing the new asymmetric complex to be formed is obtained. For example, the solution may be concentrated, etc. to extract a novel asymmetric complex and used for the reaction of a cyclic ether compound and a phenol described later.

  Next, an optically active alcohol compound is produced by reacting a cyclic ether compound and a phenol with the novel asymmetric complex formed by reacting the optically active metal complex (1) and the metal alkoxide as a catalyst. A method will be described.

（式中、Ｒ¹¹は水素原子を、Ｒ¹²は水素原子あるいは置換されていてもよいアルキル基を表すか、またはＲ¹¹とＲ¹²が結合して炭素数２〜６のアルキレン基を表す。Ｒ¹³は置換されていてもよいアルキル基、置換されていてもよいアリール基または置換されていてもよいアラルキル基を表す。ｎは、０または１を表す。）
で示される環状エーテル化合物（以下、環状エーテル化合物（２）と略記する。）が挙げられる。 Any cyclic ether compound may be used as long as it causes a ring-opening reaction by reaction with phenols.

(In the formula, R ¹¹ represents a hydrogen atom, R ¹² represents a hydrogen atom or an optionally substituted alkyl group, or R ¹¹ and R ¹² are bonded to each other to represent a C 2-6 alkylene group. R ¹³ represents an alkyl group that may be substituted, an aryl group that may be substituted, or an aralkyl group that may be substituted, and n represents 0 or 1.
And a cyclic ether compound (hereinafter abbreviated as cyclic ether compound (2)).

Examples of the alkyl group include linear or branched alkyl groups having 1 to 4 carbon atoms such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, and an isobutyl group. Examples of the substituent which may be present on these alkyl groups include halogen atoms such as fluorine atom, chlorine atom, bromine atom and iodine atom; methoxy group, ethoxy group, n-propoxy group, isopropoxy group, and alkoxy groups such as n-butoxy group, isobutoxy group, sec-butoxy group and tert-butoxy group; Specific examples of the alkyl group substituted with these substituents include a fluoromethyl group, a trifluoromethyl group, a methoxymethyl group, and a hydroxymethyl group. Examples of the alkylene group having 2 to 6 carbon atoms formed by combining R ¹¹ and R ¹² include an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group, and a hexamethylene group.

  As an aryl group, C6-C10 aryl groups, such as a phenyl group and a naphthyl group, are mentioned, for example. Examples of the substituent which may be present on these aryl groups include halogen atoms such as fluorine atom, chlorine atom, bromine atom and iodine atom; methyl group, ethyl group, n-propyl group, isopropyl group, n -Alkyl groups such as butyl group and isobutyl group; alkoxy groups such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group and tert-butoxy group; Can be mentioned. Specific examples of the aryl group substituted with such a substituent include a toluyl group, a xylyl group, and a methoxyphenyl group.

  Examples of the optionally substituted aralkyl group include those in which one or two or more hydrogen atoms of the optionally substituted alkyl group are substituted with the optionally substituted aryl group, Specific examples include benzyl group, triphenylmethyl group, 1-methyl-1-phenylethyl group and the like.

  Examples of such cyclic ether compounds include propylene oxide, chloromethyloxirane, bromomethyloxirane, iodomethyloxirane, 1,2-epoxybutane, 1,2-epoxyhexane, 1,3-epoxyhexane, 1,2-epoxy- Examples include 4-methylpentane, 1,2-epoxy-3-phenylpropane, styrene oxide, 2,3-epoxy-1-propanol, cyclohexene oxide, cyclopentene oxide, 1,2-epoxycyclooctane, and the like. Preferred cyclic ether compounds include propylene oxide and 1,2-epoxybutane.

（式中、Ｘは酸素原子または硫黄原子を表し、Ｒ¹⁴、Ｒ¹⁵、Ｒ¹⁶、Ｒ¹⁷およびＲ¹⁸は、それぞれ同一または相異なって、水素原子、ハロゲン原子、ニトロ基、置換されていてもよいアルキル基、置換されていてもよいアルコキシ基または置換されていてもよいフェノキシ基を表す。）
で示されるフェノール類（以下、フェノール類（３）と略記する。）が挙げられる。 The phenol is not particularly limited as long as it is a phenol having a phenolic hydroxyl group and a thiophenol in which the oxygen atom of the hydroxyl group of the phenol is replaced by a sulfur atom. For example, the phenol (3)

(In the formula, X represents an oxygen atom or a sulfur atom, and R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ are the same or different and each represents a hydrogen atom, a halogen atom, a nitro group, or a substituted group. Represents an optionally substituted alkyl group, an optionally substituted alkoxy group or an optionally substituted phenoxy group.)
(Hereinafter abbreviated as phenols (3)).

  Examples of the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom.

  Examples of the alkyl group include linear or branched carbon number such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, n-pentyl group, and n-hexyl group. 1-6 alkyl groups are mentioned. Examples of the substituent which may be present on these alkyl groups include halogen atoms such as fluorine atom, chlorine atom and bromine atom; methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy Group, an alkoxy group such as an isobutoxy group, a sec-butoxy group, and a tert-butoxy group; and the like. Specific examples of the alkyl group substituted with such a substituent include a chloromethyl group, a trifluoromethyl group, and a methoxymethyl group.

  Examples of the alkoxy group include linear or branched methoxy groups, ethoxy groups, n-propoxy groups, isopropoxy groups, n-butoxy groups, isobutoxy groups, n-pentyloxy groups, n-hexyloxy groups, and the like. And an alkoxy group having 1 to 6 carbon atoms. Examples of the substituent which may be present on these alkoxy groups include halogen atoms such as fluorine atom, chlorine atom and bromine atom; methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy Group, an alkoxy group such as an isobutoxy group, a sec-butoxy group, and a tert-butoxy group; and the like. Specific examples of the alkoxy group substituted with such a substituent include a chloromethoxy group, a trifluoromethoxy group, and a methoxymethoxy group.

  Examples of the substituent that may be present on the phenoxy group include halogen atoms such as fluorine atom, chlorine atom and bromine atom; methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl Group, alkyl group such as n-pentyl group, n-hexyl group; methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, etc. An alkoxy group; a phenoxy group; and the like. Specific examples of the phenoxy group substituted with such a substituent include 4-chlorophenoxy group, 2-bromophenoxy group, 2-methylphenoxy group, 3-methylphenoxy group, 4-methylphenoxy group, 4-ethylphenoxy group. 4-propylphenoxy group, 2-methoxyphenoxy group, 3-methoxyphenoxy group, 4-methoxyphenoxy group, 4-ethoxyphenoxy group, 4-phenoxyphenoxy group, and the like.

  Examples of such phenols include phenol, 4-chlorophenol, 2-bromophenol, 4-bromophenol, o-cresol, m-cresol, p-cresol, 2-methoxyphenol, 3-methoxyphenol, 4-methoxyphenol. 4-phenoxyphenol, 4-nitrophenol, 2,3-difluoro-6-nitrophenol, thiophenol, 2-bromo-4-methylthiophenol, 4-chlorothiophenol, 4-methoxythiophenol, 4-phenoxythio Phenol etc. are mentioned. Preferable phenols include phenol, 2-methoxyphenol, 3-methoxyphenol, 4-methoxyphenol, 4-phenoxyphenol, 4-methoxythiophenol, and 4-phenoxythiophenol.

  The amount of the cyclic ether compound used is usually 2 mol times or more with respect to phenols, and there is no particular upper limit. However, if it is too much, it tends to be economically disadvantageous. It is.

  The reaction temperature is usually in the range of −50 ° C. to the reflux temperature of the reaction mixture, preferably −25 to 50 ° C.

  The reaction may be performed by contacting and mixing a novel asymmetric complex obtained by reacting the optically active metal complex (1) and the metal alkoxide, a cyclic ether compound and phenols, and the mixing order is not particularly limited.

  The amount of the novel asymmetric complex used in the present invention can achieve the object of the present invention when it is usually 0.1 mol% or more based on the optically active metal complex (1) based on phenols. Although the upper limit is not particularly limited, practical use is in the range of 0.1 to 10 mol%, preferably 0.1 to 5 mol%, because it is economically disadvantageous if used too much.

  Usually, the reaction is carried out in the presence of an organic solvent. Examples of the organic solvent include aliphatic hydrocarbon solvents such as hexane and heptane; aromatic hydrocarbon solvents such as toluene; ether solvents such as diethyl ether and tert-butyl methyl ether; halogenated hydrocarbon solvents such as chloroform and chlorobenzene. And the like, and the use amount thereof is not particularly limited.

  After completion of the reaction, for example, water and, if necessary, an organic solvent insoluble in water are added, followed by extraction treatment, whereby the objective optically active alcohol compound can be isolated. The isolated optically active alcohol compound may be further purified by ordinary purification means such as distillation, recrystallization, column chromatography and the like. Examples of the organic solvent insoluble in water include aromatic hydrocarbon solvents such as toluene and xylene; aliphatic hydrocarbon solvents such as hexane and heptane; halogenated hydrocarbon solvents such as chloroform and chlorobenzene; diethyl ether and tert-butylmethyl. Ether solvents such as ether; and the like, and the amount used is not particularly limited.

（式中、Ｒ¹¹、Ｒ¹²、Ｒ¹³、Ｒ¹⁴、Ｒ¹⁵、Ｒ¹⁶、Ｒ¹⁷、Ｒ¹⁸、Ｘおよびｎは、それぞれ上記と同一の意味を表し、＊は不斉炭素原子を表す。）
で示される光学活性なアルコール化合物が得られる。 When the cyclic ether compound (2) is reacted with the phenol (3), the formula (4)

(Wherein R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , X and n each represent the same meaning as above, and * represents an asymmetric carbon atom) .)
An optically active alcohol compound represented by is obtained.

  Examples of the optically active alcohol compound thus obtained include optically active 1-phenoxy-2-propanol, optically active 1- (4-chlorophenoxy) -2-propanol, 1- (2-bromophenoxy) -2-propanol, Optically active 1- (4-bromophenoxy) -2-propanol, optically active 1- (2-methylphenoxy) -2-propanol, 1- (3-methylphenoxy) -2-propanol, optically active 1- (4- Methylphenoxy) -2-propanol, optically active 1- (2-methoxyphenoxy) -2-propanol, optically active 1- (3-methoxyphenoxy) -2-propanol, optically active 1- (4-methoxyphenoxy) -2 -Propanol, 1- (4-phenoxyphenoxy) -2-propanol, optically active 1- (4-ni Rophenoxy) -2-propanol, optically active 1- (2,3-difluoro-6-nitrophenoxy) -2-propanol, optically active 1-phenylthio-2-propanol, 1- (2-bromo-4-methylphenyl) Thio) -2-propanol, optically active 1- (4-chlorophenylthio) -2-propanol, optically active 1- (4-methoxyphenylthio) -2-propanol, optically active 1- (4-phenoxyphenylthio)- 2-propanol,

Optically active 1-phenoxy-2-butanol, optically active 1- (4-chlorophenoxy) -2-butanol, optically active 1- (2-bromophenoxy) -2-butanol, optically active 1- (4-bromophenoxy) 2-butanol, optically active 1- (2-methylphenoxy) -2-butanol, optically active 1- (3-methylphenoxy) -2-butanol, optically active 1- (4-methylphenoxy) -2-butanol, Optically active 1- (4-methoxyphenoxy) -2-butanol, optically active 1- (4-phenoxyphenoxy) -2-butanol, optically active 1- (4-nitrophenoxy) -2-butanol, optically active 1- ( 2,3-difluoro-6-nitrophenoxy) -2-butanol, optically active 1-phenylthio-2-butanol, optically active 1- (2- Lomo-4-methylphenylthio) -2-butanol, optically active 1- (4-chlorophenylthio) -2-butanol, optically active 1- (4-methoxyphenylthio) -2-butanol, optically active 1- (4 -Phenoxyphenylthio) -2-butanol,

Optically active 1-phenoxy-2-hexanol, optically active 1- (4-chlorophenoxy) -2-hexanol, optically active 1- (2-bromophenoxy) -2-hexanol, optically active 1- (4-bromophenoxy) 2-hexanol, optically active 1- (2-methylphenoxy) -2-hexanol, optically active 1- (3-methylphenoxy) -2-hexanol, 1- (4-methylphenoxy) -2-hexanol, optically active 1- (4-methoxyphenoxy) -2-hexanol, optically active 1- (4-phenoxyphenoxy) -2-hexanol, optically active 1- (4-nitrophenoxy) -2-hexanol, optically active 1- (2, 3-difluoro-6-nitrophenoxy) -2-hexanol, optically active 1-phenylthio-2-hexanol, light Active 1- (2-bromo-4-methylphenylthio) -2-hexanol, optically active 1- (4-chlorophenylthio) -2-hexanol, optically active 1- (4-methoxyphenylthio) -2-hexanol, Optically active 1- (4-phenoxyphenylthio) -2-hexanol,

Optically active 2-phenoxy-1-phenylethanol, optically active 2- (4-chlorophenoxy) -1-phenylethanol, optically active 2- (2-bromophenoxy) -1-phenylethanol, optically active 2- (4- Bromophenoxy) -1-phenylethanol, optically active 2- (2-methylphenoxy) -1-phenylethanol, optically active 2- (3-methylphenoxy) -1-phenylethanol, optically active 2- (4-methylphenoxy) ) -1-phenylethanol, optically active 2- (4-methoxyphenoxy) -1-phenylethanol, optically active 2- (4-phenoxyphenoxy) -1-phenylethanol, 2- (4-nitrophenoxy) -1- Phenylethanol, optically active 2- (2,3-difluoro-6-nitrophenoxy) -1- Phenylethanol, optically active 2-phenylthio-1-phenylethanol, optically active 2- (2-bromo-4-methylphenylthio) -1-phenylethanol, optically active 2- (4-chlorophenylthio) -1-phenylethanol Optically active 2- (4-methoxyphenylthio) -1-phenylethanol, optically active 2- (4-phenoxyphenylthio) -1-phenylethanol,

Optically active 1-chloro-3-phenoxy-2-propanol, optically active 1-chloro-3- (4-chlorophenoxy) -2-propanol, optically active 1-chloro-3- (2-bromophenoxy) -2-propanol , Optically active 1-chloro-3- (4-bromophenoxy) -2-propanol, optically active 1-chloro-3- (2-methylphenoxy) -2-propanol, optically active 1-chloro-3- (3- Methylphenoxy) -2-propanol, optically active 1-chloro-3- (4-methylphenoxy) -2-propanol, optically active 1-chloro-3- (2-methoxyphenoxy) -2-propanol, optically active 1- Chloro-3- (3-methoxyphenoxy) -2-propanol, optically active 1-chloro-3- (4-methoxyphenoxy) -2-propano , Optically active 1-chloro-3- (4-phenoxyphenoxy) -2-propanol, optically active 1-chloro-3- (4-nitrophenoxy) -2-propanol, optically active 1-chloro-3- (2 , 3-Difluoro-6-nitrophenoxy) -2-propanol, optically active 1-chloro-3-phenylthio-2-propanol, optically active 1-chloro-3- (2-bromo-4-methylphenylthio) -2 -Propanol, optically active 1-chloro-3- (4-chlorophenylthio) -2-propanol, optically active 1-chloro-3- (4-methoxyphenylthio) -2-propanol, optically active 1-chloro-3- (4-phenoxyphenylthio) -2-propanol,

Optically active 1-bromo-3-phenoxy-2-propanol, 1-bromo-3- (4-chlorophenoxy) -2-propanol, optically active 1-chloro-3- (2-bromophenoxy) -2-propanol, Optically active 1-bromo-3- (4-bromophenoxy) -2-propanol, optically active 1-bromo-3- (2-methylphenoxy) -2-propanol, optically active 1-bromo-3- (3-methyl Phenoxy) -2-propanol, 1-bromo-3- (4-methylphenoxy) -2-propanol, optically active 1-bromo-3- (2-methoxyphenoxy) -2-propanol, optically active 1-bromo-3 -(3-methoxyphenoxy) -2-propanol, optically active 1-bromo-3- (4-methoxyphenoxy) -2-propanol, optically active 1 Bromo-3- (4-phenoxyphenoxy) -2-propanol, optically active 1-bromo-3- (4-nitrophenoxy) -2-propanol, optically active 1-bromo-3- (2,3-difluoro-6 -Nitrophenoxy) -2-propanol, optically active 1-bromo-3-phenylthio-2-propanol, optically active 1-bromo-3- (2-bromo-4-methylphenylthio) -2-propanol, optically active 1 -Bromo-3- (4-chlorophenylthio) -2-propanol, optically active 1-bromo-3- (4-methoxyphenylthio) -2-propanol, optically active 1-bromo-3- (4-phenoxyphenylthio) ) -2-propanol,

Optically active 3-phenoxypropane-1,2-diol, optically active 3- (4-chlorophenoxy) propane-1,2-diol, optically active 3- (2-bromophenoxy) propane-1,2-diol, optical Active 3- (4-bromophenoxy) propane-1,2-diol, optically active 3- (2-methylphenoxy) propane-1,2-diol, optically active 3- (3-methylphenoxy) propane-1,2 -Diol, optically active 3- (4-methylphenoxy) propane-1,2-diol, optically active 3- (4-methoxyphenoxy) propane-1,2-diol, optically active 3- (4-phenoxyphenoxy) propane -1,2-diol, optically active 3- (4-nitrophenoxy) propane-1,2-diol, optically active 3- (2,3-difluoro- -Nitrophenoxy) propane-1,2-diol, optically active 3-phenylthiopropane-1,2-diol, optically active 3- (2-bromo-4-methylphenylthio) propane-1,2-diol, optical Active 3- (4-chlorophenylthio) propane-1,2-diol, optically active 3- (4-methoxyphenylthio) propane-1,2-diol, optically active 3- (4-phenoxyphenylthio) propane-1 , 2-diol,

Optically active 2-phenoxycyclohexanol, optically active 2- (4-chlorophenoxy) cyclohexanol, optically active 2- (2-bromophenoxy) cyclohexanol, optically active 2- (4-bromophenoxy) cyclohexanol, optically active 2 -(2-methylphenoxy) cyclohexanol, optically active 2- (3-methylphenoxy) cyclohexanol, optically active 2- (4-methylphenoxy) cyclohexanol, optically active 2- (4-methoxyphenoxy) cyclohexanol, optical Active 2- (4-phenoxyphenoxy) cyclohexanol, optically active 2- (4-nitrophenoxy) cyclohexanol, optically active 2- (2,3-difluoro-6-nitrophenoxy) cyclohexanol, optically active 2- (phenylthio ) Cyclohex Optically active 2- (2-bromo-4-methylphenylthio) cyclohexanol, optically active 2- (4-chlorophenylthio) cyclohexanol, optically active 2- (4-methoxyphenylthio) cyclohexanol, optically active 2 -(4-phenoxyphenylthio) cyclohexanol,

Optically active 2-phenoxycyclopentanol, optically active 2- (4-chlorophenoxy) cyclopentanol, optically active 2- (2-bromophenoxy) cyclopentanol, optically active 2- (4-bromophenoxy) cyclopentanol , Optically active 2- (2-methylphenoxy) cyclopentanol, optically active 2- (3-methylphenoxy) cyclopentanol, optically active 2- (4-methylphenoxy) cyclopentanol, optically active 2- (4- Methoxyphenoxy) cyclopentanol, optically active 2- (4-phenoxyphenoxy) cyclopentanol, optically active 2- (4-nitrophenoxy) cyclopentanol, optically active 2- (2,3-difluoro-6-nitrophenoxy ) Cyclopentanol, optically active 2- (phenylthio) cyclopen , Optically active 2- (2-bromo-4-methylphenylthio) cyclopentanol, optically active 2- (4-chlorophenylthio) cyclopentanol, optically active 2- (4-methoxyphenylthio) cyclopentanol, Optically active 2- (4-phenoxyphenylthio) cyclopentanol,

Optically active 2-phenoxycyclooctanol, optically active 2- (4-chlorophenoxy) cyclooctanol, optically active 2- (2-bromophenoxy) cyclooctanol, optically active 2- (4-bromophenoxy) cyclooctanol, optically active 2 -(2-methylphenoxy) cyclooctanol, optically active 2- (3-methylphenoxy) cyclooctanol, optically active 2- (4-methylphenoxy) cyclooctanol, optically active 2- (4-methoxyphenoxy) cyclooctanol, optical Active 2- (4-phenoxyphenoxy) cyclooctanol, optically active 2- (4-nitrophenoxy) cyclooctanol, optically active 2- (2,3-difluoro-6-nitrophenoxy) cyclooctanol, optically active 2- (phenylthio ) Cyclooct , Optically active 2- (2-bromo-4-methylphenylthio) cyclooctanol, optically active 2- (4-chlorophenylthio) cyclooctanol, optically active 2- (4-methoxyphenylthio) cyclooctanol, optically active 2 -(4-phenoxyphenylthio) cyclooctanol and the like.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples. The yield was calculated from the result of high performance liquid chromatography analysis, and the optical purity was calculated from the result of high performance liquid chromatography analysis using an optically active column (CHIRALCEL OD: manufactured by Daicel).

Example 1
In a flask purged with nitrogen, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (II) 150.9 mg Then, 9.25 mL of tert-butyl methyl ether was added, 0.5 mL of a 0.25 M iodine / tert-butyl methyl ether solution was added, and the mixture was stirred at room temperature for 30 minutes. Further, 0.25 mL of 1.0 M tetra (tert-butoxy) zirconium / tert-butyl methyl ether solution was added and stirred for 30 minutes to prepare a catalyst solution. The catalyst solution was cooled to 5 ° C., 4.81 g of phenol and 8.71 g of propylene oxide were added, and the mixture was stirred at the same temperature for 20 hours to be reacted. After completion of the reaction, tert-butyl methyl ether was distilled off to obtain an oily substance containing 1-phenoxy-2-propanol.
Yield: 99% (phenol basis), optical purity: 97.4% e.e. e. (S body)

Example 2
In a flask purged with nitrogen, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (II) 150.9 mg Then, 9.0 mL of tert-butyl methyl ether was charged, 0.5 mL of a 0.25 M iodine / tert-butyl methyl ether solution was added, and the mixture was stirred at room temperature for 30 minutes. Further, 0.5 mL of a 0.5 M tetra (tert-butoxy) hafnium / tert-butyl methyl ether solution was added and stirred for 30 minutes to prepare a catalyst solution. The catalyst solution was cooled to 5 ° C., 4.71 g of phenol and 6.39 g of propylene oxide were added, and the mixture was stirred at the same temperature for 20 hours to be reacted. After completion of the reaction, tert-butyl methyl ether was distilled off to obtain an oily substance containing 1-phenoxy-2-propanol.
Yield: 87% (based on phenol), optical purity: 94.9% e.e. e. (S body)

Comparative Example 1
In a flask purged with nitrogen, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (II) 150.9 mg Then, 9.25 mL of tert-butyl methyl ether was added, 0.5 mL of a 0.25 M iodine / tert-butyl methyl ether solution was added, and the mixture was stirred at room temperature for 30 minutes. Further, 0.25 mL of 1.0 M tetraisopropoxy titanium / tert-butyl methyl ether solution was added and stirred for 30 minutes to prepare a catalyst solution. The catalyst solution was cooled to 5 ° C., 4.71 g of phenol and 8.71 g of propylene oxide were added, and the mixture was stirred at the same temperature for 20 hours to be reacted. After completion of the reaction, tert-butyl methyl ether was distilled off to obtain an oily substance containing 1-phenoxy-2-propanol.
Yield: 82% (based on phenol), optical purity: 97.2% e.e. e. (S body)

Example 3
In a flask purged with nitrogen, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (II) 301.9 mg Then, 9.0 mL of tert-butyl methyl ether was charged, 1.0 mL of a 0.25 M iodine / tert-butyl methyl ether solution was added, and the mixture was stirred at room temperature for 30 minutes. Further, 164 mg of tetraisopropoxyzirconium was added and stirred for 30 minutes to prepare a catalyst solution. The catalyst solution was cooled to 5 ° C., 4.71 g of phenol and 8.71 g of propylene oxide were added, and the mixture was stirred at the same temperature for 20 hours to be reacted. After completion of the reaction, tert-butyl methyl ether was distilled off to obtain an oily substance containing 1-phenoxy-2-propanol.
Yield: 96% (based on phenol), optical purity: 97.8% e.e. e. (S body)

Example 4
In a flask purged with nitrogen, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (II) 301.9 mg Then, 2.0 mL of tert-butyl methyl ether was added, 1.0 mL of a 0.25 M iodine / tert-butyl methyl ether solution was added, and the mixture was stirred at room temperature for 30 minutes. Further, 2.0 mL of 0.5 M tetra (tert-butoxy) zirconium / tert-butyl methyl ether solution was added and stirred for 30 minutes to prepare a catalyst solution. The catalyst solution was cooled to 5 ° C., 3.10 g of 3-methoxyphenol and 6.94 g of 2-chloromethyloxirane were added, and the mixture was stirred at the same temperature for 28 hours to be reacted. After completion of the reaction, tert-butyl methyl ether was distilled off to obtain an oily substance containing 1-chloro-3- (3-methoxyphenoxy) -2-propanol.
Yield: 89% (based on 3-methoxyphenol), optical purity: 98.0% e.e. e. (S body)

Example 5
In Example 4, it replaces with 3-methoxyphenol, and it carries out similarly to Example 4 except using 4-methoxyphenol, and the oil containing 1-chloro-3- (4-methoxyphenoxy) -2-propanol I got a thing.
Yield: 99% (4-methoxyphenol standard), optical purity: 97.6% e.e. e. (S body)

Comparative Example 2
In a flask purged with nitrogen, (R, R)-(−)-N, N′-bis (3,5-di-tert-butylsalicylidene) -1,2-cyclohexanediaminocobalt (II) 301.9 mg Then, 3.0 mL of tert-butyl methyl ether was added, 1.0 mL of a 0.25 M iodine / tert-butyl methyl ether solution was added, and the mixture was stirred at room temperature for 30 minutes. Further, 1.0 mL of 1.0 M tetraisopropoxy titanium / tert-butyl methyl ether solution was added and stirred for 30 minutes to prepare a catalyst solution. The catalyst solution was cooled to 5 ° C, 1.24 g of 3-methoxyphenol and 2.78 g of 2-chloromethyloxirane were added, and the mixture was stirred at the same temperature for 20 hours to be reacted. After completion of the reaction, tert-butyl methyl ether was distilled off to obtain an oily substance containing 1-chloro-3- (3-methoxyphenoxy) -2-propanol.
Yield: 81% (based on 3-methoxyphenol), optical purity: 98.6% e.e. e. (S body)

Comparative Example 3
In Comparative Example 2, the same procedure as in Comparative Example 2 was performed except that 4-methoxyphenol was used instead of 3-methoxyphenol, and an oil containing 1-chloro-3- (4-methoxyphenoxy) -2-propanol I got a thing.
Yield: 97% (4-methoxyphenol standard), optical purity: 93.0% e.e. e. (S body)

Example 6
In Example 1, except that 4-phenoxyphenol was used in place of phenol, the same procedure as in Example 1 was carried out to obtain an oily substance containing optically active 1- (4-phenoxyphenoxy) -2-propanol. Can be obtained.

Example 7
In Example 2, an oily substance containing optically active 1- (4-phenoxyphenoxy) -2-propanol was obtained by carrying out in the same manner as in Example 2 except that 4-phenoxyphenol was used instead of phenol. Can be obtained.

Claims (8)

Formula (1)

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, an alkynyl group, Represents an alkoxy group, a haloalkyl group, a haloalkoxy group, an optionally substituted aryl group, an aralkyl group, a hydroxyl group, a nitro group, an amino group, a carbamoyl group, a carboxyl group or a silyl group, or R ¹ , R ² , R ^3, R ^4, R ^5, R ^6, R ⁷ and of R ^8, by bonding two groups adjacent, together with the benzene ring to which they are attached form a ring, represents a naphthalene ring .R ⁹ and R ¹⁰ represents any one of them represents a hydrogen atom, and the other represents an alkyl group having 1 to 4 carbon atoms which may be substituted with a halogen atom, or an alkoxy having 1 to 4 carbon atoms which may be substituted with a halogen atom. Basic And a phenyl group or a naphthyl group which may be substituted with at least one selected from the group consisting of halogen atoms, or any pair of R ⁹ and R ¹⁰ bonded to different carbon atoms. Are bonded to form a tetramethylene group, and the other pair represents a hydrogen atom, and Q represents a single bond or an alkylene group having 1 to 4 carbon atoms.
Also,

May represent a 2,2′-binaphthyl group. Here, · indicates a binding site with a nitrogen atom. M represents cobalt ions, chromium ions or manganese ions, when the coordination number of the ion valence and a ligand of the ions of the same, A is absent, when the coordination number and the ionic valency is different phases, A represents a counter ion or a ligand. )
An optically active metal complex represented by the formula (1) and an aromatic complex obtained by reacting a zirconium alkoxide or hafnium alkoxide with a cyclic ether compound and phenols. A method for producing an alcohol compound. Formula (1)

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, an alkynyl group, alkoxy group, a haloalkyl group, a haloalkoxy group, an aralkyl group, a hydroxyl group, a nitro group, an amino group, or a carbamoyl group or a carboxyl group, or ^{R 1, R 2, R 3} , R 4, R 5, R 6,, Of R ⁷ and R ⁸ , two adjacent groups are bonded to form a ring together with the benzene ring to which they are bonded, and represents a naphthalene ring, and either of R ⁹ and R ¹⁰ represents a hydrogen atom. A small amount selected from the group consisting of an alkyl group having 1 to 4 carbon atoms which may be substituted with a halogen atom, an alkoxy group having 1 to 4 carbon atoms which may be substituted with a halogen atom, and a halogen atom. It represents a phenyl group or a naphthyl group which may be substituted with at least one, or, among the pairs consisting of R ⁹ and R ¹⁰ bonded to different carbon atoms, any one pair is bonded to form a tetramethylene group. And the other pair represents a hydrogen atom, and Q represents a single bond or an alkylene group having 1 to 4 carbon atoms.
Also,

May represent a 2,2′-binaphthyl group. Here, · indicates a binding site with a nitrogen atom. M represents a cobalt ion, a chromium ion or a manganese ion, and when the ionic valence of the ion and the coordination number of the ligand are the same, A does not exist, and when the ionic valence and the coordination number are different, A represents a halide ion . )
An asymmetric complex obtained by reacting the optically active metal complex represented by formula (II) with zirconium alkoxide or hafnium alkoxide. Formula (1)

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, an alkynyl group, Represents an alkoxy group, a haloalkyl group, a haloalkoxy group, an optionally substituted aryl group, an aralkyl group, a hydroxyl group, a nitro group, an amino group, a carbamoyl group, a carboxyl group or a silyl group, or R ¹ , R ² , R ^3, R ^4, R ^5, R ^6, R ⁷ and of R ^8, by bonding two groups adjacent, together with the benzene ring to which they are attached form a ring, represents a naphthalene ring .R ⁹ and R ¹⁰ represents any one of them represents a hydrogen atom, and the other represents an alkyl group having 1 to 4 carbon atoms which may be substituted with a halogen atom, or an alkoxy having 1 to 4 carbon atoms which may be substituted with a halogen atom. Basic And a phenyl group or a naphthyl group which may be substituted with at least one selected from the group consisting of halogen atoms, or any pair of R ⁹ and R ¹⁰ bonded to different carbon atoms. Are bonded to form a tetramethylene group, and the other pair represents a hydrogen atom, and Q represents a single bond or an alkylene group having 1 to 4 carbon atoms.
Also,

May represent a 2,2′-binaphthyl group. Here, · indicates a binding site with a nitrogen atom. M represents a cobalt ion, a chromium ion or a manganese ion, and when the ionic valence of the ion and the coordination number of the ligand are the same, A does not exist, and when the ionic valence and the coordination number are different, A represents a counter ion or a ligand. )
An asymmetric complex catalyst for producing an optically active alcohol compound obtained by reacting an optically active metal complex represented by formula (II) with zirconium alkoxide or hafnium alkoxide. The cyclic ether compound has the formula (2)

(In the formula, R ¹¹ represents a hydrogen atom, R ¹² represents a hydrogen atom or an optionally substituted alkyl group, or R ¹¹ and R ¹² are bonded to each other to represent a C 2-6 alkylene group. R ¹³ represents an alkyl group that may be substituted, an aryl group that may be substituted, or an aralkyl group that may be substituted, and n represents 0 or 1.
A compound represented by
The phenol is represented by the formula (3)

(In the formula, X represents an oxygen atom or a sulfur atom, and R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ are the same or different and each represents a hydrogen atom, a halogen atom, a nitro group, or a substituted group. Represents an optionally substituted alkyl group, an optionally substituted alkoxy group or an optionally substituted phenoxy group.)
A compound represented by
The optically active alcohol compound has the formula (4)

(Wherein R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , X and n each represent the same meaning as above, and * represents an asymmetric carbon atom) .)
The manufacturing method of Claim 1 which is a compound shown by these. In the formula (3), at least one substituent selected from the group consisting of R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ and R ¹⁸ is an optionally substituted alkyl group or an optionally substituted alkoxy group. Or the manufacturing method of Claim 4 which is the phenoxy group which may be substituted. The production method according to claim 1, wherein the counter ion or ligand represented by A in the formula (1) is a halide ion. In the formula (1), it is indicated by A Ruha androgenic compound ions, chloride ions, asymmetric complex according to claim 2 is bromide ion or iodide ion.
The asymmetric complex catalyst for producing an optically active alcohol compound according to claim 3, wherein the counter ion or ligand represented by A in the formula (1) is a halide ion.