JPH09241231A - Optically active beta-iminoalcohols, their production, production of optically active beta-aminoalcohols with the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new optically active β-iminoalcohol useful as an intermediate for an optically active β-aminoalcohol useful as an optical resolution auxiliary. SOLUTION: This optically active B-iminoalcohol is expressed by formula I (R<1> -R<3> are each H, a lower alkyl, a lower alkoxy, a halogen; R<4> is a lower alkyl, an acyl, a trialkylsilyl or an aryl or aralkyl which may be substituted by a lower alkyl or a lower alkoxy; * exhibits an asymmetric carbon), e.g. (S)-2-benzyloximino-1,2-diphenylethanol. The compound of formula I is obtained by asymmetrically reducing the syn isomer or anti isomer of an α-iminoketone compound of formula II or their mixture wherein either one of the syn isomer and the anti isomer is excessive with a borane derivative and an optically active amino alcohol borane complex obtained from a borane compound and an optically active aminoalcohol of formula III (R<5> -R<7> are each H, an alkyl, phenyl, etc.; R<8> , R<9> are each H, an alkyl, etc.). The compound of formula I can be reduced into a compound of formula IV.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an optically active β-imino alcohol, a method for producing the same, and a method for producing optically active β-amino alcohol using the same.

[0002]

BACKGROUND OF THE INVENTION Optically active β-amino alcohols are important compounds, for example, as an optical resolution aid or a ligand of a catalyst for asymmetric synthesis. Conventionally, as a method for producing β-amino alcohols, a method for reducing α-imino ketones (Ber. , 2
9, 295 (1896)), etc. are known, but the product obtained by this method is a racemate, which requires a very complicated operation such as optical resolution to obtain the optically active substance. There was a problem.

[0003]

Under the circumstances, the present inventors have conducted extensive studies to find a more efficient method for producing an optically active β-amino alcohol, and as a result, 3-
An optically active aminoalcohol borane complex obtained from a specific optically active aminoalcohol having a substituted silyloxy group at the position and borane, and a corresponding α
Asymmetric reduction of the syn-form, anti-form of imino ketones, or a mixture in which one of these is in excess, to first obtain an optically active β-imino alcohol that is an intermediate, and then reduce the imino group According to the above, it is found that an optically active β-amino alcohol having high optical purity can be produced without complicated operations, and a method for reducing an imino group is
The present invention has been completed by finding that the configuration of optically active β-aminoalcohols can be arbitrarily created depending on whether catalytic reduction or a method using a reducing agent is used.

That is, the present invention has the formula [II] (In the formula, R ¹ , R ² and R ³ are each independently a hydrogen atom,
Represents a lower alkyl group, a lower alkoxy group or a halogen atom, R ⁴ represents a lower alkyl group, an acyl group, a trialkylsilyl group, an aryl group optionally substituted with a lower alkyl or a lower alkoxy, or a lower alkyl or a lower alkoxy. It represents an optionally substituted aralkyl group, and * represents an asymmetric carbon. ) Optically active β-
The present invention provides an imino alcohol, a method for producing the same, and a method for producing an optically active β-amino alcohol using the same.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below. The optically active β-imino alcohols of the present invention are
As represented by the formula [II], the substituents R ¹ , R ² ,
R ³ is, for example, a hydrogen atom, a lower alkyl group such as methyl, ethyl, propyl or butyl, methoxy,
Examples thereof include lower alkoxy groups such as ethoxy, propoxy and butoxy, and halogen atoms such as chlorine, bromine and fluoro. The substituent R ⁴ may be a lower alkyl group, an acyl group, a trialkylsilyl group, an aryl group such as a phenyl group which may be substituted with lower alkyl or lower alkoxy, or a lower alkyl or lower alkoxy. It represents a good aralkyl group such as a benzyl group.
Examples of such lower alkyl group and lower alkoxy group include
Examples of the substituents are the same as those listed for the substituents R ¹ , R ² and R ³ , examples of the acyl group include acetyl group, propionyl group, butyryl group, benzoyl group and the like, and examples of the trialkylsilyl group include: Examples thereof include a trimethylsilyl group, a triethylsilyl group, a dimethylethylsilyl group and a t-butyldimethylsilyl group. Representative examples of the optically active β-imino alcohol [II] include, for example, 2-methoxyimino-1,2-diphenylethanol, 2-ethoxyimino-1,2-diphenylethanol, 2-propoxyimino-
1,2-diphenylethanol, 2-butoxyimino-1,2-
Diphenylethanol, 2-phenoxyimino-1,2-diphenylethanol, 2-tolyloxyimino-1,2-diphenylethanol, 2- (methoxyphenoxy) imino-1,2
-Diphenylethanol, 2-benzyloxyimino-1,2
-Diphenylethanol, 2-mesitylmethyloxyimino-1,2-diphenylethanol, 2-phenoxyimino-
1,2-bis (methylphenyl) ethanol, 2-phenoxyimino-1,2-bis (dimethylphenyl) ethanol,
2-mesitylmethyl okoshiimino-1,2-bis (methoxyphenyl) ethanol, 2-mesityloxyimino-1,2-
Dimesityl ethanol, 2-chlorophenoxyimino-1,2
-Diphenylethanol, 2-phenoxyimino-1,2-bis (chlorophenyl) ethanol, 2-chlorophenoxyimino-1,2-bis (chlorophenyl) ethanol, 2-phenylmethoxyimino-1,2-diphenylethanol, 2-
Acetyloxyimino-1,2-diphenylethanol, 2-
Benzoyloxyimino-1,2-diphenylethanol,
2-Trimethylsilyloxyimino-1,2-diphenylethanol, 2-t-butyldimethylsilyloxyimino-1,2-
Diphenylethanol, 2-methoxyimino-1,2-bis (methylphenyl) ethanol, 2-methoxyimino-1,2
-Bis (methoxyphenyl) ethanol, 2-benzyloxyimino-1,2-bis (methoxyphenyl) ethanol, 2-benzyloxyimino-1,2-bis (dimethylphenyl) ethanol, 2-methoxyimino-1,2 -Examples of optically active substances such as bis (dichlorophenyl) ethanol.

The optically active β-imino alcohol [II] of the present invention has the formula [I] (In the formula, R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above.) A syn-form or anti-form of α-imino ketones, or a mixture containing one of these in excess is represented by the formula [ III) (In the formula, R ⁵ , R ⁶ and R ⁷ are each independently a hydrogen atom,
It represents a lower alkyl group, a phenyl group optionally substituted with lower alkyl or a benzyl group optionally substituted with lower alkyl, but not all hydrogen atoms at the same time. R ⁸ and R ⁹ each independently represent a hydrogen atom, a lower alkyl group or a lower alkoxy group, and * represents an asymmetric carbon. ) The compound is produced by asymmetric reduction with an optically active aminoalcohol borane complex obtained from an optically active aminoalcohol and borane represented by the formula (1) and a borane derivative. The α-imino ketones [I] that are to be reduced correspond to the β-imino alcohol [II] that is a reduction product, and representative compounds thereof include, for example, 2-methoxyimino-1,2- Diphenylethanone, 2-ethoxyimino
-1,2-diphenylethanone, 2-propoxyimino-1,2-
Diphenylethanone, 2-butoxyimino-1,2-diphenylethanone, 2-phenoxyimino-1,2-diphenylethanone, 2-tolyloxyimino-1,2-diphenylethanone, 2- (methoxyphenoxy) Imino-1,2-diphenylethanone, 2-benzyloxyimino-1,2-diphenylethanone, 2-mesitylmethyloxyimino-1,2-diphenylethanone, 2-phenoxyimino-1,2-bis (Methylphenyl) ethanone, 2-phenoxyimino-1,2-bis (dimethylphenyl) ethanone, 2-mesitylmethylokioshiimino-1,2-bis (methoxyphenyl) ethanone, 2-mesityloxyimino-1 , 2-Dimesityl ethanone, 2-Chlorophenoxyimino-1,2-diphenylethanone, 2-Phenoxyimino-1,2-bis (chlorophenyl) ethanone, 2
-Chlorophenoxyimino-1,2-bis (chlorophenyl) ethanone, 2-phenylmethoxyimino-1,2-diphenylethanone, 2-acetyloxyimino-1,2-diphenylethanone, 2-benzoyloxyimino-1 , 2-Diphenylethanone, 2-Trimethylsilyloxyimino-1,2-diphenylethanone, 2-Triethylsilyloxyimino-
1,2-diphenylethanone, 2-t-butyldimethylsilyloxyimino-1,2-diphenylethanone, 2-methoxyimino-1,2-bis (methylphenyl) ethanone, 2-methoxyimino-1,2 -Bis (methoxyphenyl) ethanone, 2-
Benzyloxyimino-1,2-bis (methoxyphenyl)
Ethanone, 2-benzyloxyimino-1,2-bis (dimethylphenyl) ethanone, 2-methoxyimino-1,2-bis (dichlorophenyl) ethanone and the like can be mentioned. The α-imino ketones [I] can be produced by a known method, for example, by reacting the corresponding benzyls with a hydrochloride of a hydroxyamine ether in a basic solvent such as pyridine. Here, benzyls are, for example, Tetrahedro
n Asymm., 6 , 3 (1995).
Also, α-imino ketones [I] are usually obtained as a mixture of syn-form and anti-form by these methods, but both of them may be isolated by means of recrystallization, various chromatography or the like, if necessary. You can

In the present invention, in the asymmetric reduction of the syn-form, anti-form of α-imino ketones [I] or a mixture containing one of these in excess, an optical compound obtained from optically active amino alcohols [III] is used. An active amino alcohol borane complex is used. Examples of the substituents R ⁵ , R ⁶ and R ^{7 in} the optically active amino alcohols [III] are, for example, a hydrogen atom, a lower alkyl group such as methyl, ethyl, propyl and butyl, methyl, ethyl,
Examples thereof include a phenyl group which may be substituted with lower alkyl such as propyl and butyl, and a benzyl group which may be substituted with lower alkyl such as methyl, ethyl, propyl and butyl. Absent. Examples of the substituents R ⁸ and R ⁹ include, for example, a hydrogen atom, a lower alkyl group such as methyl, ethyl, propyl and butyl,
Examples thereof include lower alkoxy groups such as methoxy, ethoxy, propoxy and butoxy. Representative examples of the optically active amino alcohols [III] include, for example, optically active 2-amino-3-trimethylsiloxy-1,1-diphenylbutanol and 2-amino-3- (t-butyldimethyl). Siloxy)-
1,1-diphenylbutanol, 2-amino-3- (t-butyldiethylsiloxy) -1,1-diphenylbutanol, 2-amino
-3- (t-butyldi-i-propylsiloxy) -1,1-diphenylbutanol, 2-amino-3- (t-butyldiphenylsiloxy) -1,1-diphenylbutanol, 2- Amino-3-trimethylsiloxy-1,1-ditolylbutanol, 2-amino-3
Examples thereof include-(t-butyldimethylsiloxy) -1,1-bis (methoxyphenyl) butanol.

These optically active amino alcohols [II
I] can be easily produced using an optically active threonine as a starting material. For example, benzyloxycarbonyl halide is allowed to act on optically active threonine to protect the amino group, diazomethane is allowed to act on the carboxylic acid to esterify carboxylic acid, and then t-butylsilyl halide is allowed to act on t-butylsilyl group at the hydroxy group. The optically active aminoalcohol [III] can be produced in good yield by introducing a group, then reacting with phenylmagnesium halide to diphenylate the ester group, and then deprotecting the amino group.

The boranes used to obtain the optically active aminoalcohol borane complex in the present invention include, for example, diborane, tetraborane, hexaborane, tetrahydrofuran borane complex, dimethyl sulfide borane complex, dioxane borane complex and thioxane borane complex. Can be mentioned. The boranes are α-imino ketones [I] for optically active amino alcohols [III].
Depending on the amount of the optically active aminoalcohol [III] to be used, it is usually about 0.8 to 10 mol times, preferably about 1 to 5 mol times in terms of boron.

A solvent is usually used to obtain an optically active aminoalcohol borane complex from the optically active aminoalcohol [III] and boranes. Examples of such a solvent include tetrahydrofuran, 1,3-dioxane,
Ethers such as 1,4-dioxane, 1,3-dioxolane, thioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and methyl-t-butyl ether; aromatics such as benzene, toluene, xylene and chlorobenzene; 1,2-methoxyethane , Hydrocarbons such as hexane, heptane, and cyclohexane; halogenated hydrocarbons such as methylene chloride, ethylene chloride and carbon tetrachloride; and mixtures thereof. The solvent is
Normally 0.5 for optically active amino alcohols [III]
Used up to 20 times as much. A specific method for obtaining the optically active aminoalcohol borane complex includes, for example, a method of adding boranes to a mixture of a solvent and the optically active aminoalcohols [III].
At this time, the reaction temperature is usually -20 to 100 ° C, preferably 0 to
80 ° C. The optically active aminoalcohol borane complex thus obtained can be isolated and used, but it is usually used as it is.

In the asymmetric reduction of α-imino ketones [I] using the optically active amino alcohol borane complex, the optically active amino alcohol borane complex is
It is generally used in an amount of about 0.01 to 3 mol, preferably about 0.05 to 2 mol, calculated as the optically active amino alcohol [III], based on the imino ketone [I].

The borane derivative used in the present invention together with the optically active aminoalcohol borane complex is a trialkylamine borane complex such as trimethylamine borane complex, triethylamine borane complex, tripropylamine borane complex or tributylamine borane complex,
A catechol borane complex etc. can be mentioned. The borane derivative is usually about 0.5 to 5 mol times, preferably 0.8 to 3 times, in terms of boron, with respect to the α-imino ketone [I].
It is used in molar times. The borane derivative may be prepared in advance. For example, when the borane triethylamine complex is used, the α
-In the system of asymmetric reduction reaction of α-imino ketones [I] by a method such as adding boranes to a mixture of imino ketones [I], optically active amino alcohol borane complex and triethylamine, the asymmetric reduction reaction It can also be adjusted at the same time as. Examples of the boranes used here include the same ones as exemplified when obtaining the above-mentioned optically active amino alcohol borane complex.

The asymmetric reduction of α-imino ketones [I] to obtain β-imino alcohol [II] can be carried out in the presence of a Lewis acid. The Lewis acid used here is not particularly limited, for example, aluminum compounds such as aluminum chloride, aluminum bromide, triphenoxyaluminum, triisopropoxyaluminum, methyldiphenoxyaluminum, zinc compounds such as zinc chloride and zinc bromide. Examples thereof include titanium compounds such as titanium chloride and titanium bromide, boron compounds such as boron chloride, boron bromide and boron fluoride, and silicon compounds such as trimethylsilyl chloride and t-butyldimethylsilyl chloride. When a Lewis acid is used, its amount is usually the amount based on α-imino ketones [I].
It is about 0.1 to 3 mol, preferably about 0.5 to 2 mol.

Α-Iminoketones [I] in the present invention
As a specific method for asymmetric reduction of, for example, a method of adding α-imino ketones [I] or a mixture of the same and a solvent to a mixture of an optically active amino alcohol borane complex, a borane derivative and a solvent, α-imino ketones A method of adding a mixture of an optically active aminoalcohol borane complex and a borane derivative, or a mixture of them and a solvent to [I] or a mixture thereof with a solvent, an optically active aminoalcohol [III], a borane derivative and a solvent. Examples of the method include simultaneously adding α-imino ketones [I] or a mixture of the α-imino ketones [I] or a solvent and boranes to the mixture.
Further, as described above, when the adjustment of the borane derivative is carried out simultaneously with the asymmetric reduction reaction, for example, when a trialkylamine borane complex is used as the borane derivative, α-imino ketones [I] or It is possible to employ a method in which a trialkylamine is added to a mixture with a solvent, and then an optically active amino alcohol borane complex and boranes which are raw materials of borane derivatives are simultaneously added. Examples of the solvent used in the asymmetric reduction reaction include the same solvents as those shown in the step of obtaining the optically active aminoalcohol borane complex. When a solvent is used, its amount is usually about 0.5 to 30 times by weight with respect to the α-imino ketone [I]. The temperature of the asymmetric reduction reaction is
It is usually -20 to 100 ° C, preferably 0 to 80 ° C. Further, the asymmetric reduction reaction is usually carried out in the presence of an inert gas such as argon or nitrogen.

Thus, the optically active β-imino alcohols [II] are produced. For isolation of the β-imino alcohols [II], for example, a mineral acid such as hydrochloric acid or an aqueous solution such as a phosphate buffer is added to the reaction mass to give an optically active substance. It can be easily isolated by decomposing the active amino alcohol borane complex, adding a poorly water-soluble organic solvent to extract a crude product, and then distilling the solvent off from the separated organic phase. . The isolated optically active β-imino alcohol [II] can be further purified, if necessary, by subjecting it to purification means such as recrystallization or various chromatography. Moreover, the optically active amino alcohols [III] used in the reaction should be separated, recovered and reused from the reaction mass after isolation of the optically active β-imino alcohols [II] by the above-mentioned method. You can The optically active β-iminoalcohols [II] obtained in the present invention are the α used as a starting material.
-Corresponding to imino ketones [I], representative compounds include, for example, 2-hydroxyimino-1,2-diphenylethanol, 2-hydroxyimino-1,2-bis (methylphenyl) ethanol, 2- Hydroxyimino-1,2-
Bis (dimethylphenyl) ethanol, 2-hydroxyimino-1,2-bis (methoxyphenyl) ethanol, 2-hydroxyimino-1,2-dimesitylethanol, 2-hydroxyimino-1,2-bis (chlorophenyl) Methyl oxime ether such as ethanol, ethyl oxime ether,
Propyl oxime ether, butyl oxime ether,
Phenyl oxime ether, tolyl oxime ether,
Methoxyphenyl oxime ether, benzyl oxime ether, mesityl oxime ether, mesityl methyl oxime ether, chlorophenyl oxime ether,
Examples of the optically active substance include bromophenyl oxime ether, acetyl oxime ether, benzoyl oxime ether, trimethylsilyl oxime ether, and triethylsilyl oxime ether.

Next, the optically active β-imino alcohol [II] is reduced to give the compound of the formula [IV] (In the formula, R ¹ , R ² , R ³ and * have the same meanings as described above.) A method for producing the optically active β-amino alcohol [IV] will be described. Such reduction reaction can be carried out by both a catalytic reduction method and a method using a reducing agent, but depending on which method is carried out, the configuration of the optically active β-amino alcohols [IV] is arbitrarily set. Can be made differently. For example, when the target optically active β-aminoalcohol [IV] is an erythro isomer, a catalytic reduction method is used, and when it is a threo isomer, a reducing agent is used. In the catalytic reduction method, for example, a catalyst such as palladium carbon or Raney nickel is used, and the amount thereof is about 0.01 to 1 mol, preferably 0.01 to 1 mol, based on the optically active β-imino alcohol [II]. 0.5 mol, usually -2
It is carried out at a temperature of 0 to 80 ° C, preferably -5 to 60 ° C. Palladium on carbon is preferably used. In the method using a reducing agent, for example, a reducing agent such as lithium aluminum hydride or sodium aluminum hydride is used in an amount of about 0.1 to 10 mol, preferably 1 to 10 mol, based on the optically active β-imino alcohol [II].
It is used in an amount of about 8 mol and is usually -10 to 100 ° C, preferably
It is carried out at a temperature of -5 to 80 ° C. Lithium aluminum hydride is preferably used. A solvent may be used in these reduction reactions, and examples of such a solvent include those shown in the step of obtaining the optically active aminoalcohol borane complex and alcohols such as ethanol. In addition, the reaction is usually carried out under an atmosphere of an inert gas such as argon or nitrogen or an atmosphere of generated hydrogen under atmospheric pressure to 10
It is carried out under a pressure of kgf / cm ² .

Thus, the optically active β-amino alcohol [IV] is produced.
After decomposing the catalyst with a phosphate buffer or the like as necessary, the catalyst-derived components are removed by a method such as filtration, and a crude product is further extracted by adding a poorly water-soluble organic solvent as necessary, After that, the solvent used in the extraction or the reaction is distilled off to easily isolate it. The isolated optically active β-amino alcohol [IV] can be further purified by subjecting it to a purification means such as recrystallization or various chromatography.
The optically active β-amino alcohols [IV] obtained in the present invention are the β-imino alcohols [II] used.
And a representative compound is, for example,
2-amino-1,2-diphenylethanol, 2-amino-1,2-
Bis (methylphenyl) ethanol, 2-amino-1,2-bis (dimethylphenyl) ethanol, 2-amino-1,2-bis (methoxyphenyl) ethanol, 2-amino-1,2-dimesityl ethanol, An optically active substance such as 2-amino-1,2-bis (chlorophenyl) ethanol can be mentioned.

[0018]

INDUSTRIAL APPLICABILITY According to the present invention, an optically active aminoalcohol borane complex obtained from a specific optically active aminoalcohol having a substituted silyloxy group at the 3-position and borane, and a borane derivative, corresponding α-iminoketones Of a syn-form, an anti-form, or a mixture in which one of these is excessive, is asymmetrically reduced to obtain an intermediate β-iminoalcohol, and then the imino group is reduced to obtain high optical purity. Optically active β-amino alcohols can be produced without complicated operations, and depending on whether the reduction method of the imino group is catalytic reduction or a method using a reducing agent, optically active β-amino alcohols can be produced. The configuration of alcohols can be arbitrarily created.

[0019]

The present invention will be described in more detail with reference to the following examples, but it goes without saying that the present invention is not limited to these examples.

Example 1 (2S, 3R) -2-in a 30 ml flask at room temperature under an argon atmosphere.
Amino-3- (t-butyldimethylsiloxy) -1,1-diphenylbutanol 476.7 mg (1.5 mmol) in 1,2-dimethoxyethane solution (2 ml) was added, and then tetrahydrofuran borane complex was added.
3 ml of a 3 mmol tetrahydrofuran solution was added and stirred for 2 hours to prepare an optically active aminoalcohol borane complex. Place the mixture in a 100 ml flask at room temperature under an argon atmosphere with syn.
2-benzyloxyimino with body 1% or less and anti body 99% or more
1,2-diphenylethanone 410 mg (1.3 mmol) in 1,2-dimethoxyethane 7 ml and triethylamine 131.3 mg (1.3 m
(mol) was added, and the optically active aminoalcohol borane complex prepared above was added dropwise over 50 minutes. Next, 1.4 ml of a tetrahydrofuran solution containing 1.4 mmol of tetrahydrofuran borane complex was added in two portions, and the mixture was stirred for 1 hour, and then 10 ml of a phosphate buffer was added. Then extract with 50 ml of ethyl acetate,
Separated. The obtained extract layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give an oily substance. Flash chromatography (elution solvent hexane / ethyl acetate =
After purification by 10/1), 242.2 mg of (S) -2-benzyloxyimino-1,2-diphenylethanol was obtained (yield
59%). [Α] ²³ _D −30 ° (c 0.64, CHCl ₃ ) ¹ H-NMR (270MHz, CDCl ₃ ) δ 3.66 (d, J = 7.91Hz, 1H), 5.17 (d, J = 12.2Hz, 1H), 5.22
(d, J = 12.2Hz, 1H), 6.16 (d, J = 7.91Hz, 1H), 7.22-7.39 (m, 1
3H), 7.51-7.55 (m, 2H) Moreover, the optical purity was 86% ee or higher as determined by high performance liquid chromatography using an optically active column.

Example 2 To a 30 ml flask, 14.4 mg of 5% palladium carbon was added at room temperature under an argon atmosphere, and then 41.7 mg of (S) -2-benzyloxyimino-1,2-diphenylethanol having an optical purity of 90% ee.
After adding 3 ml of the above ethanol solution to the mixture, stir at room temperature in a hydrogen atmosphere at atmospheric pressure for 21 hours, then raise the temperature to 40 ° C and keep at the same temperature.
Stirred for hours. This was filtered through Celite, the obtained filtrate was concentrated under reduced pressure, and then silica gel thin layer chromatography (eluting solvent: methanol / ethyl acetate = 1/20).
22.5 mg of optically active 2-amino-1,2-diphenylethanol was obtained by purification with (yield 81%). ¹ H-NMR (270MHz, CDCl ₃ ) δ 2.40 (brs, 1H), 3.98 (d, J = 6.52Hz, 0.47H), 4.15 (d, J =
6.27Hz, 0.53H), 4.64 (d, J = 6.52Hz, 0.47H), 4.74 (d, J = 6.2
7Hz, 0.53H), 7.14-7.29 (m, 10H) ¹ H-NMR shows diastereomeric ratio threo body / erythr
o Body = 6/94 was found. After this was converted to MTPA, it was analyzed by high performance liquid chromatography,
The optical purities were threo isomer 60% ee and erythro isomer 90% ee.

Example 3 Lithium aluminum hydride 3 was added to a 30 ml flask.
A mixed solution of 8.1 mg (1 mmol) and 1,2-dimethoxyethane (1 ml) was added, and an optical purity of 90% ee was added here under an argon atmosphere at 0 ° C.
2 ml of a 1,2-dimethoxyethane solution containing 49.8 mg of (S) -2-benzyloxyimino-1,2-diphenylethanol was added dropwise over 30 minutes. This was heated to room temperature, stirred at the same temperature for 3 hours, further heated to 70 ° C. and stirred at the same temperature for 1 hour. Then, 2 ml of phosphate buffer was added and the mixture was filtered through Celite, and the obtained filtrate was adjusted to pH 10-11 with 1N aqueous sodium hydroxide solution. Add this to chloroform 25
The mixture was extracted with ml and separated, and the obtained extracted layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give an oily substance. When purified according to Example 2, the optically active 2-amino-1,2-
20.2 mg of diphenylethanol was obtained (59% yield). The diastereomer ratio was threo isomer / erythro isomer = 92/8, and the optical purities were threo isomer 96% ee and erythro isomer 90% ee.

Example 4 1.4 ml of a tetrahydrofuran solution containing 1.4 mmol of a tetrahydrofuran borane complex added in two portions without adding triethylamine in Example 1 was added to 291 m of catechol borane.
The procedure of Example 1 was repeated except that g (6.6 mmol) was replaced with 270.9 mg of (S) -2-benzyloxyimino-1,2-diphenylethanol (yield 66%). Optical purity is 90
% ee.

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Claims (6)

[Claims] 1. The formula [II] (In the formula, R ¹ , R ² and R ³ are each independently a hydrogen atom,
Represents a lower alkyl group, a lower alkoxy group or a halogen atom, R ⁴ represents a lower alkyl group, an acyl group, a trialkylsilyl group, an aryl group optionally substituted with a lower alkyl or a lower alkoxy, or a lower alkyl or a lower alkoxy. Represents an aralkyl group which may be substituted with, and * represents an asymmetric carbon. ) Optically active β
-Imino alcohols. 2. A formula [I] (Wherein R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above), a syn-form or anti-form of α-imino ketones, or a mixture containing one of these in excess is [II
I] (In the formula, R ⁵ , R ⁶ and R ⁷ are each independently a hydrogen atom,
It represents a lower alkyl group, a phenyl group optionally substituted with lower alkyl or a benzyl group optionally substituted with lower alkyl, but not all hydrogen atoms at the same time. R ⁸ and R ⁹ each independently represent a hydrogen atom, a lower alkyl group or a lower alkoxy group, and * represents an asymmetric carbon. ) Asymmetric reduction with an optically active aminoalcohol borane complex obtained from an optically active aminoalcohol and a borane, and the production of an optically active β-iminoalcohol according to claim 1. Method. 3. The method for producing an optically active β-imino alcohol according to claim 2, wherein the borane derivative is a trialkylamine borane complex or a catechol borane complex. 4. The formula [IV], which is characterized by reducing the optically active β-imino alcohol according to claim 1. (In the formula, R ¹ , R ² , R ³ and * have the same meanings as described above.) A method for producing an optically active β-amino alcohol. 5. The method for producing an erythro form of an optically active β-amino alcohol according to claim 4, wherein the reduction is carried out by a catalytic reduction method. 6. The method for producing a threo body of an optically active β-aminoalcohol according to claim 4, which comprises reducing with a reducing agent.