JPH062707B2 - Process for producing optically active 4-hydroxy-2-cyclopentenones - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing optically active 4-hydroxy-2-cyclopentenones. More specifically, the present invention isomerizes the epoxy compound by contacting 3,4-epoxycyclopentanone with a complex of optically active 1,1'-bi-2-naphthol to give 4-hydroxy-2-cyclopentane. This is a standard method for producing a compound in which tenon is obtained, and at the same time, R- or S-coordinated optical activity is induced in the 4-position asymmetric carbon, and the obtained optically active 4-hydroxy-2-cyclopentenone is required next. And a method for producing an optically active 4-hydroxy-2-cyclopentenone by protecting a hydroxyl group.

According to such a production method, an optically active 4-hydroxy-2-cyclopentynone, which is an intermediate for various production of pharmaceuticals such as brostaglandin having various pharmacological actions or maytansine having anticancer action, can be prepared at a high concentration. It can be efficiently obtained in a yield, and such a production method is a stereochemically extremely significant production method.

<Prior Art> Conventionally, (R) -4-hydroxy-2-cyclopentenone,
As a method for producing an optically active 4-hydroxy-2-cyclopentenone such as (S) -4-hydroxy-2-cyclopentenone, for example, the following production method is known.

That is, (1) diacetoxycyclopent-1-ene obtained from cyclopentadiene is hydrolyzed with an enzyme to give 3
(R) -acetoxy-5 (R) -hydroxycyclopent-1
Obtaining ene, which is then oxidized with manganese dioxide,
Method for producing 4 (R) -acetoxycyclopent-2-en-1-one (tetrahedron, 32 , 1713-1)
718 (1977), tetrahedron, 32 , 1893.
(See (1977)), (2) D or L-tartaric acid is used as a starting compound, and D or L-1,4-diiodo-2,3-
Isobropyridenedioxybutane was prepared, and this was reacted with a lithio compound and then hydrolyzed to give (R) or (S) -4.
-Hydroxy-2-cyclopentenone (Tetrahedron Letters, 10 , 759-762)
(See (1976)), (3) A method of producing 4 (R) -acetoxy-2-cyclopentenone from a compound called terein, which is a metabolite of a microorganism, as a starting material through 5 steps (tetohedron letters, ( 29) , 2553 to 2556 (1978)), (4) 2,4,6-trichlorophenol was reacted with chlorine to give 3,5,5-trichloro-1,4-dihydroxycyclopent-2-ene. -1-carboxylic acid was obtained, which was subjected to optical resolution with brucine, and then subjected to 4 steps to obtain (R) -4
Method for producing -t-butyldimethylsiloxycyclopent-2-enone (Tetrahedron Letters, 1539
-42 (1979) (17)), (5) 1-cyclopentene-3.5-dione is asymmetrically reduced with a compound obtained from a chiral binaphthol compound, an alcohol and lithium aluminum hydride to give (R) or (S )
Of 4-hydroxy-2-cyclopentenone, and protecting the hydroxyl group as necessary (see Noyori et al., JP 56-123932; Pure Appl chem, 53 (1981)), (6 ) d / -4-Hydroxy-2-cyclopentenone is combined with an optical resolving agent, the product is separated as two diastereomers, and the resolving agent is deprotected by a reaction to obtain an optically active substance. Method for protecting and protecting as necessary (Hari et al., JP-A-57-159777 and Noyori et al., Tetrahedron
Litt, 23, 4057 (1982)), (7) d / -4-hydroxy-2-cyclopentenone was used as a half ester of ortho-phthalic acid, and this was converted to a salt with an optically active amine and recrystallized. One of the isomers is separated, deprotected to obtain an optically active substance, and the hydroxyl group is protected as necessary to produce (see Watanabe et al., JP-A-57-14560).

Among these methods, the methods of (1) and (2) can be obtained.
The optical yields of -hydroxy-2-cyclopentenones are not sufficiently satisfactory, and the total yields thereof are low, and the optical yields of the methods (3) and (4) are However, the compound (terein), which is difficult to obtain by the method (3), is used as a starting material, and the method (4) involves optical resolution in the production process. The total yields of both methods (3) and (4) are not fully satisfactory. Method (5) is a raw material 1
The disadvantage is that cyclopentene-3,5-dione is used as a starting material, which is expensive and relatively difficult to obtain. Furthermore, in the method of optical resolution of (6) and (7), 50% is theoretically usable as one of the optically active substances.
Therefore, the total yield is not sufficient.

<Object of the Invention> As described above, the conventional methods for producing optically active 4-hydroxy-2-cyclopentenones are not necessarily industrially excellent.

Therefore, the present inventors have found an industrially advantageous method for producing 4-hydroxy-2-cyclopentenones, which uses a compound that is easily available and has a high optical yield and a high total yield. I studied as much as possible. Known from the past
The finding that 3,4-epoxycyclopentanone isomerizes to dl-4-hydroxy-2-cyclopetenone by the action of activated alumina (Noyori et al., J. Amer. Chm. Soc, 10
1,1623 (1979); see Japanese Patent Laid-Open No. 54-154735).
-By contacting an asymmetrically modified aluminum complex or other metal complex with epoxycyclopentanone as a raw material, 4-hydroxy-2-cyclopentenones having high optical yield and industrially advantageous optically active That is, the present invention has been achieved and the present invention has been achieved.

<Structure and Operation and Effect of Invention> That is, the present invention has the following formula [I]. Which is characterized in that 3,4-epoxycyclopentanone represented by the formula (1) is brought into contact with an optically active 1,1′-bi-2-naphthol complex, and then the hydroxyl group is protected if necessary [II] (In the formula, * represents an asymmetric carbon atom in which optical activity is induced, and R represents a hydrogen atom or a protective group.) A process for producing an optically active 4-hydroxy-2-cyclopentenone Is.

In the production method of the present invention, 3,4-epoxycyclopentanone represented by the above formula [I] is used as a starting material. Such a compound can be easily obtained from cyclopentadiene by a conventionally known method (Noyori et al., JP-A-54-54).
154734, Noyori et al. Tetrahedron Lett, 22 , 441
3 (1981)).

Such 3,4-epoxycyclopentanone is converted into an optically active
Treatment with a complex of 1'-bi-2-naphthol gives the optically active 4-hydroxy-2-cyclopentene. Optically active 1,1'-bi-2 used here
-Naphthol is Bull.Soc.Chim.Fr. 43, 1388.
(±) -obtained by the method described in (1928).
By optically resolving binaphthylphosphate with cinchonine and treating it with lithium aluminum hydride (S)
-(-)-1,1'-bi-2-naphthol or (R)-(+)-
It can be obtained as 1,1'-bi-2-naphthol.
The complex of this used in the present invention is prepared as follows.

That is, trialkylaluminum which is a ligand represented by the following formula [III] ▲ R ¹ ₃ ▼ Al ... (III) (R ¹ represents an alkyl group having 1 to 4 carbon atoms) and alcohols, phenols or It is adjusted by a combination of an auxiliary ligand of sulfonic acid and optically active 1,1′-bi-2-naphthol, or is represented by the following formula [IV] R ² -Metal-R ³ (IV) (R ² represents an alkyl group having 1 to 4 carbon atoms, R ³ is R ²
Represents the same or a halogen atom, and Metal represents a magnesium atom or a zinc atom. ) Organometallic compound which is a ligand represented by
Prepared by combination with 1'-bi-2-naphthol.

In the above formula [III], R ¹ is an alkyl group having 1 to 4 carbon atoms, for example, methyl, ethyl, propyl, n-butyl, iSo-butyl group, and a methyl group is particularly preferable.

Alcohols, phenols, or sulfonic acids having an oxygen atom with a strong affinity for an aluminum atom used as a monodentate auxiliary ligand are used. Examples of the alcohols include lower alcohols having 1 to 10 carbon atoms such as methanol, ethanol, isopropanol, n-decyl alcohol and the like, and methanol is particularly preferable. Examples of the phenols include alkyl-substituted phenols having 1 to 10 carbon atoms, such as 2,6-di-butyl-4-methylphenol,
2,6-di-isopropylphenol and the like, and other substituted phenols such as 4-methoxyphenol, 0
-Chlorophenol, 2-nitrophenol, 4-nitrophenol, 2,4-dinitrophenol, 2,6-dinitrophenol, 2,6-di-t-ethyl-4-nitrophenol, etc., especially 4-nitro A phenol is preferably used in terms of optical yield. 4- as sulfonic acids
Examples include methylbenzene sulfonic acid and 2,4,6-trimethylbenzene sulfonic acid.

In the above formula (IV), R ² is an alkyl group having 1 to 4 carbon atoms, for example, methyl, ethyl, propyl, n-butyl, i
There is a So-butyl group, and methyl and ethyl groups are particularly preferable. R ³ is the same as R ² or represents a halogen atom,
A bromine atom is preferably used as the halogen atom.

To prepare the complex, the ligand was added to the solution of the above formula [III] as a monodentate ligand (denoted as R ⁴ H), and then optically active 1,1′-bi-2-naphthol (denoted as ^* BN (OH) ₂ ). Liquid by adding and stirring under an inert gas atmosphere such as nitrogen or argon (method A) and <method A> Optically active 1,1'-bi-2-naphthol solution and then monodentate ligand are added to the solution of the above formula [III] (method B).
It can be created by either method.

<Method B> There is also a method for preparing a complex that does not use a monodentate ligand. That is, it is achieved by using the ligand of the above formula (IV). As a method, (i) dialkylmagnesium or dialkylzinc (IV) solution is added to optically active 1,1′-bi-2-
Method of adding naphthol, (ii) optically active 1,1'-bi-2
-After lithiation of one hydroxyl group of naphthol with, for example, n-butyllithium, n-propyllithium, n-methyllithium, etc. Optically active 1,1'-bi-2-naphthol solution and then monodentate ligand are added to the solution of the above formula [III] (method B).
It can be created by either method.

<Method B> There is also a method for preparing a complex that does not use a monodentate ligand. That is, it is achieved by using the ligand of the above formula (IV). As a method, (i) dialkylmagnesium or dialkylzinc (IV) solution is added to optically active 1,1′-bi-2-
Method of adding naphthol, (ii) optically active 1,1'-bi-2
Any one of the methods in which one hydroxyl group of naphthol is lithiated with, for example, n-butyllithium, n-propyllithium, n-methyllithium, etc., and then alkyl-metal-halogen (IV), which is a gene, is added to this Will be achieved.

An inert medium is used for the preparation and reaction of the complex. For example, halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane, dibromomethane, etc., or aromatic hydrocarbons such as benzene, toluene, xylene, etc., or ethers such as diethyl ether,
Tetrahydrofuran, dioxane and the like, nitonyl compounds such as acetonitrile and propionitrile and the like are used, and among them, halogenated hydrocarbons are preferably used, and dichloromethane and chloroform are particularly preferably used.
The amount of the solvent used may be an amount sufficient to allow the reaction to proceed smoothly, and is in the range of 100 ml to 10, preferably 0.5 to 2 per mol of the complex. Since the type and amount of the medium used have a great influence on the optical purity of the reaction product, an appropriate combination and selection may be made.

With respect to the equivalent relationship of the ligands, the optically active 1,1'-bi-2-naphthol is 0.1 to 5.0 equivalents, preferably 0.5 to 3.0 equivalents, and particularly preferably 1.5 to 19 relative to the trialkylaluminum of the above formula [III]. It is better to use the equivalent amount. Further, it is optically active with respect to the alkyl organometallic compound of the above formula [IV].
0.2-0.5 equivalents of 1,1'-bi-2-naphthol, preferably
Use 0.8 to 1.5 equivalents. For the monodentate ligand, optically active 1,1'-bi-2-naphthol is used in an amount of 0.1 to 3.0 equivalents, preferably 0.8 to 1.5 equivalents.

Thus, since the complex is prepared by the above-mentioned method, the aging time after preparation is 0.5 to 100 hours, preferably 1 to 75 hours. The amount of the complex used is 1 to 50 mol%, preferably 5 to 20% based on the raw materials.
Mol% is used.

Thus, the complex and the raw material are subjected to an isomerization reaction while inducing optical activity using the same medium as that used for preparing the complex. The reaction usually proceeds at 0 ° C to 70 ° C, preferably 10 to 40 ° C. The progress of the reaction can be traced by means such as thin layer chromatography. The reaction time is set according to the purpose. That is, the stereochemistry may be reversed in the early and late stages of the reaction.

Since the product is very soluble in water, phosphate buffer (pH
7.4) is added and the mixture is extracted with an organic solvent. The aqueous layer portion is again concentrated under reduced pressure and then extracted with an organic solvent to further obtain a product. Ethyl acetate or methyl isobutyl ketone is preferably used as the extraction solvent.

Thus, crude optically active 4-hydroxy-2-cyclopentenone in which R is a hydrogen atom in the above formula [II] is obtained, which is purified by a conventional means such as distillation column chromatography.

This product may further protect its hydroxyl group, if necessary.

To protect the hydroxyl group of such a compound, a known reaction can be adopted.

That is, when the protecting group is an acyl group such as an acetyl group, a propanoyl group, a chloroacetyl group, a benzoyl group, a p-bromobenzoyl group, a p-nitrobenzoyl group or the like, an acid halide or an acid anhydride and pyridine are combined. A protective group can be easily introduced by reacting. In addition, the protecting group is trimethylsilyl group, dimethyl-
In the case of a trialkylsilyl group such as t-butylsilyl group, a protecting group can be introduced by reacting a trialkylsilyl halide with imidazole and hexamethylphosphoric triamide. When the protecting group is a 2-tetrahydropyranyl group; a 2-tetradodofuranyl group, an α-ethoxyethyl group, an α-ethoxy-α-methylethyl group or the like, the corresponding vinyl ether compound is dihydropyran or dihydrofuran. A protective group can be introduced by bringing ethyl vinyl ether and ethyl isopropenyl ether into contact with each other in the presence of an acidic catalyst such as paratoluenesulfonic acid.

Thus, 4-hydroxy-2-cyclopentenones of the above formula [II] in which the optical activity is induced are produced.

Further, the product having a protected hydroxyl group may be treated by means such as recrystallization in order to further improve its optical purity.
In particular, when R is a butyldimethylsilyl group, it can be recrystallized at low temperature using hydrocarbons such as pentane and hexane to improve the optical purity.

As described above, optically active 4-hydroxy-2-cyclopentenones, which can be intermediates for the synthesis of various prostaglandins, have higher optical yields than readily available 3,4-epoxycyclopentanone. It can be manufactured efficiently at a high rate.

The feature of the method of the present invention is that relatively high optical activity can be easily induced at the same time as isomerization under mild conditions, and the number of steps is extremely short as compared with the conventional method to obtain an objective optically active substance. It can be said that it is a new and advantageous method.

Hereinafter, the present invention will be described in more detail with reference to Examples.

Examples 1 to 4 Reaction with Aluminum Complex Method A An ampoule heated and dried under reduced pressure was replaced with argon, dry degassed methylene chloride was added, and a hexane solution of trimethylaluminum (0.95M, 0.10 ml, 0.095 mmol) was added. While stirring, p -nitrophenol (13.3mg, 0.096mmo
A solution of l) in methylene chloride was added. Then, a methylene chloride solution of (s) -binaphthol (27.2 mg, 0.095 mmol) was added, and the mixture was stirred for 2 hours at room temperature (20-25 ° C). A solution of 3,4-epoxycyclopentanone (95.1 mg, 0.97 mmol) in methylene chloride was added to carry out the reaction. Liquid volume is 10-1
It became 2 ml.

Method B The ampoule heated and dried under reduced pressure was replaced with argon, dry degassed methylene chloride was added, and a hexane solution of trimethylaluminum (0.95M, 0.10 ml 0.095 mmol) was added. With stirring, a solution of (s) -binaphthol (27.2 mg, 0.095 mmol) in methylene chloride, and then p -nitrophenol (13.2 mg, 0.
A methylene chloride solution (095 mmol) was added and the mixture was stirred at room temperature (20
It stirred at -25 degreeC).

3,4-epoxycyclopentanone (95.1mg, 0.97mmol)
Methylene chloride solution was added to carry out the reaction. The total liquid volume was 10-12 m.

Post-treatment and purification method for isomerization reaction 1. Add phosphate buffer (pH 7.4) and hexane to the reaction mixture, transfer to a separating funnel, and shake well. The aqueous layer (containing hydroxycyclopentenone) was separated.

The organic layer was extracted again by adding phosphate buffer. (Do this operation twice). Binaphthol and phenol were extracted in the organic layer, and epoxy compounds and hydroxyenone were extracted in the aqueous layer.

The aqueous layer was carefully concentrated using a vacuum pump to near dryness. Ethyl acetate was added to this solution, and the solution was placed in an ultrasonic bath for extraction. The organic layer was separated and extracted again. The organic layer was concentrated and Kugelrohr distillation (3 mmHg, 108-112
C.) to give 4-hydroxy-2-cyclopentenone.

2. Add a small amount of phosphoric acid buffer solution to the reaction solution, add methyl i- butyl ketone (MIBK), transfer to a separating funnel, and shake well.
The aqueous layer was separated, methyl isobutyl ketone was added, and extraction was performed again. The organic layers were collected and concentrated with an evaporator (with an oilless vacuum pump). Concentrated liquid is Microbeads 5D
Column chromatography was carried out with 10 g of (100-200 mesh, Fuji Devison Co., Ltd.) using hexane-ethyl acetate (6: 1) to separate binaphthol, phenol, epoxy compound, and hydroxyenone.

3. A few drops of phosphate buffer was added to the reaction solution, and it was placed in an ultrasonic bath. I used qualitative filter paper (Toyo filter paper No. 2).

The precipitate was washed with an additional 20 m of methylene chloride.

Collect the washing solution and pass it through a Silipoa filter (Toyo Membrane Filter, 0.45 μm TYPE RC), and use 10 g of concentrated Microbease 5D (Fuji Davison) to perform column chromatography with 6: 1 hexane-ethyl acetate. I went.

Spectral data of 4-hydroxy-2-cyclopentenone ′ HNMR (CDCl ₃ ) δ, 2.26 (1H, dd, J = 18,2Hz), 2.78 (1H, dd, J
＝ 18,6Hz), 3.10 (1H br), 5.05 (1H, m), 6.22 (1H, dd, J ＝ 6,1
Hz), 7.57 (1H, dd, J = 6,2Hz). Determination of asymmetric yield The optical purity of 4-hydroxy-2-cyclopentenone is
The MTRA ester was derived and the 1 H NMR was measured.

MTPA esterified 4-hydroxy-2-cyclopentenone (10 mg, 0.1 mmo
l) was dissolved in 0.2 ml of methyl chloride, and pyridine (4A, dried from Molecular Sieve) was used for 25 μ (0.3 mmol, 3e 9 ) MTPAC ₁ ((+)-MTP) using a microsyringe.
50 μ (0.2 mmol, 2e 9 ) was added.
The liquid became cloudy immediately. The mixture was stirred as it was overnight.

Ether and saturated aqueous copper sulfate solution were added for extraction. The organic layer was separated, and an aqueous copper sulfate solution was added again for extraction. The organic layer was separated, dried by adding Na ₂ SO _4, and concentrated spent. Column chromatography was performed using 5 g of silica gel (Merck 7743) with hexane-ethyl acetate (8: 1) to measure'H NMR.

Spectral data of MTPA ester form (s) form'HNMR (CDC ₃ ) δ, 2.39 (1H, dd, J = 18.7,2.4Hz), 2.94 (1H, dd, J = 18.7,
6.2Hz), 3.01 (3H, t, J = 1.3Hz), 5.68 (1H, m), 6.40 (1H, dd, J
= 5.7Hz), 7.45-7.65 (6H, m) (R) body'HNMR (CDC ₃ ) δ, 2.29 (1H, dd, J = 18.7,2.4Hz), 2.87 (1H, dd, J = 18.7,
6.2Hz), 3.01 (3H, t, J = 1.3Hz), 5.68 (1H, m), 6.40 (1H, dd, J
= 5.7Hz), 7.45-7.65 (6H, m). Examination of the effect by the preparation method of the complex (method A and method B) Table 1
Got the result.

Example 5 Argon containing a Stirling bar was heated and dried under reduced pressure, and the atmosphere was replaced with argon. Degassed chloroform (3 ml) was added to this, and a trimethylaluminum hexane solution (0.10 ml, 0.095 mmol) was added by a syringe. While stirling, p -nitrophenol (13.2mg, 0.095mm
ol) in chloroform (4 ml) was added under argon pressure using a stainless steel tube. The liquid immediately became a yellow suspension. Then (s) -binaphthol (46.1 mg, 1.61 mm
ol) in chloroform (4 ml) was added in the same manner, and the mixture was stirred at room temperature for 2 hours.

Add 3,4-epoxycyclopentanone (91.5 mg, 0.95
mmol) in chloroform was added. The liquid becomes an almost transparent solution. The stirring was continued at room temperature for 55 hours as it was. The reaction solution became a yellow and colored suspension.

Add a few drops of pH 7.4 phosphate buffer and infiltrate with ultrasound. This was filtered using a quantitative filter paper (Toyo filter paper, 5c).
It was rinsed in with about 20 ml of methylene chloride.
The liquid and the washing liquid were concentrated. OD _S resin (Fuji Devuison, microbeads 5D, 100-200 mesh screen) using a 10 g, hexane - ethyl acetate 8: KoTsuta column chromatography 1 as a developing solvent.

An epoxy compound (yield 23%) and an alcohol compound (40%) were separately collected. A portion of the alcohol was esterified with (R) -α-methoxy-α-trifluoromethyl-phenylacetic acid chloride (2 eq) pyridine (1.5 eq). Ether and saturated copper sulfate ice solution were added to the reaction solution for extraction. The organic layer was concentrated, and column chromatography was performed using 2 g of silica gel with a developing solvent of hexane-ethyl acetate 8: 1. Sample was collected MTPA ester, concentrated, 'HNMR in 70% ee was measured, the (s) integrally 4
It was found that -hydroxy-2-cyclopentenone was obtained.

Examples 6 to 11 The optically active 1,1'-bi-2-naphthol / trialkylaluminum ratio was examined and the results shown in Table 2 were obtained. Here, 4-nitrophenol was used as the monodentate ligand.

The results of using 2,6-dimethyl-4-nitrophenol and 2,6-di-t-butyl-4-nitrophenol as monodentate ligands are shown in Table 3.

Examples 12 to 25 The effects of the types of monodentate ligands were examined and shown in Tables 4, 5, 6
It was shown to.

Examples 26 to 33 The types of media in the case of using 2,6-di-t-butyl-4-methylphenol and 4-nitrophenol as monodentate ligands were examined, and the results shown in Tables 7 and 8 are shown. Got

Examples 34 to 36 When 4-nitrophenol was used as the monodentate ligand, the amount of the medium with respect to the complex was examined, and the results shown in Table 9 were obtained.

Examples 37-43 Results of studying aging times 1 and 2 and amounts used in complex preparations carried out with the monodentate ligand 4-nitrophenol. The results shown in Tables 10 and 11 below were obtained.

Example 44 Isomerization Reaction Using Magnesium Complex A reaction tube heated and dried under reduced pressure was replaced with argon, and methylene chloride (4 ml) that had been frozen and degassed was added to Et ² Mg (0.625 M, 0.08 m).
l, 0.050 mmol) was added (s) -binaphthol (14.2 mg, 0.0
A solution of 50 mmol) in methylene chloride (4 ml) was added. 3,4-
A methylene chloride solution of epoxycyclopentanone (48.3 mg, 0.50 mmol) was added, and the mixture was stirred at 0 ° for 72 hours.

Work-up was carried out according to Example 1 and the hydroxyenone (2
4.5 mg, 0.25 mmol) yield 51% was obtained. Optical purity is 36
MTPA was esterified by the method described on the page and'HMNR was measured, and it was determined to be 10% ee. The results are summarized in Table 12.

Examples 45 and 46 Dry degassed T.I. HF (2 ml)
Then, (s) -binaphthol (15.3 mg, 0.053 mmol) was added and the mixture was cooled to −78 ° C. under an argon atmosphere, and n- Buli (1.6
M, 0.035 ml, 0.056 mmol) was added and the temperature was raised to room temperature. It was cooled again to -78 ° C and CH ₂ MgBr (3.36M, 0.015ml, 0.05
(0 mmol) was added and the temperature was raised to room temperature. In 1 ml of THF
3,4-epoxycyclopentanone (53.0mg, 0.054mmol)
Was added and the mixture was stirred at 0 ° for 1 hour. The post-treatment, purification, and determination of the optical yield of the reaction were performed in the same manner as the previous page. The results are summarized in Table 12.

Example 47B The same operation as in Example B was carried out using benzene instead of THF. The results are summarized in Table 12.

Examples 48, 49 Isomerization Reaction Using Zinc Medium An ampoule heated and dried under reduced pressure was replaced with argon, and (s) −
A toluene solution of binaphthol (28.0 mg, 0.098 mmol) was added, diethyl zinc (1.96 M, 0.05 ml, 0.098 mmol) was added, and the mixture was stirred at room temperature. 3,4-Epoxycyclopentanone (97.5 mg, 0.99 mmol) was added and stirred at 0 °. Work-up of the reaction was carried out according to the method of the Examples. The results are summarized in Table 12.

Optically active 1,1 'using magnesium- and zinc-based ligands
-Bi-2-naphthol It carried out using the complex of. The results are shown in Table 12.

Examples 50 to 55 Purification by recrystallization It was protected with a dimethyl- t -butylsilyl group prepared to 70% ee. Enone (772 mg) was cooled to -45 ° C under an atmosphere of argon dissolved in 40 ml of pentane.

An optically active enone protected with a dimethyl-t-butylsilyl group was inoculated and recrystallized. After sufficient crystals were formed, the mother liquor was removed using a stainless steel tube under argon pressure.
The crystals were washed with pentane (3 ml) cooled to -45 ° C, and the washing liquid was removed using a stainless tube again. The crystals were dried by sucking with a vacuum pump the day before yesterday. Yield 16
It was in%. From this, 9.21 mg was weighed and diluted with 2 ml of methanol, and the optical rotation was measured. ▲ ［α］ ²⁸ _D ▼ ＋ 6
1.9 ° ( c 0.4605, methanol) Optical rotation of optically active silyl-protected enone ▲ [α] ²⁸ _D ▼ + 67.4 ° ( c 0.4, methanol) Calculated from the obtained crystal was 92% ee.
(Example 54) The results of examination under other conditions are summarized in Table 13.

Claims (8)

[Claims] 1. The following formula [I]: The following formula [II] is characterized in that 3,4-epoxycyclopentanone represented by the formula (1) is brought into contact with an optically active 1,1′-bi-2-naphthol complex, and then the hydroxyl group is protected if necessary. [In the formula, * represents an asymmetric carbon atom in which optical activity was induced, and R represents a hydrogen atom or a protecting group. ] The manufacturing method of optically active 4-hydroxy-2- cyclopentenone represented by these. 2. A complex is represented by the following formula _{^{[III] ▲ R 1 3 ▼}} Al ... [III] [R 1 represents an alkyl group having 1 to 4 carbon atoms. ] A combination of a trialkylaluminum, which is a ligand represented by the following formula, an auxiliary ligand of alcohols, phenols or sulfonic acids, and optically active 1,1'-bi-2-naphthol. A method for producing the optically active 4-hydroxy-2-cyclopentenones according to the item 1. 3. A complex represented by the following formula [IV] R ² -Metal-R ³ ... [IV] [R ² represents an alkyl group having 1 to 4 carbon atoms, and R ³ represents R ²
Represents the same or a halogen atom, and Metal represents a magnesium atom or a zinc atom. ] An organometallic compound which is a ligand represented by
The method for producing an optically active 4-hydroxy-2-cyclopentenone according to claim 1, which is a combination with 1'-bi-2-naphthol. 4. The method for producing an optically active 4-hydroxy-2-cyclopentenone according to claim 2, wherein the trialkylaluminum is trimethylaluminum. 5. The optically active compound according to claim 2, wherein the auxiliary ligand phenols are nitrophenols.
A method for producing hydroxy-2-cyclopentenones. 6. The optically active 4 according to claim 2, wherein the sulfonic acids of the auxiliary ligand are benzenesulfonic acids.
-Method for producing hydroxy-2-cyclopentenones. 7. The optical activity according to claim 1, wherein R in the formula [II] is a t-butyldimethylsilyl group, and the product in which the optical activity is induced is further recrystallized to increase the optical purity. -Method for producing hydroxy-2-cyclopentenones. 8. The method for producing an optically active 4-hydroxy-2-cyclopentenone according to claim 3, wherein R ² in the formula [IV] is a methyl group or an ethyl group.