KR100392710B1 - Method for preparing of chiral compound by asymmetric ring opening reactions of epoxides - Google Patents

Abstract

The present invention relates to a method for preparing a chiral compound using an asymmetric ring opening reaction with a nucleophile of an epoxy compound. Specifically, the asymmetric ring opening reaction of an epoxy compound and a nucleophile is carried out in the presence of a salt represented by the following formula (1) and a chiral salen metal catalyst. The present invention relates to a method for preparing a chiral compound, and thus, an expensive catalyst can be easily recovered after the reaction, and the chiral compound can be economically prepared because the optical selectivity can be maintained and reused.

In Formula 1, R ¹ , R ² , R ³ , R ⁴ , X, Z, n and Y ⁻ are as described in the specification.

Description

Method for preparing chiral compound by asymmetric ring opening reactions of epoxides

The present invention relates to a method for preparing a chiral compound using an asymmetric ring opening reaction with a nucleophile of an epoxy compound, and specifically, asymmetry of an epoxy compound and a nucleophile in the presence of a solvent-based and chiral salen metal catalyst including a salt represented by the following general formula (1): The present invention relates to a method for preparing a chiral compound by performing a ring-opening reaction, and asymmetrical of an epoxy compound that can be easily reused by recovering the chiral salen metal catalyst in a form immobilized in an imidazolysin salt by distillation or organic extraction after the reaction. It relates to a method for producing a chiral compound using a ring-opening reaction.

Formula 1

In Chemical Formula 1,

If X is nitrogen, then Z is -C (R ⁵ )-,

R ¹ and R ² represent C ₁ to C ₁₈ alkyl groups that are independent of each other,

R ³ , R ⁴ and R ⁵ are independent of each other and represent hydrogen or an alkyl group of C _{1 to} C ₁₈ ,

If X is carbon, then Z is -C (R ⁵ ) -C (R ⁶ )-,

R ¹ is an alkyl group of C ₁ ~C _18,

R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independent of each other and represent hydrogen or an alkyl group having _{1 to 18} carbon atoms,

n is an integer of 1 to 3,

Y is an anion capable of forming a salt.

Chiral compounds are rapidly increasing in demand in the pharmaceutical, agrochemical and fragrance industries. In particular, the demand in the pharmaceutical industry has led to the adoption of optically pure chiral products, rather than racemates, in the case of new drug candidates in the US Food and Drug Administration (FDA) 's approval of chiral drugs. If a product sold as a racemic mixture also proves that one enantiomer is effective or has fewer side effects, it is a new drug-licensed policy and if the new drug candidate has an asymmetric center in the molecule. The demand for chirotechnology is exploding due to the policy that separate racemates and individual enantiomers should be tested for physiological activity.

Currently used chiral compound production methods are divided into methods using chiral pools and optical resolution. The chiral pool is a method of preparing chiral compounds such as sugars or natural amino acids which exist in nature using a conventional organic synthesis method as a starting material. However, this method is limited in the kind of chiral compounds, and there is a disadvantage in that the optical polarization, such as sugar of the D-form or amino acids of the L-form.

Another method of optical splitting is a method of splitting using an optical splitting reagent, which has a disadvantage of discarding more than 50% of the racemate if there is no special use of the isomer remaining after the splitting. I can't.

In order to solve this problem, methods of obtaining a desired chiral compound using a chiral catalyst have recently been developed. In particular, the method of using a chiral salen metal catalyst as a chiral catalyst is one of the most successful methods in view of the technical aspects and industrial use of the reaction product, and it is possible to obtain a desired asymmetric ring opening reaction of a racemic or meso epoxy compound using the catalyst. The preparation of chiral compounds has been made possible [EN Jacobsen and MH Wu, Ring Opening of Epoxides and Related Reactions, in Comprehensive Asymmetric Catalysis III, ed. EN Jacobsen, A. Pfaltz and H. Yamamoto, Springer Verlag, Berlin-Heidelberg-New York, 1999 , p. 1309.

In Scheme 1, * means a position having a stereo structure of R or S and showing optical activity.

Asymmetric ring-opening reaction of the epoxy compound of Scheme 1 is a useful reaction that can be prepared by reacting nucleophiles with a chiral salen metal catalyst to produce a chiral compound having various functional groups. The nucleophile used is N ₃ ^-, use and the like ^{_{-, NH 3, H 2 NR}} , HNR 2, H 2 O, ROH, PhOH, RSH, H -, RCH 2.

Various types of chiral salen metal catalysts have been usefully used for this asymmetric ring opening reaction [EN Jacobsen and MH Wu, Ring Opening of Epoxides and Related Reactions, in Comprehensive Asymmetric Catalysis III , ed. EN Jacobsen, A. Pfaltz and H. Yamamoto, Springer Verlag, Berlin-Heidelberg-New York, 1999 , p. 1309; Jacobsen et al., US 5,665,890 (1997); Jacobsen et al., US 5,929,232 (1999); Jacobsen et al., WO 9628402 (1996); Jacobsen et al., WO 0009463 (1999); Jacobsen et al., Science , 1997 , 277 , 936; Jacobsen et al., J. Am. Chem. Soc. , 1996 , 118 , 7420; Jacobsen et al., J. Org. Chem. , 1998 , 63 , 5252].

Chiral salen metal catalysts were synthesized to prepare chiral epoxides through asymmetric epoxidation reactions in addition to the asymmetric ring opening reactions, which can be used for asymmetric ring opening reactions. Heavy Mn metal is mainly used, and Cr or Co metal is mainly used in the asymmetric ring opening reaction. [US 5,637,739 (1997); US 5,663,393 (1997); US 5,420,314 (1995); US 5,599,957 (1997); WO 93/03838 (1993); WO 94/03271 (1994); US 5,352,814 (1994); US 5,639,889 (1997); US 5,916,975 (1999).

The asymmetric ring opening of the epoxy compound using the chiralsalen metal catalyst can be classified into kinetic resolution of racemic epoxides and enantioselective ring opening reaction of meso epoxides. Can be.

Kinetic optical splitting is a method of preparing various chiral compounds by reacting only one enantiomer with a nucleophile in the presence of a chiral catalyst using the different reactivity of each enantiomer to nucleophiles. For example, when water is used as a nucleophile in a racemic epoxy compound, one enantiomer is ring-opened by water to produce chiral diol, a very important intermediate in various fine chemical industries, and the other enantiomer does not react and is an epoxy compound as it is. Will remain [Tokunaga, M .; Larrow, JF; Kakiuchi, F; Jacobsen. E. Science , 1997 , 277 , 936].

Asymmetric ring-opening reaction of meso epoxy compound is a method for producing various chiral compounds by reacting meso epoxy compound with various nucleophiles in the presence of chiral salen metal catalyst [Martiez, LE; Leighton, JL; Carsten, DH; Jacobsen, E. J. Am. Chem. Soc. , 1995 , 117 , 5897]. As an example of the reaction, when reacting a meso epoxy compound with a nucleophile such as azide or water, an enantiomerically enriched beta-azido alcohol or chiral diol can be obtained and these compounds are used in the pharmaceutical and various fine chemical industries. It can be used as a very important intermediate in.

Although the asymmetric ring opening reaction of the racemic epoxy compound and the meso epoxy compound is an excellent method for producing industrially useful chiral materials with a high level of optical purity, the chiral salen metal catalyst used is a multi-step manufacturing process under difficult reaction conditions. Because it is manufactured through and is very expensive, it remains difficult to use industrially. Therefore, researches to recover the chiral salen metal catalyst after the asymmetric ring opening reaction and reuse it have been conducted in various ways. However, according to the research reports so far, it is known that the process for obtaining the desired chiral compound after the asymmetric ring opening reaction and recovering the used chiral salen metal catalyst is very difficult and almost impossible for industrial application. In particular, when trimethylsilyl azide is used as a nucleophile during asymmetric ring reaction, the azido alcohol produced is separated by vacuum distillation, and when the remaining chiral salen metal catalyst is to be reused, It is practically impossible to apply it to mass production [LE Martiez, JL Leighton, DH Carsten, EN Jacobsen, J. Am. Chem. Soc., 1995 , 117 , 5897].

In addition, there have been many studies on various methods of immobilizing a chiral salen metal catalyst on a solid support to facilitate the recovery of the catalyst and to use the catalyst repeatedly. For example, a method of recovering the chiral salen metal catalyst by partially modifying the chemical structure of the chiral salen metal catalyst is chemically bonded to a terminal group of silica gel or polystyrene, which is a solid support, and then filtered after an asymmetric ring opening reaction. Was developed [S. Peukert, EN Jacobsen, Organic Letters. 1999 , 1 , 1245; DA Annis, EN Jacobsen, J. Am. Chem. Soc. 1999 , 121 , 4147-4154. However, the above method has a disadvantage in that the structure of the chiral salen metal catalyst has to be modified and it is very difficult, such as a method of attaching to a stationary phase such as a solid support.

Accordingly, the present inventors have endeavored to develop a method for easily recovering and reusing a catalyst after an asymmetric ring opening of an epoxy compound without modifying the chemical structure of the chiral salen metal catalyst. After the asymmetric ring opening of the epoxy compound is carried out using a chiral salen metal catalyst in a solvent system, the product is obtained by direct distillation or a conventional organic extraction method, and the catalyst can be easily separated and recovered in a form immobilized in a salt represented by the formula (1). At this time, the recovered catalyst was found to be reused repeatedly while maintaining the activity and engineering selectivity, thereby completing the present invention.

An object of the present invention is a method for producing a chiral compound using an asymmetric ring opening reaction of an epoxy compound in the presence of a chiral salen metal catalyst, asymmetric ring opening of the epoxy compound in the salt system represented by the formula (1) or a solvent containing the salt It is to provide a method for producing a chiral compound that can be easily recovered or reused chiral salem metal catalyst by the reaction.

In order to achieve the above object, the present invention is a method for preparing a chiral compound using an asymmetric ring opening reaction of an epoxy compound in the presence of a chiral salen metal catalyst, a salt represented by the formula (1) or an epoxy compound in a solvent system containing the salt It provides a method for producing a chiral compound that can be easily recovered or reused chiral salem metal catalyst by performing an asymmetric ring opening reaction of.

Scheme 1

The nucleophile used is N ₃ ^-, use and the like ^{_{-, NH 3, H 2 NR}} , HNR 2, H 2 O, ROH, PhOH, RSH, H -, RCH 2.

I. salt

In the present invention, salts represented by the following general formula (1) are used.

Formula 1

In Chemical Formula 1,

If X is nitrogen, then Z is -C (R ⁵ )-,

R ¹ and R ² represent C ₁ to C ₁₈ alkyl groups that are independent of each other,

R ³ , R ⁴ and R ⁵ are independent of each other and represent hydrogen or an alkyl group of C _{1 to} C ₁₈ .

If X is carbon, then Z is -C (R ⁵ ) -C (R ⁶ )-,

R ¹ is an alkyl group of C ₁ ~C _18,

R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independent of each other and represent hydrogen or an alkyl group having _{1 to 18} carbon atoms,

n is an integer of 1 to 3,

Y is an anion capable of forming a salt, a halogen atom, MX _k ^- or R ⁷ O ^-, where M is an element of the 1B, 2B, IIIA, IVA, VA group on the periodic table (CAS version), X is a halogen Is an element, k is 2-6 and R ⁷ is alkylsulfonyl, haloalkyl sulfonyl, phosphoryl or alkylcarbonyl.

La alkyl group of C ₁ -C ₁₈ in the present specification also includes a primary alkyl groups, secondary alkyl groups and tertiary alkyl groups of C ₁ -C _18, and examples thereof include methyl, ekil, propyl, isopropyl, butyl, isobutyl , t-butyl, pentyl, 2-methyl-butyl, 3-methyl-butyl, hexyl, heptyl, octyl and the like.

Preferably, it is an imidazolysin salt represented by following formula (2).

In Formula 2, R ¹ , R ² , Y and n are as defined in Formula 1.

Specific examples of imidazolysin salts include 1-ethyl-3-methyl-imidazolysone, 1-methyl-3-propyl-imidazolysone, 1-butyl-3-methyl-imidazolysone, 1-methyl Cations and hexafluoroantimonate (SbF ₆ ), such as 3-pentyl-imidazoli 윰, 1-hexyl-3-methyl-imidazoli 윰, 1-heptyl-3-methyl-imidazoli 윰, It is an imidazoline salt containing anions such as hexafluorophosphate (PF ₆ ), tetrafluoroborate (BF ₄ ), tripulolomethanesulfonate (OTf) and acetate (OAc).

Among the salts represented by Formula 1, compounds which are generally present in a liquid phase at 100 ^° C. or lower are also called ionic liquids. In the present invention, they may be used alone or in combination with other organic solvents, and include benzene, toluene, and chlorobenzene. And diethyl ether, tetrahydrofuran, dioxane, dichloromethane, chloroform, ethyl acetate, and acetonitrile.

The salt has many advantages such as being stable to air and moisture, environmentally friendly, volatile, non-flammable, excellent in thermal stability, high solvation ability, and hardly coordinating with metals, thus being used for catalytic reactions. It has the advantage of being very suitable [P. Waaserscheid, W. Keim, Angew. Chem. Int. Ed. 2000 , 39 , 3772; T. Welton, Chem. Rev. 1999 , 99 , 2071; KR Seddon, J. Chem. Tech. Biotechnol. 1997 , 68 , 351; Y. Chauvin, H. Olivier, CHEMTECH , 1995 , 26 ]. This feature can be used for the purpose of immobilizing a catalyst having polar or ionic properties, such as a chiral salen metal catalyst, in an ionic liquid to perform a catalytic reaction and to easily separate a product from the catalyst.

II. Chiral Salen Metal Catalyst

The chiral salen metal catalyst which can be used in the present invention can be effectively used with all the chiral salen metal catalysts previously reported, together with the salt represented by the formula (1) characterized by the present invention.

1. The chiral salen metal catalyst which can be used in the present invention can be classified into various forms according to the structure. The first specific example is a chiral salen metal catalyst having a structure represented by the following Chemical Formula 3.

In Chemical Formula 3,

R ¹ , R ² , R ³ and R ⁴ are chiral substituents which are independently of each other hydrogen, alkyl, carboxyl group, aryl, and substituted aryl groups. Substituents for aryl groups are halogen, alkyl, alkoxy, cyano and Or a nitro group or R ¹ , R ² , R ³ and R ⁴ may be linked to each other to form a ring of C ₄ to C ₈ ,

X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ and X ⁸ are independently of each other hydrogen, halogen, alkyl, silyl, silyloxy, alkenyl, alkynyl, hydroxy, alkoxy, amino , Nitro, cyano, thiol, thioether, imino, amido, phosphoryl, carbonyl and sulfonyl,

Y ¹ and Y ² are independent of each other and are hydrogen or an alkyl group,

M is a metal, preferably Al, Mn, Cr, Fe, Co, Ti, V, Ru or Os, more preferably Cr or Co, and

A ^- represents an anion preferably Cl _{^{-, N 3 -, CH 3}} C00 -, BF 4 -, PF 6 - or SbF ₆ ^- a.

Many chiral salen metal catalysts having the structure of Formula 3 have been synthesized and used [Jacobsen et al., J. Org. Chem., 1996, 61, 389; Jacobsen et al., Tetrahedron Letters, 1997, 38, 773; Jacobsen et al., US 5,665,890 (1997); Jacobsen et al., US 5,929,232 (1999). Representative catalysts are compounds represented by the following formulas 3a, 3b, 3c and 3d, and MA is mainly used Cr-Cl, Co-OAc, Cr-N ₃ , Co-BF ₄ , Co-PF ₆ and Co-SbF ₆ .

2. A specific second example is a chiral salen metal catalyst having a structure represented by the following formula (4).

In Chemical Formula 4,

R ¹ and R ² are in the trans position of each other, and are hydrogen, alkyl, carboxyl group, aryl and substituted aryl group independent of each other, and substituents of the aryl group are halogen, alkyl, alkoxy, cyano and nitro group,

B is oxygen, NR, sulfur, sulfone or sulfoxide, in which R is alkyl, aryl, alkylcarbonyl (-C (O) R), arylcarbonyl (-C (O) Ar), alkylcarboxyl (-C (O) OR), arylcarboxyl (-C (O) OAr), alkylsulfonyl (-S (O) ₂ R) and arylsulfonyl group (-S (O) ₂ Ar),

n is 1 to 3

X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ , X ⁸ , Y ¹ , Y ² , M and A ⁻ are the same as those shown in Chemical Formula 3.

The specific chiral salen metal catalyst represented by Chemical Formula 4 is preferably a catalyst represented by Chemical Formulas 4a and 4b [RG Konsler, J. Karl, EN Jacobsen, J. Am. Chem. Soc. , 1998 , 120 , 10780; CE Song et al., Chem. Commun. 2000 , 615].

3. A third specific example is the chiral salen metal catalyst represented by the following chemical formula [Jacobsen et al., US 5,665,890 (1997); Jacobsen et al., US 5,929,232 (1999).

In Chemical Formula 5,

Z ¹ , Z ² , Z ³ and Z ⁴ are hydrogen, alkyl, halogen, cyano or nitro groups independent of each other,

X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ , X ⁸ , Y ^1, Y ² , M and A ⁻ are the same as those shown in Chemical Formula 3.

The chiral salen metal catalyst represented by Chemical Formula 5 is preferably a chiral salen metal catalyst represented by Chemical Formula 5a (Jacobsen et al., US 5,665,890 (1997)).

4. A fourth specific example is the chiral salen metal catalyst represented by the following Chemical Formula 6. [Jacobsen et al., US 5,665,890 (1997); Jacobsen et al., US 5,929,232 (1999); US 5,420,314 (1995); US 5,599,957 (1997); US 5,352,814 (1994); US 5,639,889 (1997).

In Chemical Formula 6,

X ¹ , X ² , X ³ , X ⁴ , X ⁵ and X ⁶ are independently of each other hydrogen, halogen, alkyl, silyl, silyloxy, alkenyl, alkynyl, hydroxy, alkoxy, amino, nitro, thiol, thio Ether, cyano, imino, amido, phosphoryl, carbonyl or sulfonyl,

X ¹ and X ² and X ⁴ and X ⁵ can be connected to each other to form a benzene ring,

R ⁵ , R ⁶ , R ⁷ and R ⁸ are chiral substituents and are independently alkyl, aryl or substituted aryl groups,

The substituent of the aryl group is halogen, alkyl, alkoxy, cyano or nitro group

R ⁵ and R ⁶ , R ⁷ and R ⁸ may be connected to each other to form a naphthyl group or a naphthyl group in which an alkyl or aryl group is substituted.

R ¹ , R ² , R ³ , R ⁴ , Y ¹ , Y ² , M and A ⁻ are the same as those shown in Chemical Formula 3 above.

The chiral salen metal catalyst represented by Chemical Formula 6 is preferably a chiral salen metal catalyst represented by the following Chemical Formulas 6a, 6b, 6c, and 6d commonly used as Katsuki's Catalyst.

In the above formula, hydrogen atoms (1) and (2) are in a trans position with each other,

R ¹ is hydrogen or a methyl group,

R ² is a methyl group or a phenyl group, preferably a phenyl group.

M is a metal, preferably Cr or Co,

A ⁻ is an anion, preferably Cl, N ₃ or OAc.

The chiral salen metal catalyst represented by Chemical Formula 6 may be used in the asymmetric ring-opening reaction of the present invention as a catalyst mainly used to prepare chiral epoxide using an asymmetric epoxidation reaction.

III. Asymmetric Ring Opening Reaction of Epoxy Chemicals

The asymmetric ring-opening reaction of the epoxy compound by the nucleophile using the chiral salen metal catalyst is carried out under normal asymmetric ring-opening reaction conditions except that the reaction is carried out in a solvent system containing a salt of the formula [US 5,665,890 (1997). ); Jacobsen et al., US 5,929,232 (1999); Jacobsen et al., WO 9628402 (1996); Jacobsen et al., WO 0009463 (1999); LE Martiez, JL Leighton, DH Carsten, EN Jacobsen, J. Am. Chem. Soc. 1995 , 117 , 5897; M. Tokunaga, JF Larrow, F. Kakiuchi, EN Jacobsen, Science , 1997 , 277 , 936]. The nucleophile is an uncharged compound such as alcohol, water, amine, mercaptan and alkoxide, thiolate, carbanion, azide, cyanide, thiocyanate, acetate, formate, chloroformate And anions such as bisulfite, organocuprates, organozinc compounds, organolithium compounds, Grignard reagents, enolates and acetylides. Organometallic reagents such as acetylides and hydrogen anion can be used.

IV. Recovery method of chiral salen metal catalyst

Specifically, in order to obtain a product after the asymmetric ring opening reaction, the recovery of the chiral salen metal catalyst used after the preparation of the chiral compound in the asymmetric ring opening reaction using the chiral salen metal catalyst is performed by adding an organic solvent to the reaction mixture after the asymmetric ring opening reaction. This can be accomplished by separating the salt layer of formula 1 in which the catalyst is present and then evaporating it under reduced pressure.

The organic solvent used in the organic extraction method can dissolve the target compound, that is, the chiral compound, as long as it is not mixed with the salt of the formula (1). Pentane, hexane, heptane, benzene, toluene, diethyl ether, isopropanol and the like are preferably used. At this time, in order to extract more effectively, it is preferable to add the organic solvent and then stir. After extraction, the salt is divided into two layers. In general, the salt of formula 1 is dense, so it is collected in the lower layer of the reaction vessel, and the organic layer, which is the upper layer of the reaction vessel, contains the reaction product. After removal, the product is separated through purification, such as column chromatography, distillation or recrystallization. Since the lower layer of the reaction vessel contains a chiral salen metal catalyst as the salt layer of formula (1), the catalyst dissolved or dispersed in the salt of formula (1) can be easily separated and recovered by separating the upper layer and the lower layer of the reaction vessel.

In addition, the reaction product may be separated directly by distillation, wherein the catalyst may be reused in a dissolved or dispersed form in a salt represented by Formula 1 without undergoing a separate separation process. At this time, the recovered chiral salen metal catalyst maintains the activity and optical selectivity almost intact and can be reused for the asymmetric ring opening of the epoxy compound.

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

However, the following examples are merely to illustrate the content of the present invention is not limited to the scope of the invention.

Example 1 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

In a 10 ml three-necked flask, a compound of formula 3a (38 mg, 0.06 mmol) and cyclopentene oxide (0.175 ml, 2 mmol) in which MA is Cr-Cl in a chiral salen metal catalyst were added to 3-butyl-1-methyl. Put 1 ml of PF ₆ salt of midazolybine and stir under nitrogen. Trimethylsilyl azide (0.28 ml, 2.1 mmol) is added slowly. Stir for 28 hours under nitrogen atmosphere at 20 ℃. 10 ml of hexane is added and vigorously stirred for 30 minutes. The optical purity of the azido silyl ether of the hexane layer was measured by gas chromatography, and the column was separated using chromium pack chiralsildex-CB, and each enantiomer was separated at 95 ° C isothermal conditions (24.7 minutes (1 R , 2 R ), 26.9 min (1 S , 2 S )). In addition, the compound of Formula 3a was recovered in a form immobilized in a salt of Formula 1, and infrared spectroscopy (IR) confirmed the structure of the catalyst A is N ₃ . The hexane layer is concentrated, dissolved in 5 ml of methanol, camphorsulfonic acid (24 mg, 0.1034 mmol) is added and stirred at room temperature for 30 minutes. Methanol was evaporated under reduced pressure, and the obtained product was subjected to column chromatography under a solvent condition of ethyl acetate: hexane = 1: 2 to obtain 193.4 mg (76% yield, 94% ee) of pure azido alcohol.

Example 2 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

Azido alcohol was prepared in the same manner as in Example 1, except that the reaction of the compound of Formula 1 was carried out in a solvent of 1 ml of SbF ₆ salt of 3-butyl-1-methylimidazolidone, and a chiral catalyst was prepared. The separation was recovered and the yield was 75%, and the optical purity was 87%.

Example 3 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

In a 10 ml three-necked flask, a compound of formula 3a (38 mg, 0.06 mmol) and a cyclohexene oxide (0.20 ml, 2 mmol) in which MA is Cr-Cl in a chiral salen metal catalyst were added to 3-butyl-1-methyl. Add 1 ml of PF ₆ salt of midazolyne and stir under nitrogen. Trimethylsilyl azide (0.28 ml, 2.1 mmol) is added slowly. Stir for 18 hours under nitrogen atmosphere at 20 ° C. 10 ml of hexane is added and vigorously stirred for 30 minutes. Optical purity of the azido ether in the hexane layer was measured by gas chromatography using the same column as Example 1, and the respective enantiomers were separated at 110 ° C isothermal conditions (24.3 min (1 R , 2 R ), 27.1 min (1 S , 2 S )). In addition, the compound of Formula 3a was recovered in a form immobilized in a salt of Formula 1, and infrared spectroscopy (IR) confirmed the structure of the catalyst A is N ₃ . The hexane layer is concentrated, dissolved in 5 ml of methanol, camphorsulphonic acid (24 mg, 0.1034 mmol) is added, and the mixture is stirred at room temperature for 30 minutes. After methanol was removed under reduced pressure, the obtained product was subjected to column chromatography under a solvent condition of ethyl acetate: hexane = 1: 2 to obtain 242.7 mg (86% yield, 84% ee) of pure azido alcohol.

Example 4 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

Azido alcohol was prepared in the same manner as in Example 3, except that the reaction of the compound of Formula 1 was carried out in a solvent of 1 ml of SbF ₆ salt of 3-butyl-1-methylimidazolidone, and a chiral catalyst was prepared. The separation was recovered and the yield was 28%, and the optical purity was 72%.

Example 5 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

In a 10 ml three-necked flask, a compound of formula 3a (38 mg, 0.06 mmol) and 3,4-epoxytetrahydrofuran (173.5 mg, 2 mmol) in which MA is Cr-Cl in a chiral salen metal catalyst were added to 3-butyl It is added to 1 ml of PF ₆ salt of -1-methylimidazolysin and stirred under nitrogen. Trimethylsilyl azide (0.28 ml, 2.1 mmol) is added slowly. Stir for 28 hours under nitrogen atmosphere at 20 ℃. 10 ml of hexane is added and vigorously stirred for 30 minutes. The optical purity of the azido ether in the hexane layer was measured by gas chromatography using the same column as Example 1, at an initial temperature of 75 ° C. for 10 minutes, at a temperature rising rate of 2 ° C. per minute, and at a final temperature of 200 ° C. for 5 minutes. Under the conditions of minutes, each enantiomer was separated (34.4 minutes (3 R , 3 R ), 35.2 minutes (3 S , 3 S )). In addition, the compound of Formula 3a was recovered in a form immobilized in a salt of Formula 1, and infrared spectroscopy (IR) confirmed the structure of the catalyst A is N ₃ . The hexane layer is concentrated, dissolved in 5 ml of methanol, camphorsulphonic acid (24 mg, 0.1034 mmol) is added and stirred at room temperature for 30 minutes. After methanol was removed under reduced pressure, the obtained product was subjected to column chromatography under a solvent condition of ethyl acetate: hexane = 1: 2 to obtain 192.1 mg of pure azido alcohol (74% yield, 97% ee).

Example 6 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

Azido alcohol was prepared in the same manner as in Example 5, except that the compound of Formula 1 was reacted in a solvent of 1 ml of SbF ₆ salt of 3-butyl-1-methylimidazolyzin, to prepare a chiral catalyst. The separation was recovered and the yield was 45%, and the optical purity was 97%.

The yield, optical purity, and working conditions of the azido alcohol compound prepared in Examples 1 to 6 are shown in Table 1 below.

Example catalyst Epoxy compound Solvent ^a Response time (hours) yield(%) % ee ^b Solid structure One Catalyst of Formula 3a (M-A = Cr-Cl) [bmim] [PF ₆ ] 28 76 94 (1 S , 2 S ) 2 Catalyst of Formula 3a (M-A = Cr-Cl) [bmim] [SbF ₆ ] 28 75 87 (1 S , 2 S ) 3 Catalyst of Formula 3a (M-A = Cr-Cl) [bmim] [PF ₆ ] 18 86 84 (1 S , 2 S ) 4 Catalyst of Formula 3a (M-A = Cr-Cl) [bmim] [SbF ₆ ] 18 28 72 (1 S , 2 S ) 5 Catalyst of Formula 3a (M-A = Cr-Cl) [bmim] [PF ₆ ] 28 74 97 (3 S , 3 S ) 6 Catalyst of Formula 3a (M-A = Cr-Cl) [bmim] [SbF ₆ ] 28 45 97 (3 S , 3 S ) a: [bmim] [PF ₆ ] represents the PF ₆ salt of 3-butyl-1-methylimidazolysone and [bmim] [SbF ₆ ] represents the SbF ₆ salt of 3-butyl-1-methylimidazolysone B: Analysis by chiral gas chromatography.

Example 7 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

In a 10 ml three-necked flask, a catalyst of formula 3b (38 mg, 0.06 mmol) and 3- (1-naphthyloxy) propylene oxide (400 mg, 2 mmol) in which MA is Cr-Cl in a chiral salen metal catalyst were added. Add 1 ml of PF ₆ salt of butyl-1-methylimidazolysin and stir under nitrogen. Trimethylsilyl azide (0.13 ml, 1 mmol) is added slowly. Stir for 48 hours under nitrogen atmosphere at 0 ° C. 10 ml of hexane is added and vigorously stirred for 30 minutes. The optical purity of the azido ether in the hexane layer was measured by HPLC (High Performance Liquid Chromatography), and the column used was separated by chiralpak AD, wherein the developing solvent condition was hexane / isopropanol = 99/1 and the flow rate was 1 ml / min. as measured by 254nm were each isolated from 9.7 minutes (2 R), 11.2 bun (2 S). In addition, the catalyst of Formula 3b was recovered in a form immobilized in a salt of Formula 1 and IR confirmed the structure of the catalyst A is N ₃ . The hexane layer was concentrated, dissolved in 5 ml of methanol, camphorsulphonic acid (24 mg, 0.1034 mmol) was added, and the mixture was stirred at room temperature for 2 hours. Methanol was evaporated under reduced pressure, and the obtained product was subjected to column chromatography under a solvent condition of ethyl acetate: hexane = 1: 2 to obtain 128.7 mg (26% yield, 37.9% ee) of pure azido alcohol.

Example 8 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

Azido alcohol in the same manner as in Example 7, except that the reaction was carried out in a mixed solvent of 1.5 ml of THF and 0.5 ml of PF ₆ salt of 3-butyl-1-methylimidazolybene. Was prepared and the chiral catalyst was separated and recovered, where the yield was 20%, and the optical purity was 68%.

Example 9 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

Azido alcohol was prepared in the same manner as in Example 7, except that 1 ml of dichloromethane and 1 ml of PF ₆ salt of 3-butyl-1-methylimidazolybene were reacted in a mixed solvent. To prepare and separate the chiral catalyst was recovered and the yield was 28%, optical purity was 65%.

Example 10 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

Azido alcohol in the same manner as in Example 7, except that 1 ml of dichloromethane and 0.5 ml of PF ₆ salt of 3-butyl-1-methylimidazolithel were reacted in a mixed solvent of the compound of Formula 1 Was prepared and the chiral catalyst was separated and recovered, where the yield was 23%, and the optical purity was 67%.

Example 11 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

Azido was reacted in the same manner as in Example 7, except that 1.5 ml of dichloromethane and 0.5 ml of PF ₆ salt of 3-butyl-1-methylimidazolithel were reacted in a mixed solvent of the compound of Formula 1. Alcohol was prepared and the chiral catalyst was separated and recovered, where the yield was 32% and the optical purity was 78%.

Example 12 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

Azido alcohol in the same manner as in Example 7, except that 2 ml of dichloromethane and 0.5 ml of PF ₆ salt of 3-butyl-1-methylimidazolithel were reacted in a mixed solvent of the compound of Formula 1 Was prepared and the chiral catalyst was separated and recovered, where the yield was 33%, and the optical purity was 85%.

Example 13 Preparation of Chiral Azido Alcohol and Recovery of Chiral Catalyst

Azido was reacted in the same manner as in Example 7, except that 1.5 ml of chlorobenzene and 0.5 ml of PF ₆ salt of 3-butyl-1-methylimidazolybene were reacted in a mixed solvent. An alcohol was prepared (see Scheme 2 below) and the chiral catalyst was separated and recovered with a yield of 23% and an optical purity of 94%. In Scheme 1 below, PhCl represents chlorobenzene.

Example 14 Preparation of Chiral Epoxy Compound and Chiral Diol and Recovery of Chiral Catalyst

In a 10 ml flask, a catalyst of formula 3a (27.2 mg, 0.04 mmol) and styrene oxide (0.57 ml, 5 mmol) in which the MA is Co-OAc and a butyl oxide (0.57 ml, 5 mmol) in a 10 ml flask were Add 3 ml of PF ₆ salt of midazolysin and stir. Water (0.063 ml, 3.5 mmol) is added slowly. Stir at room temperature for 44 hours. 10 ml of hexane is added and vigorously stirred for 30 minutes. The upper hexane layer is separated and 10 ml of water is added to the lower salt layer of Formula 1 and stirred vigorously (see Scheme 3 below). The water layer was separated and diethyl ether was added to the water layer to extract 1-phenyl-1,2-ethanediol. The optical purity of the styrene oxide of the hexane layer was measured by gas chromatography, and the column used was chromium pack chiraldex-CB, and each enantiomer was separated at 80 ° C isothermal conditions (7.8 min ( R ), 8.7 min ( S). )). The optical purity of 1-phenyl-1,2-ethanediol of the diethyl ether layer was also determined by gas chromatography, and the column used was chromium pack chiraldex-CB, with 120 ° C. (20 minutes) at 1 ° C. per minute. Each enantiomer was separated (28 minutes ( S ), 29.3 minutes ( R )) under conditions rising to 140 ° C (5 minutes). The solvents of each obtained product were removed under reduced pressure, followed by column chromatography under a solvent condition of ethyl acetate: hexane = 1: 6 under 1% triethylamine buffer solution to obtain 252.3 mg (42% yield, 96% ee) of pure styrene oxide. ) Was subjected to column chromatography under a solvent condition of ethyl acetate: hexane = 1: 1 to give 262.5 mg (38% yield, 96% ee) of pure 1-phenyl-1,2-ethanediol.

Example 15 Preparation of Chiral Epoxy Compound and Chiral Diol and Recovery of Chiral Catalyst

In a 10 ml flask, a catalyst of formula 3a (27.2 mg, 0.04 mmol) and epichlorohydrin (0.39 ml, 5 mmol) in which MA is Co-OAc in a chiral salen metal catalyst were added to 3-butyl-1-methyl. Add 3 ml of PF ₆ salt of imidazolysin and stir. Water (0.063 ml, 3.5 mmol) is added slowly. Stir at room temperature for 17 hours (see Scheme 4 below). Epichlorohydrin and 3-chloro-1,2-propanediol are obtained by direct fractional distillation from the reaction mixture under reduced pressure. The optical purity of epichlorohydrin was measured by gas chromatography, and the column used was chiraldex γ-TA, and each enantiomer was separated at 40 ° C isothermal conditions (16.0 minutes ( S ), 20.6 minutes ( R )). . The optical purity of 3-chloro-1,2-propanediol was synthesized as a ketal derivative by reacting 3-chloro-1,2-propanediol with 2,2-dimethoxypropane in the presence of a catalytic amount of p-toluenesulfonic acid. It was measured by gas chromatography, and the column used was separated by chrompakchiraldex-CB (11.2 min ( S ), 12.7 min ( R )). (S) -Epichlorohydrin obtained by fractional distillation yielded 200 mg (43% yield, 96% ee), and (R) -3-chloro-1,2-propanediol 268 mg (48% yield, 96% ee) Got.

Example 16 Preparation of Chiral Epoxy Compound and Chiral Diol and Recovery of Chiral Catalyst

(R, R)-(-)-N, N'-bis (3,5-dibutylbutyl salicylidene) -1,2-cyclohexanediaminocobalt (II) (24.1 mg, 0.04 mmol) in a 10 ml flask ) Is dissolved in 1.5 ml of dichloromethane, acetic acid (0.005 ml, 0.08 mmol) and stirred for 1 hour under air to produce a catalyst of formula 3a in which MA is Co-OAc, which is used as a direct catalyst for the following reaction ( See Scheme 5). In the compound of Formula 1, 1.5 ml of PF ₆ salt of 3-butyl-1-methylimidazolysin was added thereto, and styrene oxide (0.57 ml, 5 mmol) was added thereto, followed by stirring. Water (0.063 ml, 3.5 mmol) is added. Stir at room temperature for 44 hours. 10 ml of hexane is added and vigorously stirred for 30 minutes. The upper hexane layer is separated and 10 ml of water is added to the lower salt layer of Formula 1 and stirred vigorously. The water layer was separated and diethyl ether was added thereto to extract 1-phenyl-1,2-ethanediol. The optical purity of the styrene oxide of the hexane layer was measured by gas chromatography, and the column used was chromium pack chiraldex-CB, and each enantiomer was separated at 80 ° C isothermal conditions (7.8 min ( R ), 8.7 min ( S). )). The optical purity of 1-phenyl-1,2-ethanediol of the diethyl ether layer was also determined by gas chromatography. The column used was chromium pack chiraldex-CB, and was heated at 120 ° C. (20 minutes) at 1 ° C. per minute. Each enantiomer was separated (28 minutes ( S ), 29.3 minutes ( R )) under conditions that rose to 140 ° C (5 minutes). The solvents of each obtained product were removed under reduced pressure, followed by column chromatography under a solvent condition of ethyl acetate: hexane = 1: 6 under 1% triethyl amine buffer solution to obtain 228.3 mg of pure styrene oxide (38% yield, 98% ee). ) Was subjected to column chromatography under a solvent condition of ethyl acetate: hexane = 1: 1 to obtain 269.4 mg (39% yield, 94% ee) of pure 1-phenyl-1,2-ethanediol.

Example catalyst Epoxy compound Solvent ^a Response time (hours) yield(%) % ee 7 Catalyst of Formula 3b (M-A = Cr-Cl) 3- (1-naphthyl) propylene oxide [bmim] [PF ₆ ] 0.5 26 37.9 8 Catalyst of Formula 3b (M-A = Cr-Cl) 3- (1-naphthyl) propylene oxide [bmim] [PF ₆ ] + THF 1.5 ml 0.5 20 68 9 Catalyst of Formula 3b (M-A = Cr-Cl) 3- (1-naphthyl) propylene oxide [bmim] [PF ₆ ] 1 ml + CH ₂ Cl ₂ 1 ml 0.5 28 65 10 Catalyst of Formula 3b (M-A = Cr-Cl) 3- (1-naphthyl) propylene oxide [bmim] [PF ₆ ] 1 ml + CH ₂ Cl ₂ 0.5 ml 0.5 23 67 11 Catalyst of Formula 3b (M-A = Cr-Cl) 3- (1-naphthyl) propylene oxide [bmim] [PF ₆ ] 0.5 mL + CH ₂ Cl ₂ 1.5 mL 0.5 32 78 12 Catalyst of Formula 3b (M-A = Cr-Cl) 3- (1-naphthyl) propylene oxide [bmim] [PF ₆ ] 0.5 mL + CH ₂ Cl _{2 2} mL 0.5 33 85 13 Catalyst of Formula 3b (M-A = Cr-Cl) 3- (1-naphthyl) propylene oxide [bmim] [PF ₆ ] 0.5 ml + chlorobenzene 1.5 ml 0.5 23 94 14 Catalyst of Formula 3a (M-A = Co-OAc) Styrene oxide [bmim] [PF ₆ ] 3 ml 44 42 96 ^b 33 96 ^c 15 Catalyst of Formula 3a (M-A = Co-OAc) Epichlorohydrin [bmim] [PF ₆ ] 3 ml 17 43 96 ^d 48 96 ^e 16 Catalyst of Formula 3a (M-A = Co-OAc) Styrene oxide [bmim] [PF ₆ ] 1.5 mL + CH ₂ Cl ₂ 1.5 mL 44 38 98 ^b 39 94 ^c

a: [bmim] [PF ₆ ] represents the PF ₆ salt of 3-butyl-1-methylimidazolysone.

b: styrene oxide

c: 1-phenyl-1,2-ethyldiol

d: (s) -epichlorohydrin

e: (R) -3-chloro-1,2-propanediol

Experimental Example 1 Reuse of Chiral Catalyst

Using the salt represented by the formula (1) as a solvent to carry out the asymmetric ring opening reaction of the epoxy compound and to test whether the activity and optical selectivity of the catalyst is maintained even if the recovered chiral salen metal catalyst is reused.

In the same manner as in Example 1, of the compound of formula 1, a compound of formula 3a, in which MA is Cr-Cl, in a chiral salen metal catalyst in a PF ₆ salt solvent of 3-butyl-1-methylimidazolysin The cyclopentene oxide was then reacted with trimethylsilyl azide to effect asymmetric ring opening. The ring-opening reaction was performed five times in total, using the catalyst recovered in the same manner as in Example 1 as it is in the next ring-opening reaction. For the cyclopentene oxide 3 mol% of catalyst was used (see Scheme 6 below). [bmim] [PF ₆ ] represents the PF ₆ salt of 3-butyl-1-methylimidazolysone and TMSN ₃ represents trimethylsilyl azide.

As a result of the five ring-opening reaction, the yield and optical purity of the resulting azido alcohol compound are shown in Table 3 below.

Repeat use count Yield (%) Optical purity (% ee) One 76 94 2 74 90 3 78 93 4 76 93 5 78 93

As can be seen from Table 3 , azido alcohol compounds exhibiting high optical purity with a high yield of 70% or more were obtained even when the catalyst of Formula 3a immobilized in the salt of Formula 1 was reused.

Experimental Example 2 Reuse of Chiral Catalyst

If the asymmetric ring-opening reaction of the epoxy compound is carried out in a solvent system in which various kinds of salts represented by the formula (1) are mixed and the recovered catalyst and the salt of the formula (1) are reused, it is known whether the activity and optical selectivity of the catalyst are maintained. The following experiment was conducted to see.

In a 10 ml three-necked flask, a catalyst of formula 3a (38 mg, 0.06 mmol) and cyclopentene oxide (0.175 ml, 2 mmol) in which MA is Cr-Cl in a chiral salen metal catalyst were added to 3-butyl-1-methyl. Trifluurosulfonate (CF ₃ SO ₃ ⁻ , hereinafter abbreviated as “OTf”) salt of 3-butyl-1-methylimidazolybene in 0.5 ml of PF ₆ salt of midazolyb; Put in ml and stir under nitrogen. Trimethylsilyl azide (0.28 ml, 2.1 mmol) is added slowly. Stir for 28 hours under nitrogen atmosphere at 20 ℃. 10 ml of hexane is added and vigorously stirred for 30 minutes. The supernatant obtained by stopping the stirring was taken to obtain azido ether, and the lower ring salt of the formula (1) containing the catalyst of 3a in the form of A is N ₃ was used as it is in the next ring-opening reaction. Was carried out. 3 mol% of the catalyst of Formula 3a, wherein MA is Cr-Cl, was used for cyclopentene oxide (see Scheme 7 below). [bmim] [PF ₆ ] is the PF ₆ salt of 3-butyl-1-methylimidazolysone, [bmim] [OTf] is the OTf salt of 3-butyl-1-methylimidazolysone and TMSN ₃ is Trimethylsilyl azide.

The yield and optical purity of the azido alcohol compound produced as a result of the three ring-opening reactions are shown in Table 4 below.

Repeat use count Yield (%) Optical purity (% ee) One 51 85 2 71 93 3 36 70

Experimental Example 3 Reuse of Chiral Catalyst

If the asymmetric ring-opening reaction of the epoxy compound is carried out in a solvent system in which various kinds of salts represented by the formula (1) are mixed, and the recovered catalyst and the salt of the formula (1) are reused, the activity and optical selectivity of the catalyst are maintained. The following experiment was conducted to see.

In the compound of the formula (1), 1 ml of PF ₆ salt of 3-butyl-1-methylimidazolysone and 0.2 ml of the OTf salt of 3-butyl-1-methylimidazolybene in the compound of the formula (1) Except for the asymmetric ring-opening reaction of the cyclopentene oxide using a catalyst of formula 3a in which MA is Cr-Cl in the same manner as in Example 18. The ring-opening reaction was performed five times in total, using the catalyst and solvent recovered in the same manner as in Example 8 as it is in the next ring-opening reaction. For the cyclopentene oxide, 3 mol% of the catalyst of Formula 3a in which MA is Cr-Cl was used (see Scheme 8 below).

The yield and optical purity of the azido alcohol compound produced as a result of the five ring-opening reactions are shown in Table 5 below.

Repeat use count Yield (%) Optical purity (% ee) One 58 94 2 72 92 3 85 93 4 75 94 5 76 94

As can be seen in Table 5 , the PF ₆ salt of 3-butyl-1-methylimidazolysin in the compound of Formula 1 and the OTf salt of 3-butyl-1-methylimidazolysin in the compound of Formula 1 Using a mixed solvent (5: 1 by volume) to reuse the (R, R) -catalyst of Formula 3a, in which MA is Cr-Cl, an azido alcohol compound showing high yield and optical purity was obtained.

Example 17 Preparation of Chiral Epoxide and Chiral Diol and Recovery of Chiral Catalyst

(R, R)-(-)-N, N'-bis (3,5-dibutylbutyl salicylidene) -1,2-cyclohexanediaminocobalt (II) (30.2 mg, 0.05 mmol) in a 10 ml flask ) Was dissolved in 1.5 milliliter of dichloromethane, and ferrocenium hexafluorophosphate (16.5mg, 0.05mmol) was added thereto, stirred at room temperature for 2 hours, and a catalyst of 3a having Co-PF _{6 as} MA was produced during the reaction. It is used directly as a catalyst (Scheme 9). In the compound of the formula (1), 0.5 milliliter of PF ₆ salts of 3-butyl-1-methylimidazolidone were added and stirred, and then dichloromethane was removed under reduced pressure, followed by epichlorohydrin (0.78 ml, 10 mmol) and water ( 0.126 ml, 7 mmol) is added and stirred at 20 ° C. for 24 hours. Fractional distillation from the reaction mixture under reduced pressure yields epichlorohydrin. 10 milliliters of water is added to the distillation residue to extract 3-chloro-1,2-propanediol. Epichlorohydrin in dichloromethane was obtained by distillation. The water layer was concentrated and diethyl ether was added to extract 3-chloro-1,2-propanediol. The optical purity of the epichlorohydrin obtained by distillation was measured by gas chromatography. The column used was separated by chiraldex γ-TA, and the temperature conditions were 10.1 minutes ( S ) and 13.2 minutes ( R , respectively, at 40 ° C isothermal conditions. ) The optical purity of 3-chloro-1,2-propanediol was synthesized as a ketal derivative by reacting 3-chloro-1,2-propanediol with 2,2-dimethoxypropane in the presence of a catalytic amount of p-toluenesulfonic acid. Measured by gas chromatography, the column used was separated by chromium pack chiraldex-CB, and the temperature conditions were separated at 11.8 minutes ( S ) and 13.4 minutes ( R ) at 60 ° C isothermal conditions, respectively. (S) -Epichlorohydrin obtained by fractional distillation yielded 36.8 mg (39.8% yield,> 99% ee) and 55.7 mg (50.4% yield) of (R) -3-chloro-1,2-propanediol. Got it.

Example 18 Preparation of Chiral Epoxides and Chiral Diols and Recovery of Chiral Catalysts

In a 10 ml flask, 3a (37.4 mg, 0.05 mmol) having MA of Co-PF ₆ was added to 1.5 milliliters of tetrahydrofuran and 0.5 milliliters of PF ₆ salt of 3-butyl-1-methylimidazolysin in a compound of Formula 1 Dissolve in and add epichlorohydrin (0.78ml, 10mmol) and water (0.126ml, 7mmol) and stir at 20 ° C for 24 hours. Fractional distillation from the reaction mixture under reduced pressure yields epichlorohydrin. 10 mL of water is added to the distillation residue to extract 3-chloro-1,2-propanediol. The water layer was concentrated and diethyl ether was added to extract 3-chloro-1,2-propanediol. The optical purity of ( S ) -epichlorohydrin obtained by distillation was measured by gas chromatography, and the column used was separated by chiraldex γ-TA, and the temperature conditions were 10.1 minutes ( S ) at 40 ° C isothermal conditions, respectively. Isolated at 13.2 min ( R ). And the optical purity of (R) -3-chloro-1,2-propanediol is obtained by reacting 3-chloro-1,2-propanediol with 2,2-dimethoxypropane in the presence of a catalytic amount of p-toluenesulfonic acid. Synthesis was carried out by gas chromatography and the column was separated by chromium-pack chiraldex-CB, and the temperature conditions were separated at 11.8 minutes ( S ) and 13.4 minutes ( R ) at 60 ° C isothermal conditions, respectively. Epichlorohydrin obtained by fractional distillation yielded 34.1 mg (36.8% yield,> 99% ee), and 52.0 mg (47.1% yield, 92% ee) of (R) -3-chloro-1,2-propanediol. Got it.

Example 19 Preparation of Chiral Epoxides and Chiral Diols and Recovery of Chiral Catalysts

In a 10 ml flask, 3a (37.4 mg, 0.05 mmol) in which MA is Co-PF ₆ was added to 1.0 milliliter of PF ₆ salt of 3-butyl-1-methylimidazolysin in the compound of Formula 1 and stirred. Epichlorohydrin (0.78ml, 10mmol) and water (0.126ml, 7mmol) were added and stirred at 20 ° C for 24 hours. Fractional distillation from the reaction mixture under reduced pressure yields ( S ) -epichlorohydrin. 10 milliliters of water is added to the distillation residue to extract 3-chloro-1,2-propanediol. The water layer was concentrated and diethyl ether was added to extract 3-chloro-1,2-propanediol. The optical purity of the epichlorohydrin obtained by distillation was measured by gas chromatography. The column used was separated by chiraldex γ-TA, and the temperature conditions were 10.1 minutes ( S ) and 13.2 minutes ( R , respectively, at 40 ° C isothermal conditions. ) The optical purity of 3-chloro-1,2-propanediol was synthesized as a ketal derivative by reacting 3-chloro-1,2-propanediol with 2,2-dimethoxypropane in the presence of a catalytic amount of p-toluenesulfonic acid. Measured by gas chromatography, the column used was separated by chromium pack chiraldex-CB, and the temperature conditions were separated at 11.8 minutes ( S ) and 13.4 minutes ( R ) at 60 ° C isothermal conditions, respectively. ( S ) -Epichlorohydrin obtained by fractional distillation gave 35.6 mg (38.5% yield,> 99% ee), and (R) -3-chloro-1,2-propanediol 57.0 mg (51.6% yield, 90 % ee) was obtained.

Example 20 Preparation of Chiral Epoxide and Chiral Diol and Recovery of Chiral Catalyst

In a 10 ml flask, 3a (37.4 mg, 0.05 mmol) having Co of PF ₆ was dissolved in 1.5 milliliter of dichloromethane and 0.5 milliliter of PF ₆ salt of 3-butyl-1-methylimidazolysin in 1.5 mL of the compound of Formula 1. Epichlorohydrin (0.78ml, 10mmol) and water (0.126ml, 7mmol) were added and stirred at 20 ° C for 24 hours. Fractional distillation from the reaction mixture under reduced pressure yields ( S ) -epichlorohydrin. 10 milliliters of water is added to the distillation residue to extract 3-chloro-1,2-propanediol. ( S ) -Epichlorohydrin in dichloromethane was obtained by distillation. The water layer was concentrated and diethyl ether was added to extract 3-chloro-1,2-propanediol. The optical purity of ( S ) -epichlorohydrin obtained by distillation was measured by gas chromatography, and the column used was separated by chiraldex γ-TA, and the temperature conditions were 10.1 minutes ( S ) at 40 ° C isothermal conditions, respectively. 13.2 minutes ( R ) and the optical purity of 3-chloro-1,2-propanediol was determined to be 3-chloro-1,2-propanediol in the presence of a catalytic amount of p-toluenesulfonic acid 2,2-dimethoxypropane After reacting with a ketal derivative, it was synthesized by gas chromatography, and the column was separated by chromium pack chiraldex-CB, and the temperature conditions were 11.8 minutes ( S ) and 13.4 minutes ( R ) at 60 ° C isothermal conditions, respectively. Separated from. ( S ) -Epichlorohydrin obtained by fractional distillation gave 35.8 mg (38.7% yield,> 99% ee), and (R) -3-chloro-1,2-propanediol 45.9 mg (41.5% yield, 92 % ee) was obtained.

Example 21 Preparation of Chiral Epoxide and Chiral Diol and Recovery of Chiral Catalyst

In a 10 ml flask, 3a (18.7 mg, 0.025 mmol) having MA of Co-PF _{6 was} mixed with 1.5 milliliters of tetrahydrofuran and 0.5 milliliters of PF ₆ salt of 3-butyl-1-methylimidazolidin in a compound of Formula 1 Dissolve in and add epichlorohydrin (0.78ml, 10mmol) and water (0.126ml, 7mmol) and stir at 20 ° C for 24 hours. Fractional distillation from the reaction mixture under reduced pressure yields epichlorohydrin. 10 milliliters of water is added to the distillation residue to extract 3-chloro-1,2-propanediol. ( S ) -Epichlorohydrin in dichloromethane was obtained by distillation. The water layer was concentrated and diethyl ether was added to extract 3-chloro-1,2-propanediol. The optical purity of ( S ) -epichlorohydrin obtained by distillation was measured by gas chromatography, and the column used was separated by chiraldex γ-TA, and the temperature conditions were 10.1 minutes ( S ) at 40 ° C isothermal conditions, respectively. Isolated at 13.2 min ( R ). And the optical purity of (R) -3-chloro-1,2-propanediol is obtained by reacting 3-chloro-1,2-propanediol with 2,2-dimethoxypropane in the presence of a catalytic amount of p-toluenesulfonic acid. Synthesis was carried out by gas chromatography and the column was separated by chromium-pack chiraldex-CB, and the temperature conditions were separated at 11.8 minutes ( S ) and 13.4 minutes ( R ) at 60 ° C isothermal conditions, respectively. Epichlorohydrin obtained by fractional distillation gave 35.1 mg (37.9% yield, 75.6% ee) and 50.0 mg (45.2% yield, 89% ee) of 3-chloro-1,2-propanediol.

Example 22 Preparation of Chiral Epoxides and Chiral Diols and Recovery of Chiral Catalysts

In a 10 ml flask, 3 a (17.3 mg, 0.025 mmol) having Co of BF ₄ in MA was mixed with 1.5 milliliters of tetrahydrofuran and 0.5 milliliters of PF ₆ salt of 3-butyl-1-methylimidazolidin in a compound of Formula 1 Dissolve in and add epichlorohydrin (0.78ml, 10mmol) and water (0.126ml, 7mmol) and stir at 20 ° C for 24 hours. Fractional distillation from the reaction mixture under reduced pressure yields ( S ) -epichlorohydrin. 10 milliliters of water is added to the distillation residue to extract 3-chloro-1,2-propanediol. ( S ) -Epichlorohydrin in tetrahydrofuran was distilled off. The water layer was concentrated and diethyl ether was added to extract 3-chloro-1,2-propanediol. The optical purity of ( S ) -epichlorohydrin obtained by distillation was measured by gas chromatography, and the column used was separated by chiraldex γ-TA, and the temperature conditions were 10.1 minutes ( S ) at 40 ° C isothermal conditions, respectively. Isolated at 13.2 min ( R ). And the optical purity of 3-chloro-1,2-propanediol was synthesized as a ketal derivative by reacting 3-chloro-1,2-propanediol with 2,2-dimethoxypropane in the presence of a catalytic amount of p-toluenesulfonic acid. Measured by gas chromatography, the column used was separated by chromium pack chiraldex-CB, and the temperature conditions were separated at 11.8 minutes ( S ) and 13.4 minutes ( R ) at 60 ° C isothermal conditions, respectively. ( S ) -Epichlorohydrin obtained by fractional distillation yielded 36.3 mg (39.2% yield, 97.2% ee), and (R) -3-chloro-1,2-propanediol 51.3 mg (46.4% yield, 91% ee).

Example 23 Preparation of Chiral Epoxides and Chiral Diols and Recovery of Chiral Catalysts

In a 10 ml flask, 3 a (21.0 mg, 0.025 mmol) of MA of Co-SbF _{6 was} mixed with 1.5 milliliters of tetrahydrofuran and 0.5 milliliters of PF ₆ salt of 3-butyl-1-methylimidazolysin in a compound of Formula 1 It is dissolved in ( S ) -Epichlorohydrin (0.78ml, 10mmol) and water (0.126ml, 7mmol) are added and stirred for 24 hours at 20 ℃. Fractional distillation from the reaction mixture under reduced pressure yields ( S ) -epichlorohydrin. 10 milliliters of water is added to the distillation residue to extract 3-chloro-1,2-propanediol. ( S ) -Epichlorohydrin in tetrahydrofuran was distilled off. The water layer was concentrated and diethyl ether was added to extract 3-chloro-1,2-propanediol. The optical purity of ( S ) -epichlorohydrin obtained by distillation was measured by gas chromatography, and the column used was separated by chiraldex γ-TA, and the temperature conditions were 10.1 minutes ( S ) at 40 ° C isothermal conditions, respectively. Isolated at 13.2 min ( R ). The optical purity of 3-chloro-1,2-propanediol was synthesized as a ketal derivative by reacting 3-chloro-1,2-propanediol with 2,2-dimethoxypropane in the presence of a catalytic amount of p-toluenesulfonic acid. Measured by gas chromatography, the column used was separated by chromium pack chiraldex-CB, and the temperature conditions were separated at 11.8 minutes ( S ) and 13.4 minutes ( R ) at 60 ° C isothermal conditions, respectively. ( S ) -Epichlorohydrin obtained by fractional distillation yielded 37.5 mg (40.5% yield,> 99% ee), and (R) -3-chloro-1,2-propanediol 54.3 mg (49.1% yield, 94 % ee) was obtained.

Example catalyst Epoxy compound Solvent ^a Response time (hours) yield(%) % ee 20 Catalyst of Formula 3a (MA = Co-PF ₆ ) Epichlorohydrin [bmim] [PF ₆ ] 0.5 mL + CH ₂ Cl ₂ 1.5 mL 24 39.8 99 ^a 50.4 ^b 21 Catalyst of Formula 3a (MA = Co-PF ₆ ) Epichlorohydrin [bmim] [PF ₆ ] 0.5 mL + THF 1.5 mL 24 36.8 99 ^a 47.1 92 ^b 22 Catalyst of Formula 3a (MA = Co-PF ₆ ) Epichlorohydrin [bmim] [PF ₆ ] 1 ml 24 38.5 99 ^a 51.6 95 ^b 23 Catalyst of Formula 3a (MA = Co-PF ₆ ) Epichlorohydrin [bmim] [PF ₆ ] 0.5 ml 24 38.7 99 ^a 41.5 92 ^b 24 Catalyst of Formula 3a (MA = Co-PF ₆ ) Epichlorohydrin [bmim] [PF ₆ ] 0.5 mL + THF 1.5 mL 24 37.9 75.6 ^a 45.2 89 ^b 25 Catalyst of Formula 3b (MA = Co-BF ₄ ) Epichlorohydrin [bmim] [PF ₆ ] 0.5 mL + THF 1.5 mL 24 39.2 97.2 ^a 46.4 91 ^b 26 Catalyst of Formula 3b (MA = Co-SbF ₆ ) Epichlorohydrin [bmim] [PF ₆ ] 0.5 mL + THF 1.5 mL 24 40.5 99 ^a 49.1 94 ^b

* PF ₆ salt of [bmim] [PF ₆ ]: 3-butyl-1-methylimidazolysone

a: (s) -epichlorohydrin

b: (R) -3-chloro 1,2-propanediol

Experimental Example 4 Reuse of Chiral Catalyst

Using the salt represented by the formula (1) as a solvent to carry out the asymmetric ring opening reaction of the epoxy compound and to test whether the activity and optical selectivity of the catalyst is maintained even if the recovered chiral salen metal catalyst is reused.

In the same manner as in Example 18, in the PF ₆ salt solvent of 3-butyl-1-methylimidazolysin among tetrahydrofuran and the compound of Formula 1, in the chiral salen metal catalyst, in particular, MA is Co-PF ₆ Using the compound of 3a, epichlorohydrin was reacted with water to carry out an asymmetric ring opening reaction. After the reaction, the catalyst recovered in the state of being present in the PF ₆ salt solvent of 3-butyl-1-methylimidazolyol in the compound of Formula 1 was used in the ring-opening reaction in the same manner as in Example 21, and all were five-opened. The reaction was carried out. For epichlorohydrin the catalyst was used at 0.5 mol%.

As a result of the five ring-opening reactions, the yield and optical purity of the divided ( S ) -epiclohydrin are shown in Table 7 below.

Repeat use count Yield (%) Optical purity (% ee) One 37 99 2 37 99 3 38 99 4 36 99 5 38 94.2

As can be seen in Table 7 , tetrahydrofuran and the compound of formula (1), using the PF ₆ salt of 3-butyl-1-methylimidazolysone, MA of Co-PF ₆ ( R, Reuse of the R ) -catalyst resulted in ( S ) -epichlorohydrin showing high yield and optical purity.

Experimental Example 5 Reuse of Chiral Catalyst

Using the salt represented by the formula (1) as a solvent to carry out the asymmetric ring opening reaction of the epoxy compound and to test whether the activity and optical selectivity of the catalyst is maintained even if the recovered chiral salen metal catalyst is reused.

In the same manner as in Example 19, of the compound of formula 1, in the PF ₆ salt solvent of 3-butyl-1-methylimidazolysin, the compound of formula 3a, in which MA is Co-PF ₆ , Epichlorohydrin was used to react with water to effect an asymmetric ring opening. After the reaction, the catalyst recovered in the state of being present in the PF ₆ salt solvent of 3-butyl-1-methylimidazolyol in the compound of Formula 1 was used in the ring-opening reaction in the same manner as in Example 22, and all three times ring-opening The reaction was carried out. For epichlorohydrin the catalyst was used at 0.5 mol%.

As a result of the three ring opening reactions, the yield and optical purity of the divided ( S ) -epichlorohydrin are shown in Table 8 below.

Repeat use count Yield (%) Optical purity (% ee) One 39 99 2 38 99 3 38 89.9

As shown in Table 8 , the ( R, R ) -catalyst of Chemical Formula 3a, wherein MA is Co-PF ₆ , was prepared using the PF ₆ salt of 3-butyl-1-methylimidazolyol in the compound of Chemical Formula 1 As a result of reuse, ( S ) -epichlorohydrin showing high yield and optical purity was obtained.

Experimental Example 6 Reuse of Chiral Catalyst

Using the salt represented by the formula (1) as a solvent to carry out the asymmetric ring opening reaction of the epoxy compound and to test whether the activity and optical selectivity of the catalyst is maintained even if the recovered chiral salen metal catalyst is reused.

In the same manner as in Example 18, in the PF ₆ salt solvent of 3-butyl-1-methylimidazolysin among dichloromethane and the compound of Formula 1, in the chiral salen metal catalyst, in particular, MA is Co-SbF ₆ Epichlorohydrin was reacted with water using a compound of to carry out an asymmetric ring opening reaction. After the reaction, the catalyst recovered in the state of being present in the PF ₆ salt solvent of 3-butyl-1-methylimidazolyol in the compound of Formula 1 was used in the ring-opening reaction in the same manner as in Example 31, and all three times were ring-opened. The reaction was carried out. For epichlorohydrin the catalyst used 0.25 mol%.

As a result of the three ring-opening reactions, the yield and optical purity of the divided ( S ) -epiclohydrin are shown in Table 9 below.

Repeat use count Yield (%) Optical purity (% ee) One 41 99 2 40 92.5 3 42 92.1

As can be seen in Table 9, in the compound of Formula 1, MA is Co-SbF ₆ ( R, R ) using PF ₆ salt of 3-butyl-1-methylimidazolycol and dichloromethane. Reuse of the catalyst resulted in ( S ) -epichlorohydrin showing high yield and optical purity.

The present invention can simply recover the chiral salen metal catalyst without modifying the molecular structure of the catalyst by performing an asymmetric ring opening of the epoxy compound in the salt of formula (1) or a solvent system including the salt, the recovered catalyst is active and optical selectivity Since it can be reused in the reaction, the chiral salen metal catalyst recovery method can be industrially useful.

Claims (16)

A method for producing a chiral compound using asymmetric ring-opening reaction of an epoxy compound in the presence of a chiral salen metal catalyst, wherein the salt represented by the following formula (1) or a mixed solvent comprising the salt is used. Formula 1 In Chemical Formula 1, If X is nitrogen, then Z is -C (R ⁵ )-, R ¹ and R ² are each independently a C ₁ to C ₁₈ alkyl group, R ³ , R ⁴ and R ⁵ are independent of each other and represent hydrogen or an alkyl group of C _{1 to} C ₁₈ . If X is carbon, then Z is -C (R ⁵ ) -C (R ⁶ )-, R ¹ is an alkyl group of C ₁ ~C _18, R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independent of each other and represent hydrogen or an alkyl group of C _{1 to} C ₁₈ , n is an integer of 1 to 3, Y ⁻ is an anion capable of forming a salt. The method of claim 1, wherein the salt is represented by the following formula (2). Formula 2 In Chemical Formula 2, R ¹ and R ² are each independently a C ₁ to C ₁₈ alkyl group, n is an integer of 1 to 3, Y ⁻ represents an anion capable of forming a salt. The method of claim 2, wherein, R ¹ and R ² independently represents an alkyl group of C ₁ -C ₈ with each other, Y ^- is a halogen atom, MX _k ^- or RO ^-, and wherein M is 1B on the periodic table (CAS version), An element of Groups 2B, IIIA, IVA, VA, X is a halogen, k is 2-6, and R is alkylsulfonyl, haloalkyl sulfonyl, phosphoryl or alkylcarbonyl. Manufacturing method. The method for producing a chiral compound according to claim 3, wherein X is fluoride. The compound of claim 2, wherein R ¹ is methyl, R ² is ethyl, propyl, butyl, isobutyl, pentyl, 2-methylbutyl, 3-methylbutyl, hexyl, 2-methylpentyl, 3-methylpentyl, 4- methyl-pentyl, heptyl, and octyl, Y ^- is _{^{CH 3 C00 -, PF 6 -}} , BF 4 -, SbF 6 - or CF ₃ SO ₃ ^- process for producing a chiral compound, characterized in that. The compound of claim 5, wherein in the salt represented by the formula (2)^OneIs methyl and R²Is butyl and Y^-PF₆ ^-, SbF₆ ^-, BF₄ ^-Or CF₃SO₃ ^-Method for producing a chiral compound, characterized in that. The method of claim 1, wherein the chiral salen metal catalyst is represented by the following Chemical Formula 3. Formula 3 In Chemical Formula 3, R ¹ , R ² , R ³ and R ⁴ are chiral substituents which are independent of each other hydrogen, alkyl, carboxyl, aryl, and substituted aryl groups. Substituents for aryl groups are halogen, alkyl, alkoxy, cyano and nitro. Or R ¹ , R ² , R ³ and R ⁴ may be linked to each other to form a ring of C ₄ -C ₈ , X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ and X ⁸ are independently of each other hydrogen, halogen, alkyl, silyl, silyloxy, alkenyl, alkynyl, hydroxy, alkoxy, amino , Nitro, cyano, thiol, thioether, imino, amido, phosphoryl, carbonyl and sulfonyl, Y ¹ and Y ² are independent of each other and are a hydrogen and an alkyl group. M is a metal A represents an anion. The method of claim 7, wherein the chiral salen metal catalyst represented by Chemical Formula 3 is represented by the following Chemical Formulas 3a, 3b, 3c and 3d. Formula 3a Formula 3b Formula 3c Chemical formula 3d In Chemical Formulas 3a, 3b, 3c, and 3d, M is Al, Mn, Cr, Fe, Ti, V, Ru, Co or Os A ^- is _{^{Cl -, N 3-, CH 3}} COO -, BF 4 -, PF 6 - or SbF ₆ ^- a. According to claim 8, MA in the chiral salen metal catalyst represented by the following formulas 3a, 3b, 3c and 3d is Cr-Cl, Cr-N ₃ , Co-OAc, Co-BF ₄ , Co-PF ₆ and Co- SbF ₆ A process for producing a chiral compound The method of claim 1, wherein the chiral salen metal catalyst is represented by the following general formula (4). Formula 4 In Chemical Formula 4, R ¹ and R ² are hydrogen, alkyl, carboxyl, aryl and substituted aryl groups which are independent of each other in the position of trans and are substituents of aryl groups are halogen, alkyl, alkoxy, cyano and nitro groups, B is oxygen, NR, sulfur, sulfone or sulfoxide and in the NR group R is alkyl, aryl, alkylcarbonyl (-C (O) R), arylcarbonyl (-C (O) Ar), alkylcarboxyl ( -C (O) OR), arylcarboxyl (-C (O) OAr), alkylsulfonyl (-S (O) ₂ R) and arylsulfonyl group (-S (O) ₂ Ar), n is 1 to 3, X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ and X ⁸ are independently of each other hydrogen, halogen, alkyl, silyl, silyloxy, alkenyl, alkynyl, hydroxy, alkoxy, amino , Nitro, cyano, thiol, thioether, imino, amido, phosphoryl, carbonyl and sulfonyl. Y ¹ and Y ² are independent of each other and are hydrogen or an alkyl group, M is a metal A is an anion. The method of claim 10, wherein the chiral salen metal catalyst represented by Chemical Formula 4 is represented by Chemical Formulas 4a and 4b. Formula 4a Formula 4b In Chemical Formulas 4a and 4b, R is alkyl, aryl, alkylcarbonyl (-C (O) R), arylcarbonyl (-C (O) Ar), alkylcarboxyl (-C (O) OR), arylcarboxyl (-C (O ) OAr), alkylsulfonyl (-S (O) ₂ R) and arylsulfonyl group (-S (O) ₂ Ar), M is Al, Mn, Cr, Fe, Ti, V, Ru, Co or Os A ^- is _{^{Cl -, N 3 -, CH}} 3 COO -, BF 4 -, PF 6 - or SbF ₆ ^- a. The method according to claim 11, wherein in the chiral salen metal catalyst represented by the following formulas 4a and 4b MA is Cr-Cl, Cr-N ₃ , Co-OAc, Co-BF ₄ , Co-PF ₆ and Co-SbF ₆ Method for producing a chiral compound The method of claim 1, wherein the chiral salen metal catalyst is represented by the following formula (5): Formula 5 In Chemical Formula 5, X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ , X ⁷ and X ⁸ are independently of each other hydrogen, halogen, alkyl, silyl, silyloxy, alkenyl, alkynyl, hydroxy, alkoxy, amino , Nitro, cyano, thiol, thioether, imino, amido, phosphoryl, carbonyl and sulfonyl, Y ¹ and Y ² are independent of each other and are hydrogen or an alkyl group, Z ¹ , Z ² , Z ³ and Z ⁴ are hydrogen, alkyl, halogen, cyano or nitro groups independent of each other. M is a metal A is an anion. The method of claim 13, wherein the chiral salen metal catalyst represented by Chemical Formula 5 is represented by Chemical Formula 5a. Formula 5a In Chemical Formula 5a, M is Al, Mn, Cr, Fe, Ti, V, Ru, Co or Os A is _{^{Cl -, N 3-, CH 3}} COO -, BF 4 -, PF 6 - or SbF ₆ ^- a. The method of claim 1, wherein the chiral salen metal catalyst is represented by the following formula (6): Formula 6 In Chemical Formula 6, R ¹ , R ² , R ³ and R ⁴ are hydrogen, alkyl, carboxyl, aryl or substituted aryl groups independent of each other and the substituents of the aryl groups are halogen, alkyl, alkoxy, cyano or nitro groups, R ¹ , R ² , R ³ and R ⁴ may be linked to each other to form a ring of C ₄ to C ₈ , X ¹ , X ² , X ³ , X ⁴ , X ⁵ and X ⁶ are independently of each other hydrogen, halogen, alkyl, silyl, silyloxy, alkenyl, alkynyl, hydroxy, alkoxy, amino, nitro, thiol, thio Ether, cyano, imino, amido, phosphoryl, carbonyl or sulfonyl, X ¹ and X ² , X ⁴ and X ⁵ can be connected to each other to form a benzene ring, R ⁵ , R ⁶ , R ⁷ and R ⁸ are substituents giving chirality and are independently alkyl, aryl or substituted aryl groups, and substituents of aryl groups are halogen, alkyl, alkoxy, cyano or nitro groups and R ⁵ And R ⁶ , R ⁷ and R ⁸ may be linked to each other to form a naphthyl group or a naphthyl group substituted with an alkyl or aryl group. Y ¹ and Y ² are independent of each other and are hydrogen, an alkyl group, M is a metal A is an anion. The method of claim 15, wherein the chiral salen metal catalyst represented by Chemical Formula 6 is represented by the following Chemical Formulas 6a, 6b, 6c and 6d. Formula 6a Formula 6b Formula 6c Chemical Formula 6d In Chemical Formulas 6a, 6b, 6c, and 6d, Hydrogen atoms (1) and (2) are in trans position with each other R ¹ is hydrogen or a methyl group, R ² is a methyl group or a phenyl group, preferably a phenyl group. M is Cr or Co, A ^- is _{^{Cl -, N 3-, CH 3}} COO -, BF 4 -, PF 6 - or SbF ₆ ^- a.