JP2015061834A - Imidazolium salt, asymmetric synthesis catalyst using the same, and method for producing imidazolium salt - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel optically active imidazolium salt for the synthesis of nitrogen-containing heterocyclic carbene as the ligand of organic catalyst and metal catalyst, in particular a bicyclic optically active imidazolium salt, and a method of producing the same.SOLUTION: The present invention provides an imidazolium salt represented by formula (1). (R1-R5 are H, hydrocarbon groups each independently or adjacently forming a ring, alkoxy groups, aryloxy groups, alkylthio groups, arylsulfonyl groups, or the like; X is a substituted/unsubstituted C1-C4 carbon chain, a substituted/unsubstituted N, O, S, or an atom group comprising a combination of Cs optionally substituted with these hetero atoms; Z is a halogen atom, PF6, BF4, ClO4, or BPh4).

Description

  The present invention relates to an imidazolium salt, an asymmetric synthesis catalyst using the imidazolium salt, and a method for producing an imidazolium salt.

  Nitrogen-containing heterocyclic carbenes prepared from optically active imidazolium salts are useful as ligands for organic catalysts and metal catalysts. Recently, the use of polycyclic optically active imidazolium salts has attracted attention. Examples of known synthesis methods include the following Non-Patent Documents 1 to 4.

N-Heterocyclic Carbanes in Synthesis; P. Ed. Wiley-VCH; Weinheim, 2006 .; N-Heterocyclic Carbanes in Transition Metal Catalysis; Glorius, F .; Ed. Springer; Berlin, 2007 .; Enders, D.D. Niemeier, O .; Henseler, A .; Chem. Rev. 2007, 107, 5606-5655. Diez-Gonzalez, S.A. Marion, N .; Nolan, S .; P. Chem. Rev. 2009, 109, 3612-3676.

  However, there are many imidazolium salts that are difficult to synthesize with the above synthesis method.

  Then, in view of the said subject, this invention aims at manufacturing various optically active imidazolium salt efficiently and simply, and providing these.

  The present inventors have studied the above problems, developed a new bicyclic optically active imidazole, and reacted it with an electrophile such as an alkyl halide to produce various optically active bicyclic imidazolium salts. Synthesized.

That is, the imidazolium salt according to the first aspect of the present invention is represented by the following general formula (1).

In the above formula, R ^{1 to} R ⁵ are each a hydrogen atom, a C _{1 to} C ₂₀ hydrocarbon group that may have a substituent, a C _{1 to} C ₂₀ alkoxy group that may have a substituent, or a substituent. good C ₆ -C ₂₀ aryloxy group which may have a group, which may have a substituent amino group, which may have a substituent phosphino group, which may have a substituent A silyl group, an alkylthio group which may have a substituent (-SY ¹ , wherein Y ¹ represents a C _{1 to} C ₂₀ alkyl group which may have a substituent), and a substituent. An optionally substituted arylthio group (—SY ² , wherein Y ² represents an optionally substituted C _{6 to} C ₂₀ aryl group), an optionally substituted alkylsulfonyl group _(SO 2 ^{Y 3,} wherein, ^{Y 3} good _C 1 _{-C 20} alkyl which may have a substituent A group.), Which may have a substituent or an arylsulfonyl group _(-SO 2 ^{Y 4,} in ^the formula, ^{Y 4} is a good _C 6 _{-C 20} aryl group which may have a substituent. ), A hydroxyl group or a halogen atom. R ^{1 to} R ⁵ are independent of each other and may be the same or different. In addition, R ¹ and R ² , R ³ and R ⁴ , and R ⁴ and R ⁵ may be mutually bridged to form a C _{4 to} C ₁₀ saturated ring or unsaturated ring. represents an oxygen atom, a sulfur atom, a silicon atom, tin atom, germanium atom or -N (B) - interrupted by a group represented by (wherein B is a hydrogen atom or a _C 1 _{-C 10} hydrocarbon group.) And may have a substituent. Further, X in the above formulas may have a substituent group C ₁ -C ₄ carbon atoms, a nitrogen atom which may have a substituent, an oxygen atom, a sulfur atom, also substituent as these heteroatoms Is an atomic group composed of any combination of carbon atoms which may have Z in the above formula represents a halogen atom, PF ₆ , BF ₄ , ClO ₄ , or BPh ₄ .

Moreover, the imidazolium salt which concerns on the 2nd viewpoint of this invention is represented by following General formula (2).

In the above formula, R ^{2 to} R ⁵ are each a hydrogen atom, a C _{1 to} C ₂₀ hydrocarbon group that may have a substituent, a C _{1 to} C ₂₀ alkoxy group that may have a substituent, A C ₆ -C ₂₀ aryloxy group which may have a substituent, an amino group which may have a substituent, a phosphino group which may have a substituent, or a substituent. A good silyl group, an alkylthio group optionally having a substituent (-SY ¹ , wherein Y ¹ represents a C _{1 to} C ₂₀ alkyl group optionally having a substituent), a substituent; An optionally substituted arylthio group (—SY ² , wherein Y ² represents an optionally substituted C ₆ -C ₂₀ aryl group), an optionally substituted alkyl a sulfonyl group _(-SO 2 ^{Y 3,} wherein, ^{Y 3} good _C 1 _{-C 20} which may have a substituent Shows the alkyl group.), Showing also an optionally substituted arylsulfonyl group _(-SO 2 ^{Y 4,:} in ^the formula, ^{Y 4} is optionally substituted _C 6 _{-C 20} aryl group ), A hydroxyl group or a halogen atom. R ^{2 to} R ⁵ are independent of each other and may be the same or different. R ³ and R ⁴ , and R ⁴ and R ⁵ may be bridged with each other to form a C _{4 to} C ₁₀ saturated ring or unsaturated ring. In the case of the ring, an oxygen atom, sulfur atom, silicon atom, tin atom, germanium atom, or -N (B) - group (where B is a hydrogen atom or a C ₁ -C ₁₀ hydrocarbon group.) represented by may be interrupted by, And you may have a substituent. W in the above formula can be a cross-linked chain, and represents, for example, a C _{1 to} C ₂₀ carbon atom which may have a substituent. Further, X in the above formulas may have a substituent group C ₁ -C ₄ carbon atoms, a nitrogen atom which may have a substituent, an oxygen atom, a sulfur atom, also substituent as these heteroatoms Is an atomic group composed of any combination of carbon atoms which may have Z in the above formula represents a halogen atom, PF ₆ , BF ₄ , ClO ₄ , or BPh ₄ .

Moreover, the manufacturing method of the imidazolium salt which concerns on the 3rd viewpoint of this invention makes the imidazole represented by following General formula (3) react with an electrophile.

In the above formula, R ^{1 to} R ⁵ are each a hydrogen atom, a C _{1 to} C ₂₀ hydrocarbon group that may have a substituent, a C _{1 to} C ₂₀ alkoxy group that may have a substituent, A C ₆ -C ₂₀ aryloxy group which may have a substituent, an amino group which may have a substituent, a phosphino group which may have a substituent, or a substituent. A good silyl group, an alkylthio group optionally having a substituent (-SY ¹ , wherein Y ¹ represents a C _{1 to} C ₂₀ alkyl group optionally having a substituent), a substituent; An optionally substituted arylthio group (—SY ² , wherein Y ² represents an optionally substituted C ₆ -C ₂₀ aryl group), an optionally substituted alkyl a sulfonyl group _(SO 2 ^{Y 3,} wherein, ^{Y 3} good _C 1 _{-C 20} a may have a substituent Indicating Kill group.) Shows also an optionally substituted arylsulfonyl group _(-SO 2 ^{Y 4,:} in ^the formula, ^{Y 4} is optionally substituted _C 6 _{-C 20} aryl group ), A hydroxyl group or a halogen atom. R ^{1 to} R ⁵ are independent of each other and may be the same or different. In addition, R ¹ and R ² , R ³ and R ⁴ , and R ⁴ and R ⁵ may be mutually bridged to form a C _{4 to} C ₁₀ saturated ring or unsaturated ring. represents an oxygen atom, a sulfur atom, a silicon atom, tin atom, germanium atom, or -N (B) - interrupted by a group represented by (wherein B is a hydrogen atom or a _C 1 _{-C 10} hydrocarbon group.) And may have a substituent. Further, X in the above formulas may have a substituent group C ₁ -C ₄ carbon atoms, a nitrogen atom which may have a substituent, an oxygen atom, a sulfur atom, also substituent as these heteroatoms Is an atomic group composed of any combination of carbon atoms which may have

  The asymmetric synthesis catalyst according to the fourth aspect of the present invention is an asymmetric synthesis catalyst using a nitrogen-containing heterocyclic carbene prepared from the imidazolium salt according to the first aspect or the second aspect. .

  Hereinafter, embodiments for carrying out the present invention will be described in detail. However, the present invention can be implemented in many different forms, and is not limited to the description of the following embodiments and examples.

(Embodiment 1)
(Imidazolium salt)
The imidazolium salt according to this embodiment is represented by the following general formula (1).

In the above formula, R ^{1 to} R ⁵ are each a hydrogen atom, a C _{1 to} C ₂₀ hydrocarbon group that may have a substituent, a C _{1 to} C ₂₀ alkoxy group that may have a substituent, A C ₆ -C ₂₀ aryloxy group which may have a substituent, an amino group which may have a substituent, a phosphino group which may have a substituent, or a substituent. A good silyl group, an alkylthio group optionally having a substituent (-SY ¹ , wherein Y ¹ represents a C _{1 to} C ₂₀ alkyl group optionally having a substituent), a substituent; An optionally substituted arylthio group (—SY ² , wherein Y ² represents an optionally substituted C ₆ -C ₂₀ aryl group), an optionally substituted alkyl a sulfonyl group _(-SO 2 ^{Y 3,} wherein, ^{Y 3} good _C 1 _{-C 20} which may have a substituent Shows the alkyl group.), Showing also an optionally substituted arylsulfonyl group _(-SO 2 ^{Y 4,:} in ^the formula, ^{Y 4} is optionally substituted _C 6 _{-C 20} aryl group ), A hydroxyl group or a halogen atom. R ^{1 to} R ⁵ are independent of each other and may be the same or different. In addition, R ¹ and R ² , R ³ and R ⁴ , and R ⁴ and R ⁵ may be mutually bridged to form a C _{4 to} C ₁₀ saturated ring or unsaturated ring. represents an oxygen atom, a sulfur atom, a silicon atom, tin atom, germanium atom, or -N (B) - interrupted by a group represented by (wherein B is a hydrogen atom or a _C 1 _{-C 10} hydrocarbon group.) And may have a substituent. Further, X in the above formulas may have a substituent group C ₁ -C ₄ carbon atoms, a nitrogen atom which may have a substituent, an oxygen atom, a sulfur atom, also substituent as these heteroatoms Is an atomic group composed of any combination of carbon atoms which may have Z in the above formula represents a halogen atom, PF ₆ , BF ₄ , ClO ₄ , or BPh ₄ .

In the present specification and claims, the hydrocarbon group of the “C ₁ -C ₂₀ hydrocarbon group” may be a saturated or unsaturated acyclic group, or a saturated or unsaturated ring. It may be a formula. When the C _{1 to} C ₂₀ hydrocarbon group is acyclic, it may be linear or branched. “C ₁ -C ₂₀ hydrocarbon group” includes C ₁ -C ₂₀ alkyl group, C ₂ -C ₂₀ alkenyl group, C ₂ -C ₂₀ alkynyl group, C ₄ -C ₂₀ alkyl dienyl group, C ₆ -C ₂₀ ants - le _group, C 6 _{-C 20} alkylaryl _group, C 6 _{-C 20} arylalkyl _group, C 3 _{-C 20} cycloalkyl _group, C 3 _{-C 20} cycloalkenyl _{group, (C} 3 _{~C 10} cycloalkyl ), etc. _C 1 _{-C 20} alkyl group.

In the present specification and claims, _"C 1 _{-C 20} alkyl group" _is preferably C 1 _{-C 10} alkyl _group, more preferably a C 1 -C ₆ alkyl group. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, dodecanyl and the like.

In the present specification and claims, _"C 2 _{-C 20} alkenyl group" _is preferably C 2 _{-C 10} alkenyl _group, more preferably a C 2 -C ₆ alkenyl group. Examples of alkenyl groups include, but are not limited to, vinyl, allyl, propenyl, isopropenyl, 2-methyl-1-propenyl, 2-methylallyl, 2-butenyl and the like.

In the present specification and claims, _"C 2 _{-C 20} alkynyl group" _is preferably C 2 _{-C 10} alkynyl _group, more preferably a C 2 -C ₆ alkynyl group. Examples of alkynyl groups include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, and the like.

In the present specification and claims, _"C 4 _{-C 20} alkyldienyl group" _is preferably C 4 _{-C 10} alkadienyl _group, are C 4 -C ₆ alkadienyl group More preferably. Examples of alkyldienyl groups include, but are not limited to, 1,3-butadienyl.

In the present specification and claims, the “C ₆ -C ₂₀ aryl group” is preferably a C ₆ -C ₁₀ aryl group. Examples of the aryl group include, but are not limited to, phenyl, 1-naphthyl, 2-naphthyl, indenyl, biphenylyl, anthryl, phenanthryl and the like.

In the present specification and claims, the “C ₆ -C ₂₀ alkyl aryl group” is preferably a C ₆ -C ₁₂ alkyl aryl group. Examples of alkylaryl groups include, but are not limited to, o-tolyl, m-tolyl, p-tolyl, 2,3-xylyl, o-cumenyl, m-cumenyl, p-cumenyl, mesityl, and the like. Can be mentioned.

In the present specification and claims, the “C ₆ -C ₂₀ arylalkyl group” is preferably a C ₆ -C ₁₂ arylalkyl group. Examples of arylalkyl groups include, but are not limited to, benzyl, phenethyl, diphenylmethyl, triphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 2,2-diphenylmethyl, 3-phenylpropyl, 4-phenyl Examples include phenylbutyl and 5-phenylpentyl.

In the present specification and claims, the “C ₃ -C ₂₀ cycloalkyl group” is preferably a C ₃ -C ₁₀ cycloalkyl group. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

In the present specification and claims, the “C ₃ -C ₂₀ cycloalkenyl group” is preferably a C ₃ -C ₁₀ cycloalkenyl group. Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, 2-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-cyclohexen-1-yl, and the like.

In the present specification and claims, the “C ₁ -C ₂₀ alkoxy group” is preferably a C ₁ -C ₁₀ alkoxy group, and more preferably a C ₁ -C ₆ alkoxy group. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, pentyloxy and the like.

In the present specification and claims, the “C ₆ -C ₂₀ aryloxy group” is preferably a C ₆ -C ₁₀ aryloxy group. Examples of aryloxy groups include, but are not limited to, phenyloxy, naphthyloxy, biphenylyloxy, and the like.

In the present specification and claims, “alkylthio group (—SY ¹ , wherein Y ¹ represents an optionally substituted C ₁ -C ₂₀ alkyl group)” and “alkylsulfonyl”. In the group (—SO ₂ Y ³ , wherein Y ³ represents an optionally substituted C ₁ -C ₂₀ alkyl group) ”, Y ¹ and Y ³ are C ₁ -C ₁₀ alkyl. It is preferably a group, and more preferably a C ₁ -C ₆ alkyl group. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, dodecanyl and the like.

Further, in the present specification and claims, “C ₁ -C ₂₀ hydrocarbon group”, “C ₁ -C ₂₀ alkoxy group”, “C ₆ -C ₂₀ aryloxy group” represented by R ^{1 to} R ¹⁶ ”,“ Amino group ”,“ silyl group ”,“ alkylthio group ”,“ arylthio group ”,“ alkylsulfonyl group ”, and“ arylsulfonyl group ”may have a substituent introduced therein. Examples of the substituent include a C _{1 to} C ₁₀ hydrocarbon group (for example, methyl, ethyl, propyl, butyl, phenyl, naphthyl, indenyl, tolyl, xylyl, benzyl, etc.), a C _{1 to} C ₁₀ alkoxy group (for example, , Methoxy, ethoxy, propoxy, butoxy, etc.), C ₆ -C ₁₀ aryloxy groups (eg, phenyloxy, naphthyloxy, biphenyloxy, etc.) amino groups, hydroxyl groups, halogen atoms (eg, fluorine, chlorine, bromine, iodine) Or a silyl group etc. can be mentioned. In this case, one or more substituents may be introduced at substitutable positions, and preferably 1 to 6 substituents may be introduced. When the number of substituents is 2 or more, each substituent may be the same or different.

  In the present specification and claims, examples of the “optionally substituted amino group” include, but are not limited to, amino, dimethylamino, methylamino, methylphenylamino, phenyl There are amino and the like.

In the present specification and claims, examples of “atom group consisting of any combination of heteroatoms and optionally substituted carbon atoms” are not limited, but include —CH _{2 -CH 2 -CH 2 -O -,} - CH 2 -S-CH 2 -, - there is CH 2 -O- and the like.

  Further, in the present specification and claims, examples of “optionally substituted silyl group” include, but are not limited to, trimethylsilyl, triethylsilyl, trimethoxysilyl, triethoxysilyl, Examples include diphenylmethylsilyl, triphenylsilyl, triphenoxysilyl, dimethylmethoxysilyl, dimethylphenoxysilyl, methylmethoxyphenyl, and the like.

In the present specification and claims, the substituents represented by R ^{1 to} R ⁵ may be bridged with each other to form a C _{4 to} C ₂₀ saturated ring or an unsaturated ring. The ring formed by these substituents is preferably a 4- to 12-membered ring, more preferably a 4- to 6-membered ring. This ring may be an aromatic ring such as a benzene ring or an aliphatic ring. One or more rings may be further formed on the ring formed by these substituents. It said saturated ring or unsaturated ring, oxygen atom, sulfur atom, silicon atom, tin atom, germanium atom or -N (B) - is a hydrogen atom or a C ₁ is (B represented by -C ₂₀ hydrocarbon group. ) May be interrupted. That is, the saturated ring or unsaturated ring may be a heterocyclic ring. And you may have a substituent. The unsaturated ring may be an aromatic ring such as a benzene ring. B is preferably a hydrogen atom or a C _{1 to} C ₁₀ hydrocarbon group, more preferably a hydrogen atom or a C _{1 to} C ₇ hydrocarbon group, and B is a hydrogen atom, a C _{1 to} C ₃ alkyl group. Still more preferably, it is a phenyl group or a benzyl group. This saturated ring or unsaturated ring may have a substituent, for example, a C _{1 to} C ₁₀ hydrocarbon group (for example, methyl, ethyl, propyl, butyl group), a C _{1 to} C ₁₀ alkoxy group ( For example, methoxy, ethoxy, propoxy, butoxy, etc.), C ₆ -C ₁₀ aryloxy groups (eg, phenyloxy, naphthyloxy, biphenyloxy etc.), amino groups, hydroxyl groups, halogen atoms (eg, fluorine, chlorine, bromine, etc.) Substituents such as iodine) or silyl groups may be introduced.

  In the present specification and claims, the “aromatic ring” includes a monocyclic aromatic ring and a polycyclic aromatic ring. Examples of the “monocyclic aromatic ring” include a benzene ring, a 5-membered or 6-membered heterocyclic ring. Examples of the “5-membered or 6-membered heterocyclic ring” include furan, thiophene, pyrrole, pyran, thiopyran, pyridine, thiazole, imidazole, pyrimidine, 1,3,5-triazine and the like. Examples of the “polycyclic aromatic ring” include a polycyclic aromatic hydrocarbon and a polycyclic heteroaromatic ring. Examples of the “polycyclic heterohydrocarbon” include biphenyl, triphenyl, naphthalene, indene, anthracene, phenanthrene and the like. Examples of the “polycyclic heteroaromatic ring” include indole, quinoline, purine and the like.

In the present specification and claims, W can be a crosslinked chain, and represents, for example, a C _{1 to} C ₂₀ carbon atom which may have a substituent. X is a C _{1 to} C ₄ carbon atom which may have a substituent, a nitrogen atom, an oxygen atom or a sulfur atom which may have a substituent. Z represents a halogen atom, PF ₆ , BF ₄ , ClO ₄ , or BPh ₄ .

(Method for producing imidazolium salt)
Moreover, the imidazolium salt which concerns on this embodiment can be manufactured by making the imidazole represented by following General formula (3) react with an electrophile.

In the above formula, R ^{2 to} R ⁵ and X are the same as defined above.

In the present specification and claims, the electrophile is not limited as long as it can modify the nitrogen atom, and examples thereof include an alkyl halide (R ¹ Z). R ¹ and Z are the same as defined above.

  In this embodiment, imidazole and an electrophile may be used as they are, or may be supported on a substance that does not dissolve in a solvent used for the reaction, such as carbon, silica, alumina, and the like. In such a reaction, the amount of imidazole used is usually 0.01 mol times or more, usually 100 mol times or less, preferably 0.5 mol times or more and 2 times or less with respect to the electrophile.

  This reaction is usually performed in an organic solvent. Examples of organic solvents include aprotic polar solvents such as N-methylpyrrolidone, N, N-dimethylformamide, dimethyl sulfoxide and acetonitrile, protic solvents such as water, methanol and ethanol, diethyl ether, diisopropyl ether, diethylene glycol dimethyl ether, 1 Ether solvents such as 1,4-dioxane and tetrahydrofuran, aromatic hydrocarbons such as benzene, toluene and xylene, aliphatic hydrocarbons such as hexane and heptane, and halogen-containing solvents such as dichloromethane, chloroform and dichloroethane. . The solvents are used alone or in combination of two or more, and the amount used is usually 1 to 2000 times, preferably 5 to 500 times, the raw material.

  Further, the above reaction may be performed in air or in an atmosphere of nitrogen or argon gas. The gas pressure is usually about 1 to 500 atmospheres, preferably about 1 to 5 atmospheres.

  The above reaction is preferably performed in a temperature range of −78 ° C. or higher and 200 ° C. or lower, more preferably in a temperature range of 0 ° C. or higher and 150 ° C. or lower, and still more preferably in a temperature range of 20 ° C. or higher and 100 ° C. or lower.

  The reaction time for the above reaction is not particularly limited, but is preferably 1 minute to 120 hours, more preferably 10 minutes to 72 hours.

  And after completion | finish of this reaction, the produced | generated imidazolium salt represented by the said General formula (1) can be taken out from a reaction mass by distilling a solvent off, for example. Further, the obtained imidazolium salt can be further purified by applying means such as recrystallization as necessary.

  In this reaction, imidazole, electrophile, and solvent can be added in any order.

(Method for producing imidazole (1))
Next, a method for producing the imidazole represented by the general formula (3) will be described.

The imidazole represented by the general formula (3) is obtained by obtaining the peptide of the general formula (6) from the amino acid derivative represented by the following general formula (4) or (5), and further by the following general formula (7). It can be obtained via the represented oxazoline.

  Here, the peptide represented by the general formula (6) may be used as it is, or may be supported on a substance that does not dissolve in the solvent used in the reaction, for example, carbon, silica, alumina or the like.

  This reaction is usually performed in an organic solvent. Examples of organic solvents include aprotic polar solvents such as N-methylpyrrolidone, N, N-dimethylformamide, dimethyl sulfoxide, acetonitrile, protic solvents such as water, methanol, ethanol, diethyl ether, diisopropyl ether, diethylene glycol dimethyl ether. Ether solvents such as 1,4-dioxane and tetrahydrofuran, aromatic hydrocarbons such as benzene, toluene and xylene, aliphatic hydrocarbons such as hexane and heptane, and halogen-containing solvents such as dichloromethane, chloroform and dichloroethane. Can be mentioned. The solvents are used alone or in combination of two or more, and the amount used is usually 1 to 2000 times, preferably 5 to 500 times, the raw material.

  Further, the above reaction may be performed in air or in an atmosphere of nitrogen or argon gas. The gas pressure is usually about 1 to 500 atmospheres, preferably about 1 to 5 atmospheres.

  The above reaction is preferably performed in a temperature range of −78 ° C. or higher and 200 ° C. or lower, more preferably 0 ° C. or higher and 150 ° C. or lower, and further preferably 20 ° C. or higher and 100 ° C. or lower.

  The reaction time for the above reaction is not particularly limited, but is preferably 1 minute to 120 hours, more preferably 10 minutes to 72 hours.

  And after completion | finish of this reaction, the produced | generated imidazole represented by the said General formula (3) can be taken out from a reaction mass by distilling a solvent off, for example. Moreover, the obtained imidazole can be further purified by applying means such as recrystallization as necessary.

(Method for producing imidazole (2))
The imidazole represented by the general formula (3) is converted from the aldehyde represented by the general formula (9) obtained from the urocaic acid derivative (8) via the alcohol represented by the general formula (10). Can be obtained.

  In this production method, the aldehyde represented by the general formula (9) may be used as it is, or may be supported on a substance that does not dissolve in the solvent used for the reaction, such as carbon, silica, alumina, and the like.

  This reaction is usually performed in an organic solvent. Examples of the organic solvent include aprotic polar solvents such as N-methylpyrrolidone, N, N-dimethylformamide, dimethyl sulfoxide, and acetonitrile, protic solvents such as water, methanol and ethanol, diethyl ether, and diisopropyl ether. -Ether solvents such as ter, diethylene glycol dimethyl ether, 1,4-dioxane, tetrahydrofuran, aromatic hydrocarbons such as benzene, toluene, xylene, aliphatic hydrocarbons such as hexane, heptane, dichloromethane, And halogen-containing solvents such as chloroform and dichloroethane. The solvents are used alone or in combination of two or more, and the amount used is usually 1 to 2000 times, preferably 5 to 500 times, the raw material.

  The above reaction may be performed in air or in an atmosphere of nitrogen or argon gas. The gas pressure is usually about 1 to 500 atmospheres, preferably about 1 to 5 atmospheres.

  The above reaction is preferably performed in a temperature range of −78 ° C. or higher and 200 ° C. or lower, more preferably 0 ° C. or higher and 150 ° C. or lower, and further preferably 20 ° C. or higher and 100 ° C. or lower.

  The reaction time for the above reaction is not particularly limited, but is preferably 1 minute to 120 hours, more preferably 10 minutes to 72 hours.

  After the reaction is completed, the imidazole represented by the general formula (3) can be removed from the reaction mass by, for example, distilling off the solvent. Moreover, the obtained imidazole can be further purified by applying means such as recrystallization as necessary.

  When the imidazole represented by the general formula (3) is obtained as a racemate, optically active imidazole can be obtained by performing resolution. The optical resolution is preferably a method of deriving to a diastereomer, but separation by a chiral column is also possible.

(Method for producing asymmetric synthesis catalyst using nitrogen-containing heterocyclic carbene)
Next, a method for producing an asymmetric catalyst using a nitrogen-containing heterocyclic carbene from the imidazolium salt represented by the general formula (1) according to the present embodiment will be described.

  This nitrogen-containing heterocyclic carbene can be obtained by allowing a base or the like to act on the imidazolium salt represented by the general formula (1). This carbene has optical activity. The carbene can be used as an organic catalyst as it is, or can be used as a metal catalyst coordinated with carbene by reacting with various metal complexes.

  In the present specification and claims, the base and the like are not limited as long as they can generate carbene, and examples thereof include butyl lithium, tert-butoxy potassium, and sodium hydroxide.

  In this production method, the imidazolium salt and the base may be used as they are, or may be supported on a substance that does not dissolve in the solvent used for the reaction, for example, carbon, silica, alumina or the like. In such a reaction, the amount of imidazole used is usually 0.01 mol times or more, usually 100 mol times or less, preferably 0.5 mol times or more and 2 times or less, relative to the base or the like.

  This reaction is usually performed in an organic solvent. Examples of the organic solvent include aprotic polar solvents such as N-methylpyrrolidone, N, N-dimethylformamide, dimethyl sulfoxide and acetonitrile, water, methanol, ethanol and other protic solvents, diethyl ether, diisopropyl ether, Ether solvents such as diethylene glycol dimethyl ether, 1,4-dioxane and tetrahydrofuran; aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as hexane and heptane; and halogen-containing solvents such as dichloromethane, chloroform and dichloroethane. Etc. The solvents are used alone or in combination of two or more, and the amount used is usually 1 to 2000 times, preferably 5 to 500 times, the raw material.

  Further, the above reaction may be performed in air or in an atmosphere of nitrogen or argon gas. The gas pressure is usually about 1 to 500 atmospheres, preferably about 1 to 5 atmospheres.

  The above reaction is preferably performed in a temperature range of −78 ° C. or higher and 200 ° C. or lower, more preferably in a temperature range of 0 ° C. or higher and 150 ° C. or lower, and still more preferably in a temperature range of 20 ° C. or higher and 100 ° C. or lower.

  The reaction time for the above reaction is not particularly limited, but is preferably 1 minute to 120 hours, more preferably 10 minutes to 72 hours.

  Next, a metal is coordinated to the nitrogen-containing heterocyclic carbene obtained by the above reaction to form a metal complex, and an asymmetric synthesis catalyst is obtained.

  Examples of the metal that can be used when forming the metal complex include rhodium, ruthenium, iridium, palladium, copper, nickel, platinum, cobalt, silver, gold, and iron. As a method of forming a complex with a metal, a known method can be used. For example, it can be obtained by following the methods described in Non-Patent Document 1 and Non-Patent Document 2.

  As described above, according to the present embodiment, an imidazolium salt, which was difficult to synthesize by a conventional method, can be produced efficiently and simply, and further, based on this, a nitrogen-containing heterocyclic carbene and an asymmetric synthesis catalyst can be obtained. it can.

(Embodiment 2)
The present embodiment is almost the same as the first embodiment, and only different parts are described, and the description of the same parts as the first embodiment is omitted.

(Imidazolium salt)
The imidazolium salt according to the present embodiment is represented by the following general formula (2).

In the above formula, R ^{2 to} R ⁵ are each a hydrogen atom, an optionally substituted C _{1 to} C ₂₀ hydrocarbon group, an optionally substituted C _{1 to} C ₂₀ alkoxy group, or a substituted group. good C ₆ -C ₂₀ aryloxy group which may have a group, which may have a substituent amino group, which may have a substituent phosphino group, which may have a substituent A silyl group, an alkylthio group which may have a substituent (-SY ¹ , wherein Y ¹ represents a C _{1 to} C ₂₀ alkyl group which may have a substituent), and a substituent. An optionally substituted arylthio group (—SY ² , wherein Y ² represents an optionally substituted C ₆ -C ₂₀ aryl group), may have a substituent. alkylsulfonyl group _(-SO 2 ^{Y 3,} wherein, ^{Y 3} good _C 1 _{-C 20} aralkyl which may have a substituent . Showing the Le group), which may have a substituent arylsulfonyl group _(-SO 2 ^{Y 4,} wherein, ^{Y 4} good _C 6 _{-C 20} ants may have a substituent - Le group A hydroxyl group or a halogen atom. R ^{2 to} R ⁵ are independent of each other and may be the same or different. R ³ and R ⁴ , and R ⁴ and R ⁵ may be bridged with each other to form a C _{4 to} C ₁₀ saturated ring or unsaturated ring. In the case of the ring, an oxygen atom, sulfur atom, silicon atom, tin atom, germanium atom, or -N (B) - group (where B is a hydrogen atom or a C ₁ -C ₁₀ hydrocarbon group.) represented by may be interrupted by, And you may have a substituent. W in the above formula can be a cross-linked chain, and represents, for example, a C _{1 to} C ₂₀ carbon atom which may have a substituent. Further, X in the above formulas may have a substituent group C ₁ -C ₄ carbon atoms, a nitrogen atom which may have a substituent, an oxygen atom, a sulfur atom, also substituent as these heteroatoms Is an atomic group composed of any combination of carbon atoms which may have Z in the above formula represents a halogen atom, PF ₆ , BF ₄ , ClO ₄ , or BPh ₄ .

(Method for producing imidazolium salt)
The imidazolium salt in the present embodiment is the same as that in the first embodiment, but is different in that it is crosslinked. Specifically, it can be produced by reacting imidazole two-to-one with an electrophile having two electrophilic sites in the molecule.

  In addition, the imidazolium salt in this embodiment can be obtained by making a base etc. act like the imidazolium salt which concerns on the said Embodiment 1. FIG. This carbene has optical activity. Further, this carbene can be used as an organic catalyst as it is as in the above embodiment, or can be used as a metal catalyst coordinated with carbene by reacting with various metal complexes.

  As described above, according to the present embodiment, an imidazolium salt, which was difficult to synthesize by a conventional method, can be produced efficiently and simply, and further, based on this, a nitrogen-containing heterocyclic carbene and an asymmetric synthesis catalyst can be obtained. it can. In particular, since the asymmetric synthesis catalyst comprising the imidazolium salt according to this embodiment has C2 symmetry ideal for asymmetric induction, the transition metal catalyst asymmetric hydrogenation, asymmetric carbon-carbon bond formation reaction It is expected to exhibit excellent performance.

  Hereinafter, specific implementation was performed as confirmation of the effect of the imidazolium salt according to the above embodiment. This will be described below. However, this is merely an example and does not limit the invention.

Example 1
In this example, (R) -7-isopropyl-3-phenyl-2,3-dihydro-imidazo [5,1-b] oxazole ((R) -3a) represented by the following formula was synthesized. This will be described in detail below. Furthermore, the reaction scheme of this example is also shown below.

Prior to the synthesis of (R) -3a, (S) -N, N′-formylvalyl- (R) -2-phenylglycinol (6a) shown below was synthesized.

  First, (S) -N-formylvaline (2.93 g, 20.2 mmol) in dry THF (72 ml) was mixed with N-methylmorpholine (2.53 mL, 2.33 g, 23.0 mmol) and isobutyl at −15 ° C. Chloroformate (2.63 ml, 2.76 g, 20.2 mmol) was added dropwise under a nitrogen atmosphere.

  After the above operation, the mixture was stirred at the same temperature for 15 minutes, and then (R) -2-phenylglycinol (2.74 g, 20.0 mmol) was further added to the mixture, followed by stirring at room temperature for 2 hours.

And after concentrating this mixed solution under reduced pressure, water (25 ml) was added and filtration operation was carried out. The solid after filtration was washed with water, ethyl acetate and a small amount of CH 3 Cl to obtain the compound represented by 6a in the above formula (4.17 g, 15.8 mmol, 79% yield) as a white solid. The melting point (mp), optical rotation ([α] ²⁰ _D ), ¹ H NMR, ¹³ C NMR, and HRMS data of this compound were as follows.

mp 211-213 ° C

[Α] ²⁰ D-91.9 (c 0.939, MeOH)

¹ H NMR (DMSO-d ₆ ) δ 0.80 (d, J = 6.7 Hz, 3H), 0.83 (d, J = 6.7 Hz, 3H), 1.96-2.04 (m, 1H), 3.59-3.62 (m, 2H), 4.42 (t, J = 7.3 Hz, 1H), 4.89-4.94 (m, 2H), 7.27-7. 36 (m, 5H), 8.12 (s, 1H), 8.21 (d, J = 8.9 Hz, 1H), 8.57 (d, J = 7.6 Hz, 1H)

¹³ C NMR (DMSO-d ₆ ) δ 17.73, 19.24, 31.03, 55.12, 55.99, 64.67, 126.86, 126.94, 128.07, 141.14 161.07, 170.31

_{HRMS (ESI) calcd for C 14} H 20 N 2 NaO 3 (M + + Na) 287.1366, found 287.1361.

Next, 2-[(S) -N-formyl-1-amino-2-methylpropyl]-(R) -4-phenyloxazoline (7a) represented by the following formula was synthesized from the above compound (6a). Details are shown below.

  Under a nitrogen atmosphere at room temperature, triethylamine (7.20 ml, 5.23 g, 51.7 mmol) was added to the compound of the above formula (6a) (3.17 g, 12.0 mmol) and N, N-dimethyl-4-aminopyridine. (24.4 mg, 0.200 mmol) in 1,2-dichloroethane (96 ml) suspension.

  Thereafter, a dry 1,2-dichloroethane (46 ml) solution of p-toluenesulfonyl chloride (2.32 g, 12.2 mmol) was added to the reaction solution, and the mixture was stirred at room temperature for 1 hour and then refluxed for another 3 hours.

Then saturated NaHCO ₃ solution was added, the aqueous layer was extracted twice with CH ₂ Cl ₂ and the organic layer was dried with Na ₂ SO ₄ . After filtration, the filtrate was concentrated, and the obtained residue was subjected to silica gel (ethyl acetate) chromatography to obtain the compound (7a) (2.33 g, 9.47 mmol, 79% yield, diastereomeric mixture). (9/1)) was obtained. The obtained compound was colorless crystals.

In the following, ¹ H NMR, ¹³ C NMR, and HRMS data on main diastereomers are shown.

¹ H NMR (CDCl ₃ ) d 0.92 (d, J = 6.7 Hz, 3H), 0.98 (d, J = 6.7 Hz, 3H), 2.19-2.24 (m, 1H) 4.15 (t, J = 8.8 Hz, 1H), 4.72 (dd, J = 10.1, 8.6 Hz, 1H), 4.81 (dd, J = 8.6, 4.H. 3 Hz, 1 H), 5.17-5.21 (m, 1 H), 6.74 (br d, J = 8.3 Hz, 1 H), 7.20-7.25 (m, 2 H), 7.29 (Tt, J = 7.3, 1.6 Hz, 1H), 7.34-7.38 (m, 2H), 8.23 (s, 1H)

¹³ C NMR (CDCl ₃ ) δ 17.28, 18.76, 30.89, 50.68, 69.09, 75.23, 126.59, 127.68, 128.66, 141.31, 161. _{00, 168.11; HRMS (ESI)} calcd for C 14 H 18 N 2 NaO 2 (M + + Na) 269.1260, found 269.1255.

  Next, niline pentoxide (1.84 g, 13.0 mmol) and the above (7a) (800 mg, 3.25 mmol) were placed in a Schlenk flask and replaced with nitrogen gas three times, and then dry toluene (15 ml) was added. . Thereafter, the mixture was heated to 100 ° C. and stirred for 23 hours.

And after cooling to room temperature, the solvent was removed. 1M HCl (15 ml) was added to the remaining brown solid, and then KOH was added so that the pH of the aqueous layer was 12. The resulting solution was extracted with CH ₂ Cl ₂ (3 × 15 ml).

The organic layer after extraction was dried and filtered using Na2SO4, concentrated under vacuum, and the residue was chromatographed using silica gel (ethyl acetate) to obtain the above (R) -3a (620 mg, (2.72 mmol, 84% yield) Obtained as a colorless oil. In the following, the optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data of this substance are shown.

[Α] ²⁰ _D- 160.2 (c 0.915, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 1.29 (d, J = 7.1 Hz, 3H), 1.30 (d, J = 7.1 Hz, 3H), 2.89 (septet, J = 7.1 Hz, 1H), 4.72 (dd, J = 8.8, 6, 8 Hz, 1H), 5.24 (dd, J = 8.8, 7.8 Hz, 1H), 5.42 (t, J = 7 .3 Hz, 1H), 6.94 (s, 1H), 7.17-7.19 (m, 2H), 7.36-7.43 (m, 3H)

¹³ C NMR (CDCl ₃ ) δ 21.94, 22.00, 26.39, 58.77, 84.26, 116.67, 121.83, 126.24, 129.02, 129.23, 137. 18, 148.17

_{HRMS (ESI) calcd for C 14} H 17 N 2 O (M + + H) 229.1335, found 229.1333.

  As mentioned above, the novel imidazole was able to be obtained by the present Example.

(Example 2)
In this example, (R) -3c and (S) -3c shown below were synthesized. This will be described in detail below. A scheme for synthesizing (R) -3c and (S) -3c is also shown below.

First, 4-[(3-phenyl) -3-hydroxyprop-1-yl] -1-trityl-1H-imidazole (10b) represented by the following formula (10b) was synthesized. This will be described below.

  First, a solution of 3- (l-trityl-1H-imidazol-4-yl) propionaldehyde (9b) (430 mg, 1.17 mmol) in dry THF (25 ml) was added to a solution of phenylmagnesium bromide in THF (0.93 M, 2 0.52 ml, 2.34 mmol) was added in a nitrogen atmosphere at −40 ° C., and the temperature was raised to room temperature while gradually raising the temperature. Then, it stirred for 18 hours.

After stirring, it was cooled to 0 ° C. and quenched with saturated NH ₄ Cl solution and brine. Thereafter, the aqueous layer was extracted twice with CH ₂ Cl ₂ , and the organic layer was dried using Na ₂ SO ₄ , filtered, and concentrated under vacuum.

Thereafter, chromatography was performed using silica gel (ethyl acetate / hexane) to obtain the compound represented by the above formula (10b) (420 mg, 0.945 mmol, 81% yield) as a white solid. In the following, the melting point, ¹ H NMR, ¹³ C NMR, and HRMS data of this substance are shown.

mp 185-189 ° C

¹ H NMR (CDCl ₃ ) δ 2.00-2.11 (m, 2H), 2.68 (t, J = 6.7 Hz, 2H), 4.81 (dd, J = 7.7, 4. 6 Hz, 1 H), 5.14 (br s, 1 H), 6.53 (s, 1 H), 7.12-7.16 (m, 6 H), 7.22 (t, J = 7.3 Hz, 1 H ), 7.30-7.39 (m, 14H)

¹³ C NMR (CDCl ₃ ) δ 24.95, 38.54, 73.84, 75.12, 117.84, 125.84, 126.82, 127.95, 127.97, 128.10, 129. 72, 138.04, 140.97, 142.39, 145.41

_{HRMS (ESI) calcd for C 31} H 29 N 2 O (M + + H) 445.2274, found 445.2257.

  Next, (R) -phenyl-6,7-dihydro-5H-pyrrolo- [1,2-c] imidazole ((R) -3b) and (S) -phenyl-6,7-dihydro-5H -Pyrrolo- [1,2-c] imidazole ((S) -3b) was synthesized. It is shown below.

First, thionyl chloride (252 μl, 411 mg, 3.45 mmol) was added to a CH ₂ Cl ₂ solution containing the compound represented by the above formula (10b) (438 mg, 0.985 mmol) under a nitrogen atmosphere, and the mixture was heated to 40 ° C. Stir for 1 hour.

After stirring, it is cooled to 0 ° C., quenched with saturated NaHCO ₃ solution, the organic layer is dried with Na ₂ SO ₄ , filtered and concentrated in vacuo to give crude 4-[(3-phenyl) -3-Chloroprop-1-yl] -1-trityl-1H-imidazole (492 mg) was obtained.

  The above compound was dissolved in 30 ml of CH3CN and refluxed for 20 hours. Thereafter, 30 ml of methanol was added to the mixture, and the mixture was further refluxed for 11 hours.

Thereafter, a liquid separation operation was performed with diethyl ether and water, and the organic layer was extracted twice with 1N HCl (10 mL). The aqueous layer was adjusted by adding NaOH so that the pH was 8, and extracted three times with CH ₂ Cl ₂ .

Then, the organic layer was dried using Na ₂ SO ₄ , filtered, concentrated, and chromatographed using silica gel (CHCl ₃ / MeOH) to obtain the racemic 3b (104 mg, 0.564 mmol, 57%). ) Was obtained as a pale yellow solid. In the following, the melting point, ¹ H NMR, ¹³ C NMR, and HRMS data of this substance are shown.

mp 68-73 ° C

¹ H NMR (CDCl ₃ ) δ 2.47-2.55 (m, 1H), 2.83-3.07 (m, 3H), 5.29 (t, J = 6.8 Hz, 1H), 6 .80 (s, 1H), 7.10-7.12 (m, 2H), 7.27-7.37 (m, 4H)

¹³ C NMR (CDCl ₃ ) δ 21.17, 40.30, 60.40, 119.62, 126.02, 128.23, 128.98, 130.45, 137.14, 140.48

_{HRMS (ESI) calcd for C 12} H 13 N 2 (M + + H) 185.1073, found 185.1073.

  For the racemic 3b obtained above, HPLC (Daicel, OD-H, 2 cm × 25 cm (3 cycles = 2 cm × 75 cm), hexane / isopropanol = 9/1, 5.0 mL / min; tR = 163 min By performing optical resolution by ((R) -3b), tR = 204 min ((S) -3b)), pure (R) -3b and (S) -3b were obtained. The optical rotation of each compound is shown below.

(R) -3b: [α] ²⁰ _D +186.4 (c 1.00, CHCl ₃ )
(S) -3b: [α] ²⁰ _D -185.7 (c 1.00, CHCl ₃ )

(Examples 3 to 14)
In Examples 3 to 14, chiral imidazole salts (1) and (2) were obtained from imidazole represented by the following (3). This will be described in detail below.

(Example 3)
Here, (R) -7-isopropyl-6-methyl-3-phenyl-2,3-dihydro-imidazo [5,1-b] oxazolium iodide (1a) shown in (1a) below was first obtained. Details are shown below.

To a dry CH ₃ CN solution (10 mL) containing (R) -3a (114 mg, 0.499 mmol), CH ₃ I (623 μL, 1.42 g, 10.0 mmol) was added under a nitrogen atmosphere and heated to 70 ° C. And sealed for 12 hours.

After stirring, the mixture was cooled to room temperature and concentrated under reduced pressure. This was followed by the addition of CH ₂ Cl ₂ / Et ₂ O to precipitate, the precipitate was filtered, washed with diethyl ether and dried under vacuum to give (R) -1a as a yellow powder (148 mg, 0.400 mmol, 80% yield). The melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data of this compound are shown below.

mp 177 ° C (decomposition)

[Α] ²⁰ _D- 51.5 (c1.00, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 1.37 (d, J = 7.0 Hz, 3H), 1.37 (d, J = 7.0 Hz, 3H), 2.94 (septet, J = 7.0 Hz, 1H), 3.89 (s, 3H), 4.98 (dd, J = 8.9, 5.5 Hz, 1H), 5.48 (dd, J = 9.2, 8.6 Hz, 1H), 6.43 (dd, J = 8.3, 5.5 Hz, 1H), 7.41-7.46 (m, 5H), 9.14 (s, 1H)

¹³ C NMR (CDCl ₃ ) δ 20.92, 21.56, 23.38, 35.81, 60.64, 83.86, 113.13, 125.42, 126.85, 129.70, 130. 03, 134.43, 146.99

_{HRMS (ESI) calcd for C 15} H 19 N 2 O (M + -I) 243.1492, found 243.1490.

Example 4
Next, (R, R) -1,3-bis [(S) -7-isopropyl-3-phenyl-2,3-dihydro-imidazo [5,1-b] oxazolium represented by the following formula (2a) -6-yl] propanedibromide was obtained. It is shown below.

To a dry CH ₃ CN (4 mL) solution of (R) -3a (228 mg, 0.999 mmol) above was added 1,3-dibromopropane (45.7 μL, 90.9 mg, 0.450 mmol) under a nitrogen atmosphere, Stir at 70 ° C. for 5 days.

After stirring, the reaction liquid was concentrated under reduced pressure after cooling to room temperature. Thereafter, liquid separation was performed with diethyl ether and a saturated aqueous NaHCO ₃ solution, the aqueous layer was taken out, washed 5 times with diethyl ether, and water was evaporated under reduced pressure.

The residue was then dissolved in CHCl ₃ , filtered and dried under vacuum to give (R, R) -2a (244 mg, 0.371 mmol, 82% yield) as a hygroscopic yellow solid. In the following, melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data are shown.

mp 120-123 ° C

[Α] ²⁰ _D- 71.5 (c0.200, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 1.33 (d, J = 6.7 Hz, 6H), 1.34 (d, J = 7.0 Hz, 6H), 2.52 (quintet, J = 7.3 Hz, 2H), 3.29 (septet, J = 6.9 Hz, 2H), 4.65 (dt, J = 14.4, 7.1 Hz, 2H), 4.81 (dt, J = 14.7, 7 .1 Hz, 2H), 4.88 (dd, J = 8.9, 5.8 Hz, 2H), 5.52 (t, J = 8.9 Hz, 2H), 6.21 (dd, J = 8. 0, 5.8 Hz, 2H), 7.33-7.42 (m, 10H), 9.49 (s, 2H)

¹³ C NMR (CDCl ₃ ) δ 20.79, 21.56, 22.78, 31.18, 44.53, 60.38, 83.59, 113.09, 124.63, 126.20, 129. 28, 129.52, 133.88, 146.65

_{HRMS (ESI) calcd for C 31} H 38 BrN 4 O 2 (M + -Br) 577.2178, found 577.2184.

(Example 5)
Here, (R, R) -α, α′-bis [(S) -7-isopropyl-3-phenyl-2,3-dihydro-imidazo [5,1-b] oxazolium represented by the following formula (2b) -6-yl] -o-xylene dibromide was synthesized. This will be described below.

The compound represented by (R) -3a (300 mg, 1.31 mmol) and α, α′-dibromo-o-xylene (158 mg, 0.599 mmol) were dissolved in dry CH ₃ CN (4 mL), The mixture was heated to 70 ° C. and stirred for 40 hours under a nitrogen atmosphere.

After stirring, the mixture was cooled to room temperature and concentrated under reduced pressure. Then, to carry out a liquid separation operation using CHCl ₃ and 1M HCl, and the organic layer was removed, dried with _Na 2 SO _4, and filtered. This filtrate was dried under reduced pressure. As a result, (R, R) -2b represented by the above formula was obtained as a yellow powder (430 mg, 0.597 mmol, 99% yield). In the following, melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data are shown.

mp 115 ° C (decomposition)

[Α] ²⁰ _D- 125.1 (c1.05, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 1.16 (d, J = 6.8 Hz, 6H), 1.21 (d, J = 7.2 Hz, 6H), 3.15 (septet, J = 6.8 Hz, 2H), 4.94 (dd, J = 8.8, 5.6 Hz, 2H), 5.57 (t, J = 8.4 Hz, 2H), 5.99 (d, J = 16.0 Hz, 2H) ), 6.14 (dd, J = 8.4, 6.0 Hz, 2H), 6.41 (d, J = 16.4 Hz, 2H), 6.98 (t, J = 4.8 Hz, 2H) , 7.33-7.45 (m, 12H), 9.70 (s, 2H)

¹³ C NMR (CDCl ₃ ) δ 21.05, 21.66, 23.34, 50.75, 60.78, 83.94, 114.38, 125.52, 126.60, 128.58, 129. 30, 129.70, 129.95, 132.55, 134.65, 147.43

_{HRMS (ESI) calcd for C 36} H 40 BrN 4 O 2 (M + -Br) 639.2329, found 639.2327.

(Example 6)
Here, a compound represented by the following formula (1b) in which an imidazolium salt was bonded to a Merrifield resin was synthesized. This will be described below.

  Compound (151 mg, 0.661 mmol) represented by the above formula (R) -3a and Merrifield resin (1.28 mmol / g, 100-200 mesh, 1% DVB) (49.9 mg, 0.0639 mmol) were dried in toluene. (2 mL), heated to 70 ° C. and stirred for 5 days under nitrogen atmosphere.

Then it was cooled to room temperature and the resin was collected by filtration and washed with ethanol, ether and acetone. After drying under reduced pressure, resin (R) -1b of the above formula was obtained as a yellow powder (64.1 mg, 0.0622 mmol, 97%). In the IR measurement of this compound, a broad peak was observed at 1670 cm ⁻¹ .

(Example 7)
Here, (R) -2-methyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-c] imidazole hexafluorophosphate represented by the following (1c) was synthesized. This will be described below.

A compound of the above formula ((3) -3b) (92.1 mg, 0.500 mmol) and iodomethane (623 μl, 1.42 g, 10.0 mmol) added to dry CH ₃ CN (2 ml) is heated to 70 ° C. And stirred for 3 days under a nitrogen atmosphere.

  After stirring, the mixture was cooled to room temperature and concentrated under reduced pressure to obtain imidazolium iodide as a sticky solid.

  Potassium hexafluorophosphate (110 mg, 0.598 mmol) was added to a solution of the obtained product in acetone (1 ml) at room temperature, and the mixture was stirred in air at room temperature for 12 hours.

Then, this mixture was filtered and concentrated under vacuum to obtain a grease-like compound represented by the above formula (1c) (158 mg, 0.459 mmol, 92% yield). In the following, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data are shown.

[Α] ²⁰ _D- 55.4 (c 1.07, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 2.59-2.67 (m, 1H), 3.07-3.20 (m, 3H), 3.94 (s, 3H), 5.78 (t, J = 6.8 Hz, 1H), 7.25-7.28 (m, 3H), 7.35-7.42 (m, 3H), 8.47 (s, 1H)

¹³ C NMR (CDCl ₃ ) δ 22.65, 37.27, 37.54, 64.19, 116.03, 126.49, 129.35, 129.44, 130.48, 136.45, 138. 91

_{HRMS (ESI) calcd for C 13} H 15 N 2 (M + -PF6) 199.1230, found 199.1230.

(Example 8)
Here, (R) -2-isopropyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-c] imidazolium bromide represented by the following formula (1d) was synthesized. This will be described below.

First, the compound represented by the above formula ((R) -3b) (92.1 mg, 0.500 mmol) and 2-bromopropane (939 μl, 1.23 g, 10.0 mmol) were added to dry CH ₃ CN (2 ml). The mixture was heated to 70 ° C. and stirred for 5 days under a nitrogen atmosphere.

Thereafter, reprecipitation operation was performed with CH ₂ Cl ₂ and Et ₂ O, and after filtration, the filtrate was washed with diethyl ether and dried under vacuum to obtain (R) -1d as a light brown solid (152 mg, 0.495 mmol, 99% yield). In the following, melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data are shown.

mp 153-159 ° C

[Α] _D = −69.2 (c 1.06, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 1.60 (d, J = 6.7 Hz, 6H), 2.64-2.71 (m, 1H), 3.11-3.22 (m, 3H), 4 .93 (septet, J = 6.8 Hz, 1H), 6.01-6.04 (m, 1H), 7.30-7.31 (m, 2H), 7.37-7.42 (m, 4H), 9.33 (s, 1H)

¹³ C NMR (CDCl ₃ ) δ 22.67, 23.09, 23.15, 37.18, 53.60, 63.79, 112.23, 126.47, 129.22, 129.41, 129. 95,137.08,138.79

_{HRMS (ESI) calcd for C 15} H 19 N 2 (M + -Br) 227.1543, found 227.1541.

Example 9
Here, (R) -5-phenyl-2- (2-pyridinylmethyl) -6,7-dihydro-5H-pyrrolo [1,2-c] imidazolium bromide represented by the following formula ((R) -1e) is used. Synthesized. This will be described below.

A saturated NaHCO ₃ solution was added to an aqueous solution in which 2-bromomethylpyridine hydrobromide (22.4 mg, 0.0886 mmol) was dissolved, and the mixture was extracted with diethyl ether. The extracted organic layer was washed 4 times with saturated NaHCO ₃ solution, dried using Na ₂ SO ₄ , further filtered and concentrated under vacuum.

  Next, the obtained 2-bromomethylpyridine and the compound of the above formula ((R) -3b) (13.6 mg, 0.0738 mmol) were added to methanol (1.5 mL) and stirred for 48 hours under a nitrogen atmosphere. did.

After stirring, the mixture is cooled to room temperature, concentrated under reduced pressure, and reprecipitated using CH ₂ Cl ₂ and Et ₂ O to obtain the compound represented by the above formula ((R) -1e) as a hygroscopic light brown solid. (26.7 mg, 0.0749 mmol,> 99% yield). In the following, melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data are shown.

mp 80-83 ° C

[Α] ²⁰ _D −3.2 (c 0.20, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 2.59-2.68 (m, 1H), 3.09-3.20 (m, 3H), 5.84 (s, 2H), 5.88 (t, J = 7.0 Hz, 1H), 7.22-7.25 (m, 2H), 7.28 (dd, J = 7.6, 4.9 Hz, 1H), 7.35-7.42 (m, 3H), 7.66 (s, 1H), 7.73 (td, J = 7.6, 1.6 Hz, 1H), 7.88 (d, J = 7.7 Hz, 1H), 8.52 ( d, J = 4.9 Hz, 1H), 9.47 (s, 1H)

¹³ C NMR (CDCl ₃ ) δ 22.50, 37.69, 54.38, 64.08, 115.37, 123.79, 124.19, 126.20, 129.34, 129.46, 131. 34, 136.52, 133.57, 138.14, 149.51, 152.67

_{HRMS (ESI) calcd for C 18} H 18 N 3 (M + -Br) 276.1495, found 276.1489.

(Example 10)
Here, (R) -6- (2-bromoethyl) -7-isopropyl-3-phenyl-2,3-dihydroimidazo [5,1-b] oxazole-6-ium bromide represented by the following formula (1f) is used. Synthesized. This will be described below.

  To a solution of the compound represented by the above formula ((R) -3a) (92.9 mg, 0.407 mmol) in dry CH3CN (500 μL), 1,2-dibromoethane (351 μl, 765 mg, 4.07 mmol) in a nitrogen atmosphere. In addition, the mixture was stirred at 70 ° C. for 21 hours.

After stirring, the mixture was cooled to room temperature, concentrated under reduced pressure, and subjected to liquid separation using Et ₂ O and saturated NaHCO ₃ . The aqueous layer was washed with diethyl ether and water was evaporated under reduced pressure.

Thereafter, the residue was dissolved in CHCl ₃ , filtered, and dried under vacuum to obtain (R) -N-2-bromoethylimidazolium salt represented by the above formula (1f) (144 mg, 0.346 mmol). , 85% yield). The 1H NMR data is shown below.

¹ H NMR (CDCl ₃ ) δ 1.35 (d, J = 6.9 Hz, 3H), 1.39 (d, J = 6.9 Hz, 3H), 3.02 (septet, J = 6.9 Hz, 1H), 3.83-3.93 (m, 2H), 4.60-4.65 (m, 1H), 4.83-4.89 (m, 1H), 4.97 (dd, J = 9.2, 5.6 Hz, 1H), 5.46 (t, J = 8.8 Hz, 1H), 6.28 (dd, J = 8.0, 5.6 Hz, 1H), 7.34− 7.39 (m, 2H), 7.43-7.47 (m, 3H), 9.67 (s, 1H)

  In addition, when the mixing ratio of 1,2-bromoethane and (R) -3a (2equiv) was changed and stirred at 80 ° C. for 4 days and the same procedure was performed, 7-isopropyl-3-phenyl-2,3- Dihydro-imidazo [5,1-b] oxazole hydrobromide ((R) -5a · HBr) was produced in a large amount, and only a small amount of N-2-bromoethylimidazolium salt was obtained.

(Example 11)
Here, (R, R) -1,1-bis [5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-c] imidazolium-2-yl] represented by the following formula (2c) is used. Methane dibromide was synthesized. This will be described below.

  The compound represented by the above formula ((R) -3b) (184 mg, 0.999 mmol) and methylene dibromide (351 μl, 869 mg, 5.00 mmol) are dissolved in dry CH 3 CN (1 ml) and heated to 70 ° C. under a nitrogen atmosphere. For 5 days.

Thereafter, the mixture was cooled to room temperature, concentrated under reduced pressure, and the remaining solid was reprecipitated with CH ₂ Cl ₂ and Et ₂ O. The solid was filtered, washed with diethyl ether and dried under vacuum to give (R, R) -2c represented by the above formula as a light brown powder (253 mg, 0.467 mmol, 93% yield). The melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data of this compound are shown below.

mp 235 ° C (decomposition)

[Α] _D +160.3 (c0.95, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 2.65-2.69 (m, 2H), 3.07-3.18 (m, 6H), 5.81 (t, J = 6.7 Hz, 2H), 7 21-7.23 (m, 4H), 7.38-7.42 (m, 6H), 7.50 (s, 2H), 8.89 (s, 2H), 10.44 (s, 2H) )

¹³ C NMR (CDCl ₃ ) δ 22.54, 37.27, 57.52, 64.59, 116.07, 126.19, 129.67, 129.70, 132.53, 135.73, 138. 75

_{HRMS (ESI) calcd for C 25} H 26 BrN 4 (M + -Br) 461.1335, found 461.1318.

(Example 12)
Here, (S, S) -1,2-bis [5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-c] imidazolium represented by the following formula ((R) -2d) is used. 2-yl] ethane bis- (hexafluorophosphate) was synthesized. It is shown below.

A compound represented by the above formula ((S) -3b) (92.1 mg, 0.500 mmol) and 1,2-dibromoethane (20.5 μL, 44.7 mg, 0.238 mmol) were dried in CH ₃ CN (1 mL). The solution added to) was heated to 70 ° C., stirred under a nitrogen atmosphere for 2 days, and further stirred at 80 ° C. for 3 days.

  Thereafter, the mixture was cooled to room temperature and concentrated under reduced pressure to obtain bis (imidazolium) dibromide as a hygroscopic solid.

This solid was dissolved in acetone (1 mL) and CH ₂ Cl ₂ (1 mL), potassium hexafluorophosphate (110 mg, 0.603 mmol) was added, and the mixture was stirred in air at room temperature for 12 hours.

After stirring, the mixture was filtered and concentrated under vacuum to obtain the compound given by the above formula ((R) -2d) (167 mg, 0.243 mmol,> 99% yield). The melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data of this compound are shown below.

mp 223-228 ° C

[Α] _D- 149 (c 0.101, MeOH)

¹ H NMR (DMSO-d ₆ ) δ 2.50-2.58 (m, 2H), 2.92-3.15 (m, 6H), 4.52-4.58 (m, 2H), 4 .63-4.68 (m, 2H), 5.70 (t, J = 7.3 Hz, 2H), 7.31-7.34 (m, 4H), 7.42-7.49 (m, 8H), 8.88 (s, 2H)

¹³ C NMR (DMSO-d ₆ ) δ 22.22, 37.51, 49.17, 63.44, 114.67, 126.73, 129.02, 129.17, 131.65, 137.60, 138.91

_{HRMS (ESI) calcd for C 26} H 28 F 6 N 4 P (M + -PF6) 541.1950, found 541.1945.

(Example 13)
Here, (S, S) -1,3-bis [5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-c] imidazolium-2-yl] propane represented by the following formula (2e) is used. Bis- (hexafluorophosphate was synthesized. This will be described below.

Compound (92.1 mg, 0.500 mmol) represented by the above formula ((S) -3b) and 1,3-dibromopropane (24.2 μl, 48.1 mg, 0.238 mmol) were added to dry CH ₃ CN (1 mL). The addition was heated to 70 ° C., stirred for 2 days under a nitrogen atmosphere, and further stirred at 80 ° C. for 3 days.

  After stirring, the mixture was cooled to room temperature and concentrated under reduced pressure to obtain bis (imidazolium) dibromide as a hygroscopic solid.

This solid was dissolved in acetone (1 mL) and CH ₂ Cl ₂ (1 mL), potassium hexafluorophosphate (111 mg, 0.603 mmol) was added, and the mixture was stirred in air at room temperature for 12 hours.

After stirring, the solid was filtered off and concentrated in vacuo to give the compound shown in (2e) above as a white powder (173 mg, 0.247 mmol,> 99% yield). The melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data of this compound are shown below.

mp 77-79 ° C

[Α] _D- 92.6 (c 0.500, MeOH)

¹ H NMR (DMSO-d ₆ ) δ 2.39 (quintet, J = 7.0 Hz, 2H), 2.51-2.58 (m, 2H), 2.94-3.08 (m, 4H) 3.10-3.19 (m, 2H), 4.12-4.23 (m, 4H), 5.74 (t, J = 7.3 Hz, 2H), 7.36 (d, J = 7.1 Hz, 4H), 7.40-7.49 (m, 6H), 7.58 (s, 2H), 8.98 (s, 2H)

¹³ C NMR (DMSO-d ₆ ) δ 22.21, 29.51, 37.45, 46.31, 63.34, 114.48, 126.69, 128.91, 129.12, 131.12 137.66, 138.76

_{HRMS (ESI) calcd for C 27} H 30 F 6 N 4 P (M + -PF6) 555.2107, found 555.2123.

(Example 14)
Here, (R, R) -2,6-bis (5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-c] imidazolium-2-yl) represented by the following formula (2f) is used. Lutidine dibromide was synthesized. This will be described below.

  The compound represented by the above formula (R) -3b (84.7 mg, 0.460 mmol) and 2,6-di (bromomethyl) pyridine (50.9 mg, 0.192 mmol) were added to dry methanol (2.0 mL). The mixture was heated to 0 ° C. and stirred for 48 hours under a nitrogen atmosphere.

After stirring, the mixture is cooled to room temperature, concentrated under reduced pressure, and reprecipitated with CH ₂ Cl ₂ and Et ₂ O to convert the compound represented by the above formula ((R, R) -2f) into a hygroscopic white solid. (118 mg, 0.186 mmol, 97% yield). The melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data of this compound are shown below.

mp 132-135 ° C

[Α] ²⁰ _D +113.0 (c 1.00, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 2.54-2.61 (m, 2H), 3.06 to 3.15 (m, 6H), 5.73 (d, J = 14.7 Hz, 2H), 5 .84 (d, J = 14.7 Hz, 2H), 6.02-6.06 (m, 2H), 7.22 (d, J = 7.1 Hz, 4H), 7.34-7.43 ( m, 6H), 7.59-7.64 (m, 3H), 7.67 (s, 2H), 9.71 (s, 2H)

¹³ C NMR (CDCl ₃ ) δ 22.35, 37.33, 53.66, 63.66, 115.63, 123.44, 126.08, 129.02, 129.27, 131.53, 137. 32, 138.08, 138.62, 153.18

_{HRMS (ESI) calcd for C 31} H 31 N 5 Br (M + -Br) 552.1757, found 552.1755.

(Example 15)
In this example, the compound represented by the above formula (2f) and the C—N—C bridged Ni complex represented by the following formula (11) [(R, R) -2,6-bis (5-phenyl-) 6,7-Dihydro-5H-pyrrolo [1,2-c] imidazolium-2-yl) lutidine] chloronickel tetrafluoroborate was synthesized. This will be described below. The synthesis scheme of this compound is also shown below.

A suspension of the compound represented by the above formula (2f) (117 mg, 0.185 mmol), Ag ₂ O (214 mg, 0.925 mmol) and powdered molecular sieve (200 mg) in 1,2-dichloroethane (2 mL) The mixture was refluxed for 24 hours under a nitrogen atmosphere.

  The mixture was then filtered and filtered using a Celite pad. The filtrate was concentrated under reduced pressure to obtain a brown compound.

Thereafter, this compound was dissolved in 70 ml of CH ₂ Cl ₂ under a nitrogen atmosphere, and a suspension of NiCl ₂ (DME) in CH ₂ Cl ₂ (20 ml) (43.9 mg, 0.200 mmol) was further added to this solution. In addition, the mixture was stirred at room temperature for 24 hours.

Then, AgBF ₄ (38.9mg, 0.200mmol) was added to the reaction mixture was further stirred for 24 hours at room temperature. Then, it filtered using the Celite pad.

After concentration under reduced pressure, the residue was purified using silica gel column chromatography to obtain the target compound as a yellow solid (CHCl ₃ / MeOH = 10/1 to 1/1) (54.3 mg, 0 .0832 mmol, 45% yield).

A single crystal for X-ray crystal structure analysis could be obtained by slowly diffusing pentane in a CH ₂ Cl ₂ solution containing the above formula (R, R) -11. The melting point, optical rotation, ¹ H NMR, ¹³ C NMR, and HRMS data of this compound are shown below.

mp 185-189 ° C

[Α] ²⁰ _D +337.5 (c 0.200, CHCl ₃ )

¹ H NMR (CDCl ₃ ) δ 2.37-2.44 (m, 2H), 2.77-2.97 (m, 6H), 5.35 (d, J = 15.0 Hz, 2H), 5 .41 (d, J = 15.0 Hz, 2H), 5.85 (dd, J = 8.3, 4.9 Hz, 2H), 7.06-7.10 (m, 6H), 7.32 -7.40 (m, 6H), 7.67-7.72 (m, 3H)

¹³ C NMR (CDCl ₃ ) δ 21.85, 37.28, 53.80, 61.38, 113.64, 125.03, 126.60, 128.17, 128.81, 138.67, 140. 21, 142.38, 156.26, 158.49

_{HRMS (ESI) calcd for C 31} H 29 ClN 5 Ni (M + -BF 4) 564.1459, found 564.1453.

  The present invention has industrial applicability as a method for synthesizing a new optically active imidazole salt and its application.

Claims (4)

An imidazolium salt represented by the following general formula (1).
(In the above formula, R ^{1 to} R ⁵ are each a hydrogen atom, an optionally substituted C _{1 to} C ₂₀ hydrocarbon group, an optionally substituted C _{1 to} C ₂₀ alkoxy group, A C ₆ -C ₂₀ aryloxy group which may have a substituent, an amino group which may have a substituent, a phosphino group which may have a substituent, or a substituent. a silyl group which may have a substituent alkylthio group (-SY1, wherein, Y1 represents a good C ₁ -C20 alkyl group which may have a substituent.), have a substituent which may be an arylthio group (-SY ^2, in the formula, Y ² is a good C ₆ -C ₂₀ aryl group which may have a substituent.), which may have a substituent, an alkylsulfonyl group ( SO ₂ Y ³ , wherein Y ³ is an optionally substituted C ₁ -C ₂₀ alkyl. An arylsulfonyl group (—SO ₂ Y ⁴ , where Y ⁴ represents a C ₆ -C ₂₀ aryl group which may have a substituent). R ^{1 to} R ⁵ may be the same or different from each other, and may be the same or different, and R ¹ and R ² , R ³ and R ⁴ , and R ⁴ and R ⁵ may be bridged with each other to form a C _{4 to} C ₁₀ saturated ring or unsaturated ring. In the case of the ring, oxygen atom, sulfur atom, silicon atom, tin atom, germanium atom , or -N (B) - group (. where B is a hydrogen atom or a C ₁ -C ₁₀ hydrocarbon group) represented by may be interrupted by, and may have a substituent X in the above formula may have a substituent, C _{1 to} C ₄ charcoal. An atomic group consisting of an elementary atom, an optionally substituted nitrogen atom, an oxygen atom, a sulfur atom, or any combination of these heteroatoms and an optionally substituted carbon atom. Z in the above formula represents a halogen atom, PF ₆ , BF ₄ , ClO ₄ , or BPh _4. ) An imidazolium salt represented by the following general formula (2).
(In the above formula, R ^{2 to} R ⁵ are each a hydrogen atom, a C _{1 to} C ₂₀ hydrocarbon group that may have a substituent, a C _{1 to} C ₂₀ alkoxy group that may have a substituent, A C ₆ -C ₂₀ aryloxy group which may have a substituent, an amino group which may have a substituent, a phosphino group which may have a substituent, or a substituent. A good silyl group, an alkylthio group optionally having a substituent (-SY ¹ , wherein Y ¹ represents a C _{1 to} C ₂₀ alkyl group optionally having a substituent), a substituent; An optionally substituted arylthio group (—SY ² , wherein Y ² represents an optionally substituted C ₆ -C ₂₀ aryl group), an optionally substituted alkyl a sulfonyl group _(-SO 2 ^{Y 3,} wherein, ^{Y 3} good _C 1 _{-C 20} a may have a substituent Indicating Kill group.) Shows also an optionally substituted arylsulfonyl group _(-SO 2 ^{Y 4,:} in ^the formula, ^{Y 4} is optionally substituted _C 6 _{-C 20} aryl group And R ^{2 to} R ⁵ may be the same or different from each other, and R ³ and R ⁴ , and R ⁴ and R ⁵ may be the same. , respectively, in the case of C ₄ -C ₁₀ may form a saturated or unsaturated ring, wherein said ring crosslinked to each other, an oxygen atom, a sulfur atom, a silicon atom, tin atom, germanium atom, or -N ( B)-(wherein B is a hydrogen atom or a C _{1 to} C ₁₀ hydrocarbon group) and may have a substituent. W in the formula can be a cross-linked chain, for example, having a substituent Show also good C ₁ -C ₂₀ carbon atoms. Further, X in the above formulas may have a substituent group C ₁ -C ₄ carbon atoms, a nitrogen atom which may have a substituent, An oxygen atom, a sulfur atom, or an atomic group consisting of any combination of these heteroatoms and optionally substituted carbon atoms, and Z in the above formula is a halogen atom, PF ₆ , BF ₄ , ClO ₄ and BPh ₄ are shown.) A method for producing an imidazolium salt, which comprises reacting an imidazole represented by the following general formula (3) with an electrophile.
(In the above formula, R ^{1 to} R ⁵ are each a hydrogen atom, an optionally substituted C _{1 to} C ₂₀ hydrocarbon group, an optionally substituted C _{1 to} C ₂₀ alkoxy group, A C ₆ -C ₂₀ aryloxy group which may have a substituent, an amino group which may have a substituent, a phosphino group which may have a substituent, or a substituent. A good silyl group, an alkylthio group optionally having a substituent (-SY ¹ , wherein Y ¹ represents a C _{1 to} C ₂₀ alkyl group optionally having a substituent), a substituent; An optionally substituted arylthio group (—SY ² , wherein Y ² represents an optionally substituted C ₆ -C ₂₀ aryl group), an optionally substituted alkyl a sulfonyl group _(SO 2 ^{Y 3,} wherein, ^{Y 3} good _C 1 _{-C 20} aralkyl which may have a substituent Shows the Le group.) Shows also an optionally substituted arylsulfonyl group _(-SO 2 ^{Y 4,:} in ^the formula, ^{Y 4} is optionally substituted _C 6 _{-C 20} aryl group ), A hydroxyl group or a halogen atom, and R ^{1 to} R ⁵ may be the same or different from each other, R ¹ and R ² , R ³ and R ⁴ , and R ⁴ and R ⁵ may be bridged with each other to form a C _{4 to} C ₁₀ saturated ring or unsaturated ring. In the case of the ring, oxygen atom, sulfur atom, silicon atom, tin atom, germanium May be interrupted by an atom or a group represented by —N (B) — (wherein B is a hydrogen atom or a C _{1 to} C ₁₀ hydrocarbon group) and has a substituent. may. also, X is good C ₁ -C be substituted in the above formula Carbon atoms, a nitrogen atom which may have a substituent, an oxygen atom, a sulfur atom, also an atomic group consisting of any combination of carbon atoms which may have a substituent as these hetero atoms.)   An asymmetric synthesis catalyst using a nitrogen-containing heterocyclic carbene prepared from the imidazolium salt according to claim 1 or 2.