JP2008230936A - Organic base-fixed montmorillonite and method for producing optically-active cyclic compound by using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a catalyst which can be available at a low price, can advance an asymmetric Diels-Alder reaction efficiently, can be separated from a reaction product and can be reused. <P>SOLUTION: Diene and dienophile are subjected to the asymmetric Diels-Alder reaction by using organic base-fixed montmorillonite, which is obtained by fixing an optically-active organic base to montmorillonite, as the catalyst to obtain a corresponding optically-active cyclic addition product. For example, a diene compound and α,β-unsaturated aldehyde are subjected to the asymmetric Diels-Alder reaction to obtain optically-active cyclic aldehyde being the cyclic addition product. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an organic base-immobilized montmorillonite obtained by immobilizing an optically active organic base on montmorillonite, and a cyclic compound such as an optically active cyclic aldehyde using the same as a catalyst for a Diels-Alder reaction. It relates to a manufacturing method.

  The Diels-Alder reaction is a carbon-carbon bond forming reaction that also proceeds thermally. Many examples of reactions using Lewis acid catalysts are known, and there are many reports of asymmetric Diels-Alder reactions using asymmetric ligands. In addition, there is an example using a metal complex for the asymmetric Diels-Alder reaction. On the other hand, as a reaction not using a metal catalyst, an organic catalytic reaction using an organic molecule as a catalyst has been developed in recent years, and as an asymmetric Diels-Alder reaction via an optically active imine, K. Ishihara and K. Nakano, J. Am. Chem. Soc., 127, 10504 (2005), the reaction of 2-acyloxyacrolein with dienes, and DWC MacMillan et al, J. Am. Chem. Soc., 122, 4243 (2000) is there. These are homogeneous reactions and require complicated operations for separation and purification of the catalyst and product after the reaction. In addition, examples in which an asymmetric organic amine is covalently fixed to a polymer to facilitate separation of the catalyst include F. Cozzi et al, Ad. Synth. Catal., 344, 149 (2002), PM Pihko et al. , Ad. Synth. Catal., 344, 941 (2002).

K. Ishihara and K. Nakano, J. Am. Chem. Soc., 127, 10504 (2005) D. W. C. MacMillan et al, J. Am. Chem. Soc., 122, 4243 (2000) F. Cozzi et al, Ad. Synth. Catal., 344, 149 (2002) P. M. Pihko et al, Ad. Synth. Catal., 344, 941 (2002)

An object of the present invention is to provide a catalyst which can be obtained at low cost, can efficiently proceed with an asymmetric Diels-Alder reaction, can be easily separated from a reaction product, and can be reused.
Another object of the present invention is to provide a corresponding cycloaddition product in a high yield and enantioselectivity by an asymmetric Diels-Alder reaction between a diene and a dienophile using an inexpensive catalyst. An object of the present invention is to provide a method for producing an optically active cyclic compound in which a product and a catalyst can be easily separated and the catalyst can be reused.

  As a result of intensive studies to achieve the above object, the present inventors have found that when an organic base-immobilized montmorillonite that can be easily prepared from montmorillonite and an optically active organic base is used as a catalyst for an asymmetric Diels-Alder reaction, It was found that the cyclized product was obtained in high yield and enantioselectivity, and the present invention was completed.

  That is, the present invention provides an organic base-immobilized montmorillonite in which an optically active organic base is immobilized on montmorillonite.

  The present invention also provides an optically active cycloaddition product corresponding to an asymmetric Diels-Alder reaction of diene and dienophile using the above organic base-immobilized montmorillonite as a catalyst. A method for producing a cyclic compound is provided.

  In the above production method, a diene and an α, β-unsaturated aldehyde can be subjected to an asymmetric Diels-Alder reaction to obtain an optically active cyclic aldehyde as a cycloaddition product.

The organic base-immobilized montmorillonite of the present invention can be obtained at a low cost and can be used as a catalyst for the asymmetric Diels-Alder reaction, and can be easily separated and recovered from the reaction product after the reaction, and can be reused.
Further, according to the production method of the present invention, the catalyst used is inexpensive, and an optically active cyclic compound is obtained with high yield and high enantioselectivity by the asymmetric Diels-Alder reaction of diene and dienophile. In addition, the reaction product and the catalyst can be easily separated, the separated and recovered catalyst can be reused, and the asymmetric source is fixed to the solid catalyst, so that the product and the asymmetric source are separated. Is easy. Furthermore, the target compound can be produced in large quantities by simple means.

[Organic base-immobilized montmorillonite]
The organic base-immobilized montmorillonite of the present invention is obtained by immobilizing an optically active organic base on montmorillonite. The montmorillonite used for immobilizing the organic base may be a metal cation type montmorillonite (sodium montmorillonite or the like), but proton montmorillonite is more preferable from the viewpoint of the catalytic activity of the asymmetric Diels-Alder reaction.

Proton type montmorillonite (H- montmorillonite; H ⁺ -mont) is obtained by replacing the cations montmorillonite with protons, for example, sodium montmorillonite (Na-montmorillonite; Na ⁺ -mont) such montmorillonite (usually powder Montmorillonite) can be easily prepared by treating with acid. Montmorillonite is a clay mineral (main component of bentonite) classified as smectite, a kind of layered silicate mineral, and the crystals of montmorillonite are silicic acid tetrahedral layer-alumina octahedral layer-silicic acid tetrahedral layer. This has a three-layer structure. The cation exchange capacity of montmorillonite is usually about 0.5 to 3 meq / g.

  As an acid when montmorillonite is treated with an acid, a strong acid is preferable, and hydrochloric acid is particularly preferable. The acid is usually used in an aqueous solution, and its concentration is not particularly limited, but is about 0.1 to 10% by weight, for example. The treatment temperature is, for example, about 20 to 150 ° C, preferably about 50 to 110 ° C. The treatment time varies depending on the treatment temperature, but is usually about 1 hour to 4 days, preferably about 10 hours to 2 days. After the acid treatment, proton type montmorillonite can be obtained by filtration, washing with water and drying. As the proton type montmorillonite, it is desirable that the metal cation (sodium ion, etc.) of montmorillonite is exchanged by 30% or more, preferably 50% or more, more preferably 90% or more with protons. The acid amount (Amount of Acid Site) of proton-type montmorillonite is usually about 0.15 to 3 mmol / g, preferably about 0.5 to 3 mmol / g. Proton-type montmorillonite is used in the form of powder or by compressing and molding the powder.

  An optically active organic base immobilized on montmorillonite acts as an asymmetric catalyst. The optically active organic base may be any optically active organic base having an asymmetric center in the molecule. For example, an asymmetric organic base known as an asymmetric ligand of a homogeneous catalyst can be used. The optically active organic base includes an optically active amine compound. The amine compound is preferably a primary amine or a secondary amine because it can be reliably fixed to montmorillonite. The amine compound may be a chain amine compound or a cyclic amine compound, but a cyclic amine compound (particularly, a cyclic secondary amine) is particularly preferable. The amino group in the amine compound is preferably close to an asymmetric center (such as an asymmetric carbon atom), and is preferably located at the α-position or β-position, particularly the α-position, of the asymmetric center.

  As a representative example of an optically active organic base, for example, (5S) -2,2,3-trimethyl-5-phenylmethyl-4-imidazolidinone represented by the following formula (A), (2S, 5S) -2- (1,1-dimethylethyl) -3-methyl-5-phenylmethyl-4-imidazolidinone represented by formula (1), but is not limited thereto.

  As a method for preparing the organic base-immobilized montmorillonite of the present invention, a known method for immobilizing an organic compound on a solid surface, such as an ion exchange method, can be employed. For example, by dispersing montmorillonite (sodium-type montmorillonite, proton-type montmorillonite, etc.) formed into powder or pellets in water, adding an optically active organic base to this, stirring, and then filtering the solid Obtainable. An organic base-immobilized montmorillonite in which an optically active organic base is immobilized on a proton-type montmorillonite is obtained by dispersing a metal cation-type montmorillonite such as sodium-type montmorillonite formed into a powder or pellet form in water. It can also be obtained by adding an optically active organic base to the mixture, further adding an acid such as hydrochloric acid and stirring, and then filtering the solid.

  The usage-amount of an optically active organic base is 0.01-10 mmol per 1 g of raw material montmorillonite, for example, Preferably it is 0.05-5 mmol, More preferably, it is 0.1-3 mmol. The temperature at the time of adding and stirring an optically active organic base to the montmorillonite dispersion is, for example, about 10 to 100 ° C., preferably about 30 to 80 ° C. The amount of acid (such as hydrochloric acid) used in preparing an organic base-immobilized montmorillonite obtained by immobilizing an optically active organic base on a proton-type montmorillonite using a metal cation-type montmorillonite as the raw material montmorillonite is, for example, It is 1-1000 mmol per 1 g of montmorillonite, preferably 2-200 mmol, more preferably 5-50 mmol.

  The supported amount of the optically active organic base in the organic base-immobilized montmorillonite of the present invention is, for example, about 1 to 25% by weight, preferably about 3 to 15% by weight.

  The organic base-immobilized montmorillonite thus obtained is useful, for example, as an asymmetric Diels-Alder reaction catalyst (heterogeneous catalyst).

[Production of optically active cyclic compound]
In the method for producing an optically active cyclic compound of the present invention, using the above organic base-immobilized montmorillonite as a catalyst, a diene and a dienophile are subjected to an asymmetric Diels-Alder reaction, and a corresponding optically active cycloaddition product is obtained. obtain.

  As the diene, a diene commonly used in Diels-Alder reaction can be used, for example, a linear diene, a diene having two double bonds in one ring, and one of the double bonds is another in the ring. A diene in which one is bonded to the ring, a diene in which the double bond is inside and outside the ring, or a diene having a double bond in each of two rings bonded by a single bond may be used. . In addition, a heterodiene having a carbon-oxygen double bond or a carbon-nitrogen double bond can also be used as the diene. Further, the diene may be a conjugated enyne having a double bond and a triple bond, or a diyne having two triple bonds.

（式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵、Ｒ⁶は、同一又は異なって、水素原子又は非金属原子含有基を示す。Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵、Ｒ⁶のうち少なくとも２つが結合して隣接する１又は２以上の炭素原子とともに環を形成していてもよい）
で表される化合物が挙げられる。 As a typical diene, the following formula (1)

(In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ are the same or different and represent a hydrogen atom or a non-metal atom-containing group. R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ may combine to form a ring with one or more adjacent carbon atoms)
The compound represented by these is mentioned.

Examples of the non-metal atom-containing group in R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ include a halogen atom, a hydrocarbon group, a heterocyclic group, a carboxyl group, a substituted oxycarbonyl group, a substituted or Unsubstituted carbamoyl group, cyano group, acyl group, nitro group, alkylsulfinyl group, sulfuric acid group, sulfuric acid ester group, hydroxyl group, substituted oxy group, mercapto group, substituted thio group, groups in which multiple of these are bonded, etc. Can be mentioned. The carboxyl group, sulfur acid group, hydroxyl group, and mercapto group may be protected with a protecting group. As the protecting group, a protecting group conventionally used in the field of organic synthesis can be used.

  Examples of the halogen atom include fluorine, chlorine, bromine and iodine atoms. Examples of the hydrocarbon group include an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an aromatic hydrocarbon group, and a group in which a plurality of these are bonded. Examples of the aliphatic hydrocarbon group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, hexyl, decyl, dodecyl, tetradecyl, hexadecyl, vinyl, allyl, ethynyl, 1-propynyl group, and the like. And a linear or branched aliphatic hydrocarbon group (alkyl group, alkenyl group, alkynyl group) having about 1 to 20 carbon atoms (preferably 1 to 10, more preferably 1 to 8). Examples of the alicyclic hydrocarbon group include about 3 to 20 (preferably 3 to 15) carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cyclooctyl, cyclodecyl, cyclododecyl, norbornyl, and adamantyl groups. And alicyclic hydrocarbon groups (cycloalkyl groups, cycloalkenyl groups, bridged carbocyclic groups, etc.). Examples of the aromatic hydrocarbon group include aromatic hydrocarbon groups having about 6 to 14 carbon atoms such as phenyl and naphthyl groups.

  Examples of the group in which an aliphatic hydrocarbon group and an alicyclic hydrocarbon group are bonded include a cyclopentylmethyl, cyclohexylmethyl, and cyclohexylethyl groups. Examples of the group in which an aliphatic hydrocarbon group and an aromatic hydrocarbon group are bonded include, for example, an aralkyl group such as benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl; 2-methylphenyl, 3-phenyl Examples include methylphenyl and 4-methylphenyl groups.

The heterocyclic ring constituting the heterocyclic group as the non-metal atom-containing group in R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ includes an aromatic heterocyclic ring and a non-aromatic heterocyclic ring. included. As such a heterocyclic ring, for example, a heterocyclic ring containing an oxygen atom as a hetero atom (for example, a 5-membered ring such as furan, tetrahydrofuran, oxazole, or isoxazole, or a 6-membered ring such as 4-oxo-4H-pyran or tetrahydropyran) Rings, condensed rings such as benzofuran, isobenzofuran, 4-oxo-4H-chromene, chromane, isochroman), heterocycles containing a sulfur atom as a heteroatom (eg, thiophene, thiazole, isothiazole, thiadiazole, etc.) , 4-membered rings such as 4-oxo-4H-thiopyran, and condensed rings such as benzothiophene).

Examples of the substituted oxycarbonyl group as the non-metal atom-containing group in R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ include methoxycarbonyl group, ethoxycarbonyl group, propyloxycarbonyl group, isopropyloxycarbonyl Group, C _1-10 alkoxy-carbonyl group such as butyloxycarbonyl group, t-butyloxycarbonyl group; C _2-10 alkenyloxycarbonyl group such as _{vinyloxycarbonyl} group; C _3-15 such as cyclohexyloxy-carbonyl group Examples thereof include a cycloalkyloxycarbonyl group; a C _6-14 aryloxy-carbonyl group such as a phenyloxycarbonyl group; an aralkyloxycarbonyl group such as a C _7-15 benzyloxycarbonyl group. Examples of the substituted or unsubstituted carbamoyl group include a carbamoyl group, a methylcarbamoyl group, and a dimethylcarbamoyl group. Examples of the acyl group include C _1-10 aliphatic acyl groups such as formyl group, acetyl group, propionyl group, butyryl group, valeryl group, hexanoyl group, acryloyl group, methacryloyl group, acetoacetyl group; cyclohexanecarbonyl group, etc. C _3-15 alicyclic acyl group; C _6-14 aromatic acyl group such as benzoyl group; heterocyclic acyl group and the like. Examples of the alkylsulfinyl group include a methylsulfinyl group and a phenylsulfinyl group. Examples of the sulfur acid ester group include a methanesulfonyl group and a p-toluenesulfonyl group.

Examples of the substituted oxy group as the non-metal atom-containing group in R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ include C _1-6 alkoxy groups such as methoxy, ethoxy, isopropyloxy, and butoxy groups Cycloalkyloxy groups such as cyclohexyloxy groups; aryloxy groups such as phenoxy groups; acyloxy groups such as acetyloxy and propionyloxy groups; Examples of the substituted thio group include C _1-6 alkylthio groups such as methylthio and ethylthio groups; cycloalkylthio groups such as cyclohexylthio groups; arylthio groups such as phenylthio groups; acylthio groups such as acetylthio groups.

Examples of the ring formed by combining at least two of R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ together with one or more adjacent carbon atoms include, for example, a cyclopropane ring, a cyclobutane ring, About 3 to 20 members (preferably 3 to 15 members) such as cyclopentane ring, cyclopentene ring, cyclohexane ring, cyclohexene ring, cyclooctane ring, cyclodecane ring, cyclododecane ring, decalin ring, norbornane ring, norbornene ring and adamantane ring Non-aromatic carbocycles (cycloalkane ring, cycloalkene ring, bridged carbocycle); from oxygen atoms and sulfur atoms such as oxirane ring, oxetane ring, oxolane ring, oxane ring, oxepane ring, thiolane ring, thiane ring A non-aromatic heterocycle having at least one heteroatom selected from the group consisting of: a benzene ring, The array type ring, aromatic carbocyclic or heterocyclic ring such as anthracene ring. These rings may have a substituent, and other rings (non-aromatic ring or aromatic ring) may be condensed.

R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are particularly preferably a hydrogen atom or a hydrocarbon group which may have a substituent. At least two of R ¹ , R ² , R ³ , R ⁴ , R ⁵ , and R ⁶ are bonded to each other together with one or more adjacent carbon atoms to form a ring (non-aromatic which may have a substituent) It is also preferable to form a carbocyclic ring or a non-aromatic heterocyclic ring.

  Specific examples of the diene include, but are not limited to, cyclohexadiene, cyclopentadiene, butadiene, and isoprene.

（式中、Ｒ⁷、Ｒ⁸、Ｒ⁹は、同一又は異なって、水素原子又は非金属原子含有基を示す。Ｒ⁷、Ｒ⁸、Ｒ⁹のうち少なくとも２つが結合して隣接する１又は２個の炭素原子とともに環を形成していてもよい）
で表される化合物が挙げられる。 As the dienophile, α, β-unsaturated aldehyde is preferably used. As an α, β-unsaturated aldehyde, for example, the following formula (2)

(In the formula, R ⁷ , R ⁸ and R ⁹ are the same or different and each represents a hydrogen atom or a non-metal atom-containing group. At least two of R ⁷ , R ⁸ and R ⁹ are bonded and adjacent to each other. A ring may be formed with two carbon atoms)
The compound represented by these is mentioned.

Examples of the non-metal atom-containing group in R ⁷ , R ⁸ and R ⁹ are the same as those shown as the non-metal atom-containing group in R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ . Can be mentioned. Examples of the ring formed by combining at least two of R ⁷ , R ⁸ and R ⁹ together with the adjacent one or two carbon atoms include R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ^6. The thing similar to what was illustrated as a ring which at least 2 couple | bonds together and it forms with the adjacent 1 or 2 or more carbon atom is mentioned.

R ⁷ , R ⁸ and R ⁹ are particularly preferably a hydrogen atom or a hydrocarbon group which may have a substituent. At least two of R ⁷ , R ⁸ , and R ⁹ are bonded to each other together with one or two adjacent carbon atoms, and a ring (non-aromatic carbocycle or non-aromatic heterocycle optionally having a substituent) Etc.) is also preferred.

  Specific examples of α, β-unsaturated aldehydes include, but are not limited to, acrolein, crotonaldehyde, 2-hexenal, 2-octenal, 2-decenal, cinnamaldehyde, and the like.

  The reaction can be carried out in a liquid phase reaction. Even in the liquid phase reaction, the reaction product and the catalyst can be easily separated, and the separated catalyst can be reused in the reaction. The liquid phase reaction is performed in the presence or absence of a solvent. The solvent may be any solvent that does not inhibit the reaction. For example, nitriles such as acetonitrile and benzonitrile; nitro compounds such as nitromethane and nitroethane; amides such as N, N-dimethylformamide; esters such as ethyl acetate; Linear or cyclic ethers such as diethyl ether, diisopropyl ether, ethylene glycol dimethyl ether and tetrahydrofuran; saturated aliphatic hydrocarbons such as hexane and octane; saturated alicyclic hydrocarbons such as cyclopentane, cyclohexane and methylcyclohexane; benzene, toluene, Aromatic hydrocarbons such as xylene and ethylbenzene; halogenated hydrocarbons such as methylene chloride; water; mixed solvents thereof and the like are used. Among these, polar organic solvents such as nitriles and nitro compounds (nitroalkanes) are preferable.

  In the present invention, when a mixed solvent of an organic solvent (particularly a polar solvent) and water is used as a solvent, enantioselectivity (asymmetric yield) may be improved. The amount of water used is, for example, about 1 to 90% by weight, preferably 5 to 70% by weight, and more preferably about 10 to 50% by weight with respect to the total amount of the solvent including water.

  In addition, when an acid is added to the reaction system, the reaction rate increases, yield increases, and high enantioselectivity is often obtained. Examples of the acid to be added include carboxylic acids such as acetic acid, difluoroacetic acid, trifluoroacetic acid, trimethylacetic acid, propionic acid and benzoic acid; sulfonic acids; inorganic acids and the like.

  The amount of the acid used is, for example, 0.1 to 40% by weight, preferably 1 to 30% by weight, and more preferably about 3 to 20% by weight as the concentration in the reaction system.

  The ratio of diene and dienophile (α, β-unsaturated aldehyde, etc.) can be selected as appropriate. In general, the amount of dienophile used is, for example, 0.5 to 30 mol, preferably 1 to 20 mol per mol of diene. Mol, more preferably about 1.2 to 15 mol.

  The amount of the organic base-immobilized montmorillonite used in the catalyst varies depending on the type of raw material, but is, for example, about 1 to 1000 g, preferably about 10 to 500 g with respect to 1 mol of the smaller compound of diene and dienophile. The reaction temperature can be appropriately selected depending on the type of raw material, and is, for example, -30 ° C to 120 ° C, preferably -20 ° C to 60 ° C, more preferably about -10 ° C to 15 ° C, and prevents the deterioration of the catalyst. From the viewpoint, a range of about −10 ° C. to 10 ° C. is particularly preferable. The reaction can be carried out in a conventional manner such as batch, semi-batch, or continuous. The reaction may be performed at normal pressure or under pressure. The reactor may be either a fluidized bed type reactor or a fixed bed type reactor.

  Due to the reaction of diene and dienophile, the asymmetric Diels-Alder reaction proceeds to produce the corresponding optically active cycloaddition product. One of the enantiomers is considered to be selectively produced because the optically active organic base immobilized on montmorillonite reacts or interacts with dienophile (for example, forms iminium ions) and then a Diels-Alder reaction occurs. .

（式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵、Ｒ⁶、Ｒ⁷、Ｒ⁸、Ｒ⁹は前記に同じ。＊は不斉炭素原子を示す） For example, when the diene represented by the formula (1) and the dienophile (α, β-unsaturated aldehyde) represented by the formula (2) are reacted, the optical represented by the following formula (3) An active cyclic aldehyde is obtained.

(In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are the same as above. * Represents an asymmetric carbon atom)

  After completion of the reaction, the reaction product can be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, adsorption, column chromatography, etc., or a separation means combining these.

  The organic base-immobilized montmorillonite used as the catalyst can be easily separated and recovered from the reaction mixture by solid-liquid separation means such as filtration and centrifugation. The recovered catalyst can be recycled to the reaction system by washing with, for example, an organic solvent.

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited by these Examples. The product was identified by ¹ H-NMR. The product was quantified by gas chromatography (GC) and gas chromatography / mass spectrometry (GC-MS) (internal standard method).

Production Example 1 (Preparation of organic base-immobilized montmorillonite 1)
In 100 mL of water, sodium-type montmorillonite [manufactured by Kunimine Industry Co., Ltd., trade name “Kunipia F”, elemental analysis value: Na, 2.69; Mg, 1.97; Al, 11.8; Fe, 1.46 %] 1.0 g was added, and the mixture was stirred at room temperature and further dispersed with a homogenizer. Next, at 50 ° C., 100 mL of an aqueous solution of 0.5 mmol of (5S) -2,2,3-trimethyl-5-phenylmethyl-4-imidazolidinone monohydrochloride in water was added and stirred for 1 hour. Further, 1.6 mL (40 drops) of 36 wt% hydrochloric acid was added dropwise, and the mixture was stirred at 50 ° C. for 2 hours. The mixture was filtered with suction, washed with water and dried in a vacuum desiccator to give a white solid product [Amine-mont (H ⁺ -type)]. As a result of elemental analysis, the supported amount of amine was 7.4% by weight.

Production Example 2 (Preparation 2 of organic base-immobilized montmorillonite)
In 100 mL of water, sodium-type montmorillonite [manufactured by Kunimine Industry Co., Ltd., trade name “Kunipia F”, elemental analysis value: Na, 2.69; Mg, 1.97; Al, 11.8; Fe, 1.46 %] 1.0 g was added, and the mixture was stirred at room temperature and further dispersed with a homogenizer. Next, at 50 ° C., 100 mL of an aqueous solution of 0.5 mmol of (5S) -2,2,3-trimethyl-5-phenylmethyl-4-imidazolidinone monohydrochloride in water was added and stirred for 1 hour. The mixture was further stirred at 50 ° C. for 2 hours. The mixture was filtered with suction, washed with water and dried in a vacuum desiccator to give a white solid product [Amine-mont (Na ⁺ -type)].

Example 1
In a Pyrex (registered trademark) reactor, 0.1 g of organic base-immobilized montmorillonite [Amine-mont (H ⁺ -type)] obtained in Production Example 1, acetonitrile 2 mL, water 0.2 mL, cyclohexadiene 0.5 mmol Then, 1.5 mmol of acrolein was added, and the mixture was stirred at 26 ° C. for 24 hours under an argon atmosphere. The catalyst was filtered off and the filtrate was analyzed. The conversion of cyclohexadiene was 98%, and the cyclic aldehyde (endo-form) represented by the following formula (4) was 70% in yield and enantioselectivity 84 % (84% ee) (endo isomer / exo isomer = 12).

Example 2
In a Pyrex (registered trademark) reactor, 0.1 g of organic base-immobilized montmorillonite [Amine-mont (Na ⁺ -type)] obtained in Production Example 2, acetonitrile 2 mL, water 0.2 mL, cyclohexadiene 0.5 mmol Then, 1.5 mmol of acrolein was added, and the mixture was stirred at 26 ° C. for 24 hours under an argon atmosphere. When the catalyst was filtered off and the filtrate was analyzed, the conversion of cyclohexadiene was 66%, and the cyclic aldehyde represented by the formula (4) was 47% in yield and 81% in enantioselectivity (endo-form). / Exo form = 12).

Comparative Example 1
To a Pyrex (registered trademark) reactor, 0.1 g of proton-type montmorillonite (H ⁺ -mont), 2 mL of acetonitrile, 0.2 mL of water, 0.5 mmol of cyclohexadiene and 1.5 mmol of acrolein were added, and the reaction was performed at 26 ° C. under an argon atmosphere. For 24 hours. The catalyst was filtered off and the filtrate was analyzed. As a result, the cyclic aldehyde represented by the formula (4) was trace. The conversion of cyclohexadiene was 56%.

Comparative Example 2
To a Pyrex (registered trademark) reactor, 0.1 g of sodium montmorillonite (Na ⁺ -mont), 2 mL of acetonitrile, 0.2 mL of water, 0.5 mmol of cyclohexadiene and 1.5 mmol of acrolein were added, and the reaction was performed at 26 ° C. under an argon atmosphere. For 24 hours. When the catalyst was filtered off and the filtrate was analyzed, the cyclic aldehyde represented by the formula (4) was not produced at all. The conversion of cyclohexadiene was 47%.

Example 3
The same operation as in Example 1 was performed except that the amount of water added was 0.4 mL. As a result, the conversion of cyclohexadiene was 98%, and the cyclic aldehyde represented by the formula (4) was produced in a yield of 73% and an enantioselectivity of 86% (endo isomer / exo isomer = 14). It was.

Example 4
The same operation as in Example 1 was performed except that the amount of water added was 0.8 mL. As a result, the conversion of cyclohexadiene was 98%, and the cyclic aldehyde represented by the formula (4) was produced in a yield of 80% and an enantioselectivity of 86% (endo isomer / exo isomer = 13). It was.

Example 5
The same operation as in Example 1 was performed except that the amount of water added was 1.0 mL. As a result, the conversion of cyclohexadiene was 98%, and the cyclic aldehyde represented by the formula (4) was produced in a yield of 81% and an enantioselectivity of 85% (endo isomer / exo isomer = 13). It was.

Example 6
The same operation as in Example 1 was performed except that 2 mL of water was used instead of 2 mL of acetonitrile and 0.2 mL of water as the solvent. As a result, the conversion of cyclohexadiene was 99%, and the cyclic aldehyde represented by the formula (4) was produced with a yield of 49% and an enantioselectivity of 75% (endo isomer / exo isomer = 17). It was.

Example 7
In a Pyrex (registered trademark) reactor, 0.1 g of organic base-immobilized montmorillonite obtained in Production Example 1 [Amine-mont (H ⁺ -type)], acetonitrile 2 mL, water 0.8 mL, acetic acid 0.2 mL, Cyclohexadiene 0.5 mmol and acrolein 1.5 mmol were added, and the mixture was stirred at 2 ° C. for 24 hours under an argon atmosphere. When the catalyst was filtered off and the filtrate was analyzed, the conversion of cyclohexadiene was 98%, and the cyclic aldehyde represented by the formula (4) was produced in a yield of 81% and an enantioselectivity of 89%. It was.

Example 8
The same operation as in Example 7 was performed except that 0.2 mL of trifluoroacetic acid was used instead of acetic acid. As a result, the conversion of cyclohexadiene was 97%, and the cyclic aldehyde represented by the formula (4) was produced with a yield of 79% and an enantioselectivity of 87%.

Example 9
The same operation as in Example 7 was performed except that 0.2 mL of difluoroacetic acid was used instead of acetic acid. As a result, the conversion of cyclohexadiene was 98%, and the cyclic aldehyde represented by the formula (4) was produced in a yield of 72% and an enantioselectivity of 92%.

Example 10
The same operation as in Example 7 was performed except that 0.2 mL of trimethylacetic acid was used instead of acetic acid. As a result, the conversion of cyclohexadiene was 92%, and the cyclic aldehyde represented by the formula (4) was produced at a yield of 83% and an enantioselectivity of 92%.

Example 11
The same operation as in Example 7 was performed except that 0.2 mL of propionic acid was used instead of acetic acid. As a result, the conversion of cyclohexadiene was 95%, and the cyclic aldehyde represented by the formula (4) was produced at a yield of 78% and an enantioselectivity of 90%.

Example 12
The same operation as in Example 7 was performed except that 0.2 mL of benzoic acid was used instead of acetic acid. As a result, the conversion of cyclohexadiene was 94%, and the cyclic aldehyde represented by the formula (4) was produced at a yield of 77% and an enantioselectivity of 92%.

Example 13
The same operation as in Example 7 was performed except that acetic acid was not added. As a result, the conversion of cyclohexadiene was 71%, and the cyclic aldehyde represented by the formula (4) was produced in a yield of 53% and an enantioselectivity of 92%.

Example 14
The same operation as in Example 7 was performed except that acetic acid was not added and the reaction time was 48 hours. As a result, the conversion of cyclohexadiene was 97%, and the cyclic aldehyde represented by the formula (4) was produced at a yield of 82% and an enantioselectivity of 92%.

Example 15
A Pyrex (registered trademark) reactor was charged with 0.1 g of organic base-immobilized montmorillonite [Amine-mont (H ⁺ -type)] obtained in Production Example 1, acetonitrile 2 mL, water 0.8 mL, and cyclopentadiene 0.5 mmol. Then, 2.5 mmol of crotonaldehyde was added, and the mixture was stirred at 2 ° C. for 48 hours under an argon atmosphere. When the catalyst was filtered off and the filtrate was analyzed, the corresponding cycloaddition product (cyclic aldehyde) was produced in a yield of 85%. The enantioselectivity of the exo form was 86%, and the enantioselectivity of the endo form was 89%.

Example 16
The same operation as in Example 15 was performed except that 2.5 mmol of 2-hexenal was used instead of crotonaldehyde. As a result, the corresponding cycloaddition product (cyclic aldehyde) was produced with a yield of 80%. The enantioselectivity of the exo form was 87%, and the enantioselectivity of the endo form was 96%.

Example 17
In a Pyrex (registered trademark) reactor, 0.1 g of organic base-immobilized montmorillonite [Amine-mont (H ⁺ -type)] obtained in Production Example 1, acetonitrile 2 mL, water 0.8 mL, cyclopentadiene 0.3 mmol Then, 1.5 mmol of cinnamaldehyde was added, and the mixture was stirred at 2 ° C. for 48 hours under an argon atmosphere. When the catalyst was filtered off and the filtrate was analyzed, the corresponding cycloaddition product (cyclic aldehyde) was produced in a yield of 73%. The enantioselectivity of the exo form was 93%, and the enantioselectivity of the endo form was 97%.

Example 18
In a Pyrex (registered trademark) reactor, 0.1 g of organic base-immobilized montmorillonite [Amine-mont (H ⁺ -type)] obtained in Production Example 1, acetonitrile 2 mL, water 2.0 mL, isoprene 0.5 mmol, 2.5 mmol of acrolein was added, and the mixture was stirred at 26 ° C. for 24 hours under an argon atmosphere. The catalyst was filtered off and the filtrate was analyzed. As a result, the corresponding cycloaddition product (cyclic aldehyde; endo) was produced at a yield of 82% and an enantioselectivity of 74%.

Example 19
A Pyrex (registered trademark) reactor was charged with 0.1 g of organic base-immobilized montmorillonite [Amine-mont (H ⁺ -type)] obtained in Production Example 1, acetonitrile 2 mL, water 0.8 mL, and cyclopentadiene 0.5 mmol. Then, 2.5 mmol of acrolein was added, and the mixture was stirred at 26 ° C. for 16 hours under an argon atmosphere. When the catalyst was filtered off and the filtrate was analyzed, the corresponding cycloaddition product (cyclic aldehyde) was produced in a yield of 85%. The exo enantioselectivity was 30% and the endo enantioselectivity was 16%.

Example 20
In a Pyrex (registered trademark) reactor, 0.1 g of organic base-immobilized montmorillonite obtained in Production Example 1 [Amine-mont (H ⁺ -type)], acetonitrile 2 mL, water 0.8 mL, acetic acid 0.2 mL, 0.5 mmol of cyclohexadiene and 1.5 mmol of acrolein were added, and the mixture was stirred at 26 ° C. for 24 hours under an argon atmosphere. The catalyst was filtered off and the filtrate was analyzed. The conversion of cyclohexadiene was 98%, and the cyclic aldehyde represented by the formula (4) was produced in a yield of 83% and an enantioselectivity of 88%. It was.
The catalyst separated by filtration was washed with a mixed solution of ethyl acetate / hexane, and the same reaction as described above was performed using this catalyst as a catalyst. This operation was repeated. In the first reuse, the conversion of cyclohexadiene was 98%, the yield of the cyclic aldehyde represented by the formula (4) was 80%, and the enantioselectivity was 85%. In the second reuse, the conversion of cyclohexadiene was 98%, the yield of the cyclic aldehyde represented by the formula (4) was 58%, and the enantioselectivity was 79%.

Example 21
In a Pyrex (registered trademark) reactor, 0.1 g of organic base-immobilized montmorillonite obtained in Production Example 1 [Amine-mont (H ⁺ -type)], acetonitrile 2 mL, water 0.8 mL, acetic acid 0.2 mL, Cyclohexadiene 0.5 mmol and acrolein 1.5 mmol were added, and the mixture was stirred at 2 ° C. for 24 hours under an argon atmosphere. The catalyst was filtered off and the filtrate was analyzed. The conversion of cyclohexadiene was 98%, the cyclic aldehyde represented by the formula (4) was 82% in yield, and the enantioselectivity of the endo was 89%. It was generated with.
The catalyst separated by filtration was washed with a mixed solution of ethyl acetate / hexane, and the same reaction as described above was performed using this catalyst as a catalyst. This operation was repeated. In the first reuse, the conversion of cyclohexadiene was 98%, the yield of the cyclic aldehyde represented by the formula (4) was 77%, and the enantioselectivity was 89%. In the second reuse, the conversion of cyclohexadiene was 98%, the yield of the cyclic aldehyde represented by the formula (4) was 80%, and the enantioselectivity was 90%. In the third reuse, the conversion of cyclohexadiene was 98%, the yield of the cyclic aldehyde represented by the formula (4) was 84%, and the enantioselectivity was 88%. In the fourth reuse, the conversion of cyclohexadiene was 98%, the yield of the cyclic aldehyde represented by the formula (4) was 80%, and the enantioselectivity was 88%.

Claims (3)

  Organic base-immobilized montmorillonite in which optically active organic base is immobilized on montmorillonite.   An optically active cyclic compound characterized in that a diene and a dienophile are subjected to an asymmetric Diels-Alder reaction using the organic base-immobilized montmorillonite according to claim 1 as a catalyst to obtain a corresponding optically active cycloaddition product. Manufacturing method.   The method for producing an optically active cyclic compound according to claim 2, wherein the diene and an α, β-unsaturated aldehyde are subjected to an asymmetric Diels-Alder reaction to obtain an optically active cyclic aldehyde as a cycloaddition product.