JPH09227460A - Production of asymmetric cyclopropanecarboxylic acid compound - Google Patents

Abstract

(57) [Abstract] [Problem] The presence of a copper salt of an olefin and a diazoacetic acid ester by using a stable azoline which can be easily produced in a high yield from nitriles or orthoesters in one step. A method for producing asymmetric cyclopropanecarboxylic acids by reacting below is provided. SOLUTION: The diazoacetic acid ester represented by the general formula (1) N ₂ CHCOOR ¹ (1) and the general formula (2) And an olefin represented by the formula: optically active dialkyl tartaric acid ester, optically active di-O-aroyl tartaric acid, optically active di-O-alkyloyl tartaric acid, optically active 1,
One selected from 1'-bi (2-naphthol) s, copper salt and general formula (3) Represented by the general formula (4) characterized by reacting in the presence of azolines A method for producing an asymmetric cyclopropanecarboxylic acid represented by:

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing asymmetric cyclopropanecarboxylic acids.

[0002]

BACKGROUND OF THE INVENTION Asymmetric cyclopropanecarboxylic acids are useful as intermediates for medicines, agricultural chemicals, etc., and are produced by reacting olefins with diazoacetic acid esters in the presence of a copper salt and an asymmetric ligand. It is known that Optically active methylenebisoxazolines have been known as such chiral ligands [Tetrahedron Letters, Vo
l.32, No.50, pp.7373-7376, (1991)], such methylenebisoxazolines are not only unstable and easily decomposed, but also produced at low yield through multiple steps using malononitrile as a raw material. (Helvetica Chimica Acta, Vol.74, p.2 (199
1)], The method for producing asymmetric cyclopropanecarboxylic acids using such methylenebisoxazolines as an asymmetric ligand has not been industrially advantageous.

[0003]

Therefore, the present inventor has made use of stable azolines which can be easily produced in high yield from nitriles and orthoesters in one step, and is stable. The present invention has been accomplished as a result of extensive studies to develop a method for producing asymmetric cyclopropanecarboxylic acids by reacting and in the presence of a copper salt.

[0004]

That is, the present invention is
Formula (1) N_TwoCHCOOR¹ (1) (where R¹Is an alkyl group which may have a substituent,
An aralkyl group or a substituent which may have a substituent
The aryl group which may be possessed is shown. ) Zia
Zoacetic acid esters and general formula (2)(Where R^Two, R^Three, R^Four, R^FiveIs a hydrogen atom,
Alkenyl group optionally having substituent, having substituent
Optionally substituted alkyl group, optionally substituted alkyl group
Aralkyl group or aryl group which may have a substituent
And R^TwoAnd R ^ThreeAnd may combine to form a ring
Yes. Where R^Two, R^Three, R^Four, R^FiveAre the same at the same time
Never. ) With olefins
Dialkyl tartaric acid esters, optically active di-O-aro
Iltartaric acids, optically active di-O-alkyloyltartaric acid
, Optically active 1,1'-bi (2-naphthol)
One type, copper salt and general formula (3)(Where R⁶, R⁷, R⁸, R⁹, R^TenIs hydrogen
Atoms, halogen atoms, and optionally substituted alkyl groups
Group, aralkyl group which may have a substituent, a substituent
Optionally having an aryl group or having a substituent
Good alkenyl group, optionally substituted alkoxy group
Oxycarboni which may have a silyl group or a substituent
Represents a hydrogen atom, and X represents an oxygen atom or a sulfur atom. )so
Characterized by reacting in the presence of the indicated azolines
General formula (4)(Where R¹, R^Two, R^Three, R^Four, R^FiveAre the above
Has the same meaning as, and * represents an asymmetric carbon atom. )
A method for producing asymmetric cyclopropanecarboxylic acids
Is what you do.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION In the substituents R ⁶ , R ⁷ , R ⁸ , R ⁹ and R ¹⁰ of the azolines used in the method of the present invention, the halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. As the alkyl group, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-
Butyl group, isobutyl group, t-butyl group, n-amyl group, neopentyl group, n-hexyl group, cyclohexyl group, n-octyl group, n-nonyl group, menthyl group, 2,
3,4-trimethyl-3-pentyl group, 2,4-dimethyl-3-pentyl group, etc., aralkyl group such as benzyl group, aryl group such as phenyl group, naphthyl group, biphenyl group, furyl group, thiophenyl Examples of the alkenyl group include 2-methyl-1-propenyl group, 2-butenyl group, trans-β-styryl group and 3-
Phenyl-1-propenyl group, 1-cyclohexenyl group and the like, alkoxy group as a methoxy group, ethoxy group, n-propoxy group, t-butoxy group and the like, oxycarbonyl group as a methoxycarbonyl group, ethoxycarbonyl group, Examples thereof include t-butylcarbonyl group, benzyloxycarbonyl group and phenyloxycarbonyl group. Examples of these substituents include halogen atoms such as fluorine atom, chlorine atom, bromine atom and iodine atom, methoxy group, ethoxy group, n-propoxy group and t-
Alkoxy group of butoxy group, aryloxy group such as phenoxy group, methyl group, ethyl group, isopropyl group,
lower alkyl group such as n-butyl group, t-butyl group, n-amyl group, n-hexyl group, n-propylthio group, t
It may be substituted with a lower alkylthio group such as -butylthio group, an arylthio group such as phenylthio group, a nitro group or a hydroxyl group.

Examples of such azolines include 4-phenylthiazoline, 2-methyl-4-t-butylthiazoline, 2-phenyl-4-phenylmethylthiazoline,
2-methoxymethyl-4- (2,6-di-t-butyl-
p-tolyl) thiazoline, 4-methoxycarbonylthiazoline, 2-methyl-4-ethoxycarbonylthiazoline, 2-phenyl-4-methoxycarbonylthiazoline, 2-methoxymethyl-4-ethoxycarbonylthiazoline and the like in general formula (3). Thiazolines in which the substituent X corresponds to a sulfur atom, 4-phenyloxazoline,
2-Methyl-4-t-butyloxazoline, 2-phenyl-4-phenylmethyloxazoline, 2-methoxymethyl-4- (2,6-di-t-butyl-p-tolyl) oxazoline, 4-methoxycarbonyloxazoline Two
-Methyl-4-ethoxycarbonyloxazoline, 2-
Phenyl-4-methoxycarbonyloxazoline, 2-
Examples include oxazolines corresponding to the substituent X oxygen atom in the general formula (3) such as methoxymethyl-4-ethoxycarbonyloxazoline.

In these azolines, the substituents R ⁶ and R ⁷ may be different from each other or may be the same. In the former case, the azolines have substituents R ⁶ and R
There are at least two types of optically active substances having a carbon atom to which ⁷ is bonded as an asymmetric center, but in the present invention, any optically active substance or racemic body thereof may be used.

The method for producing such an azoline is not particularly limited, but for example, it is easily produced by a method in which 2-aminothiols or 2-aminoethanols are reacted with nitriles or orthoesters in the presence of a Lewis acid. be able to.

Examples of 2-aminothiols include 2
-Amino-3,3-dimethyl-1-butanethiol, 2
-Amino-2-phenylethanethiol, 2-amino-
3-phenyl-1-propanethiol, erythro-α-
(1-Aminoethyl) benzylthiol, cysteine ethyl ester, cysteine methyl ester, etc.
Examples of the aminoethanols include t-leucinol, phenylglycinol, phenylalaninol, erythro-α- (1-aminoethyl) benzyl alcohol, and valinol. These two
-The aminothiols or 2-aminoethanols may be an optically active substance or a racemate, and the configuration corresponding to the configuration of the used 2-aminothiols or 2-aminoethanols Azolines can be obtained.

The nitriles include, for example, acetonitrile, propionitrile, benzonitrile, phenylacetonitrile, etc., and the orthoesters include, for example, orthoformate methyl ester, orthoformate ethyl ester, orthoacetic acid methyl ester, orthoacetic acid ethyl ester, Benzoic acid orthomethyl ester, benzoic acid orthoethyl ester and the like can be mentioned, respectively, and the amount thereof is usually 0.5 mol times or more, preferably 0.5 to 2 times, with respect to 2-aminothiols or 2-aminoethanols.
The range is 3 mole times.

Examples of the Lewis acid include aluminum trichloride, boron trifluoride, zinc chloride, iron chloride, iron bromide, tin chloride, aluminum triisopropoxide,
Zinc acetate and the like are used, and these are used alone or in admixture of two or more, and the amount thereof is usually 0.01 to 10 mol times with respect to 2-aminothiols or 2-aminoethanols. It is a range.

The reaction may be carried out without solvent depending on the kind of nitriles or orthoesters used,
It may be performed in a solvent. In the former case, the amount of nitriles or orthoesters used is usually more than the above-mentioned amount used, and in the latter case, the solvent is, for example, a Lewis acid such as toluene, xylene, hexane, octane or chlorobenzene. A solvent inert to the reaction used is used, and the amount used is usually in the range of 2 to 100 times by weight with respect to 2-aminothiols or 2-aminoethanols.

In the reaction, a molecular sieve or the like may be allowed to coexist, and such a molecular sieve may be in the form of beads or pellets 3A, 4A, 5A and the like, and the amount thereof is 2-aminothiols or 2-aminothiols.
The amount is usually 0.01 to 100 times by weight, preferably 0.5 to 10 times by weight, that of aminoethanols.

In the reaction, for example, 2-aminothiols or 2-aminoethanols, nitriles or orthoesters and Lewis acid may be mixed in a solvent, and the reaction temperature is usually in the range of 50 to 250 ° C. is there.

After the reaction, an alkaline aqueous solution such as an aqueous solution of sodium hydrogencarbonate is added to the obtained reaction mixture, and then the precipitated solid is removed, and then a conventional method is used, for example, after concentration, water is added, and then toluene and ethyl acetate are added. Azolines can be easily obtained by a method in which an organic solvent insoluble in water, such as diethyl ether and dichloromethane, is subjected to extraction treatment, and the obtained organic layer is concentrated.

The azolines represented by the general formula (3) can be easily produced in this manner in a high yield, but all of these azolines are stable and can be easily handled.

Diazo vinegar used in the method of the present invention
Substituent R of acid esters¹Alkyl groups in
As the kill group and the aryl group, a substituent R⁶, R⁷,
R⁸, R ⁹, R^TenThe same as above
Can be mentioned.

Examples of such diazoacetic acid esters include methyl ester, ethyl ester, isopropyl ester, n-propyl ester, t-butyl ester, isobutyl ester, n-butyl ester, benzyl ester, cyclohexyl ester, l- of diazoacetic acid.
Menthyl ester, n-pentyl ester, neopentyl ester, n-hexyl ester, n-heptyl ester and the like can be mentioned.

Substituent R of olefins^Two, R^Three, R^Four,
R^FiveAlkenyl group, alkyl group, aralkyl in
As the group and the aryl group, a substituent R⁶, R⁷, R⁸, R
⁹, R ^TenThe same as described above as R^TwoAnd R^ThreeWhen
When the two are combined to form a ring, the ring is
Examples thereof include a rohexenyl ring. These placements
The substituent and ring are the above-mentioned substituents R⁶, R⁷, R⁸,
R⁹, R^TenIt may have a substituent similarly to the above.

Examples of such olefins include 2,
5-dimethyl-2,4-hexadiene, isobutylene,
2-methyl-2-butene, 3-methyl-1-butene,
3,3-Dimethyl-1-butene, 2-pentene-4-methyl-1-pentene, 2-methyl-2-pentene, 1-
Hexene, 2-hexene, 2-heptene, isoprene,
1-Methyl-1-cyclohexene, vinylcyclopentane, styrene, 4-phenyl-1-butene and the like can be mentioned, and the amount thereof used is usually in the range of 0.5 to 30 moles per diazoacetic acid ester. .

Examples of the optically active dialkyl tartaric acid esters include (L) -dimethyl tartaric acid ester and (L)
-Diisopropyl tartaric acid ester, (L) -di-t-butyl tartaric acid ester, (L) -dicyclohexyl tartaric acid ester, and compounds in which (L) in each of the above compounds corresponds to (D). Examples of the optically active di-O-aroyl tartaric acid include (L) -di-O-benzoyl tartaric acid, (L) -di-O-metachlorobenzoyl tartaric acid, (L) -di-O-paramethylbenzoyl tartaric acid, Examples include (L) -di-O- (2,4,6-tribromobenzoyl) tartaric acid and compounds in which (L) in each of the above compounds corresponds to (D). Examples of the optically active di-O-alkyloyl tartaric acids include (L)-
Di-O-acetyl tartaric acid, (L) -di-Ot-butyroyl tartaric acid, (L) -di-O-pivaloyl tartaric acid,
(L) -di-O-n-hexyloyl tartaric acid and compounds in which (L) in each of the above compounds corresponds to (D) and the like can be mentioned. Optically active 1,1'-bi (2-naphthol)
Examples of the class include (L) -1,1'-bi (2-naphthol), (L) -1,1'-bi (4-methyl-2-naphthol), (L) -1,1'-. Bi (6,4-dibromo-
2-naphthol), (L) -1,1'-bi (7,5-dichloro-2-naphthol), (L) -1,1'-bi (6
-T-butyl-2-naphthol) and compounds in which (L) in each of the above compounds corresponds to (D).

Such optically active dialkyl tartaric acid esters, optically active di-O-aroyl tartaric acid, optically active di-
O-Alkyloyl tartaric acid or optically active 1,1'-
The amount of bi (2-naphthol) used is usually in the range of 0.001 to 2 mol times, preferably 0.01 to 1 mol times, relative to the diazoacetic acid esters.

Examples of the copper salt include organic acid salts of copper (I) such as copper (I) trifluoromethanesulfonate, copper (I) acetate, and copper (I) trifluoroacetate, copper (I) chloride, and odor. A monovalent copper salt such as an inorganic acid salt of copper (I) such as copper (I) chloride; an organic acid salt of copper (II) in which copper (I) in each of the above compounds corresponds to copper (II); Examples of the divalent copper salt such as the inorganic acid salt of (II) include optically active dialkyl tartaric acid esters, optically active di-O-aroyl tartaric acid, optically active di-O-alkyloyl tartaric acid or It is usually in the range of 0.01 to 2 mol times, preferably 0.1 to 1 mol times, with respect to the optically active 1,1′-bi (2-naphthol) s.

The amount of azoline used is usually in the range of 0.001 to 4 mol times, preferably 0.01 to 2 mol times, relative to the diazoacetic acid esters.

The reaction of olefins with diazoacetic acid esters may be carried out without solvent depending on the kind of olefins used, but it is usually carried out in a solvent, and examples of such a solvent include diethyl ether and diethoxy. methane,
Tetrahydrofuran, dimethoxyethane, ether solvents such as dioxane, hydrocarbon solvents such as hexane,
Examples of the solvent that are inert to the reaction include halogenated hydrocarbon solvents such as chloroform, dichloromethane and 1,2-dichloroethane, ester solvents such as ethyl acetate. These solvents are used alone or in admixture of two or more, and the amount used is usually in the range of 2 to 200 times by weight with respect to the diazoacetic acid esters.

In the reaction, for example, olefins, azolines and copper salts and optically active dialkyl tartaric acid esters, optically active di-O-aroyl tartaric acid, optically active di-O-alkyloyl tartaric acid or optically active 1 in a solvent. , 1'-bi (2-naphthol) are mixed,
Diazoacetic acid esters may be added, and the reaction temperature is usually -50 to 200 ° C, preferably 0 to 50 ° C.

When a divalent copper salt is used as the copper salt, the reaction rate between the olefins and the diazoacetic acid ester can be increased by adding hydrazine before adding the diazoacetic acid ester. ,preferable.
Examples of such hydrazines include phenylhydrazine and the like, and the amount thereof used is usually in the range of 0.8 to 1.2 times the molar amount of the copper salt.

After the reaction, the desired asymmetric cyclopropanecarboxylic acid is taken out from the obtained reaction mixture. At that time, the reaction mixture may be subjected to silica gel column chromatograph treatment, or an alkali such as ammonium chloride aqueous solution may be used. After adding the aqueous solution, the usual method, for example toluene,
The organic layer obtained may be concentrated by performing an extraction treatment using an organic solvent insoluble in water such as ethyl acetate, diethyl ether, and dichloromethane.

Examples of the asymmetric cyclopropanecarboxylic acids thus obtained include 1- (S) -ethoxycarbonyl-2- (S) -phenylcyclopropane and 1- (S) -ethoxycarbonyl-2- (S) -phenylcyclopropane.
(R) -Ethoxycarbonyl-2,2-dimethylcyclopropane, 1- (R) -ethoxycarbonyl-2-
(R)-(2-Methyl-1-propenyl) cyclopropane, 1- (S) -ethoxycarbonyl-2- (S) -t
-Butylcyclopropane and the like.

[0030]

According to the method of the present invention, nitriles and orthoesters can be easily produced in a single step in a high yield,
Moreover, asymmetric cyclopropanecarboxylic acids can be easily produced by reacting olefins with diazoacetic acid esters in the presence of a copper salt using stable azolines.

[0031]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Reference Example 1 Acetonitrile 500 ml, L-cysteine methyl ester hydrochloride 3 g (17.5 mmol), zinc chloride 1.
5 g (11 mmol) and 50 g molecular sieves
Were mixed and stirred under heating under reflux for 10 hours. Then, 100 g of sodium hydrogencarbonate powder and 100 g of saturated aqueous sodium hydrogencarbonate solution were added to the reaction mixture, and the mixture was stirred for 30 minutes. The precipitated solid was filtered off, concentrated, and then 100 g of water was added, followed by chloroform (200 g × 3
The organic layer thus obtained was washed with 100 g of water. After drying over anhydrous sodium sulfate, concentrate and
2.56 g (16.1 mmol) of S) -2-methyl-4-methoxycarbonylthiazoline was obtained (yield 92).
%). ¹ H-NMR (CDCl ₃ , TMS) δ 2.30 (d,
3H), 3.50 to 3.70 (m, 2H), 3.85
(S, 3H), 5.08 (t, 1H)

Reference Example 2 Orthoformic acid methyl ester 50 instead of acetonitrile
0 ml was used, and 2.4 g (1) of (R) -phenylglycinol was used instead of the hydrochloride of L-cysteine methyl ester.
(4R) -4-phenyloxazoline (2.43 g) by the same procedure as in Reference Example 1 except that (7.5 mmol) is used.
(16.5 mmol) was obtained (94% yield). ¹ H-NMR (CDCl ₃ , TMS) δ 4.06 (t,
1H), 4.58 (t, 1H), 5.20 (t, 1
H), 7.04 (S, 1H), 7.20 to 7.40.
(M, 5H)

Reference Example 3 Orthoformic acid methyl ester 50 instead of acetonitrile
0 ml was used, and instead of the hydrochloride of L-cysteine methyl ester, 2.65 g (1) of (S) -phenylalaninol
(4S) -4-benzyloxazoline (2.65 g) by the same procedure as in Reference Example 1 except that (7.5 mmol) was used.
(16.5 mmol) was obtained (94% yield). ¹ H-NMR (CDCl ₃ , TMS) δ 2.68 (d
d, 1H), 3.10 (dd, 1H), 3.91 (t,
1H), 4.18 (t, 1H), 4.32 to 4.48.
(M, 1H), 6.82 (S, 1H), 7.20 to 7.
40 (m, 5H)

Example 1 18 mg of copper (II) trifluoromethanesulfonate
(0.05 mmol), (4S) -2-methyl-4-methoxycarbonylthiazoline 79.5 mg (0.5 mm
ol), (D) -tartaric acid diisopropyl ester 58.
6 mg (0.25 mmol) was dissolved in 3 g of chloroform and stirred at 25 ° C. for 15 minutes, then 5 μl (0.05 mmol) of phenylhydrazine was added and stirred for 5 minutes. Then, at the same temperature, 1.02 g (10 mmol) of 2,5-dimethyl-2,4-hexadiene was added, and the mixture was further stirred for 10 minutes. Then, a chloroform solution (1 g) of 114 mg (1 mmol) of diazoacetic acid ethyl ester was added dropwise over 2 hours with stirring at the same temperature, and the mixture was further stirred for 3 hours at the same temperature, and then the solvent was distilled off. The obtained residue was treated with silica gel column chromatography (hexane: ethyl acetate = 30: 1) to give trans-1- (R) -ethoxycarbonyl-2- (R)-(2-methyl-1-propenyl) cyclo. Propane 73.5 mg (0.375 mm
ol, 35.2% ee, yield 37.5%) and cis-1-
(R) -Ethoxycarbonyl-2- (S)-(2-methyl-1-propenyl) cyclopropane 58.2 mg
(0.297 mmol, 34.1% ee, yield 29.7)
%) And got.

Example 2 (4R) -4-phenyloxazoline 7 in place of (4S) -2-methyl-4-methoxycarbonylthiazoline
Using 3.5 mg (0.5 mmol), instead of (D) -tartaric acid diisopropyl ester, (R) -1,1′-bi (2-naphthol) 71.6 mg (0.25 mmol)
The same procedure as in Example 1 except that
1- (R) -ethoxycarbonyl-2- (R)-(2-
Methyl-1-propenyl) cyclopropane 95.2 mg
(0.486 mmol, 20.9% ee, yield 48.6
%) And cis-1- (R) -ethoxycarbonyl-2-
(S)-(2-Methyl-1-propenyl) cyclopropane 65.8 mg (0.336 mmol, 41.1% e)
e, yield 33.6%).

Example 3 (4S) -4-Benzyloxazoline 8 in place of (4S) -2-methyl-4-methoxycarbonylthiazoline
Example 1 except using 0.5 mg (0.5 mmol)
Operating in the same manner as above, trans-1- (S) -ethoxycarbonyl-2- (S)-(2-methyl-1-propenyl) cyclopropane 83.3 mg (0.425 mmo
1, 14.2% ee, yield 42.5%) and cis-1-
(S) -Ethoxycarbonyl-2- (R)-(2-methyl-1-propenyl) cyclopropane 34.7 mg
(0.177 mmol, 31.3% ee, yield 17.7)
%) And got.

Example 4 (4S) -4-benzyloxazoline 8 in place of (4S) -2-methyl-4-methoxycarbonylthiazoline
The same procedure as in Example 1 was repeated except that 0.5 mg (0.5 mmol) was used and 89.6 mg (0.25 mmol) of (L) -O-dibenzoyltartaric acid was used instead of (D) -tartaric acid diisopropyl ester. , Transformer-1-
(S) -Ethoxycarbonyl-2- (S)-(2-methyl-1-propenyl) cyclopropane 58.8 mg
(0.3 mmol, 25.2% ee, yield 30%) and cis-1- (S) -ethoxycarbonyl-2- (R)-.
(2-Methyl-1-propenyl) cyclopropane 40.
4 mg (0.206 mmol, 35.9% ee, yield 2
0.6%).

Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical display area C07C 67/343 C07C 67/343 69/74 69/74 A // C07B 61/00 300 C07B 61/00 300 C07M 7:00

Claims (5)

[Claims] 1. General formula (1) N_TwoCHCOOR¹ (1) (where R¹Is an alkyl group which may have a substituent,
An aralkyl group or a substituent which may have a substituent
The aryl group which may be possessed is shown. ) Zia
Zoacetic acid esters and general formula (2)(Where R^Two, R^Three, R^Four, R^FiveIs a hydrogen atom,
Alkenyl group optionally having substituent, having substituent
Optionally substituted alkyl group, optionally substituted alkyl group
Aralkyl group or aryl group which may have a substituent
And R^TwoAnd R ^ThreeAnd may combine to form a ring
Yes. Where R^Two, R^Three, R^Four, R^FiveAre the same at the same time
Never. ) With olefins
Dialkyl tartaric acid esters, optically active di-O-aro
Iltartaric acids, optically active di-O-alkyloyltartaric acid
, Optically active 1,1'-bi (2-naphthol)
One type, copper salt and general formula (3)(Where R⁶, R⁷, R⁸, R⁹, R^TenIs hydrogen
Atoms, halogen atoms, and optionally substituted alkyl groups
Group, aralkyl group which may have a substituent, a substituent
Optionally having an aryl group or having a substituent
Good alkenyl group, optionally substituted alkoxy group
Oxycarboni which may have a silyl group or a substituent
Represents a hydrogen atom, and X represents an oxygen atom or a sulfur atom. )so
Characterized by reacting in the presence of the indicated azolines
General formula (4)(Where R¹, R^Two, R^Three, R^Four, R^FiveAre the above
Has the same meaning as, and * represents an asymmetric carbon atom. )
A method for producing asymmetric cyclopropanecarboxylic acids. 2. The method for producing an asymmetric cyclopropanecarboxylic acid according to claim 1, wherein the substituents R ⁶ and R ⁷ in the azolines represented by the general formula (3) are different from each other. 3. The method for producing an asymmetric cyclopropanecarboxylic acid according to claim 2, wherein the azoline is an optically active substance. 4. The method for producing an asymmetric cyclopropanecarboxylic acid according to claim 1, wherein the copper salt is a divalent copper salt. 5. The method for producing an asymmetric cyclopropanecarboxylic acid according to claim 4, wherein the divalent copper salt is an organic acid salt of copper (II).