JP2002275170A - Fluorine-containing lithiooxirane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new intermediate containing a trifluoromethyl group on an oxirane ring and to provide a method for producing a 3- or 4-substituted oxirane ring and an olefin using the intermediate. SOLUTION: An alcohol represented by general formula (1) (R<1> is an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic group which contains a substituent group on not) is reacted with an organolithium compound represented by general formula (2) R<2> -Li (2) (R<2> is an alkyl group, an alkenyl group or an aryl group) in a solvent to give a chemical species which is stable at -98 deg.C and active to an electrophilic reagent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a chemical species having a trifluoromethyl group on an oxirane ring in the production of intermediates of pharmaceuticals and agricultural chemicals, functional substances, and the like, and to the production of fluorine-containing compounds using the same.

[0002]

2. Description of the Related Art A large number of compounds having a trifluoromethyl group on an oxirane ring are known, for example, the following compounds.

[0003]

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In the literature (Chem. Ber. 1992, 125, 1273-1281), nBuLi dissolved in normal hexane was added to ether in which diisopropylamine was dissolved at -78 ° C under an argon atmosphere, and after 30 minutes, R- (+)-4,
4,4-Trifluoro-3-hydroxybutyric acid ethyl ester / ether solution was added dropwise so as not to exceed -72 ° C, and once to -35 ° C, again an ether solution of iodine at a temperature not exceeding -70 ° C. Is added dropwise, water is added and DBU is added.
To give (R, R) -3-trifluoromethyloxirane-2-carboxylic acid-ethyl ester. It also describes that a Grignard reagent is allowed to act on this ester to obtain (2R, 3R) -4-butyl-2,3-epoxy-1,1,1-trifluoro-4-octanol.

[0005]

In the method described in the above-mentioned literature, it is impossible to introduce a further substituent into the oxirane ring. Accordingly, the present invention provides a novel intermediate having a trifluoromethyl group on the oxirane ring, and further provides a method for producing a 3- or 4-substituted oxirane ring and an olefin using the intermediate.

[0006]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and have found that 1,1-dichloro-3,3,3-trifluoroacetone is reacted with a Grignard reagent. An organic lithium compound is reacted at -98 ° C. with dichloromethyl-trifluoromethyl-R ¹ -methanol obtained by hydrolysis, and an electrophile is acted on the compound to give a 3- or 4-substituted oxirane including a trifluoromethyl group. Are found to be generated, and the present invention has been achieved.

That is, the present invention provides a compound represented by the general formula (1)

[0008]

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(Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). alcohol and the general formula represented ^{(2), R 2 -Li (} 2) ( wherein, R ² represents an alkyl group, an alkenyl group, an aryl group.) obtained by reacting an organolithium compound represented by It is a chemical species that exists stably at −98 ° C. and is an active chemical species for electrophiles.

This species has the general formula (3)

[0011]

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(Wherein, R ³ represents a monovalent organic group based on an electrophile, and R ¹ and R ² are the same as general formulas (1) and (2), respectively). Can be given. The chemical species is represented by the general formula (4),

[0013]

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(Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and R ² represents an alkyl group, an alkenyl group or an aryl group. Represents a lithiooxirane. The chemical species of the present invention has the general formula (1)

[0015]

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(Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). Manufactured by reacting an alcohol represented by the formula (2) with an organolithium compound represented by the general formula (2), R ² -Li (2) (wherein R ² represents an alkyl group, an alkenyl group, or an aryl group). can do. Further, the present invention provides a compound represented by the general formula (1):

[0017]

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(Wherein R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). Reacting the alcohol represented by the formula (2) with an organolithium compound represented by the formula: R ² -Li (2) (wherein R ² represents an alkyl group, an alkenyl group, or an aryl group);
Then, an electrophile is added to the reaction system to cause a reaction.

[0019]

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(In the formula, R ³ represents a monovalent organic group based on an electrophile, and R ¹ and R ² are the same as general formulas (1) and (2), respectively.) And a general formula (1):

[0021]

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(Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). Reacting the alcohol represented by the formula (2) with an organolithium compound represented by the formula: R ² -Li (2) (wherein R ² represents an alkyl group, an alkenyl group, or an aryl group);
Then, R ⁴ BZ ₂ (5) wherein R ⁴ represents a monovalent organic group, Z represents an alkyl group,
Represents an alkenyl group, an alkynyl group, an aryl group, or an alkoxy group. Z ₂ may be a divalent alkoxy group. A) reacting an organoboron compound represented by the general formula (6):

[0023]

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(Wherein R ¹ , R ² , and R ⁴ are the same as described above). Further, the present invention provides a compound represented by the general formula (1):

[0025]

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(Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). The alcohol represented by the formula (2) is reacted with an organolithium compound represented by the formula: R ⁵ — (CH ₂ ) ₂ —Li (2) (wherein, R ⁵ represents a monovalent organic group). General formula (7) consisting of raising the temperature to −78 ° C. or higher,

[0027]

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(Wherein R ¹ and R ⁵ are the same as described above).

The general formula (1) according to the present invention

[0030]

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In the alcohol represented by the formula, R ¹ is
An alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic group, which may have a substituent. X is chlorine, bromine or iodine. Alkyl group,
Examples of the alkenyl group and the alkynyl group include a linear or branched group having 1 to 5 carbon atoms, or a linear or branched group having 1 to 5 carbon atoms having a substituent at a terminal. Examples of the aryl group include a phenyl group and a substituted phenyl group. Here, the substituent may be any substituent that is inactive in the method of the present invention, and includes an alkyl group, an alkenyl group,
In the alkynyl group, an aryl group, a heterocyclic group,
An alkoxy group, a tertiary amino group, and the like, and in the case of an aryl group or a heterocyclic group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heterocyclic group, an alkoxy group, a tertiary amino group, etc. It is.

A particularly preferred group is an alkyl group having or not having a substituent, which is a straight-chain or branched alkyl group having 1 to 5 carbon atoms, or a straight-chain or branched alkyl group having an aryl group at the terminal. An alkyl group, alkenyl group, or alkynyl group having a chain or a branch.

The alcohol represented by the general formula (1) is
It can be obtained by reacting 1,1-dichloro-3,3,3-trifluoroacetone with Grignard reagent R ¹ MgX followed by hydrolysis (Japanese Patent Application No. 2000-402).
896).

[0034] In an organolithium compound represented by the general formula according to the present invention ^{(2) R 2 -Li (2} ), R 2 is or without an alkyl group having a substituent, alkenyl group, alkynyl group, aryl Group or heterocyclic group. Examples of the alkyl group, alkenyl group, and alkynyl group include a linear or branched group having 1 to 5 carbon atoms or a linear or branched group having 1 to 5 carbon atoms having a substituent at a terminal. Examples of the aryl group include a phenyl group and a substituted phenyl group. Here, the substituent may be any substituent which is inactive in the method of the present invention, and in the case of an alkyl group, an alkenyl group, or an alkynyl group, an aryl group, a heterocyclic group, an alkoxy group, a tertiary amino group And, in the case of an aryl group or a heterocyclic group,
Examples include an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heterocyclic group, an alkoxy group, and a tertiary amino group. Examples of the alkyl group include a linear or branched group having 1 to 5 carbon atoms, or a 1 to 5 carbon atom having a substituent at a terminal.
It is an alkyl group having 5 straight or branched chains. Here, the substituent is a linear or branched group having 1 to 5 carbon atoms, or a linear or branched alkyl group having 1 to 5 carbon atoms having a substituent at a terminal. Here, the substituent may be any substituent which is inactive in the method of the present invention, and in the case of an alkyl group, an alkenyl group, or an alkynyl group, an aryl group, a heterocyclic group, an alkoxy group, a tertiary amino group And an aryl group or a heterocyclic group, such as an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heterocyclic group, an alkoxy group, or a tertiary amino group.

As R ² , a group having a relatively low bulk is preferable to a group having a bulk, and a particularly preferable group is a group having 1 carbon atom.
To 5 linear alkyl groups, alkenyl groups, alkynyl groups,
Examples include a phenyl group or a phenyl group substituted with a lower alkyl group.

The electrophile according to the present invention is not particularly restricted but includes carbonyl compounds such as ketones, aldehydes and esters, alkyl halides, trialkylsilanes and water.

The carbonyl compound is not particularly limited as long as it has a carbonyl group in the molecule. The carbonyl compound is represented by the general formula (8) R ⁶ —CO—R ⁷ (8) (wherein, R ⁶ and R ⁷ represent a hydrogen atom or a monovalent organic, or R ⁶ and R ⁷ are linked to form a divalent Represents an organic group, provided that R
⁶ and R ⁷ are not simultaneously hydrogen atoms. ). R ⁶ and R ⁷ may be different or the same. R ⁶ and R ⁷ are an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heterocyclic group or an alkoxy group which may have a substituent, or an alkylene group when R ⁶ and R ⁷ are connected. No. The alkyl group, alkenyl group, alkynyl group, alkoxy group and alkylene group have 1 to 5 carbon atoms (in the case of an alkylene group, 2 to 5 carbon atoms).
8) a linear or branched group or a linear or branched group having 1 to 5 carbon atoms (2 to 8 in the case of an alkylene group) having a substituent at the terminal. These groups may contain an oxy (-O-) group or an oxo (O =) group in the molecule. Here, the substituent may be any substituent which is inactive in the method of the present invention, and in the case of an alkyl group, an alkenyl group, an alkynyl group or an alkylene group, a fluorine atom, an aryl group, a heterocyclic group, an alkoxy group Group, tertiary amino group, etc., and in the case of an aryl group and a heterocyclic group, a fluorine atom, an alkyl group, a fluoroalkyl group, an alkenyl group, a fluoroalkenyl group, an alkynyl group, an aryl group, a heterocyclic group A formula group, an alkoxy group or a tertiary amino group;

As the aryl group, a phenyl group, a naphthyl group or a ring hydrogen atom thereof is a fluorine atom, an alkyl group, a fluoroalkyl group, an alkenyl group, a fluoroalkenyl group, an alkynyl group, an aryl group, a heterocyclic group, an alkoxy group. And a group substituted with a tertiary amino group or the like.

Examples of the heterocyclic group include those having an oxygen, nitrogen or sulfur atom.

In the method of the present invention, the method for producing oxirane can be represented by a two-step reaction of (a) and (b) as represented by the following formula (9).

[0041]

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The reaction represented by (a) is carried out as follows to obtain a lithiooxirane represented by the general formula (4). This is performed by adding an organic lithium compound R ² Li represented by the general formula (2) to an alcohol represented by the general formula (1) at a low temperature in an inert solvent. At this time, stirring may be performed. The temperature at this time is preferably −78 ° C. or less, and more preferably about −90 ° C. or less. -98 ° C is preferred because temperature control is relatively easy. If it exceeds -78 ° C, the lithiooxirane represented by the general formula (4) may be decomposed, which is not preferable. As the solvent, an inert solvent can be used in a reaction which is liquid at -78 ° C or lower, preferably -100 ° C, and dimethyl ether, diethyl ether,
Examples include diisopropyl ether, tetrahydrofuran, propane, butane, pentane, hexane, heptane and the like, and these can be used together. , (B) can be carried out continuously without isolating the product of the reaction of (a). Following the reaction of (a), an electrophile (E) is added to the reaction system at a low temperature. The temperature at this time is preferably −78 ° C. or less, and more preferably about −90 ° C. or less. -98 ° C is preferred because temperature control is relatively easy. If it exceeds -78 ° C, the lithiooxirane represented by the general formula (4) may decompose, which is not preferable. At this time, stirring may be performed, and then the temperature is gradually increased. After reaching a predetermined temperature, a terminating agent such as a saturated ammonium chloride solution is added to the reaction solution.

The oxirane represented by the general formula (3) can be obtained by purifying the obtained reaction solution by a conventional purification method in organic synthesis such as extraction, dehydration / drying, distillation, solvent evaporation, column chromatography and the like. .

In the reaction, when the electrophile (E) is a carbonyl compound, and when the carbonyl compound is represented by the general formula (8) R ⁶ —CO—R ⁷ (8), R ³ is represented by the general formula (11) )

[0045]

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(Wherein, R ⁶ and R ⁷ are the same as those in the formula (8)). When alkyl halide, trialkylsilane, water and the like are used as the electrophile, R ³ is an alkyl group, a trialkylsilyl group, and a hydrogen atom, respectively.

The oxirane represented by the general formula (3) obtained by the method of the present invention can be applied as a reagent in various reactions. In the method of the present invention, the method for producing a 3- or 4-substituted olefin comprises the steps of (a)
It can be represented by a two-step reaction of (c).

[0048]

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The reaction represented by (c) can be carried out continuously without isolating the product of the reaction of (a).
Following the reaction of (a), R ⁴ BZ ₂ (5) wherein R ⁴ represents a monovalent organic group, Z represents an alkyl group,
Represents an alkenyl group, an alkynyl group, an aryl group, or an alkoxy group. Z ₂ may be a divalent alkoxy group. ) Is added to the reaction system at a low temperature. R ⁴ is not particularly limited, but may be an alkyl group,
Examples include an alkenyl group, an alkynyl group, an aryl group, a group having these substituents, and a group substituted with a hetero atom. The temperature at this time is preferably -78 ° C or less.
The temperature is preferably about 90 ° C. or less. -98 ° C is preferred because temperature control is relatively easy. If it exceeds -78 ° C, the lithiooxirane represented by the general formula (4) may be decomposed, which is not preferable. At this time, stirring may be carried out, and then the temperature is gradually increased, and depending on the type of the reaction reagent, it is also preferable to heat to 150 ° C. or the reflux temperature of the solvent. After reaching a predetermined temperature, a terminating agent such as a saturated ammonium chloride solution is added to the reaction solution.

The obtained reaction solution is purified by a conventional purification method in organic synthesis such as extraction, dehydration / drying, distillation, solvent distillation, column chromatography, etc., to obtain the olefin represented by the general formula (6). .

When the thiolyoxirane represented by the general formula (4) obtained in (a) is heated to room temperature without adding other reagents, allyl alcohol is obtained. General formula (2)
When an organolithium compound represented by the general formula (13), R ⁵ — (CH ₂ ) ₂ —Li (13) (where R ⁵ represents a monovalent organic group) is used as the organolithium compound of , General formula (7)

[0052]

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(Wherein R ¹ and R ⁵ are the same as described above). R ⁵ is not particularly limited, but represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heterocyclic group, or the like having or not having a substituent.

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited to these Examples.

[0055]

EXAMPLES [Substrate Synthesis] Freshly distilled 3,3-dichloro-1,1,1-trifluoroacetone (DCTFA)
23 ml (28 mmol) of R ¹ MgBr (30
mmol) in THF. The mixture was stirred at 0 ° C. for 10-30 minutes before removing the ice bath. Thereafter, stirring was continued overnight, and then a saturated ammonium chloride solution was added to the reaction solution to stop the reaction. The resulting aqueous solution was extracted three times with diethyl ether. The extract was collected, dried over anhydrous magnesium sulfate (MgSO ₄ ), and the solvent was removed in vacuo. The resulting crude product was purified by silica gel column chromatography (developing solution, hexane: ethyl acetate = 10: 1). The corresponding alcohol was obtained. [Examples 1 to 15] Synthesis of oxirane THF of alcohol (1 mmol) obtained by substrate synthesis
An organic lithium compound (R ² Li) (3
mmol) in hexane (1.9 ml, 1.56 M)
Was added at −98 ° C., and the mixture was stirred at −98 ° C. for 15 minutes. (. Which expressed in E in Table 1, represented by the reaction after -R ³⁾ thereto electrophile in THF (1.5 mmol) of (2 ml) over a period of 3 hours after the addition at -98 ° C. -
The temperature was gradually raised to 78 ° C., and then the reaction was stopped by adding a saturated ammonium chloride solution. The resulting aqueous solution was extracted three times with diethyl ether. The extracts were collected, dried over anhydrous magnesium sulfate (MgSO ₄ ), and the solvent was removed in vacuo. The resulting crude product was subjected to silica gel column chromatography (eluent, hexane: ethyl acetate = 10:
1) and gel permeation chromatography (GP
Purification in C) gave the corresponding oxirane. Table 1 shows the reagents, products, and yields used in the reaction.

[0056]

[Table 1]

The following shows the spectrum data of the product. Example 1: (E) -3-butyl-2-phenethyl-2-trifluoromethyloxirane [(E) -3-Butyl-2-phenethyl-2-trifluoromethyloxiran
e]

[0058]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 0.94 (t,
J = 6.8 Hz, 3H), 1.25-1.72 (m, 6H), 2.07 (t, J =
9.0 Hz, 2H), 2.86 (t, J = 8.2 Hz, 1H), 3.26 (t, J
= 6.0 Hz, 1H), 7.21-7.38 (m, 5H); ¹⁹ F NMR (188 MH
z, CDCl ₃ , δ): -75.4 (s, 3F). Example 2: (E) -3-butyl-2-phenylethynyl-2-trifluoromethyloxirane [(E) -3-Butyl-2-phenylethynyl-2-trifluoromethyloxi
rane]

[0060]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 0.95 (t,
J = 7.2 Hz, 3H), 1.37-1.63 (m, 4H), 1.79-1.90 (m,
2H), 3.44 (t, J = 6.0 Hz, 1H), 7.34-7.42 (m, 3H),
7.49-7.54 (m, 2H); ¹⁹ F NMR (188 MHz, CDCl ₃ , δ):-
75.8 (s, 3F). Example 3: (Z) -2-Butyl-2- (hydroxydiphenyl) methyl-3-phphenylethynyl-3-trifluoromethyloxirane [(Z) -2-Butyl-2- (hydroxydiphenyl) methyl-3- phenylet
hynyl-3-trifluoromethyloxirane]

[0062]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 0.29-0.47
(m, 1H), 0.52 (t, J = 7.2Hz, 3H), 0.79-0.94 (m, 2
H), 0.98-1.26 (m, 1H), 1.83 (dt, J = 12.2, 4.8 Hz,
1H), 2.26 (dt, J = 13.0, 4.8 Hz, 1H), 3.23 (brs, 1
H), 7.24-7.52 (m, 15H); ¹⁹ FNMR (188 MHz, CDCl ₃ , δ)
: -60.6 (s, 3F). Example 5: (Z) -2-butyl-2- (hydroxydiphenyl) methyl-3- (E) -styryl-3-trifluoromethyloxirane [(Z) -2-Butyl-2- (hydroxydiphenyl) methyl- 3- (E) -styr
yl-3-trifluoromethyloxirane]

[0064]

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[0065]¹H NMR (200 MHz, CDCl_Three, δ): 0.09-0.26
 (m, 1H), 0.38 (t, J = 7.0 Hz, 3H), 0.48-0.88 (m,
3H), 1.69 (dt, J = 10.8, 5.4 Hz, 2H), 3.47 (brs, 1
H), 6.44 (d, J = 16.0 Hz, 1H), 6.84 (d, J = 16.0 H
z, 1H), 7.27-7.48 (m, 15H); ¹⁹F NMR (188 MHz, CDC
l_Three, δ): -60.7 (s, 3F). Example 6: (E) -2- (dimethylphenyl) silyl-2-butyl-
3-phenylethynyl-3-trifluoromethyloxirane [(E) -2- (Dimethylphenyl) silyl-2-Butyl-3-phenylethy
nyl-3-trifluoromethyloxirane

[0066]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 0.46 (s,
3H), 0.52 (s, 3H), 0.71 (t, J = 7.2 Hz, 3H), 0.89-
1.62 (m, 5H), 1.90 (dt, J = 12.2, 4.5 Hz, 1H), 7.2
9-7.64 (m, 10H); ¹⁹ F NMR (188 MHz, CDCl ₃ , δ): -70.
4 (s, 3F). Example 7: (E) -2-butyl-2-methyl-3-phenylethynyl
-3-trifluoromethyloxirane [(E) -2-Butyl-2-methyl-3-phenylethynyl-3-trifluoro
methyloxirane]

[0068]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 0.94 (t,
J = 7.2 Hz, 3H), 1.26-1.60 (m, 4H), 1.54 (s, 3H),
1.72-1.96 (m, 2H), 7.26-7.40 (m, 3H), 7.43-7.51
(m, 2H); ¹⁹ F NMR (188 MHz, CDCl ₃ , δ): -67.9 (s, 3
F). Example 8: (Z) -2-allyl-2-butyl-3-phenylethynyl
-3-trifluoromethyloxirane [(Z) -2-Allyl-2-butyl-3-phenylethynyl-3-trifluorom
ethyloxirane]

[0070]

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4H), 1.73-2.07 (m, 2H), 2.48-2.70 (m,
2H), 5.17 (s, 1H), 5.23 (dt, J = 4.6, 1.2 Hz, 1H),
5.84 (dt, J = 17.0, 7.0 Hz, 1H), 7.29-7.39 (m, 3
H), 7.42-7.49 (m, 2H); ¹⁹ F NMR (188 MHz, CDCl ₃ , δ)
: -67.2 (s, 3F). Example 10: (Z) -2-Butyl-2- (hydroxydiethyl) methyl-3-phenylethynyl-3-trifluoromethyloxirane [(Z) -2-Butyl-2- (hydroxydiethyl) methyl-3-phenyleth
ynyl-3-trifluoromethyloxirane]

[0072]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 0.93 (t,
J = 7.0 Hz, 3H), 0.99 (t, J = 7.6Hz, 6H), 1.23-1.5
7 (m, 5H), 1.64-1.82 (m, 4H), 1.88 (brs, 1H), 2.05
-2.28 (m, 1H), 7.24-7.39 (m, 3H), 7.44-7.50 (m, 2
H); ¹⁹ F NMR (188 MHz, CDCl ₃ , δ): -60.0 (s, 3F). Example 12: (E) -3-methyl-2-phenylethynyl-2-trifluoromethyloxirane [(E) -3-Methyl-2-phenylethynyl-2-trifluoromethylox
irane]

[0074]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 1.57 (d,
J = 5.2 Hz, 3H), 3.57 (q, J = 5.2Hz, 1H), 7.27-7.3
7 (m, 3H), 7.41-7.55 (m, 2H); ¹⁹ F NMR (188 MHz, CD
Cl ₃ , δ): -75.8 (s, 3F). Example 13: (Z) -2-butyl-2-methyl-3-phenylethynyl-3-trifluoromethyloxirane [(Z) -2-Butyl-2-methyl-3-phenylethynyl-3-trifluoro
methyloxirane]

[0076]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 0.93 (t,
J = 7.0 Hz, 3H), 1.26-1.52 (m, 4H), 1.62 (s, 3H),
1.75-1.86 (m, 2H), 7.28-7.42 (m, 3H), 7.47-7.53
(m, 2H); ¹⁹ F NMR (188 MHz, CDCl ₃ , δ): -67.7 (s, 3
F). Example 14: (E) -3-Phenyl-2-phenylethynyl-2-trifluoromethyloxirane [(E) -3-Phenyl-2-phenylethynyl-2-trifluoromethylox
irane]

[0078]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 4.51 (s,
1H), 7.27-7.36 (m, 4H), 7.37-7.52 (m, 6H); ¹⁹ F NMR
(188 MHz, CDCl ₃ , δ): -75.6 (s, 3F). Example 15: (E) -2-Phenylethynyl-2-trifluoromethyl-3-vinyloxirane [(E) -2-Phenylethynyl-2-trifluoromethyl-3-vinyloxi
rane]

[0080]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 3.89 (d,
J = 7.0 Hz, 1H), 5.59-5.95 (m, 3H), 7.29-7.46 (m,
3H), 7.49-7.59 (m, 2H); ¹⁹ F NMR (188 MHz, CDCl ₃ ,
δ): -75.9 (s, 3F). Example 16: (Z) -2-butyl-2- (hydroxydiphenyl)
Methyl-3-phenethyl-3-trifluoromethyloxirane [(Z) -2-Butyl-2- (hydroxydiphenyl) methyl-3-phenethy
l-3-trifluoromethyloxirane]

[0082]

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¹ H NMR (200 MHz, CDCl ₃ , δ): 0.11-0.22
(m, 1H), 0.52 (t, J = 7.0 Hz, 3H), 0.66-0.98 (m,
4H), 1.79-1.96 (m, 2H), 2.23-2.38 (m, 1H), 2.96
(t, J = 9.6 Hz, 2H), 3.40 (brs, 1H), 7.18-7.45 (m,
15H); ¹⁹ F NMR (188 MHz, CDCl ₃ , δ): -59.7 (s, 3
F). [Synthesis of olefins] [Examples 17 to 20] A hexane solution (1.9 ml, 1. mmol) of an organolithium compound (R ² Li) (3 mmol) was added to a THF solution (5 ml) of the alcohol (1 mmol) obtained in the substrate synthesis. 56M) at −98 ° C. and the mixture was stirred at −98 ° C. for 15 minutes. An organic boron compound (2 mmol) was added thereto at -98 ° C, and the temperature was gradually raised to room temperature (about 25 ° C) overnight, and then the mixture was heated and refluxed for 4 hours. Next, a saturated ammonium chloride solution was added to the reaction solution to stop the reaction. The resulting aqueous solution was extracted three times with diethyl ether. The extracts were collected, dried over anhydrous magnesium sulfate (MgSO ₄ ), and the solvent was removed in vacuo. The resulting crude product was subjected to silica gel column chromatography (developing solution, hexane: diethyl ether = 1).
Purification by 0: 1) gave the corresponding olefin. Table 2 shows the reagents, products and yields used in the reaction.

[0084]

[Table 2]

The following shows the spectrum data of the product. Example 17: (E) -4-ethyl-1-phenyl-3-trifluoromethyloct-3-en-1-yne [(E) -4-Ethyl-1-phenyl-3-trifluoromethyloct-3-en -1
-yne]

[0086]

Embedded image

[0087]¹H NMR (200 MHz, CDCl_Three, δ): 0.95 (t,
J = 7.0 Hz, 3H), 1.10 (t, J = 7.5 Hz, 3H), 1.36-1.6
2 (m, 4H), 2.38 (ddq, J = 7.5, 1.6, 1.6 Hz, 2H),
2.45-2.53 (m, 2H), 7.28-7.35 (m, 3H), 7.38-7.48
(m, 2H);¹⁹F NMR (188 MHz, CDCl _Three, δ): -58.0 (s, 3
F). Example 18: (Z) -1-4-diphenyl-3-trifluoromethyl
Luoct-3-en-1-yne [(Z) -1-4-Diphenyl-3-trifluoromethyloct-3-en-1-yne]

[0088]

Embedded image

¹ H NMR (200 MHz, CDCl ₃ , δ): 0.89 (t,
J = 7.0 Hz, 3H), 1.27-1.44 (m, 4H), 2.80 (t, J =
6.4 Hz, 2H), 7.10-7.21 (m, 2H), 7.27-7.40 (m, 6H),
7.46-7.53 (m, 2H); ¹⁹ F NMR (188 MHz, CDCl ₃ , δ):
-57.2 (s, 3F). Example 19: (3Z, 5E) -4-butyl-1-phenyl-3-trifluoromethyldeca-3,5-dien-1-yne [(3Z, 5E) -4-Butyl-1-phenyl-3 -trifluoromethyldec-
3,5-diene-1-yne]

[0090]

Embedded image

¹ H NMR (200 MHz, CDCl ₃ , δ): 0.92 (t,
J = 7.4 Hz, 3H), 0.96 (t, J = 7.0Hz, 3H), 1.27-1.6
0 (m, 8H), 2.21 (t, J = 7.8 Hz, 2H), 2.67 (t, J =
7.5 Hz, 2H), 6.17 (dt, J = 15.6, 7.8 Hz, 1H), 6.59
(d, J = 15.6 Hz, 1H), 7.28-7.34 (m, 3H), 7.39-7.50
(m, 2H); ¹⁹ F NMR (188 MHz, CDCl ₃ , δ): -56.0 (s, 3
F). Example 20: (Z) -1-phenyl-4-phenylethynyl-3-trifluoromethyloct-3-en-1-yne [(Z) -1-phenyl-4-phenylethynyl-3-trifluoromethyloc
t-3-en-1-yne]

[0092]

Embedded image

¹ H NMR (200 MHz, CDCl ₃ , δ): 0.99 (t,
J = 7.1 Hz, 3H), 1.42 (tq, J = 7.2, 7.1 Hz, 2H),
1.74 (tt, J = 7.4, 7.2 Hz, 2H), 2.70 (t, J = 7.4 H
z, 2H), 7.32-7.41 (m, 6H), 7.44-7.53 (m, 4H); ¹⁹ FN
MR (188 MHz, CDCl ₃ , δ): -61.1 (s, 3F).

Example 21 Synthesis of (E) -allyl alcohol THF of alcohol (1 mmol) obtained by substrate synthesis
Butyl lithium (nBuLi) (3 m) was added to the solution (5 ml).
mol) in hexane (1.9 ml, 1.56 M) at -98 ° C. The mixture was stirred at −98 ° C. for 15 minutes and then gradually warmed to room temperature (about 25 ° C.) overnight. Thereafter, a saturated ammonium chloride solution was added to the reaction solution to stop the reaction. The resulting aqueous solution was extracted three times with diethyl ether. The extracts were collected, dried over anhydrous magnesium sulfate (MgSO ₄ ), and the solvent was removed in vacuo. The resulting crude product was purified by silica gel column chromatography (developing solution, hexane: ethyl acetate = 10: 1). The corresponding allyl alcohol was obtained.

[0095]

Since the chemical species of the present invention is active toward electrophiles, it is possible to introduce a trifluoromethyl group into an organic compound by applying it to various reactions.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) C07C 33/48 C07C 33/48 C07D 301/26 C07D 301/26 303/14 303/14 C07F 1/02 C07F 1/02 5/02 5/02 Z 7/08 7/08 S // C07M 9:00 C07M 9:00 F term (reference) 4C048 BB30 CC01 UU03 XX02 XX04 4H006 AA02 AC24 AC25 BB11 BB15 BC10 FC52 FC74 FC80 FE11 FE71 FE74 4H048 AA01 AB84 VA11 VA22 VA51 VB10 4H049 VN01 VP01 VQ57 VR24 VW01

Claims (7)

[Claims] 1. A compound represented by the following general formula (1): (Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). −98 ° C. obtained by reacting an alcohol with an organic lithium compound represented by the general formula (2), R ² —Li (2) (wherein R ² represents an alkyl group, an alkenyl group, or an aryl group) Is a chemical species that is stably present in and is active against an electrophile. 2. An electrophile according to the general formula (3): (Wherein R ³ represents a monovalent organic group based on an electrophile,
R ¹ and R ² are the same as general formulas (1) and (2), respectively. The chemical species according to claim 1, which can provide the oxirane represented by the formula (1). 3. A compound represented by the general formula (4): (In the formula, R ¹ represents an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic group having or not having a substituent, and R ² represents an alkyl group, an alkenyl group, or an aryl group.) A chemical species that is lithiooxirane represented by 4. A compound represented by the general formula (1): (Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). alcohol and the general formula ^{(2), R 2 -Li (} 2) ( wherein, R ² represents an alkyl group, an alkenyl group, an aryl group.) comprising reacting an organolithium compound represented by claims -98 according to any one of 1 to 3,
A method for producing a chemical species which exists stably at ℃ and which is active toward an electrophile. 5. A compound of the general formula (1) (Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). Reacting an alcohol with an organolithium compound represented by the general formula (2), R ² -Li (2) (wherein R ² represents an alkyl group, an alkenyl group, or an aryl group);
Next, an electrophile is added to the reaction system to cause a reaction. (Wherein R ³ represents a monovalent organic group based on an electrophile,
R ¹ and R ² are the same as general formulas (1) and (2), respectively. ). 6. A compound represented by the general formula (1): (Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). Reacting an alcohol with an organolithium compound represented by the general formula (2), R ² —Li (2) (wherein R ² represents an alkyl group, an alkenyl group, or an aryl group);
Then, R ⁴ BZ ₂ (5) wherein R ⁴ represents a monovalent organic group, Z represents an alkyl group,
Represents an alkenyl group, an alkynyl group, an aryl group, or an alkoxy group. Z ₂ may be a divalent alkoxy group. A) reacting an organoboron compound represented by the general formula (6): (Wherein, R ¹ , R ² and R ⁴ are the same as described above). 7. A compound represented by the general formula (1): (Wherein, R ¹ represents an alkyl group, alkenyl group, alkynyl group, aryl group or heterocyclic group having or not having a substituent, and X represents chlorine, bromine or iodine). The alcohol is reacted with an organolithium compound represented by the general formula (13), R ⁵ — (CH ₂ ) ₂ —Li (13) (where R ⁵ represents a monovalent organic group), and then General formula (7) consisting of raising the temperature to 78 ° C. or higher, (Wherein, R ¹ and R ⁵ are the same as described above).