JP2024124118A - Method for producing fluoroalkyl compounds, fluoroalkylating agents, and methods for producing fluoroalkylating agents - Google Patents

Abstract

To provide: a fluoroalkylation agent that can be derived from a fluoroalkyl sulfonic acid or carboxylic acid analogue, a method for producing the fluoroalkylation agent, and a method for producing a fluoroalkyl compound using the fluoroalkylation agent.SOLUTION: The method for producing a fluoroalkyl compound comprises a step of performing fluoroalkylation reaction using a fluoroalkylation agent represented by general formula [1] or general formula [2] and an electrophile.SELECTED DRAWING: None

Description

The present invention relates to a method for producing a fluoroalkyl compound using a fluoroalkylating agent, a fluoroalkylating agent, and a method for producing a fluoroalkylating agent.

Fluoroalkyl groups are known as important functional groups found in medicines, agricultural chemicals, functional materials, etc. Efficient methods for introducing fluoroalkyl groups into various compounds are needed.

A representative fluoroalkylating agent is (trifluoromethyl)trimethylsilane, which is a nucleophilic fluoroalkylating agent. On the other hand, 1-trifluoromethyl-1,2-benzoiodoxol-3(1H)-one (Togni Reagent II), developed by Togni et al., is known as an electrophilic fluoroalkylating agent.

Many of the existing fluoroalkylating agents are decomposable or explosive. In particular, (trifluoromethyl)trimethylsilane, for example, is known to easily hydrolyze in air, and Togni reagent II is known to pose an explosion hazard. As such, (trifluoromethyl)trimethylsilane and Togni reagent II have problems with stability and safety, and therefore cannot be said to be industrially advantageous.

In addition, most existing fluoroalkylating agents are trifluoromethylating agents, and the fluoroalkyl groups that can be introduced are very limited. One reason for this is that while trifluoromethyl compounds such as fluoromethane and trifluoroiodomethane, which are the raw materials for trifluoromethylating agents, are industrially produced and easily available, there are few fluoroalkyl compounds that are easily available for synthesizing a variety of fluoroalkylating agents.

Fluoroalkyl sulfonic acids or carboxylic acids are compounds that are industrially produced by methods including electrolytic fluorination, and are relatively easy to obtain and inexpensive. Furthermore, sulfonic acids or carboxylic acids having a variety of fluoroalkyl groups, not limited to trifluoromethyl groups, have been synthesized.

It has generally been considered difficult to cleave the carbon-sulfur bond of a fluoroalkylsulfonic acid, and therefore it has been considered difficult to use a derivative of a fluoroalkylsulfonic acid as a fluoroalkylating agent.
For example, it is known that fluoroalkylation can be achieved by converting a fluoroalkylsulfonyl fluoride, which is a derivative of a fluoroalkylsulfonic acid, into a fluoroalkylsulfinic acid with a reducing agent and reacting the fluoroalkylated acid with an alkene in the presence of a one-electron oxidizing agent (see, for example, Patent Document 1). In this reaction, the substrate is limited to an alkene.

Several fluoroalkylation reactions are known using fluoroalkyl carboxylic acids and their derivatives, in comparison with examples using fluoroalkyl sulfonic acids (see, for example, Patent Document 2 and Non-Patent Document 1). However, in many cases, conversion to a highly reactive fluoroalkylating agent or the use of an expensive metal catalyst is required.

Chinese Patent Publication No. 105693464 International Publication No. 2017/104589

Dehang Yin; Dengquan Su; Jian Jin. Cell Reports Physical Science (2020), 1(8), 100141.

The present invention has been made in view of the above circumstances, and aims to provide a fluoroalkylating agent that can be derived from an analogue of a fluoroalkylsulfonic acid or a carboxylic acid, a method for producing the fluoroalkylating agent, and a method for producing a fluoroalkyl compound using the fluoroalkylating agent.

The present inventors have invented a simple and systematic method for producing fluoroalkylating agents that can synthesize a variety of fluoroalkyl structures and can be derived from relatively easily available analogues of fluoroalkyl sulfonic acid or carboxylic acid. Furthermore, they have found that by using the obtained fluoroalkylating agents, it is possible to provide a variety of fluoroalkyl compounds for use in fields such as medicine, agricultural chemicals, and functional materials.

The present invention has the following aspects.
[1] A method for producing a fluoroalkyl compound, comprising a step of carrying out a fluoroalkylation reaction using a fluoroalkylating agent represented by the following general formula [1] or the following general formula [2] and an electrophilic agent:

（式中、Ｒ^１は、置換基を有していてもよい炭素数６～１４のアリール基を表し、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表す。）

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and Rf ¹ represents an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent consisting of a sulfonyl group or a carbonyl group, or 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.)

（式中、Ｒ^１は、置換基を有していてもよい炭素数６～１４のアリール基を表し、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表す。）

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and Rf ¹ represents an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent consisting of a sulfonyl group or a carbonyl group, or 1 to 5 ether-bonded oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.)

[2] The electrophile is a proton donor represented by the following general formula [3]:
The method for producing a fluoroalkyl compound according to [1], which obtains a fluoroalkyl compound represented by the following general formula [4]:

（式中、Ｒ^２は、水素原子、金属原子または置換基を有していてもよい炭素数１～３０のアルキル基または置換基を有していてもよい炭素数６～１４のアリール基を表し、Ｘ^５は、酸素、窒素、硫黄等のヘテロ原子を表す。）

(In the formula, ^R2 represents a hydrogen atom, a metal atom, an alkyl group having 1 to 30 carbon atoms which may have a substituent, or an aryl group having 6 to 14 carbon atoms which may have a substituent, and ^X5 represents a heteroatom such as oxygen, nitrogen, or sulfur.)

（式中、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表す。）

(In the formula, Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and which represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.)

[3] The electrophile is a silicon compound represented by the following general formula [5]:
The method for producing a fluoroalkyl compound according to [1], which obtains a fluoroalkyl compound represented by the following general formula [6]:

（式中、Ｒ^３、Ｒ^４およびＲ^５は、それぞれ独立に水素原子または炭素数１～１０の直鎖、分岐あるいは環状構造を有することもある置換基や不飽和結合を有してもよいアルキル基、アリール基、もしくは炭素数１～３０のアルキル基または置換基を有していてもよい炭素数６～１４のアリール基を含むアルコキシ基を表し、Ｘ^４は、ハロゲン原子もしくは炭素数１～３０のアルキル基または置換基を有していてもよい炭素数６～１４のアリール基を含むアルコキシ基を表す。）

(In the formula, R ³ , R ⁴ and R ⁵ each independently represent a hydrogen atom or an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent or an unsaturated bond, an aryl group, or an alkoxy group containing an alkyl group having 1 to 30 carbon atoms or an aryl group having 6 to 14 carbon atoms which may have a substituent; and X ⁴ represents a halogen atom or an alkoxy group containing an alkyl group having 1 to 30 carbon atoms or an aryl group having 6 to 14 carbon atoms which may have a substituent.)

（式中、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表し、Ｒ^３、Ｒ^４およびＲ^５は、それぞれ独立に水素原子または炭素数１～１０の直鎖、分岐あるいは環状構造を有することもある置換基や不飽和結合を有してもよいアルキル基、アリール基、もしくは炭素数１～３０のアルキル基または置換基を有していてもよい炭素数６～１４のアリール基を含むアルコキシ基を表す。）

(In the formula, Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms and which may have a straight-chain, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen; R ³ , R ⁴ and R ⁵ each independently represent a hydrogen atom, or an alkyl group having 1 to 10 carbon atoms and which may have a straight-chain, branched or cyclic structure, which may have an unsaturated bond, an aryl group, or an alkoxy group including an alkyl group having 1 to 30 carbon atoms or an aryl group having 6 to 14 carbon atoms and which may have a substituent.)

[4] The electrophile is a carbonyl compound represented by the following general formula [7]:
The method for producing a fluoroalkyl compound according to [1], which obtains a fluoroalkyl compound represented by the following general formula [8]:

（式中、Ｒ^６およびＲ^７は、それぞれ独立に水素原子または炭素数１～１０の直鎖、分岐あるいは環状構造を有することもある置換基や不飽和結合を有してもよいアルキル基、アリール基を表す。）

(In the formula, ^R6 and ^R7 each independently represent a hydrogen atom, or a substituent having a linear, branched or cyclic structure having 1 to 10 carbon atoms, or an alkyl group or aryl group which may have an unsaturated bond.)

（式中、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表し、Ｒ^６およびＲ^７は、それぞれ独立に水素原子または炭素数１～１０の直鎖、分岐あるいは環状構造を有することもある置換基や不飽和結合を有してもよいアルキル基、アリール基を表す。）

(In the formula, Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms and which may have a straight-chain, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen; R ⁶ and R ⁷ each independently represent a hydrogen atom, or a substituent having 1 to 10 carbon atoms and which may have a straight-chain, branched or cyclic structure, or an alkyl group or aryl group which may have an unsaturated bond.)

[5] The electrophile is a disulfide compound represented by the following general formula [9]:
The method for producing a fluoroalkyl compound according to [1], which obtains a fluoroalkyl compound represented by the following general formula [10]:

（式中、Ｒ^８は、炭素数１～１０の直鎖、分岐あるいは環状構造を有することもある置換基や不飽和結合を有してもよいアルキル基、アリール基を表す。）

(In the formula, ^R8 represents an alkyl group or aryl group having 1 to 10 carbon atoms, which may have a linear, branched or cyclic structure and may have a substituent or an unsaturated bond.)

（式中、Ｒ^８は、炭素数１～１０の直鎖、分岐あるいは環状構造を有することもある置換基や不飽和結合を有してもよいアルキル基、アリール基を表し、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表す。）

(In the formula, R ⁸ represents a substituent group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure, or an alkyl group or aryl group which may have an unsaturated bond; Rf ¹ represents a substituent group consisting of a sulfonyl group or a carbonyl group, or an alkyl group which may have a linear, branched or cyclic structure having 1 to 10 carbon atoms which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.)

[6] A fluoroalkylating agent represented by the following general formula [11].

（式中、Ｒ^９は、置換基を有していてもよい炭素数６～１４のアリール基を表し、Ｘ^３は、水酸基、金属塩（例えば、－ＯＫ、－ＯＮａ）、炭素数１～４のアルコキシ基（例えば、メトキシ基、エトキシ基）、アミノ基、炭素数１～４のアルキルアミノ基（例えば、メチルアミノ基、プロピルアミノ基）またはハロゲン原子（例えば、フッ素、塩素）を表す。）

(In the formula, R ⁹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and X ³ represents a hydroxyl group, a metal salt (e.g., -OK, -ONa), an alkoxy group having 1 to 4 carbon atoms (e.g., a methoxy group, an ethoxy group), an amino group, an alkylamino group having 1 to 4 carbon atoms (e.g., a methylamino group, a propylamino group), or a halogen atom (e.g., a fluorine atom, a chlorine atom).)

[7] A fluoroalkylating agent represented by the following general formula [12].

（式中、Ｒ^１０とＲ^１１は、同一もしくは独立の、置換基を有していてもよい炭素数６～１４のアリール基を表す。）

(In the formula, R ¹⁰ and R ¹¹ are the same or independent and represent an aryl group having 6 to 14 carbon atoms which may have a substituent.)

[8] A method for producing a fluoroalkylating agent, comprising the step of reacting a fluoroalkylsulfonic acid derivative represented by the following general formula [13] or the following general formula [14] with an aromatic compound represented by the following general formula [15] to obtain a fluoroalkylating agent represented by the following general formula [1].

（式中、Ｒｆ^１とＲｆ^２は、同一もしくは独立の、置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐もしくは環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表し、Ｒｆ^１とＲｆ^２は連結して、４～７員環を形成してもよい。）

(In the formula, Rf ¹ and Rf ² are the same or independent and are substituents or alkyl groups having 1 to 10 carbon atoms which may have a straight chain, branched or cyclic structure and may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represent fluoroalkyl groups having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen, and Rf ¹ and Rf ² may be bonded to form a 4- to 7-membered ring.)

（式中、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表し、Ｘ^１は、ハロゲン原子を表す。）

(In the formula, Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms which may have a straight chain, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen, and X ¹ represents a halogen atom.)

（式中、Ｒ^１は、置換基を有していてもよい炭素数６～１４のアリール基を表す。）

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent.)

（式中、Ｒ^１は、置換基を有していてもよい炭素数６～１４のアリール基を表し、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表す。）

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and Rf ¹ represents an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent consisting of a sulfonyl group or a carbonyl group, or 1 to 5 ether-bonded oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.)

[9] A method for producing a fluoroalkylating agent, comprising the step of reacting a fluoroalkyl carboxylic acid derivative represented by the following general formula [16] or the following general formula [17] with an aromatic compound represented by the following general formula [18] to obtain a fluoroalkylating agent represented by the following general formula [2].

（式中、Ｒ^１は、置換基を有していてもよい炭素数６～１４のアリール基を表し、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表し、Ｘ^２はハロゲン原子を表す。）

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms which may have a straight chain, branched or cyclic structure which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen, and X ² represents a halogen atom.)

（式中、Ｒｆ^１とＲｆ^２は、同一もしくは独立の、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐もしくは環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表し、Ｒｆ^１とＲｆ^２は連結して、４～７員環を形成してもよい。）

(In the formula, Rf ¹ and Rf ² are the same or independent and are a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms and which may have a straight chain, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and which represent a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen, and Rf ¹ and Rf ² may be bonded to form a 4- to 7-membered ring.)

（式中、Ｒ^１は、置換基を有していてもよい炭素数６～１４のアリール基を表す。）

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent.)

（式中、Ｒ^１は、置換基を有していてもよい炭素数６～１４のアリール基を表し、Ｒｆ^１は、スルホニル基もしくはカルボニル基からなる置換基または炭素原子間に１～５のエーテル結合性の酸素原子を有していてもよい炭素数１～１０の直鎖、分岐または環状構造を有することもあるアルキル基であって、スルホニルもしくはカルボニルのα炭素上がフッ素もしくはトリフルオロメチル基などの炭素で置換されて水素を持たない構造のフルオロアルキル基を表す。）

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and Rf ¹ represents an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent consisting of a sulfonyl group or a carbonyl group, or 1 to 5 ether-bonded oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.)

The present invention provides a fluoroalkylating agent that can be derived from an analog of a fluoroalkylsulfonic acid or carboxylic acid, a method for producing the fluoroalkylating agent, and a method for producing a fluoroalkyl compound using the fluoroalkylating agent.

BEST MODE FOR CARRYING OUT THEINVENTION The fluoroalkylating agent, the method for producing the fluoroalkylating agent, and the method for producing a fluoroalkyl compound using the fluoroalkylating agent according to the present invention will be described below.
It should be noted that the present embodiment is specifically described to allow a better understanding of the gist of the invention, and does not limit the present invention unless otherwise specified.

The present invention includes a fluoroalkylating agent represented by the above general formula [1] or the above general formula [2], and a method for producing a fluoroalkyl compound, comprising a step of carrying out a fluoroalkylation reaction using the fluoroalkylating agent and an electrophilic agent.

<Production of fluoroalkylating agent>
The process for producing a fluoroalkylating agent, which is a preliminary process of the process for producing a fluoroalkyl compound of the present invention, will be described below.
The fluoroalkylating agent is produced by reacting a fluoroalkylsulfonic acid derivative represented by the above general formula [13] or the above general formula [14], or a fluoroalkylcarboxylic acid derivative represented by the above general formula [16] or the above general formula [17] with an aromatic compound represented by the above general formula [15] or the above general formula [18] in the presence of a Lewis acid.

In the above general formulas [1], [2], and [13] to [18], R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, Rf ¹ and Rf ² represent the same or independent alkyl groups having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent consisting of a sulfonyl group or a carbonyl group or 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represent fluoroalkyl groups having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group to have no hydrogen, and Rf ¹ and Rf ² may be linked to form a 4- to 7-membered ring.

Examples of aryl groups which may have a substituent include a phenyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2,3-dimethylphenyl group, a 3,4-dimethylphenyl group, a 3,5-dimethylphenyl group, a 2,5-dimethylphenyl group, a 4-ethylphenyl group, a 4-chlorophenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, a 4-trifluoromethylphenyl group, a 4-cyanophenyl group, a 4-nitrophenyl group, a 3,5-dimethoxyphenyl group, a 1-naphthyl group, and a 2-naphthyl group.

Examples of fluoroalkyl groups which may have a substituent or an ether-bonded oxygen atom include 1,1,2,2,3,3,4,4-octafluoro-4-butane-1-sulfonate group, 1,1,2,2,3,3-hexafluoro-3-propane-1-sulfonate group, 1,1,2,2-butafluoro-2-ethane-1-sulfonate group, 1,1,-difluoro-1-methane-1-sulfonate group, perfluorohexyl group, perfluoropentyl group, nonafluorobutyl group, heptafluoropropyl group, -CF(CF ₃ )OCF ₂ CF ₂ CF ₃ , -CF(CF ₃ )OCF ₂ CF(CF ₃ )OCF ₂ CF ₂ CF ₃ , -CF(CF ₃ )OCF ₂ CF ₂ CF(CF ₃ ) COC ₆ H ₅ , 1H,1H,2H,2H-tridecafluorooctyl group, 1H,1H,2H,2H-nonafluorohexyl group, and the like can be mentioned.

Examples of Lewis acids used in the present invention include aluminum chloride, boron trifluoride, tin chloride, and zinc chloride. The amount of Lewis acid used relative to the fluoroalkylsulfonic acid derivative represented by the above general formula [13], the fluoroalkylsulfonic acid derivative represented by the above general formula [14], the fluoroalkylcarboxylic acid derivative represented by the above general formula [16], or the fluoroalkylcarboxylic acid derivative represented by the above general formula [17] is 0.5 to 10, preferably 1.5 to 6, in terms of molar ratio. If the amount of Lewis acid used is less than 0.5, the amount of fluoroalkylating agent produced is insufficient. Also, if the amount of Lewis acid used exceeds 10, it is not economical.

The aromatic compound represented by the above general formula [15] or the aromatic compound represented by the above general formula [18] is used in a solvent amount relative to the fluoroalkylsulfonic acid derivative represented by the above general formula [13], the fluoroalkylsulfonic acid derivative represented by the above general formula [14], the fluoroalkylcarboxylic acid derivative represented by the above general formula [16], or the fluoroalkylcarboxylic acid derivative represented by the above general formula [17]. The amount of the solvent used is not particularly limited, but is usually 2 to 15 times by mass.

The fluoroalkylsulfonic acid derivative represented by the above general formula [13], the fluoroalkylsulfonic acid derivative represented by the above general formula [14], the fluoroalkylcarboxylic acid derivative represented by the above general formula [16], or the fluoroalkylcarboxylic acid derivative represented by the above general formula [17] may be reacted with a Lewis acid in the absence of a solvent, or an aprotic solvent may be added. Examples of the aprotic solvent include ethers such as diisopropyl ether and tetrahydrofuran, and alkanes such as pentane and hexane.
The reaction temperature is not particularly limited, but is usually 0°C to 80°C.

<Fluoroalkylation reaction>
Next, the process of reacting the fluoroalkylating agent represented by the above general formula [1] or [2] with an electrophilic agent will be described.
The fluoroalkyl compound is produced by reacting a fluoroalkylating agent represented by the above general formula [1] or [2] with an electrophile.

The subsequent chemical reactions can be carried out in a solvent inert to the reaction, such as N,N-dimethylformamide, N,N-dimethylacetamide, 1,4-dioxane, tetrahydrofuran, diisopropyl ether, acetonitrile, benzene, toluene, dimethylsulfoxide, etc.
The reaction temperature is -78°C to 50°C, preferably -70°C to 25°C.

Fluoroalkylation of Proton Donors
When the proton donor represented by the above general formula [3] is used as an electrophile and reacted with a base, a fluoroalkyl compound having a hydrogen atom represented by the above general formula [4] is obtained.
In the above general formula [3] and the above general formula [4], the substituent ^R2 represents a hydrogen atom, an alkyl group having 1 to 30 carbon atoms which may have a substituent, or an aryl group having 6 to 14 carbon atoms which may have a substituent.

Examples of alkyl groups having 1 to 30 carbon atoms, which may have a substituent, include methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, iso-butyl, tert-butyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, and 1-decyl groups.

Examples of aryl groups having 6 to 14 carbon atoms which may have a substituent include a phenyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2,3-dimethylphenyl group, a 3,4-dimethylphenyl group, a 3,5-dimethylphenyl group, a 2,5-dimethylphenyl group, a 4-ethylphenyl group, a 4-chlorophenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, a 4-trifluoromethylphenyl group, a 4-cyanophenyl group, a 4-nitrophenyl group, a 3,5-dimethoxyphenyl group, a 1-naphthyl group, and a 2-naphthyl group.

The molar ratio of the proton donor represented by the general formula [3] to the fluoroalkylating agent represented by the general formula [1] or [2] is 0.5 to 10, preferably 1 to 5. If the amount of the proton donor used is less than 1, the amount of fluoroalkyl compound produced is insufficient. If the amount of the proton donor used is more than 2, it is not economical.

Examples of bases used in the fluoroalkylation of proton donors include potassium hydroxide, sodium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.

The amount of base used relative to the fluoroalkylating agent represented by the above general formula [1] or the above general formula [2] is 1 to 10, preferably 2.5 to 5.0, in terms of molar ratio. If the amount of base used is less than 1, the amount of fluoroalkyl compound produced is insufficient. If the amount of base used is more than 4, decomposition of the produced fluoroalkyl compound proceeds.

<Fluoroalkylation of silicon compounds>
When the silicon compound represented by the above general formula [5] is used as an electrophile and a reducing agent is allowed to act on it, a fluoroalkyl compound having a silicon atom represented by the above general formula [6] is obtained.

In the above general formula [5] and the above general formula [6], the substituents R ³ , R ⁴ and R ⁵ each independently represent a hydrogen atom, a substituent having a linear, branched or cyclic structure having 1 to 10 carbon atoms, an alkyl group which may have an unsaturated bond, an aryl group, or an alkoxy group including an alkyl group having 1 to 30 carbon atoms or an aryl group having 6 to 14 carbon atoms which may have a substituent.

Examples of alkyl groups having 1 to 10 carbon atoms, which may have a substituent, include methyl, ethyl, vinyl, 1-propyl, 2-propyl, allyl, acryloyl, 1-butyl, 2-butyl, iso-butyl, tert-butyl, butadienyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, and 1-decyl groups.

Examples of aryl groups which may have a substituent include phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,3-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2,5-dimethylphenyl, 4-ethylphenyl, 4-vinylphenyl, 4-allylphenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-nitrophenyl, 3,5-dimethoxyphenyl, 1-naphthyl, and 2-naphthyl groups.

The amount of the silicon compound represented by the general formula [5] used relative to the fluoroalkylating agent represented by the general formula [1] or the general formula [2] is 1 to 10, preferably 5 to 8, in terms of molar ratio. If the amount of the silicon compound used is less than 1, the amount of the fluoroalkyl compound produced is insufficient. If the amount of the silicon compound used is more than 10, it is not economical.

Reducing agents used in the fluoroalkylation of silicon compounds include, for example, magnesium, zinc, manganese, etc.

The amount of the reducing agent used relative to the fluoroalkylating agent represented by the above general formula [1] or the above general formula [2] is 1 to 4 in molar ratio, and preferably 1.5 to 2.5. If the amount of the reducing agent used is less than 1, the amount of the fluoroalkyl compound produced is insufficient. Also, if the amount of the reducing agent used exceeds 4, it is not economical.

<Fluoroalkylation of Carbonyl Compounds>
When the carbonyl compound represented by the above general formula [7] is used as an electrophile and reacted with a base, a fluoroalkyl compound having a hydroxyl group represented by the above general formula [8] is obtained.

In the above general formula [7] and the above general formula [8], R ⁶ and R ⁷ each independently represent a hydrogen atom or an alkyl group or an aryl group which may have a straight chain, branched or cyclic structure having 1 to 10 carbon atoms and which may have a substituent.

Examples of alkyl groups having 1 to 10 carbon atoms, which may have a substituent, include methyl, ethyl, vinyl, 1-propyl, 2-propyl, allyl, acryloyl, 1-butyl, 2-butyl, iso-butyl, tert-butyl, butadienyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, and 1-decyl groups.

Examples of aryl groups which may have a substituent include phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,3-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2,5-dimethylphenyl, 4-ethylphenyl, 4-vinylphenyl, 4-allylphenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-nitrophenyl, 3,5-dimethoxyphenyl, 1-naphthyl, and 2-naphthyl groups.

The amount of the carbonyl compound represented by the general formula [7] used relative to the fluoroalkylating agent represented by the general formula [1] or [2] is 0.5 to 4, preferably 1 to 3, in terms of molar ratio. If the amount of the carbonyl compound used is less than 0.5, the amount of the fluoroalkyl compound produced is insufficient. If the amount of the carbonyl compound used exceeds 4, it is not economical.

Examples of bases used in the fluoroalkylation of carbonyl compounds include potassium hydroxide, sodium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.

The amount of base used relative to the fluoroalkylating agent represented by the above general formula [1] or the above general formula [2] is 1 to 4, preferably 1.5 to 2.5, in terms of molar ratio. If the amount of base used is less than 1, the amount of fluoroalkyl compound produced is insufficient. If the amount of base used is more than 4, it is not economical.

<Fluoroalkylation of Disulfides>
When the disulfide compound represented by the above general formula [9] is used as an electrophile and reacted with a base, a fluoroalkyl compound having a sulfide bond represented by the above general formula [10] is obtained.

In the above general formula [9] and the above general formula [10], the substituent R ⁸ represents an alkyl group or an aryl group which may have a straight chain, branched or cyclic structure having 1 to 10 carbon atoms and which may have a substituent.

Examples of alkyl groups having 1 to 10 carbon atoms, which may have a substituent, include methyl, ethyl, vinyl, 1-propyl, 2-propyl, allyl, acryloyl, 1-butyl, 2-butyl, iso-butyl, tert-butyl, butadienyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, and 1-decyl groups.

Examples of aryl groups which may have a substituent include phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,3-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2,5-dimethylphenyl, 4-ethylphenyl, 4-vinylphenyl, 4-allylphenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-nitrophenyl, 3,5-dimethoxyphenyl, 1-naphthyl, and 2-naphthyl groups.

The amount of the disulfide compound represented by the general formula [9] used relative to the fluoroalkylating agent represented by the general formula [1] or [2] is 1 to 4, preferably 1.5 to 2.5, in terms of molar ratio. If the amount of the disulfide compound used is less than 1, the amount of the fluoroalkyl compound produced is insufficient. If the amount of the disulfide compound used is more than 4, it is not economical.

Examples of bases used in the fluoroalkylation of disulfide compounds include potassium hydroxide, sodium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.

The amount of base used relative to the fluoroalkylating agent represented by the above general formula [1] or the above general formula [2] is 1 to 4, preferably 1.5 to 2.5, in terms of molar ratio. If the amount of base used is less than 1, the amount of fluoroalkyl compound produced is insufficient. Also, if the amount of base used exceeds 4, it is not economical.

The fluoroalkylating agent of the present invention can be prepared from fluoroalkylsulfonic acids and carboxylic acids that are industrially produced and easily available. The use of the fluoroalkylating agent of the present invention enables a new method for producing fluoroalkyl compounds. This makes it possible to provide a wider variety of fluoroalkyl compounds to the fields of medicine, agricultural chemicals, functional materials, and the like. For these reasons, the present invention is extremely useful as a fluoroalkylating agent for producing fluoroalkyl compounds.

The present invention makes it possible to produce a variety of fluoroalkyl structures that are difficult to obtain or prepare using existing fluoroalkylating agents from easily available fluoroalkylsulfonic acids and carboxylic acids, and by using the fluoroalkylating agents, a variety of fluoroalkyl compounds can be produced. Furthermore, the inventors have discovered that fluoroalkylsulfonic acids and carboxylic acids, which have not been used as fluoroalkylating agents because it was previously thought that it was difficult to cleave carbon-sulfur bonds or carbon-carbon bonds, can be derivatized to function as fluoroalkylating agents. Furthermore, by using the obtained fluoroalkylating agent, it is possible to provide an even greater variety of fluoroalkyl compounds in the fields of medicine, agricultural chemicals, functional materials, etc., and therefore the fluoroalkylating agent has high industrial utility value.

The present invention will be explained in more detail below with reference to examples and comparative examples, but the present invention is not limited to the following examples.

The NMR apparatus used for the analysis of the Examples and Comparative Examples was an AVANCE 400 ( ¹ H-NMR: 400 MHz, ¹⁹ F-NMR: 376 MHz) manufactured by Bruker. In ¹ H-NMR, tetramethylsilane was set to a reference value of 0 ppm, and in ¹⁹ F-NMR, trichlorofluoromethane was set to a reference value of 0 ppm.

[Example 1]
A compound represented by the following formula (1), in which R ¹ in the above general formula [1] is a phenyl group and Rf ¹ is a -CF ₂ CF ₂ CF ₂ SO ₃ K group, was synthesized.

Under a nitrogen atmosphere, aluminum chloride (17.73 g, 133 mmol) was added to benzene (200 mL) and cooled to 0°C. To this, hexafluoro-1,3-propanedisulfonic anhydride (26.07 g, 88.6 mmol) was slowly added, and the mixture was stirred at room temperature for 17 hours, and then quenched with 2M aqueous hydrochloric acid (200 mL). Ethyl acetate (200 mL) was added to the obtained reaction solution and the mixture was separated, and the organic layer was washed once with 2M aqueous hydrochloric acid (100 mL), and the obtained organic layer was washed twice with 2M aqueous potassium hydroxide (100 mL). The organic layer after washing was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. 2-propanol (50 mL) was added to the obtained crude product, and the mixture was stirred at 80°C for 1 hour, and then stirred in an ice bath at 0°C for 5 hours to obtain a suspension. The suspension was filtered, washed with 2-propanol (20 mL), and the solid was dried under reduced pressure to obtain the compound represented by the above formula (1) in a yield of 64%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (1) was obtained.
^19F -NMR (acetone-d): δ-111.75 to -111.85 (m, 2F), -115.02 to -115.11 (m, 2F), -119.02 to -119.05 (m, 2F).

[Example 2]
The compound represented by the above formula (1) was used as a fluoroalkylating agent to replace the alkoxy group of tert-butyl alcohol with a -CF ₂ CF ₂ CF ₂ SO ₃ K group, thereby synthesizing a compound represented by the following formula (2).

Under a nitrogen atmosphere, the compound represented by the above formula (1) (0.50 g, 1.22 mmol) and tert-butyl alcohol (116 μL, 1.22 mmol) were added to N,N-dimethylformamide (5.0 mL). A THF solution of potassium tert-butoxide (1 M, 3.05 mL, 3.05 mmol) was slowly added thereto, and the mixture was stirred at room temperature for 1 hour, and then quenched with 2 M aqueous hydrochloric acid (10 mL). Ethyl acetate (20 mL) was added to the obtained reaction solution and the mixture was separated, and the aqueous solution was extracted once with ethyl acetate (10 mL), and all the organic layers were combined and washed with saturated saline (20 mL). The organic layer after washing was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was dissolved in water (20 mL), and 0.5 M aqueous potassium hydroxide solution (2.4 mL) was added, and the solvent was distilled off under reduced pressure. Ethanol (30 mL) was added to the obtained crude product, and the mixture was stirred at room temperature for 1 hour, and a suspension was obtained. The suspension was filtered, washed with ethanol (20 mL), and the solid was dried under reduced pressure to obtain the compound represented by the above formula (2) in a yield of 97%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (2) was obtained.
¹⁹ F-NMR (heavy water): δ -116.56 to -116.60 (m, 2F), -129.72 to -129.78 (m, 2F), -137.55 to -137.75 (m, 2F).

[Example 3]
Compounds represented by the following formula (3) and (4) in which R ¹ in the above general formula [1] is a tolyl group and Rf ¹ is a --CF ₂ CF ₂ CF ₂ SO ₃ K group were synthesized.

A mixture of the compound represented by the above formula (3) and the compound represented by the above formula (4) was obtained in a yield of 66% by the same procedure as in Example 1, except that toluene was used instead of benzene used in Example 1. The mixing ratio of the compound represented by the above formula (3) and the compound represented by the above formula (4) was 1:2 in terms of molar ratio.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (3) and the compound represented by the above formula (4) were obtained.
^19F -NMR (methanol deuterated): δ -112.13 to -112.68 (m, 2F), -115.35 to -115.51 (m, 2F), -119.62 to -119.99 (m, 2F).

[Example 4]
The compound represented by the above formula (2) was synthesized by using a mixture of the compound represented by the above formula (3) and the compound represented by the above formula (4) as a fluoroalkylating agent to replace the alkoxy group of tert-butyl alcohol with a -CF ₂ CF ₂ CF ₂ SO ₃ K group.
The same procedure as in Example 2 was carried out except that a mixture of the compound represented by the above formula (3) and the compound represented by the above formula (4) was used instead of the compound represented by the above formula (1) in Example 2, thereby obtaining the compound represented by the above formula (2) in a yield of 90%.

[Example 5]
Compounds represented by the following formula (5) and (6) in which R ¹ in the above general formula [1] is an o-xylyl group and Rf ¹ is a -CF ₂ CF ₂ CF ₂ SO ₃ K group were synthesized.

A mixture of the compound represented by the above formula (5) and the compound represented by the above formula (6) was obtained in a yield of 65% by the same procedure as in Example 1, except that o-xylene was used instead of benzene used in Example 1. The mixing ratio of the compound represented by the above formula (5) and the compound represented by the above formula (6) was 1:2 in terms of molar ratio.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (5) and the compound represented by the above formula (6) were obtained.
^19F -NMR (methanol deuterated): δ -111.93 to -112.72 (m, 2F), -115.35 to -115.51 (m, 2F), -119.64 to -120.02 (m, 2F).

[Example 6]
The compound represented by the above formula (2) was synthesized by using a mixture of the compound represented by the above formula (5) and the compound represented by the above formula (6) as a fluoroalkylating agent to replace the alkoxy group of tert-butyl alcohol with a -CF ₂ CF ₂ CF ₂ SO ₃ K group.
The same procedure as in Example 2 was carried out except that a mixture of the compound represented by the above formula (5) and the compound represented by the above formula (6) was used instead of the compound represented by the above formula (1) in Example 2, thereby obtaining the compound represented by the above formula (2) in a yield of 88%.

[Example 7]
A compound represented by the following formula (7), in which R ¹ in the above general formula [1] is an m-xylyl group and Rf ¹ is a -CF ₂ CF ₂ CF ₂ SO ₃ K group, was synthesized.

The same procedure as in Example 1 was carried out except that m-xylene was used instead of benzene, to obtain the compound represented by the above formula (7) in a yield of 60%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (7) was obtained.
^19F -NMR (methanol deuterated): δ -112.38 to -112.47 (m, 2F), -115.39 to -115.48 (m, 2F), -120.00 to -120.03 (m, 2F).

[Example 8]
The compound represented by the above formula (7) was used as a fluoroalkylating agent to replace the alkoxy group of tert-butyl alcohol with a -CF ₂ CF ₂ CF ₂ SO ₃ K group, thereby synthesizing the compound represented by the above formula (2).
The same procedure as in Example 2 was carried out except that the compound represented by the above formula (7) was used instead of the compound represented by the above formula (1) in Example 2, thereby obtaining the compound represented by the above formula (2) in a yield of 89%.

[Example 9]
A compound represented by the following formula (8), in which R ¹ in the above general formula [1] is a p-xylyl group and Rf ¹ is a -CF ₂ CF ₂ CF ₂ SO ₃ K group, was synthesized.

The same procedure as in Example 1 was carried out except that p-xylene was used instead of benzene, to obtain the compound represented by the above formula (8) in a yield of 76%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (8) was obtained.
^19F -NMR (methanol deuterated): δ -111.94 to -112.01 (m, 2F), -115.06 to -115.14 (m, 2F), -119.76 (m, 2F).

[Example 10]
The compound represented by the above formula (8) was used as a fluoroalkylating agent to substitute the alkoxy group of tert-butyl alcohol with a -CF ₂ CF ₂ CF ₂ SO ₃ K group, thereby synthesizing the compound represented by the above formula (2).
The same procedure as in Example 2 was carried out except that the compound represented by the above formula (8) was used instead of the compound represented by the above formula (1) in Example 2, thereby obtaining the compound represented by the above formula (2) in a yield of 87%.

[Example 11]
A compound represented by the following formula (9), in which R ¹ in the above general formula [1] is a phenyl group and Rf ¹ is a -CF ₂ CF ₂ SO ₃ K group, was synthesized.

The same procedure as in Example 1 was carried out except that butafluoro-1,2-ethanedisulfonic anhydride was used instead of hexafluoro-1,3-propanedisulfonic anhydride used in Example 1, to obtain the compound represented by the above formula (9) in a yield of 68%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (9) was obtained.
^19F -NMR (methanol deuterated): δ-111.04 to -111.07 (m, 2F), -113.47 to -113.54 (m, 2F).

[Example 12]
The compound represented by the above formula (9) was used as a fluoroalkylating agent to replace the alkoxy group of tert-butyl alcohol with a -CF ₂ CF ₂ SO ₃ K group, thereby synthesizing a compound represented by the following formula (10).
The same procedure as in Example 2 was carried out except that the compound represented by the above formula (9) was used instead of the compound represented by the above formula (1) in Example 2, thereby obtaining a compound represented by the following formula (10) in a yield of 95%.
¹⁹ F-NMR analysis confirmed that a compound represented by the following formula (10) was obtained.
^19F -NMR (dmethanol): δ-125.28 (dt, 2F), -137.32 (dt, 2F).

[Example 13]
A compound represented by the following formula (11), in which R ¹ in the above general formula [1] is a phenyl group and Rf ¹ is a nonafluorobutyl group, was synthesized.

Under a nitrogen atmosphere, aluminum chloride (1.72 g, 12.9 mmol) was added to benzene (20 mL) and cooled to 0 ° C. Nonafluorobutanesulfonic anhydride (5.00 g, 8.59 mmol) was slowly added thereto, and the mixture was stirred at room temperature for 17 hours, and then quenched with 2 M aqueous hydrochloric acid (20 mL). Ethyl acetate (20 mL) was added to the resulting reaction solution and the mixture was separated, and the organic layer was washed once with 2 M aqueous hydrochloric acid (10 mL), and the resulting organic layer was washed twice with 2 M aqueous potassium hydroxide (10 mL). The organic layer after washing was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was distilled under reduced pressure to obtain the compound represented by the above formula (11) in a yield of 52%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (11) was obtained.
^19F -NMR (deuterated chloroform): δ-80.77 to -80.82 (m, 3F), -111.59 to -111.67 (m, 2F), -120.85 to -120.91 (m, 2F), -125.95 to -126.04 (m, 2F).

[Example 14]
The compound represented by the above formula (11) was used as a fluoroalkylating agent to replace the alkoxy group of tert-butyl alcohol with a nonafluorobutyl group, thereby synthesizing a compound represented by the following formula (12).

Under a nitrogen atmosphere, the compound represented by the above formula (11) (0.50 g, 1.39 mmol) and tert-butyl alcohol (132 μL, 1.39 mmol) were added to tetrahydrofuran (5.0 mL). This was cooled to −70° C., and a THF solution of potassium tert-butoxide (1 M, 3.47 mL, 3.47 mmol) was slowly added and stirred for 1 hour. The resulting reaction solution was warmed to room temperature, and the generated gas was collected with a cold trap, obtaining the compound represented by the above formula (12) in a yield of 73%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (12) was obtained.
^19F -NMR (deuterated chloroform): δ-81.17 to -81.38 (m, 3F), -127.75 to -127.93 (m, 2F), -130.13 to -130.34 (m, 2F), -137.42 to -137.77 (m, 2F).

[Example 15]
A compound represented by the following formula (13), in which R ¹ in the above general formula [1] is a phenyl group and Rf ¹ is a heptafluoropropyl group, was synthesized.

The same procedure as in Example 13 was carried out except that heptafluoropropanesulfonic anhydride was used instead of nonafluorobutanesulfonic anhydride used in Example 13, to obtain the compound represented by the above formula (13) in a yield of 56%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (13) was obtained.
^19F -NMR (deuterated chloroform): δ-80.71 to -80.76 (m, 3F), -112.30 to -112.34 (m, 2F), -124.24 to -124.25 (m, 2F).

[Example 16]
The compound represented by the above formula (13) was used as a fluoroalkylating agent to substitute the alkoxy group of tert-butyl alcohol with a heptafluoropropyl group, thereby synthesizing a compound represented by the following formula (14).
The same procedure as in Example 14 was carried out except that the compound represented by the above formula (13) was used instead of the compound represented by the above formula (11) in Example 14, thereby obtaining a compound represented by the following formula (14) in a yield of 69%.
¹⁹ F-NMR analysis confirmed that a compound represented by the following formula (14) was obtained.
^19F -NMR (deuterated chloroform): δ-82.27 to -82.31 (m, 3F), -132.65 to -132.69 (m, 2F), -137.52 to -137.71 (m, 2F).

[Example 17]
A compound represented by the following formula (15), in which R ¹ in the above general formula [2] is a phenyl group and Rf ¹ is a -CF(CF ₃ )OCF ₂ CF ₂ CF ₃ group, was synthesized.

Under a nitrogen atmosphere, aluminum chloride (9.96 g, 74.7 mmol) was added to benzene (20 mL) and heated to 50° C. Perfluoro(2-methyl-3-oxahexanoyl)fluoride (9.26 g, 27.9 mmol) was slowly added thereto, and the mixture was stirred at room temperature for 7 hours, and then quenched with 2M aqueous hydrochloric acid (20 mL). After adding chloroform (40 mL) to the obtained reaction solution and separating the layers, the organic layer was washed once with 2M aqueous hydrochloric acid (10 mL), and the obtained organic layer was washed twice with 2M aqueous potassium hydroxide (10 mL). After drying the washed organic layer over magnesium sulfate, the solvent was distilled off under reduced pressure. The obtained crude product was distilled under reduced pressure to obtain the compound represented by the above formula (15) in a 55% yield.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (15) was obtained.
^19F -NMR (deuterated chloroform): δ-78.09 to -78.56 (m, 1F), -80.54 (m, 3F), -81.28 to -81.32 (m, 3F), -82.74 to -83.19 (m, 1F), -128.47 to -128.54 (m, 1F), -129.52 to -129.54 (m, 2F).

[Example 18]
The compound represented by the above formula (15) was used as a fluoroalkylating agent to replace the alkoxy group of tert- _{butyl alcohol with a -CF(CF3)OCF2CF2CF3 group , thereby} synthesizing a compound represented by the following formula (16).
Under a nitrogen atmosphere, a THF solution of potassium tert-butoxide (1M, 6.41 mL, 6.41 mmol) and tert-butyl alcohol (0.61 mL, 6.41 mmol) were added to tetrahydrofuran (20 mL). This was cooled to -70°C, and a THF solution (10 mL) of the compound represented by the above formula (15) (1.00 g, 2.56 mmol) was slowly added and stirred for 1 hour. The resulting reaction solution was warmed to room temperature and stirred for 1 hour, and then quenched with a 2M aqueous hydrochloric acid solution (30 mL). Chloroform (20 mL) was added to the resulting reaction solution and the solution was separated, and the aqueous layer was extracted once with chloroform (20 mL), and all the organic layers were combined and washed with saturated saline (20 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting liquid was distilled under reduced pressure to obtain a compound represented by the following formula (16) in 82% yield.
¹⁹ F-NMR analysis confirmed that a compound represented by the following formula (16) was obtained.
^19F -NMR (deuterated chloroform): δ-81.51 to -81.53 (m, 3F), -84.00 to -84.02 (m, 3F), -84.98 to -87.26 (m, 2F), -129.86 to -129.92 (m, 2F), -145.73 to -145.96 (m, 1F).

[Example 19]
A compound represented by the following formula (17), in which R ¹ in the above general formula [2] is a phenyl group and Rf ¹ is a -CF(CF ₃ )OCF ₂ CF(CF ₃ )OCF ₂ CF ₂ CF ₃ group, was synthesized.

The same procedure as in Example 17 was carried out except that perfluoro(2,5-dimethyl-3,6-dioxanonanoyl)fluoride was used instead of perfluoro(2-methyl-3-oxahexanoyl)fluoride used in Example 17, to obtain the compound represented by the above formula (17) in a yield of 76%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (17) was obtained.
¹⁹ F-NMR (deuterated chloroform): δ -77.27 to -78.48 (m, 1F), -80.02 to -80.11 (m, 3F), -80.76 to -81.69 (m, 9F), -128.41 to -128.62 (m, 1F), -128.64 to -129.66 (m, 2F), - 144.95~-145.23 (m, 1F).

[Example 20]
The compound represented by the above formula (17) was used as a fluoroalkylating agent to replace _the alkoxy group of tert-butyl alcohol with a -CF( _CF3 ) _OCF2CF ( _CF3 ) _OCF2CF2CF3 group, thereby synthesizing a compound represented by the following formula ( ₁₈ ).
The same procedure as in Example 18 was carried out except that the compound represented by the above formula (17) was used instead of the compound represented by the above formula (15) in Example 18, to obtain a compound represented by the following formula (18) in a yield of 79%.
It was confirmed by ¹⁹ F-NMR analysis that a compound represented by the following formula (18) was obtained.
^19F -NMR (deuterated chloroform): δ-80.10 to -80.25 (m, 3F), -81.40 to -81.52 (m, 3F), -81.77 to -81.92 (m, 2F), -83.46 to -86.33 (m, 5F), -129.73 to -129.79 (m, 2F), -145.14 to -145.30 (m, 1F), -145.67 to -145.94 (m, 1F).

[Example 21]
A compound represented by the following formula (19), in which R ⁹ in the above general formula [11] is a phenyl group and X ³ is potassium, was synthesized.

Under a nitrogen atmosphere, aluminum chloride (25.6 g, 192 mmol) was added to benzene (40 mL) and heated to 50°C. 2,2,3,3,4,4-hexafluoro-4-(fluorosulfonyl)butanoyl fluoride (20.0 g, 71.2 mmol) was slowly added thereto, and the mixture was stirred at room temperature for 2 hours, and then quenched with 2M aqueous hydrochloric acid (200 mL). After adding chloroform (200 mL) to the obtained reaction solution and separating the layers, the organic layer was washed twice with 2M aqueous hydrochloric acid (100 mL), and the obtained organic layer was washed twice with saturated aqueous sodium bicarbonate (100 mL). After drying the washed organic layer over magnesium sulfate, the solvent was distilled off under reduced pressure. The obtained crude product was distilled under reduced pressure, and then water (10 mL) and potassium carbonate (0.49 g, 0.0035 mmol) were added, and the mixture was stirred at room temperature for 1 hour, and the solvent was distilled off under reduced pressure. 2-Propanol (10 mL) was added to the obtained crude product, heated to 70° C., and then filtered. The obtained solid was dried under reduced pressure to obtain the compound represented by the above formula (19) in a 5% yield.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (19) was obtained.
^19F -NMR (d-acetonitrile): δ-113.51 to -113.57 (m, 2F), -114.25 to -114.32 (m, 2F), -120.52 (m, 2F).

[Example 22]
The compound represented by the above formula (19) was used as a fluoroalkylating agent to substitute the alkoxy group of tert-butyl alcohol with a -CF ₂ CF ₂ CF ₂ SO ₃ K group, thereby synthesizing the compound represented by the above formula (2).
Under a nitrogen atmosphere, a THF solution of potassium tert-butoxide (1M, 0.68mL, 0.68mmol) and tert-butyl alcohol (0.07mL, 0.68mmol) were added to tetrahydrofuran (5mL). This was cooled to -70°C, and a THF solution (5mL) of the compound represented by the above formula (19) (0.10g, 0.27mmol) was slowly added and stirred for 1 hour. The resulting reaction solution was warmed to room temperature and stirred for 1 hour, and then quenched with a 2M aqueous hydrochloric acid solution (10mL). Ethyl acetate (10mL) was added to the resulting reaction solution and the solution was separated, and the aqueous solution was extracted once with ethyl acetate (10mL), and all the organic layers were combined and washed with saturated saline (20mL). The washed organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was dissolved in water (10 mL), 0.1 M potassium hydroxide aqueous solution (5.6 mL) was added, and the solvent was distilled off under reduced pressure. Ethanol (10 mL) was added to the obtained crude product, and the mixture was stirred at room temperature for 1 hour to obtain a suspension. The suspension was filtered, washed with ethanol (5 mL), and the solid was dried under reduced pressure to obtain the compound represented by the above formula (2) in 83% yield.

[Example 23]
A compound represented by the following formula (20), in which R ¹⁰ and R ¹¹ in the above general formula [12] are phenyl groups, was synthesized.

Under a nitrogen atmosphere, aluminum chloride (19.8 g, 149 mmol) was added to benzene (40 mL) and heated to 50° C. 2,2′-[(tetrafluoroethylene)dioxy]bis(2,3,3,3-tetrafluoropropanoyl)=difluoride (11.7 g, 27.6 mmol) was slowly added thereto, and the mixture was stirred at room temperature for 5 hours, and then quenched with 2M aqueous hydrochloric acid (100 mL). After adding chloroform (100 mL) to the obtained reaction solution and separating the layers, the organic layer was washed once with 2M aqueous hydrochloric acid (100 mL), and the obtained organic layer was washed once with 2M aqueous potassium hydroxide (100 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was distilled under reduced pressure to obtain the compound represented by the above formula (20) in a 54% yield.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (20) was obtained.
^19F -NMR (deuterated chloroform): δ-80.18 to -80.20 (m, 6F), -82.25 to -82.99 (m, 2F), -86.03 to -86.66 (m, 2F), -128.35 to -128.50 (m, 2F).

[Example 24]
The compound represented by the above formula (20) was used as a fluoroalkylating agent to replace the alkoxy group of tert- _butyl alcohol with a -CF( _CF3 ) _OCF2CF2OCF ( _CF3 )- group, thereby synthesizing a compound represented by the following formula (21).
Under a nitrogen atmosphere, a THF solution of potassium tert-butoxide (1M, 9.20 mL, 9.20 mmol) and tert-butyl alcohol (1.95 mL, 18.4 mmol) were added to tetrahydrofuran (10 mL). This was cooled to -70°C, and a THF solution (10 mL) of the compound represented by the above formula (20) (1.00 g, 1.84 mmol) was slowly added and stirred for 1 hour. The resulting reaction solution was warmed to room temperature and stirred for 1 hour, and then quenched with a 2M aqueous hydrochloric acid solution (30 mL). Chloroform (20 mL) was added to the resulting reaction solution and the liquids were separated, and the aqueous layer was extracted once with chloroform (20 mL), and all the organic layers were combined and washed with saturated saline (20 mL). The organic layer after washing was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The liquid was distilled under reduced pressure to obtain a compound represented by the following formula (21) in a 76% yield.
¹⁹ F-NMR analysis confirmed that a compound represented by the following formula (21) was obtained.
^19F -NMR (deuterated chloroform): δ-83.78 to -83.82 (m, 6F), -88.64 to -91.17 (m, 4F), -145.16 to -145.32 (m, 2F).

[Example 25]
The compound represented by the above formula (11) was used as a fluoroalkylating agent, and a metal hydroxide or potassium tert-butoxide was used as a hydrogen source to substitute a -CF ₂ CF ₂ CF ₂ SO ₃ K group, thereby synthesizing the compound represented by the above formula (2).
Under a nitrogen atmosphere, a THF solution of potassium tert-butoxide (1M, 1.52mL, 1.52mmol) and calcium hydroxide (0.045g, 0.61mmol) were added to N,N-dimethylformamide (5.0mL). To this was slowly added a N,N-dimethylformamide solution (5mL) of the compound represented by the above formula (11) (0.25g, 0.61mmol), and the mixture was stirred at room temperature for 1 hour. Then, the mixture was quenched with a 2M aqueous hydrochloric acid solution (10mL). After adding ethyl acetate (10mL) to the obtained reaction solution and separating the liquid, the water bath was extracted once with ethyl acetate (10mL), and all the organic layers were combined and washed with saturated saline (20mL). After drying the organic layer after washing with magnesium sulfate, the solvent was distilled off under reduced pressure. The obtained crude product was dissolved in water (10mL), 0.1M aqueous potassium hydroxide solution (5.6mL) was added, and the solvent was distilled off under reduced pressure. Ethanol (10 mL) was added to the obtained crude product, and the mixture was stirred at room temperature for 1 hour to obtain a suspension. The suspension was filtered, washed with ethanol (5 mL), and the solid was dried under reduced pressure to obtain the compound represented by the above formula (2) in a yield of 91%.

[Example 26]
The compound represented by the above formula (11) was used as a fluoroalkylating agent to replace the chlorine substituent of chlorotrimethylsilane with a nonafluorobutyl group, thereby synthesizing a compound represented by the following formula (22).

Under a nitrogen atmosphere, the compound represented by the above formula (11) (0.20 g, 0.92 mmol) and chlorotrimethylsilane (350 μL, 2.78 mmol) were added to N,N-dimethylformamide (2.0 mL). Magnesium (27.0 mg, 1.11 mmol) was added to this, and the mixture was stirred for 17 hours. The resulting reaction solution was quenched with a 2M aqueous hydrochloric acid solution (10 mL). Chloroform (20 mL) was added to the resulting reaction solution, and the mixture was separated. The aqueous layer was extracted once with chloroform (10 mL), and all the organic layers were combined and washed with saturated saline (20 mL). The organic layer after washing was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. Benzotrifluoride was added to the crude product as an internal standard to determine the NMR yield. The yield of the compound represented by the above formula (22) was 16%.
¹⁹ F-NMR analysis confirmed that the compound represented by the above formula (22) was obtained.
^19F -NMR (deuterated chloroform): δ-80.74 to -80.79 (m, 3F), -120.93 to -120.94 (m, 2F), -125.95 to -126.03 (m, 2F), -128.66 to -128.73 (m, 2F).

[Example 27]
The compound represented by the above formula (11) was used as a fluoroalkylating agent to introduce a nonafluorobutyl group into the carbonyl carbon of benzaldehyde, thereby synthesizing a compound represented by the following formula (23).

Under a nitrogen atmosphere, a THF solution of potassium tert-butoxide (1M, 3.48 mL, 3.48 mmol) and benzaldehyde (0.42 mL, 4.16 mmol) were added to tetrahydrofuran (10 mL). This was cooled to -70°C, and a THF solution (10 mL) of the compound represented by the above formula (11) (0.50 g, 1.39 mmol) was slowly added and stirred for 1 hour. The resulting reaction solution was warmed to room temperature and stirred for 1 hour, and then quenched with a 2M aqueous hydrochloric acid solution (50 mL). Chloroform (20 mL) was added to the resulting reaction solution and the solution was separated, and the aqueous layer was extracted once with chloroform (20 mL), and all the organic layers were combined and washed with saturated saline (20 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting liquid was distilled under reduced pressure to obtain a compound represented by the above formula (23) in a 71% yield.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (23) was obtained.
^19F -NMR (deuterated chloroform): δ-82.30 to -82.48 (m, 3F), -117.40 to -127.70 (m, 6F).

[Example 28]
The compound represented by the above formula (15) was used as a fluoroalkylating agent to introduce a -CF( _CF3 ) _OCF2CF2CF3 group into the _{carbonyl carbon} of benzaldehyde to synthesize a compound represented by the following formula (24).

Under a nitrogen atmosphere, a THF solution of potassium tert-butoxide (1M, 3.20 mL, 3.20 mmol) and benzaldehyde (0.39 mL, 3.84 mmol) were added to tetrahydrofuran (10 mL). This was cooled to -70°C, and a THF solution (10 mL) of the compound represented by the above formula (15) (0.50 g, 1.28 mmol) was slowly added and stirred for 1 hour. The resulting reaction solution was warmed to room temperature and stirred for 1 hour, and then quenched with a 2M aqueous hydrochloric acid solution (50 mL). Chloroform (20 mL) was added to the resulting reaction solution and the solution was separated, and the aqueous layer was extracted once with chloroform (20 mL), and all the organic layers were combined and washed with saturated saline (20 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting liquid was distilled under reduced pressure to obtain a compound represented by the above formula (24) in a 44% yield.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (24) was obtained.
^19F -NMR (deuterated chloroform): δ-78.70 to -78.99 (m, 3F), -80.33 to -82.20 (m, 5F), -129.29 to -129.50 (m, 2F), -136.74 to -142.81 (m, 1F).

[Example 29]
The compound represented by the above formula (11) was used as a fluoroalkylating agent to substitute the phenyl sulfide of diphenyl disulfide with a nonafluorobutyl group, thereby synthesizing a compound represented by the following formula (25).

Under a nitrogen atmosphere, the compound represented by the above formula (11) (0.20 g, 0.92 mmol) and diphenyl disulfide (0.24 g, 1.11 mmol) were added to tetrahydrofuran (2.0 mL). This was cooled to 0° C., and a THF solution of potassium tert-butoxide (1 M, 1.39 mL, 1.39 mmol) was slowly added and stirred for 1 hour. The resulting reaction solution was slowly warmed to room temperature and then quenched with a 2 M aqueous hydrochloric acid solution (10 mL). Chloroform (20 mL) was added to the resulting reaction solution and the solution was separated, and the aqueous layer was extracted once with chloroform (10 mL), and all the organic layers were combined and washed with saturated saline (20 mL). The organic layer after washing was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. Benzotrifluoride was added to the crude product as an internal standard to determine the NMR yield. The yield of the compound represented by the above formula (25) was 10%.
It was confirmed by ¹⁹ F-NMR analysis that the compound represented by the above formula (25) was obtained.
^19F -NMR (deuterated chloroform): δ-81.03 to -81.08 (m, 3F), -87.10 to -87.17 (m, 2F), -120.07 to -120.17 (m, 2F), -125.59 to -125.67 (m, 2F).

[Comparative Example 1]
A compound represented by the following formula (26) having an alkyl group not containing fluorine in Rf ¹ in the above general formula [1] was used under the same conditions as those for the fluoroalkylating agent, and the starting material represented by the following formula (26) was recovered in a yield of 96%.

Under a nitrogen atmosphere, a THF solution of potassium tert-butoxide (1M, 4.00mL, 4.00mmol) and tert-butyl alcohol (0.38mL, 4.00mmol) were added to tetrahydrofuran (10mL). This was cooled to -70°C, and a THF solution (10mL) of compound (26) (0.25g, 1.60mmol) was slowly added and stirred for 1 hour. The resulting reaction solution was warmed to room temperature and stirred for 1 hour, and then quenched with 2M aqueous hydrochloric acid (30mL). Chloroform (20mL) was added to the resulting reaction solution and separated, and the aqueous layer was extracted once with chloroform (20mL), and all the organic layers were combined and washed with saturated saline (20mL). The washed organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The solid was dried under reduced pressure to obtain the compound represented by the above formula (26) in a 96% yield.

[Comparative Example 2]
A compound represented by the following formula (27) having an alkyl group not containing fluorine in Rf ¹ in the above general formula [2] was used under the same conditions as those for the fluoroalkylating agent, and the starting material represented by the following formula (27) was recovered in a yield of 84%.

Under a nitrogen atmosphere, a THF solution of potassium tert-butoxide (1M, 5.20 mL, 5.20 mmol) and tert-butyl alcohol (0.49 mL, 5.20 mmol) were added to tetrahydrofuran (10 mL). This was cooled to -70°C, and a THF solution (10 mL) of compound (27) (0.25 g, 2.08 mmol) was slowly added and stirred for 1 hour. The resulting reaction solution was warmed to room temperature and stirred for 1 hour, and then quenched with 2M aqueous hydrochloric acid (30 mL). Chloroform (20 mL) was added to the resulting reaction solution and separated, and the aqueous layer was extracted once with chloroform (20 mL), and all the organic layers were combined and washed with saturated saline (20 mL). The washed organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The solid was dried under reduced pressure to obtain the compound represented by the above formula (27) in 84% yield and 12% yield of benzoic acid.

[Comparative Example 3]
When a compound represented by the following formula (28) in which R ¹ in the above general formula [1] has an aryloxy group instead of an aryl group was used under the same conditions as those for the fluoroalkylating agent, the target product represented by the following formula (2) was obtained in only a 7% yield, and a disulfonic acid represented by the following formula (29) was obtained as the main product in a 93% yield.

Under a nitrogen atmosphere, the compound represented by the above formula (28) (1.00 g, 2.34 mmol) and tert-butyl alcohol (222 μL, 2.34 mmol) were added to N,N-dimethylformamide (5.0 mL). To this was slowly added a THF solution of potassium tert-butoxide (1 M, 5.85 mL, 5.85 mmol), and the mixture was stirred at room temperature for 1 hour. Benzotrifluoride was then added as an internal standard to determine the NMR yield. The yield of the compound represented by the above formula (2) was 7%, and the yield of the compound represented by the above formula (29) was 93%.

[Comparative Example 4]
When a compound represented by the following formula (29) having an oxygen substituent instead of an aryl group at R ¹ in the above general formula [1] was used under the same conditions as those for the fluoroalkylating agent, the starting material represented by the following formula (29) was quantitatively recovered.

Under a nitrogen atmosphere, the compound represented by the above formula (29) (0.91 g, 2.34 mmol) and tert-butyl alcohol (222 μL, 2.34 mmol) were added to N,N-dimethylformamide (5.0 mL). To this was slowly added a THF solution of potassium tert-butoxide (1 M, 5.85 mL, 5.85 mmol), and the mixture was stirred at room temperature for 1 hour. Benzotrifluoride was then added as an internal standard to determine the NMR yield. The compound represented by the above formula (29) was quantitatively recovered.

[Comparative Example 5]
When a compound represented by the following formula (30) in which R ¹ in the above general formula [2] has an aryloxy group instead of an aryl group was used under the same conditions as those for the fluoroalkylating agent, the target product represented by the following formula (18) was obtained in only an 18% yield, and a disulfonic acid represented by the following formula (31) was obtained as the main product in an 82% yield.

Under a nitrogen atmosphere, the compound represented by the above formula (30) (0.50 g, 0.87 mmol) and tert-butyl alcohol (0.25 mL, 2.62 mmol) were added to tetrahydrofuran (10 mL). To this was slowly added a THF solution of potassium tert-butoxide (1 M, 2.18 mL, 2.18 mmol), and the mixture was stirred at room temperature for 1 hour. Benzotrifluoride was then added as an internal standard to determine the NMR yield. The yield of the compound represented by the above formula (18) was 18%, and the yield of the compound represented by the above formula (31) was 82%.

[Comparative Example 6]
When a compound represented by the following formula (31) in which R ¹ in the general formula [2] has an oxygen substituent instead of an aryl group was used and reacted under the same conditions as those for the fluoroalkylating agent, the starting material represented by the following formula (31) was quantitatively recovered.

Under a nitrogen atmosphere, the compound represented by the above formula (31) (0.50 g, 1.15 mmol) and tert-butyl alcohol (0.27 mL, 2.88 mmol) were added to tetrahydrofuran (10 mL). To this was slowly added a THF solution of potassium tert-butoxide (1 M, 2.88 mL, 2.88 mmol), and the mixture was stirred at room temperature for 1 hour. Benzotrifluoride was then added as an internal standard to determine the NMR yield. The compound represented by the above formula (31) was quantitatively recovered.

The present invention provides a fluoroalkylating agent derived from a fluoroalkyl sulfonic acid or carboxylic acid, which can introduce a wide range of fluoroalkyl structures, such as long-chain fluoroalkyl groups, ether structures, and structures having functional groups, which are rare among existing fluoroalkylating agents, and a fluoroalkylation reaction using the fluoroalkylating agent. The fluoroalkylating agent according to the present invention makes it possible to provide a variety of fluoroalkyl compounds that are utilized in the fields of medicine, agricultural chemicals, functional materials, and the like, using various electrophiles. For example, the hydrogen-containing fluoroalkyl compound of the above general formula [4] is useful as a heat transfer medium such as a solvent, a refrigerant, and a working fluid. The silicon-containing fluoroalkyl compound of the above general formula [6] is useful as a surface treatment agent or a surface modifier. The hydroxyl-containing fluoroalkyl compound of the general formula [13] and the sulfide compound of the above general formula [10] are useful as organic synthesis intermediates and polymer raw materials.

Claims (9)

A method for producing a fluoroalkyl compound, comprising a step of carrying out a fluoroalkylation reaction using a fluoroalkylating agent represented by the following general formula [1] or the following general formula [2] and an electrophilic agent:

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and Rf ¹ represents an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent consisting of a sulfonyl group or a carbonyl group, or 1 to 5 ether-bonded oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.)

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and Rf ¹ represents an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent consisting of a sulfonyl group or a carbonyl group, or 1 to 5 ether-bonded oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.) The electrophile is a proton donor represented by the following general formula [3]:
The method for producing a fluoroalkyl compound according to claim 1, which obtains a fluoroalkyl compound represented by the following general formula [4]:

(In the formula, ^R2 represents a hydrogen atom, a metal atom, an alkyl group having 1 to 30 carbon atoms which may have a substituent, or an aryl group having 6 to 14 carbon atoms which may have a substituent, and ^X5 represents a heteroatom such as oxygen, nitrogen, or sulfur.)

(In the formula, Rf ¹ represents a potassium sulfonate structure or a substituent consisting of a benzoyl group, or an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between carbon atoms, and which represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.) The electrophile is a silicon compound represented by the following general formula [5]:
The method for producing a fluoroalkyl compound according to claim 1, which obtains a fluoroalkyl compound represented by the following general formula [6]:

(In the formula, R ³ , R ⁴ and R ⁵ each independently represent a hydrogen atom or an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent or an unsaturated bond, an aryl group, or an alkoxy group containing an alkyl group having 1 to 30 carbon atoms or an aryl group having 6 to 14 carbon atoms which may have a substituent; and X ⁴ represents a halogen atom or an alkoxy group containing an alkyl group having 1 to 30 carbon atoms or an aryl group having 6 to 14 carbon atoms which may have a substituent.)

(In the formula, Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms and which may have a straight-chain, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen; R ³ , R ⁴ and R ⁵ each independently represent a hydrogen atom, or an alkyl group having 1 to 10 carbon atoms and which may have a straight-chain, branched or cyclic structure, which may have an unsaturated bond, an aryl group, or an alkoxy group including an alkyl group having 1 to 30 carbon atoms or an aryl group having 6 to 14 carbon atoms and which may have a substituent.) The electrophile is a carbonyl compound represented by the following general formula [7]:
The method for producing a fluoroalkyl compound according to claim 1, which obtains a fluoroalkyl compound represented by the following general formula [8]:

(In the formula, ^R6 and ^R7 each independently represent a hydrogen atom, or a substituent having a linear, branched or cyclic structure having 1 to 10 carbon atoms, or an alkyl group or aryl group which may have an unsaturated bond.)

(In the formula, Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms and which may have a straight-chain, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen; R ⁶ and R ⁷ each independently represent a hydrogen atom, or a substituent having 1 to 10 carbon atoms and which may have a straight-chain, branched or cyclic structure, or an alkyl group or aryl group which may have an unsaturated bond.) The electrophile is a disulfide compound represented by the following general formula [9]:
The method for producing a fluoroalkyl compound according to claim 1, which obtains a fluoroalkyl compound represented by the following general formula [10]:

(In the formula, ^R8 represents an alkyl group or aryl group which may have a straight chain, branched or cyclic structure having 1 to 10 carbon atoms and which may have a substituent or an unsaturated bond.)

(In the formula, R ⁸ represents a substituent having a linear, branched or cyclic structure having 1 to 10 carbon atoms, or an alkyl group or aryl group which may have an unsaturated bond; Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group which may have a linear, branched or cyclic structure having 1 to 10 carbon atoms and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.) A fluoroalkylating agent represented by the following general formula [11]:

(In the formula, R ⁹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and X ³ represents a hydroxyl group, a metal salt (e.g., -OK, -ONa), an alkoxy group having 1 to 4 carbon atoms (e.g., a methoxy group, an ethoxy group), an amino group, an alkylamino group having 1 to 4 carbon atoms (e.g., a methylamino group, a propylamino group), or a halogen atom (e.g., a fluorine atom, a chlorine atom).) A fluoroalkylating agent represented by the following general formula [12]:

(In the formula, R ¹⁰ and R ¹¹ are the same or independent and represent an aryl group having 6 to 14 carbon atoms which may have a substituent.) A method for producing a fluoroalkylating agent, comprising a step of reacting a fluoroalkylsulfonic acid derivative represented by the following general formula [13] or the following general formula [14] with an aromatic compound represented by the following general formula [15] to obtain a fluoroalkylating agent represented by the following general formula [1].

(In the formula, Rf ¹ and Rf ² are the same or independent and are a substituent or an alkyl group having 1 to 10 carbon atoms which may have a straight chain, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represent a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen, and Rf ¹ and Rf ² may be bonded to form a 4- to 7-membered ring.)

(In the formula, Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms which may have a straight chain, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen, and X ¹ represents a halogen atom.)

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent.)

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and Rf ¹ represents an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent consisting of a sulfonyl group or a carbonyl group, or 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.) A method for producing a fluoroalkylating agent, comprising a step of reacting a fluoroalkylcarboxylic acid derivative represented by the following general formula [16] or the following general formula [17] with an aromatic compound represented by the following general formula [18] to obtain a fluoroalkylating agent represented by the following general formula [2].

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, Rf ¹ represents a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms which may have a straight chain, branched or cyclic structure which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen, and X ² represents a halogen atom.)

(In the formula, Rf ¹ and Rf ² are the same or independent and are a substituent consisting of a sulfonyl group or a carbonyl group, or an alkyl group having 1 to 10 carbon atoms and which may have a straight chain, branched or cyclic structure and which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and which represent a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen, and Rf ¹ and Rf ² may be bonded to form a 4- to 7-membered ring.)

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent.)

(In the formula, R ¹ represents an aryl group having 6 to 14 carbon atoms which may have a substituent, and Rf ¹ represents an alkyl group having 1 to 10 carbon atoms which may have a linear, branched or cyclic structure and which may have a substituent consisting of a sulfonyl group or a carbonyl group, or 1 to 5 ether-bonding oxygen atoms between the carbon atoms, and represents a fluoroalkyl group having a structure in which the α-carbon of the sulfonyl or carbonyl is substituted with a carbon such as a fluorine or trifluoromethyl group and has no hydrogen.)