JPWO2014024752A1

JPWO2014024752A1 - 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative and method for producing the same

Info

Publication number: JPWO2014024752A1
Application number: JP2014529448A
Authority: JP
Inventors: 哲男柴田; 洋幸河合; 豊杉田; 恵津子徳永
Original assignee: Nagoya Institute of Technology NUC
Current assignee: Nagoya Institute of Technology NUC
Priority date: 2012-08-07
Filing date: 2013-07-31
Publication date: 2016-07-25
Also published as: WO2014024752A1

Abstract

【課題】５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体およびその製造方法を提供する。【解決手段】トリフルオロメチル化試薬として、 (トリフルオロメチル)トリメチルシランを用い、反応基質として、トリフルオロメチルスルホニル基を４位に有する４−トリフルオロメチルスルホニルイソキサゾールを用いることで、トリフルオロメチルアニオンが４−トリフルオロメチルスルホニル−２−イソキサゾールの５位に付加した生成物が得られる。また、得られた５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体の４位にハロゲンを導入することができる。【選択図】なしA 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative and a method for producing the same are provided. By using (trifluoromethyl) trimethylsilane as a trifluoromethylation reagent and using 4-trifluoromethylsulfonylisoxazole having a trifluoromethylsulfonyl group at the 4-position as a reaction substrate, A product is obtained in which a fluoromethyl anion is added to the 5-position of 4-trifluoromethylsulfonyl-2-isoxazole. In addition, halogen can be introduced into the 4-position of the obtained 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative. [Selection figure] None

Description

本発明は、５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体およびその製造方法に関するものである。 The present invention relates to a 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative and a method for producing the same.

近年、５−トリフルオロメチル−２−イソキサゾリン誘導体が、有害生物防除剤として注目を集めている。これは、医薬品や電子材料などの機能性材料の製造中間体としても有用な化合物である。その有用性から、非常に多くの５−トリフルオロメチル−２−イソキサゾリン誘導体が合成されている。また、トリフルオロメチルスルホニル基は、最も強力な電子求引性基の一つとして知られている。これは、そのユニークな性質から、生理活性物質合成、キラル触媒や機能性材料の分野で広く用いられている。トリフルオロメチルスルホニル基は、トリフリル基とも呼ばれる。 In recent years, 5-trifluoromethyl-2-isoxazoline derivatives have attracted attention as pest control agents. This is a compound useful as an intermediate for the production of functional materials such as pharmaceuticals and electronic materials. Due to its usefulness, a great number of 5-trifluoromethyl-2-isoxazoline derivatives have been synthesized. A trifluoromethylsulfonyl group is known as one of the most powerful electron-withdrawing groups. Due to its unique properties, it is widely used in the fields of bioactive substance synthesis, chiral catalysts and functional materials. A trifluoromethylsulfonyl group is also called a trifuryl group.

このような事実から、トリフルオロメチルスルホニル基を有する５−トリフルオロメチル−２−イソキサゾリン誘導体は、興味深い生理活性が期待され、新しい基本骨格として有害生物防除剤への展開や、医薬品や電子材料などの機能性材料の製造中間体として期待される。しかしながら、トリフルオロメチルスルホニル基を有する５−トリフルオロメチル−２−イソキサゾリン誘導体は、これまでに合成報告例がなく、その合成方法の開発が望まれていた。 From these facts, the 5-trifluoromethyl-2-isoxazoline derivative having a trifluoromethylsulfonyl group is expected to have interesting physiological activity, and it has been developed as a new basic skeleton for pest control agents, pharmaceuticals, electronic materials, etc. It is expected as a production intermediate for functional materials. However, there has been no report on the synthesis of 5-trifluoromethyl-2-isoxazoline derivatives having a trifluoromethylsulfonyl group, and development of a synthesis method thereof has been desired.

また、５−トリフルオロメチル−２−イソキサゾリン誘導体の合成方法は、そのほとんどが、あらかじめトリフルオロメチル基を有した化合物を用いて合成するビルディングブロック法である（例えば、特許文献１、２、３、４、５、６参照）。このような背景下、本発明者は、４位にニトロ基を有するイソキサゾールに対してトリフルオロメチル基を直接的に導入する、すなわち、直接的なトリフルオロメチル化反応による５−トリフルオロメチル−２−イソキサゾリン誘導体の合成に初めて成功している（特許文献７および非特許文献１参照）。この直接的なトリフルオロメチル化反応による合成方法は、目的物の合成ルートの最終段階近くで使うことも可能であり、工業スケールでの合成を考えた場合に非常に有用な手段である。 Further, most of the synthesis methods of 5-trifluoromethyl-2-isoxazoline derivatives are building block methods in which synthesis is performed using a compound having a trifluoromethyl group in advance (for example, Patent Documents 1, 2, and 3). 4, 5, 6). Under such a background, the present inventor directly introduces a trifluoromethyl group into isoxazole having a nitro group at the 4-position, that is, 5-trifluoromethyl- by a direct trifluoromethylation reaction. The first successful synthesis of 2-isoxazoline derivatives (see Patent Document 7 and Non-Patent Document 1). This synthesis method by direct trifluoromethylation reaction can be used near the final stage of the synthesis route of the target product, and is a very useful means when considering synthesis on an industrial scale.

国際公開WO２００５／０８５２１６号公報International Publication WO2005 / 085216 国際公開WO２００８／０１９７６０号公報International Publication No. WO2008 / 019760 国際公開WO２００９／０４５９９９号公報International Publication No. WO2009 / 045999 国際公開WO２００９／００１９４２号公報International Publication No. WO2009 / 001942 国際公開WO２００９／１２６６６８号公報International Publication No. WO2009 / 126668 国際公開WO２００９／０６３９１０号公報International Publication No. WO2009 / 063910 国際公開WO２０１２／０６０２３２号公報International Publication No. WO2012 / 060232

Kawai, H.; Tachi, K.; Tokunaga, E.; Shiro, M.; Shibata, N, Angew. Chem. Int. Ed., 2011, 50, 7803.Kawai, H .; Tachi, K .; Tokunaga, E .; Shiro, M .; Shibata, N, Angew. Chem. Int. Ed., 2011, 50, 7803.

本発明は上記点に鑑みて、新規化合物群である５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体およびその製造方法を提供することを目的とする。 In view of the above points, an object of the present invention is to provide a 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative which is a novel compound group and a method for producing the same.

上記目的を達成するため、本発明者が鋭意検討した結果、トリフルオロメチル化試薬として、 (トリフルオロメチル)トリメチルシラン（ＣＦ_３ＳｉＭｅ_３）を用い、反応基質として、トリフルオロメチルスルホニル基を４位に有する４−トリフルオロメチルスルホニルイソキサゾールを用いることで、トリフルオロメチルアニオンが４−トリフルオロメチルスルホニル−２−イソキサゾールの５位に付加した生成物を得ることに成功した。また、本発明者は、得られた５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体の４位にハロゲンを導入することが可能であることも見出した。これらを経て、本発明者は本発明を完成するに至った。As a result of intensive studies by the present inventors to achieve the above object, (trifluoromethyl) trimethylsilane (CF ₃ SiMe ₃ ) is used as a trifluoromethylation reagent, and a trifluoromethylsulfonyl group is used as a reaction substrate. By using 4-trifluoromethylsulfonylisoxazole at the position, a product in which the trifluoromethyl anion was added to the 5-position of 4-trifluoromethylsulfonyl-2-isoxazole was successfully obtained. The present inventor has also found that it is possible to introduce halogen at the 4-position of the obtained 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative. Through these, the present inventors have completed the present invention.

すなわち、本発明の５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体は、下記一般式（１）で表されるものである。 That is, the 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative of the present invention is represented by the following general formula (1).

（式中、Ｒ^１およびＲ^２は、互いに独立して、水素、アルキル基、アルケニル基、アルキニル基またはアリール基を示し、Ｘは、水素またはハロゲンを示す。）
これによれば、新しい基本骨格として有害生物防除剤への展開や、医薬品や電子材料などの機能性材料の製造中間体として期待される。Ｘがハロゲンである化合物は、Ｘが水素である化合物よりも、さらなる農薬活性を有するなどの有利な効果が期待される。

(In the formula, R ¹ and R ² each independently represent hydrogen, an alkyl group, an alkenyl group, an alkynyl group, or an aryl group, and X represents hydrogen or halogen.)
According to this, it is expected to develop into a pest control agent as a new basic skeleton and as a production intermediate for functional materials such as pharmaceuticals and electronic materials. The compound in which X is halogen is expected to have an advantageous effect such as having further agrochemical activity than the compound in which X is hydrogen.

本発明の５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体の製造方法は、溶媒中、塩基存在下、下記一般式（２）で表される４−トリフルオロメチルスルホニルイソキサゾールと(トリフルオロメチル)トリメチルシランを反応させることを特徴としている。 The method for producing a 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative of the present invention comprises a 4-trifluoromethylsulfonylisoxa represented by the following general formula (2) in the presence of a base in a solvent. It is characterized by reacting sol with (trifluoromethyl) trimethylsilane.

(式中、Ｒ^１およびＲ^２は、一般式（１）と同じである。）
これによれば、直接的なトリフルオロメチル化反応によって、一般式（１）で表される５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体を製造することができる。具体的には、この反応によって、一般式（１）のＸが水素である化合物を高いジアステレオマー選択性で製造でき、この反応後に、反応物に対してハロゲン化剤を反応させることで、一般式（１）のＸがハロゲンである化合物を製造できる。

(In the formula, R ¹ and R ² are the same as those in the general formula (1).)
According to this, the 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative represented by the general formula (1) can be produced by a direct trifluoromethylation reaction. Specifically, by this reaction, a compound in which X in the general formula (1) is hydrogen can be produced with high diastereomer selectivity. After this reaction, a reaction with a halogenating agent is performed on the reactant, A compound in which X in the general formula (1) is halogen can be produced.

本発明の５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体は、上記一般式（１）で表されるものである。上記一般式（１）中のＲ^１およびＲ^２は、互いに独立して、水素、アルキル基、アルケニル基、アルキニル基またはアリール基を示す。また、上記一般式（１）中のＸは、水素またはハロゲンを示す。The 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative of the present invention is represented by the above general formula (1). R ¹ and R ² in the general formula (1) each independently represent hydrogen, an alkyl group, an alkenyl group, an alkynyl group, or an aryl group. X in the general formula (1) represents hydrogen or halogen.

Ｒ^１およびＲ^２のアルキル基としては、例えば、炭素数１乃至２０程度のアルキル基を用いることができる。具体的には、メチル基、エチル基、プロピル基、ブチル基、ペンチル基、ヘキシル基、ヘプチル基、オクチル基、ノニル基、デシル基、ウンデシル基、ドデシル基、トリデシル基、テトラデシル基、ペンタデシル基、ヘキサデシル基、ヘプタデシル基、オクタデシル基、ノナデシル基、イコシル基、または、これらの環状アルキル基、分鎖アルキル基などを用いることができる。As the alkyl group for R ¹ and R ² , for example, an alkyl group having about 1 to 20 carbon atoms can be used. Specifically, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, A hexadecyl group, a heptadecyl group, an octadecyl group, a nonadecyl group, an icosyl group, or a cyclic alkyl group or a branched alkyl group thereof can be used.

Ｒ^１およびＲ^２のアルケニル基またはアルキニル基に含まれる不飽和結合の数は特に限定されないが、好ましくは１乃至２個程度である。該アルケニル基またはアルキニル基は、直鎖状または分枝鎖状のいずれでもよい。The number of unsaturated bonds contained in the alkenyl group or alkynyl group of R ¹ and R ² is not particularly limited, but is preferably about 1 to 2. The alkenyl group or alkynyl group may be linear or branched.

Ｒ^１およびＲ^２のアリール基には、ヘテロアリール基も含有される。アリール基としては、例えば、炭素数２〜３０のアリール基が挙げられる。具体的には、フェニル基、ナフチル基、アンスラニル基、ピレニル基、ビフェニル基、インデニル基、テトラヒドロナフチル基、ピリジル基、ピリミジニル基、ピラジニル基、ピリダニジル基、ピペラジニル基、ピラゾリル基、イミダゾリル基、キニリル基、ピロリル基、インドリル基、フリル基などが挙げられる。The aryl group of R ¹ and R ² also includes a heteroaryl group. As an aryl group, a C2-C30 aryl group is mentioned, for example. Specifically, phenyl group, naphthyl group, anthranyl group, pyrenyl group, biphenyl group, indenyl group, tetrahydronaphthyl group, pyridyl group, pyrimidinyl group, pyrazinyl group, pyridanidyl group, piperazinyl group, pyrazolyl group, imidazolyl group, quinylyl group Pyrrolyl group, indolyl group, furyl group and the like.

上記アルキル基は、フッ素原子、塩素原子、臭素原子、ヨウ素原子、シアノ基、トリフルオロメチルスルホニル基、アリール基、アシル基、アルコキシ基、アリールオキシ基、アシルオキシ基などの置換基で置換されていてもよく、２個以上の置換基を有する場合には、それらは同一でも異なっていてもよい。このことは、上記アルケニル基、上記アルキニル基、上記アリール基についても同様である。 The alkyl group is substituted with a substituent such as a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a cyano group, a trifluoromethylsulfonyl group, an aryl group, an acyl group, an alkoxy group, an aryloxy group, and an acyloxy group. In the case of having two or more substituents, they may be the same or different. The same applies to the alkenyl group, the alkynyl group, and the aryl group.

Ｘのハロゲンの種類は特に限定されない。ハロゲンとしては、例えば、フッ素、塩素、臭素が挙げられる。 The type of halogen for X is not particularly limited. Examples of halogen include fluorine, chlorine, and bromine.

本発明の５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体の絶対配置は（Ｓ、Ｓ）、（Ｓ、Ｒ）、（Ｒ、Ｓ）および（Ｒ、Ｒ）配置のいずれであってもよい。すなわち、光学異性体またはジアステレオ異性体などの立体異性体はいずれも本発明の範囲に包含される。光学的に純粋な形態の異性体は本発明の好ましい態様である。また、立体異性体の任意の混合物、ラセミ体なども本発明の範囲に包含される。 The absolute configuration of the 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative of the present invention is any of (S, S), (S, R), (R, S) and (R, R) configurations. It may be. That is, any stereoisomer such as an optical isomer or a diastereoisomer is included in the scope of the present invention. Optically pure forms of isomers are a preferred embodiment of the invention. In addition, any mixture of stereoisomers, racemates, and the like are also included in the scope of the present invention.

本発明の５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体の製造方法は、溶媒中、塩基存在下、上記一般式（２）で表される４−トリフルオロメチルスルホニルイソキサゾール誘導体と（トリフルオロメチル）トリメチルシランを反応させる方法である。 The method for producing a 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative of the present invention comprises a 4-trifluoromethylsulfonylisoxa represented by the above general formula (2) in the presence of a base in a solvent. This is a method of reacting a sol derivative with (trifluoromethyl) trimethylsilane.

上記一般式（２）中のＲ^１およびＲ^２は、上記一般式（１）中のＲ^１およびＲ^２と同じであるので、その説明を省略する。 ^{R 1} and ^{R 2} in the general formula (2) in is the same as ^{R 1} and ^{R 2} in formula (1), description thereof is omitted.

反応に用いる溶媒は、４−トリフルオロメチルスルホニルイソキサゾール誘導体と（トリフルオロメチル）トリメチルシランが溶解する溶媒であれば、その種類は特に限定されない。このような溶媒としては、ジエチルエーテル、ジイソプロピルエーテル、ｎ−ブチルメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル、テトラヒドロフラン、ジオキサンなどのエーテル系溶媒；ヘプタン、ヘキサン、シクロペンタン、シクロヘキサンなどの炭化水素系溶媒；クロロホルム、四塩化炭素、塩化メチレン、ジクロロエタン、トリクロロエタンなどのハロゲン化炭化水素系溶媒；ベンゼン、トルエン、キシレン、クメン、シメン、メシチレン、ジイソプロピルベンゼン、ピリジン、ピリミジン、ピラジン、ピリダジンなどの芳香族系溶媒；ジメチルスルホキシド（ＤＭＳＯ）、ジメチルホルムアミド（ＤＭＦ）、N−メチルピロリドン(ＮＭＰ)などの溶媒；メタノール、エタノール、プロパノール、ｉ−プロピルアルコール、アミノエタノール、Ｎ，Ｎ−ジメチルアミノエタノールなどのアルコール系溶媒が挙げられる。これらの溶媒は、単独で使用し得るのみならず、２種類以上の溶媒を混合して用いることも可能である。 The solvent used in the reaction is not particularly limited as long as it is a solvent in which the 4-trifluoromethylsulfonylisoxazole derivative and (trifluoromethyl) trimethylsilane are dissolved. Examples of such solvents include ether solvents such as diethyl ether, diisopropyl ether, n-butyl methyl ether, tert-butyl methyl ether, tetrahydrofuran and dioxane; hydrocarbon solvents such as heptane, hexane, cyclopentane and cyclohexane; chloroform , Halogenated hydrocarbon solvents such as carbon tetrachloride, methylene chloride, dichloroethane, trichloroethane; aromatic solvents such as benzene, toluene, xylene, cumene, cymene, mesitylene, diisopropylbenzene, pyridine, pyrimidine, pyrazine, pyridazine; dimethyl Solvents such as sulfoxide (DMSO), dimethylformamide (DMF), N-methylpyrrolidone (NMP); methanol, ethanol, propanol, i-propyl alcohol, amino Ethanol, N, include alcohol solvents such as N- dimethylaminoethanol. These solvents can be used alone or in combination of two or more solvents.

反応に用いる塩基としては、無機塩基、有機塩基、有機金属試薬などが使用できる。具体的には、例えば、炭酸カリウム、炭酸セシウムなどの炭酸塩；酢酸ナトリウム、酢酸カリウムなどの酢酸塩；テトラメチルアンモニウムフロリド、テトラエチルアンモニウムフロリド、テトラブチルアンモニウムフロリドなどのアンモニウムフロリド；フッ化カリウム、フッ化セシウムなどのフッ化アルカリ金属類；水酸化ナトリウム、水酸化カリウムなどの水酸化物；ナトリウムメトキシド、カリウムｔｅｒｔ−ブトキシドなどのアルコキシド化合物；ＤＡＢＣＯ、ＤＢＵ、トリエチルアミン、Ｎ、Ｎ−ジメチルアミノピリジンなどの有機塩基；ｎ−ブチルリチウム、ｓｅｃ−ブチルリチウム、ｔｅｒｔ−ブチルリチウム、リチウムジイソプロピルアミド、ヘキサメチルジシラザンリチウム塩などのリチウム塩などが挙げられる。塩基の使用量は、上記一般式（２）で表される４−トリフルオロメチルスルホニルイソキサゾール誘導体に対して、１〜１０当量であればよく、好ましくは１．５当量である。 As the base used in the reaction, an inorganic base, an organic base, an organometallic reagent, or the like can be used. Specifically, for example, carbonates such as potassium carbonate and cesium carbonate; acetates such as sodium acetate and potassium acetate; ammonium fluorides such as tetramethylammonium fluoride, tetraethylammonium fluoride and tetrabutylammonium fluoride; Alkali metal fluorides such as potassium hydroxide and cesium fluoride; hydroxides such as sodium hydroxide and potassium hydroxide; alkoxide compounds such as sodium methoxide and potassium tert-butoxide; DABCO, DBU, triethylamine, N, N- Examples include organic bases such as dimethylaminopyridine; lithium salts such as n-butyllithium, sec-butyllithium, tert-butyllithium, lithium diisopropylamide, and hexamethyldisilazane lithium salt. The usage-amount of a base should just be 1-10 equivalent with respect to the 4-trifluoromethylsulfonyl isoxazole derivative represented by the said General formula (2), Preferably it is 1.5 equivalent.

反応に用いる溶媒と塩基の好ましい組み合わせは、後述する実施例からわかるように、ジメチルスルホキシド（ＤＭＳＯ）と酢酸カリウム（ＫＯＡｃ）である。これらを用いることで、短時間、かつ、高い収率で目的物を得ることができる。 A preferable combination of a solvent and a base used in the reaction is dimethyl sulfoxide (DMSO) and potassium acetate (KOAc), as can be seen from Examples described later. By using these, the target product can be obtained in a short time and with a high yield.

反応温度は、特に限定されるものではないが、通常、−８０℃乃至１２０℃であり、より好ましくは室温（２５℃）付近である。反応器は、特に限定されるものでなく、大気開放型の反応器、オートクレーブなどの密閉型の反応器のいずれも使用可能である。反応圧力は、大気圧下、または、加圧下のいずれであってもよい。反応時間は、特に限定されるものではないが、通常１〜１０時間で反応は完結する。 The reaction temperature is not particularly limited, but is usually −80 ° C. to 120 ° C., more preferably around room temperature (25 ° C.). The reactor is not particularly limited, and any of an open-air reactor and a closed reactor such as an autoclave can be used. The reaction pressure may be either atmospheric pressure or under pressure. The reaction time is not particularly limited, but the reaction is usually completed in 1 to 10 hours.

この反応によって、トリフルオロメチルアニオンが４−トリフルオロメチルスルホニル−２−イソキサゾールの５位に付加した反応物を得ることができる。この反応物は、一般式（１）のＸが水素である５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体である。必要に応じて、この反応物に酸処理することで、一方のジアステレオマーのみを得ることができる。 By this reaction, a reaction product in which a trifluoromethyl anion is added to the 5-position of 4-trifluoromethylsulfonyl-2-isoxazole can be obtained. This reactant is a 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative in which X in the general formula (1) is hydrogen. If necessary, only one diastereomer can be obtained by acid treatment of this reaction product.

反応後、一般式（１）のＸが水素である５−トリフルオロメチル−４−トリフルオロメチルスルホニル２−イソキサゾリン誘導体を反応液から単離および精製する方法としては、一般的な手法を採用することができる。例えば、反応液を濃縮した後、シリカゲル、アルミナなどの吸着剤を用いたカラムクロマトグラフ法での精製、塩析、再結晶などが挙げられる。 After the reaction, as a method for isolating and purifying the 5-trifluoromethyl-4-trifluoromethylsulfonyl 2-isoxazoline derivative in which X in the general formula (1) is hydrogen, a general method is adopted. be able to. For example, after concentrating the reaction solution, purification by column chromatography using an adsorbent such as silica gel and alumina, salting out, recrystallization and the like can be mentioned.

さらに、一般式（１）のＸが水素である５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体に対してハロゲン化剤を反応させることで、一般式（１）のＸがハロゲンである５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体を得ることができる。 Furthermore, by reacting a 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative in which X in the general formula (1) is hydrogen, X in the general formula (1) is A 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative which is a halogen can be obtained.

このハロゲン化反応に用いるハロゲン化剤、すなわち、求電子的ハロゲン化試薬の種類は特に限定されない。ハロゲン化剤としては、例えば、Selectfluor（登録商標）やＮ−フルオロベンゼンスルホンイミド、Ｎ−クロロスクシンイミド（ＮＣＳ）、Ｎ−ブロモスクシンイミド（ＮＢＳ）、Ｎ−ヨードスクシンイミドなどが挙げられる。 The type of halogenating agent used in the halogenation reaction, that is, the electrophilic halogenating reagent is not particularly limited. Examples of the halogenating agent include Selectfluor (registered trademark), N-fluorobenzenesulfonimide, N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), N-iodosuccinimide, and the like.

以下、実施例により本発明をさらに具体的に説明するが、本発明の範囲は下記の実施例に限定されることはない。
（実施例１）
下記の通り、一般式（２）で表される４−トリフルオロメチルスルホニルイソキサゾールと、（トリフルオロメチル）トリメチルシランとを反応させることにより、式（１−１）で表される化合物１ａ〜１ｑを製造した。化合物１ａ〜１ｑを表１に示す。表１中のＭｅ、Ｐｈは、それぞれ、メチル基、フェニル基を示す。なお、化合物１ａ〜１ｑは、上記一般式（１）のＲ^１がアルキル基またはアリール基であり、Ｒ^２がアリール基であり、Ｘが水素である化合物である。EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, the scope of the present invention is not limited to the following Example.
Example 1
As shown below, the compound 1a represented by the formula (1-1) is obtained by reacting 4-trifluoromethylsulfonylisoxazole represented by the general formula (2) with (trifluoromethyl) trimethylsilane. ˜1q was produced. Compounds 1a-1q are shown in Table 1. Me and Ph in Table 1 represent a methyl group and a phenyl group, respectively. In addition, the compounds 1a to 1q are compounds in which R ^{1 in the} general formula (1) is an alkyl group or an aryl group, R ² is an aryl group, and X is hydrogen.

具体的には、一般式（２）で表される４−トリフルオロメチルスルホニルイソキサゾール（０．１０ｍｍｏｌ）、および塩基としての酢酸カリウム（１４．７ｍｇ、０．１５ｍｍｏｌ）を、溶媒としてのジメチルスルホキシド０．５ｍＬに溶かし、室温で、（トリフルオロメチル）トリメチルシラン（２９．６μＬ、０．０２ｍｍｏｌ）を加えた。この溶液を１〜１０時間撹拌することにより、４−トリフルオロメチルスルホニルイソキサゾールと（トリフルオロメチル）トリメチルシランを反応させた。

Specifically, 4-trifluoromethylsulfonylisoxazole (0.10 mmol) represented by the general formula (2) and potassium acetate (14.7 mg, 0.15 mmol) as a base were added to dimethyl as a solvent. Dissolved in 0.5 mL of sulfoxide and (trifluoromethyl) trimethylsilane (29.6 μL, 0.02 mmol) was added at room temperature. By stirring this solution for 1 to 10 hours, 4-trifluoromethylsulfonylisoxazole and (trifluoromethyl) trimethylsilane were reacted.

反応後、１Ｍの塩酸を０．５ｍＬ加えて、室温でさらに１時間撹することにより、酸処理を行った。その後、酢酸エチルを用いて抽出し、集めた有機相を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥させた。乾燥後、減圧下で溶媒を留去し、シリカゲルカラムクロマトグラフィーにて精製し、化合物１ａ〜１ｑを結晶状態で得た。 After the reaction, 0.5 mL of 1M hydrochloric acid was added, and the mixture was further stirred at room temperature for 1 hour for acid treatment. Thereafter, the mixture was extracted with ethyl acetate, and the collected organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. After drying, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain compounds 1a to 1q in a crystalline state.

得られた化合物１ａ〜１ｑについて、Ｘ線結晶構造解析、ＮＭＲ、ＨＭＲＳ、ＩＲなどの各種分析を行った。その結果の一部を表１に示すとともに、その結果の詳細を以下に示す。 The obtained compounds 1a to 1q were subjected to various analyzes such as X-ray crystal structure analysis, NMR, HMRS, and IR. Some of the results are shown in Table 1, and details of the results are shown below.

化合物１ａ：（４Ｓ^＊，５Ｒ^＊）−３，５−ジフェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.64 (s, 1H), 7.47-7.56 (m, 6H), 7.71-7.78 (m, 4H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 72.7 (m), 91.0 (q, J = 29.2 Hz), 118.8 (q, J = 330.5 Hz), 123.5 (q, J = 290.7 Hz), 125.8, 126.3, 128.0, 128.2, 128.5, 128.9, 130.7, 131.8, 153.0; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 94:6) δ -78.7 (s, 0.94 × 3F), -73.0 (s, 0.94 × 3F), -71.6 (m, 0.06 × 3F), -68.8 (m, 0.06 × 3F); IR (KBr) 3076, 2913, 1499, 1451, 1387, 1332, 1217, 1166, 1112, 985, 952, 915, 885, 761, 745, 696, 625, 538, 503, 454 cm^-1; mp = 155.0-156.0 oC (CHCl₃); MS (ESI, m/z) 422 [M-H] -, HRMS (ESI) calcd. for C₁₇H₁₀F₆NO₃S [M-H] -: 422.0286 Found: 422.0288. 91％収率，dr = 94:6

Compound 1a: (4S ^* , 5R ^* )-3,5-diphenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.64 (s, 1H), 7.47-7.56 (m, 6H), 7.71-7.78 (m, 4H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 72.7 (m ), 91.0 (q, J = 29.2 Hz), 118.8 (q, J = 330.5 Hz), 123.5 (q, J = 290.7 Hz), 125.8, 126.3, 128.0, 128.2, 128.5, 128.9, 130.7, 131.8, 153.0; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 94: 6) δ -78.7 (s, 0.94 × 3F), -73.0 (s, 0.94 × 3F), -71.6 (m, 0.06 × 3F), -68.8 (m, 0.06 × 3F); IR (KBr) 3076, 2913, 1499, 1451, 1387, 1332, 1217, 1166, 1112, 985, 952, 915, 885, 761, 745, 696, 625, 538, 503, 454 cm ^-1 ; mp = 155.0-156.0 oC (CHCl ₃ ); MS (ESI, m / z) 422 [MH]-, HRMS (ESI) calcd. For C ₁₇ H ₁₀ F ₆ NO ₃ S [MH]- : 422.0286 Found: 422.0288. 91% yield, dr = 94: 6

化合物１ｂ：（４Ｓ^＊，５Ｒ^＊）−３−フェニル−５−p−トリル−５−(トリフルオロメチル)−４−(トリフルオロメチルスルホニル)−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 2.41 (s, 3H), 5.62 (s, 1H), 7.28 (d, J = 8.1 Hz, 2H), 7.46-7.57 (m, 3H), 7.64 (d, J = 8.4 Hz, 2H), 7.70-7.73 (m, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 21.3, 72.6, 91.1 (q, J = 29.2 Hz), 118.8 (q, J = 330.5 Hz), 122.7, 123.5 (q, J = 290.7 Hz), 128.0, 128.4, 128.93, 128.96, 131.7, 140.9, 152.9 ; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 93:7) δ -78.8 (s, 0.93 × 3F), -73.0 (s, 0.93 × 3F), -71.6 (m, 0.07 × 3F), -69.0 (m, 0.07 × 3F); IR (KBr) 3036, 2917, 1734, 1518, 1446, 1388, 1217, 1166, 1112, 944, 912, 884, 811, 763, 747, 690, 630, 553, 535, 505 cm^-1; mp = 133.0-136.0 oC (CHCl₃); MS (ESI, m/z) 436 [M-H] -, HRMS (ESI) calcd. for C₁₈H₁₂F₆NO₃S [M-H] -: 436.0442 Found: 436.0453. 85%収率，dr = 93:7

Compound 1b: (4S ^* , 5R ^* )-3-phenyl-5-p-tolyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 2.41 (s, 3H), 5.62 (s, 1H), 7.28 (d, J = 8.1 Hz, 2H), 7.46-7.57 (m, 3H), 7.64 (d, J = 8.4 Hz, 2H), 7.70-7.73 (m, 2H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 21.3, 72.6, 91.1 (q, J = 29.2 Hz), 118.8 (q, J = 330.5 Hz ), 122.7, 123.5 (q, J = 290.7 Hz), 128.0, 128.4, 128.93, 128.96, 131.7, 140.9, 152.9; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 93: 7) δ -78.8 (s , 0.93 × 3F), -73.0 (s, 0.93 × 3F), -71.6 (m, 0.07 × 3F), -69.0 (m, 0.07 × 3F); IR (KBr) 3036, 2917, 1734, 1518, 1446, 1388, 1217, 1166, 1112, 944, 912, 884, 811, 763, 747, 690, 630, 553, 535, 505 cm ^-1 ; mp = 133.0-136.0 oC (CHCl ₃ ); MS (ESI, m / z) 436 [MH]-, HRMS (ESI) calcd. for C ₁₈ H ₁₂ F ₆ NO ₃ S [MH]-: 436.0442 Found: 436.0453. 85% yield, dr = 93: 7

化合物１ｃ：（４Ｓ^＊，５Ｒ^＊）−５−（４−メトキシフェニル）−３−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 3.85 (s, 3H), 5.61 (s, 1H), 6.98 (d, J = 8.7 Hz, 2H), 7.47-7.57 (m, 3H), 7.66-7.72 (m, 4H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 55.3, 72.7, 91.0 (q, J = 29.7 Hz), 113.6, 117.3, 118.8 (q, J = 331.0 Hz), 123.5 (q, J = 290.7 Hz), 126.3, 128.0, 128.9, 130.1, 131.7, 152.9, 161.2; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 95:5) δ -79.0 (s, 0.95 × 3F), -73.0 (s, 0.95 × 3F), -71.6 (m, 0.05 × 3F), -69.2 (m, 0.05 × 3F); IR (KBr) 2914, 2843, 1615, 1519, 1467, 1389, 1196, 1110, 1032, 986, 913, 822, 764, 691, 630, 586, 536, 446 cm^-1; mp = 130.0-131.0 oC (CHCl₃); MS (ESI, m/z) 452 [M-H] -, HRMS (ESI) calcd. for C₁₈H₁₂F₆NO₄S [M-H] -: 452.0391 Found: 452.0403. 96%収率, dr = 95:5

Compound 1c: (4S ^* , 5R ^* )-5- (4-methoxyphenyl) -3-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 3.85 (s, 3H), 5.61 (s, 1H), 6.98 (d, J = 8.7 Hz, 2H), 7.47-7.57 (m, 3H), 7.66-7.72 ( m, 4H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 55.3, 72.7, 91.0 (q, J = 29.7 Hz), 113.6, 117.3, 118.8 (q, J = 331.0 Hz), 123.5 (q, J = 290.7 Hz), 126.3, 128.0, 128.9, 130.1, 131.7, 152.9, 161.2; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 95: 5) δ -79.0 (s, 0.95 × 3F), -73.0 (s , 0.95 × 3F), -71.6 (m, 0.05 × 3F), -69.2 (m, 0.05 × 3F); IR (KBr) 2914, 2843, 1615, 1519, 1467, 1389, 1196, 1110, 1032, 986, 913, 822, 764, 691, 630, 586, 536, 446 cm ^-1 ; mp = 130.0-131.0 oC (CHCl ₃ ); MS (ESI, m / z) 452 [MH]-, HRMS (ESI) calcd. for C ₁₈ H ₁₂ F ₆ NO ₄ S [MH]-: 452.0391 Found: 452.0403. 96% yield, dr = 95: 5

化合物１ｄ：（４Ｓ^＊，５Ｒ^＊）−５−（４−クロロフェニル）−３−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.62 (s, 1H), 7.45-7.56 (m, 5H), 7.69-7.72 (m, 4H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 72.6 (m), 90.6 (q, J = 29.7 Hz), 118.7 (q, J = 330.5 Hz), 123.3 (q, J = 290.7 Hz), 124.3, 126.0, 128.0, 128.6, 129.0, 130.0, 131.9, 137.2, 153.0; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 97:3) δ -78.8 (s, 0.97 × 3F), -73.0 (s, 0.97 × 3F), -71.5 (m, 0.03 × 3F), -68.8 (m, 0.03 × 3F); IR (KBr) 3060, 2916, 1600, 1497, 1446, 1388, 1333, 1207, 1112, 1018, 987, 946, 909, 822, 748, 690, 630, 539, 504, 445 cm^-1; mp = 154.0-155.5 oC (CHCl₃); MS (ESI, m/z) 456 [M-H] -, HRMS (ESI) calcd. for C₁₇H₉ClF₆NO₃S [M-H] -: 455.9896 Found: 455.9898. 88%収率, dr = 97:3

Compound 1d: (4S ^* , 5R ^* )-5- (4-chlorophenyl) -3-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.62 (s, 1H), 7.45-7.56 (m, 5H), 7.69-7.72 (m, 4H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 72.6 (m ), 90.6 (q, J = 29.7 Hz), 118.7 (q, J = 330.5 Hz), 123.3 (q, J = 290.7 Hz), 124.3, 126.0, 128.0, 128.6, 129.0, 130.0, 131.9, 137.2, 153.0; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 97: 3) δ -78.8 (s, 0.97 × 3F), -73.0 (s, 0.97 × 3F), -71.5 (m, 0.03 × 3F), -68.8 (m, 0.03 × 3F); IR (KBr) 3060, 2916, 1600, 1497, 1446, 1388, 1333, 1207, 1112, 1018, 987, 946, 909, 822, 748, 690, 630, 539, 504, 445 cm ^-1 ; mp = 154.0-155.5 oC (CHCl ₃ ); MS (ESI, m / z) 456 [MH]-, HRMS (ESI) calcd. For C ₁₇ H ₉ ClF ₆ NO ₃ S [MH]- : 455.9896 Found: 455.9898. 88% yield, dr = 97: 3

化合物１ｅ：（４Ｓ^＊，５Ｒ^＊）−５−（４−ブロモフェニル）−３−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.62 (s, 1H), 7.47-7.57 (m, 3H), 7.63 (s, 4H), 7.71 (d, J = 6.9 Hz, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 72.9, 91.1 (q, J = 29.7 Hz), 119.2 (q, J = 330.5 Hz), 123.6 (q, J = 289.7 Hz), 125.2, 125.9, 126.4, 128.4, 129.4, 130.6, 132.0, 132.4, 153.4; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 96:4) δ-78.8 (s, 0.96 × 3F), -72.9 (s, 0.96 × 3F), -71.4 (m, 0.04 × 3F), -68.8 (m, 0.04 × 3F); IR (KBr) 3060, 2915, 1594, 1495, 1446, 1388, 1332, 1205, 1118, 1015, 986, 946, 909, 884, 818, 763, 689, 629, 537, 503 cm^-1; mp = 145.0-146.5 oC (CHCl₃); MS (ESI, m/z) 500 [M-H] -, HRMS (ESI) calcd. for C₁₇H₉BrF₆NO₃S [M-H] -: 499.9391 Found: 499.9400. 90%収率, dr = 96:4

Compound 1e: (4S ^* , 5R ^* )-5- (4-bromophenyl) -3-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.62 (s, 1H), 7.47-7.57 (m, 3H), 7.63 (s, 4H), 7.71 (d, J = 6.9 Hz, 2H); ¹³ C NMR ( _{CDCl 3, 150.9 MHz) δ 72.9} , 91.1 (q, J = 29.7 Hz), 119.2 (q, J = 330.5 Hz), 123.6 (q, J = 289.7 Hz), 125.2, 125.9, 126.4, 128.4, 129.4, 130.6 , 132.0, 132.4, 153.4; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 96: 4) δ-78.8 (s, 0.96 × 3F), -72.9 (s, 0.96 × 3F), -71.4 (m, 0.04 × 3F), -68.8 (m, 0.04 × 3F); IR (KBr) 3060, 2915, 1594, 1495, 1446, 1388, 1332, 1205, 1118, 1015, 986, 946, 909, 884, 818, 763 , 689, 629, 537, 503 cm ^-1 ; mp = 145.0-146.5 oC (CHCl ₃ ); MS (ESI, m / z) 500 [MH]-, HRMS (ESI) calcd. For C ₁₇ H ₉ BrF ₆ NO ₃ S [MH]-: 499.9391 Found: 499.9400. 90% yield, dr = 96: 4

化合物１ｆ：（４Ｓ^＊，５Ｒ^＊）−５−（４−ニトロフェニル）−３−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.71 (s, 1H), 7.50-7.61 (m, 3H), 7.74 (d, J = 6,9 Hz, 2H), 7.99 (d, J = 8.4 Hz, 2H), 8.35 (d, J = 9.0 Hz, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 72.5, 90.4 (q, J = 29.7 Hz), 118.6 (q, J = 330.5 Hz), 123.1 (q, J = 290.7 Hz), 123.2, 125.6, 128.0, 129.1, 130.0, 132.2, 132.6, 149.2, 153.1; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 97:3) δ -78.4 (s, 0.97 × 3F), -73.1 (s, 0.97 × 3F), -71.2 (m, 0.03 × 3F), -68.2 (m, 0.03 × 3F); IR (KBr) 3125, 2916, 1705, 1604, 1523, 1449, 1385, 1356, 1217, 1117, 991, 911, 855, 801, 745, 712, 688, 625, 540, 498 cm^-1; mp = 180.0-181.0 oC (CHCl₃); MS (ESI, m/z) 467 [M-H] -, HRMS (ESI) calcd. for C₁₇H₉F₆N₂O₅S [M-H] -: 467.0136 Found: 467.0148. 80%収率, dr = 97:3

Compound 1f: (4S ^* , 5R ^* )-5- (4-nitrophenyl) -3-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.71 (s, 1H), 7.50-7.61 (m, 3H), 7.74 (d, J = 6,9 Hz, 2H), 7.99 (d, J = 8.4 Hz, 2H), 8.35 (d, J = 9.0 Hz, 2H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 72.5, 90.4 (q, J = 29.7 Hz), 118.6 (q, J = 330.5 Hz), 123.1 ( q, J = 290.7 Hz), 123.2, 125.6, 128.0, 129.1, 130.0, 132.2, 132.6, 149.2, 153.1; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 97: 3) δ -78.4 (s, 0.97 × 3F), -73.1 (s, 0.97 × 3F), -71.2 (m, 0.03 × 3F), -68.2 (m, 0.03 × 3F); IR (KBr) 3125, 2916, 1705, 1604, 1523, 1449, 1385, 1356, 1217, 1117, 991, 911, 855, 801, 745, 712, 688, 625, 540, 498 cm ^-1 ; mp = 180.0-181.0 oC (CHCl ₃ ); MS (ESI, m / z) 467 [MH]-, HRMS (ESI) calcd. For C ₁₇ H ₉ F ₆ N ₂ O ₅ S [MH]-: 467.0136 Found: 467.0148. 80% yield, dr = 97: 3

化合物１ｇ：（４Ｓ^＊，５Ｒ^＊）−５−（ナフタレン−２−イル）−３−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.73 (s, 1H), 7.49-7.62 (m, 5H), 7.74-7.77 (m, 3H), 7.88-7.96 (m, 3H), 8.33 (s, 1H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 73.2, 91.7 (q, J = 29.2 Hz), 119.2 (q, J = 331.0 Hz), 123.5, 123.9 (q. J = 290.7 Hz), 125.2, 126.7, 127.2, 128.0, 128.2, 128.4, 129.3, 129.4, 129.5, 132.2, 132.8, 134.3, 153.4; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 96:4) δ -78.3 (s, 0.96 × 3F), -72.9 (s, 0.96 × 3F), -71.5 (m, 0.04 × 3F), -68.5 (m, 0.04 × 3F); IR (KBr) 3068, 2920, 1508, 1445, 1386, 1332, 1214, 1164, 1111, 971, 910, 815, 748, 689, 625, 549, 533, 480 cm^-1; mp = 195.0-197.0 oC (CHCl₃); MS (ESI, m/z) 472 [M-H] -, HRMS (ESI) calcd. for C₂₁H₁₂F₆NO₃S [M-H] -: 472.0442 Found: 472.0445. 93%収率, dr = 96:4

Compound 1g: (4S ^* , 5R ^* )-5- (naphthalen-2-yl) -3-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.73 (s, 1H), 7.49-7.62 (m, 5H), 7.74-7.77 (m, 3H), 7.88-7.96 (m, 3H), 8.33 (s, 1H ); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 73.2, 91.7 (q, J = 29.2 Hz), 119.2 (q, J = 331.0 Hz), 123.5, 123.9 (q. J = 290.7 Hz), 125.2, 126.7 , 127.2, 128.0, 128.2, 128.4, 129.3, 129.4, 129.5, 132.2, 132.8, 134.3, 153.4; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 96: 4) δ -78.3 (s, 0.96 × 3F) , -72.9 (s, 0.96 × 3F), -71.5 (m, 0.04 × 3F), -68.5 (m, 0.04 × 3F); IR (KBr) 3068, 2920, 1508, 1445, 1386, 1332, 1214, 1164 , 1111, 971, 910, 815, 748, 689, 625, 549, 533, 480 cm ^-1 ; mp = 195.0-197.0 oC (CHCl ₃ ); MS (ESI, m / z) 472 [MH]-, HRMS (ESI) calcd. For C ₂₁ H ₁₂ F ₆ NO ₃ S [MH]-: 472.0442 Found: 472.0445. 93% yield, dr = 96: 4

化合物１ｈ：（４Ｓ^＊，５Ｒ^＊）−５−（フラン−２−イル） −３−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.58 (s, 1H), 6.53 (d, J = 1.5 Hz, 1H), 6.87 (d, J = 3.3 Hz, 1H), 7.47-7.56 (m, 3H), 7.61 (s, 1H), 7.71 (d, J = 7.2 Hz, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 71.6 (m), 87.9 (q, J = 31.7 Hz), 111.2, 114.7, 118.9 (q, J = 330.5 Hz), 122.5 (q, J = 290.7 Hz), 125.8, 128.0, 129.0, 132.0, 138.7, 145.1, 152.4; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 99:1) δ -79.5 (s, 0.99 × 3F), -72.9 (s, 0.99 × 3F), -71.8 (m, 0.01 × 3F), -69.5 (m, 0.01 × 3F); IR (KBr) 3132, 2913, 1499, 1446, 1388, 1334, 1209, 1111, 1030, 1000, 968, 912, 889, 763, 748, 690, 627, 593, 539, 498 cm^-1; mp = 120.0-121.5 oC (CHCl₃); MS (ESI, m/z) 412 [M-H] -, HRMS (ESI) calcd. for C₁₅H₈F₆NO₄S [M-H] -: 412.0078 Found: 412.0092. 85%収率, dr = 99:1

Compound 1h: (4S ^* , 5R ^* )-5- (furan-2-yl) -3-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.58 (s, 1H), 6.53 (d, J = 1.5 Hz, 1H), 6.87 (d, J = 3.3 Hz, 1H), 7.47-7.56 (m, 3H) , 7.61 (s, 1H), 7.71 (d, J = 7.2 Hz, 2H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 71.6 (m), 87.9 (q, J = 31.7 Hz), 111.2, 114.7, 118.9 (q, J = 330.5 Hz), 122.5 (q, J = 290.7 Hz), 125.8, 128.0, 129.0, 132.0, 138.7, 145.1, 152.4; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 99: 1 ) δ -79.5 (s, 0.99 × 3F), -72.9 (s, 0.99 × 3F), -71.8 (m, 0.01 × 3F), -69.5 (m, 0.01 × 3F); IR (KBr) 3132, 2913, 1499, 1446, 1388, 1334, 1209, 1111, 1030, 1000, 968, 912, 889, 763, 748, 690, 627, 593, 539, 498 cm ^-1 ; mp = 120.0-121.5 oC (CHCl ₃ ); MS (ESI, m / z) 412 [MH]-, HRMS (ESI) calcd. For C ₁₅ H ₈ F ₆ NO ₄ S [MH]-: 412.0078 Found: 412.0092. 85% yield, dr = 99: 1

化合物１ｉ：（４Ｓ^＊，５Ｒ^＊）−５−メチル−３−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 2.04 (s, 3H), 5.26 (s, 1H), 7.44-7.53 (m, 3H), 7.68 (d, J = 6.9 Hz, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 14.3, 71.1, 88.1 (q, J = 29.7 Hz), 119.0 (q, J = 330.0 Hz), 123.6 (q, J = 288.7 Hz), 126.0, 127.9, 128.9, 131.8, 151.7; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 100:0) δ -83.4 (s, 3F), -73.3 (s, 3F); IR (KBr) 3072, 2906, 1447, 1385, 1167, 1111, 913, 896, 802, 764, 746, 715, 691, 635, 611, 580, 546, 530, 484, 441 cm^-1; mp = 85.0-87.5 oC (CHCl₃); MS (ESI, m/z) 360 [M-H] -, HRMS (ESI) calcd. for C₁₂H₈F₆NO₃S [M-H] -: 360.0129 Found: 360.0127. 64%収率, single diastereomer

Compound 1i: (4S ^* , 5R ^* )-5-methyl-3-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 2.04 (s, 3H), 5.26 (s, 1H), 7.44-7.53 (m, 3H), 7.68 (d, J = 6.9 Hz, 2H); ¹³ C NMR ( _{CDCl 3, 150.9 MHz) δ 14.3} , 71.1, 88.1 (q, J = 29.7 Hz), 119.0 (q, J = 330.0 Hz), 123.6 (q, J = 288.7 Hz), 126.0, 127.9, 128.9, 131.8, 151.7 ; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 100: 0) δ -83.4 (s, 3F), -73.3 (s, 3F); IR (KBr) 3072, 2906, 1447, 1385, 1167, 1111 , 913, 896, 802, 764, 746, 715, 691, 635, 611, 580, 546, 530, 484, 441 cm ^-1 ; mp = 85.0-87.5 oC (CHCl ₃ ); MS (ESI, m / z ) 360 [MH]-, HRMS (ESI) calcd. For C ₁₂ H ₈ F ₆ NO ₃ S [MH]-: 360.0129 Found: 360.0127. 64% yield, single diastereomer

化合物１ｊ：（４Ｓ^＊，５Ｒ^＊）−５−フェニル−３−ｐ−トリル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 2.42 (s, 3H), 5.63 (s, 1H), 7.30 (d, J = 8.1 Hz, 2H), 7.44-7.49 (m, 3H), 7.62 (d, J = 7.8 Hz, 2H), 7.76 (d, J = 6.9 Hz, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 21.6, 72.8, 90.8 (q, J = 29.7 Hz), 118.8 (q, J = 330.5 Hz), 123.5 (q, J = 291.2 Hz), 123.4, 125.9, 127.9, 128.2, 128.6, 129.7, 130.6, 142.4, 152.9; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 93:7) δ -78.7 (s, 0.93 × 3F), -72.9 (s, 0.93 × 3F), -71.4 (m, 0.07 × 3F), -68.8 (m, 0.07 × 3F); IR (KBr) 3033, 2912, 1609, 1499, 1452, 1387, 1333, 1217, 1165, 1112, 985, 952, 918, 886, 815, 749, 695, 625, 539, 507 cm^-1; mp = 153.5-154.5 oC (CHCl₃); MS (ESI, m/z) 436 [M-H] -, HRMS (ESI) calcd. for C₁₈H₁₂F₆NO₃S [M-H] -: 436.0442 Found: 436.0448. 87%収率, dr = 93:7

Compound 1j: (4S ^* , 5R ^* )-5-phenyl-3-p-tolyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 2.42 (s, 3H), 5.63 (s, 1H), 7.30 (d, J = 8.1 Hz, 2H), 7.44-7.49 (m, 3H), 7.62 (d, J = 7.8 Hz, 2H), 7.76 (d, J = 6.9 Hz, 2H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 21.6, 72.8, 90.8 (q, J = 29.7 Hz), 118.8 (q, J = 330.5 Hz), 123.5 (q, J = 291.2 Hz), 123.4, 125.9, 127.9, 128.2, 128.6, 129.7, 130.6, 142.4, 152.9; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 93: 7) δ -78.7 (s, 0.93 × 3F), -72.9 (s, 0.93 × 3F), -71.4 (m, 0.07 × 3F), -68.8 (m, 0.07 × 3F); IR (KBr) 3033, 2912, 1609 , 1499, 1452, 1387, 1333, 1217, 1165, 1112, 985, 952, 918, 886, 815, 749, 695, 625, 539, 507 cm ^-1 ; mp = 153.5-154.5 oC (CHCl ₃ ); MS (ESI, m / z) 436 [MH]-, HRMS (ESI) calcd. For C ₁₈ H ₁₂ F ₆ NO ₃ S [MH]-: 436.0442 Found: 436.0448. 87% yield, dr = 93: 7

化合物１ｋ：（４Ｓ^＊，５Ｒ^＊）−３−（４−メトキシフェニル）−５−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 3.86 (s, 3H), 5.61 (s, 1H), 6.99 (d, J = 8.7 Hz, 2H), 7.44-7.49 (m, 3H), 7.68 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 7.8 Hz, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 55.4, 73.0 (m), 90.7 (q, J = 29.2 Hz), 114.4, 118.5, 118.8 (q, J = 331.0 Hz), 123.5 (q, J = 290.7 Hz), 125.9, 128.2, 128.6, 129.7, 130.6, 152.4, 162.4; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 93:7) δ -78.6 (s, 0.93 × 3F), -72.8 (s, 0.93 × 3F), -71.3 (m, 0.07 × 3F), -68.8 (m, 0.07 × 3F); IR (KBr) 2960, 2913, 2837, 1610, 1518, 1452, 1389, 1339, 1022, 953, 912, 828, 761, 724, 696, 626, 539, 471 cm^-1; mp = 156.5-157.5 oC (CHCl₃); MS (ESI, m/z) 452 [M-H] -, HRMS (ESI) calcd. for C₁₈H₁₂F₆NO₄S [M-H] -: 452.0391 Found: 452.0389. 89%収率, dr = 93:7

Compound 1k: (4S ^* , 5R ^* )-3- (4-methoxyphenyl) -5-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 3.86 (s, 3H), 5.61 (s, 1H), 6.99 (d, J = 8.7 Hz, 2H), 7.44-7.49 (m, 3H), 7.68 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 7.8 Hz, 2H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 55.4, 73.0 (m), 90.7 (q, J = 29.2 Hz), 114.4, 118.5, 118.8 (q, J = 331.0 Hz), 123.5 (q, J = 290.7 Hz), 125.9, 128.2, 128.6, 129.7, 130.6, 152.4, 162.4; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 93 : 7) δ -78.6 (s, 0.93 × 3F), -72.8 (s, 0.93 × 3F), -71.3 (m, 0.07 × 3F), -68.8 (m, 0.07 × 3F); IR (KBr) 2960, 2913, 2837, 1610, 1518, 1452, 1389, 1339, 1022, 953, 912, 828, 761, 724, 696, 626, 539, 471 cm ^-1 ; mp = 156.5-157.5 oC (CHCl ₃ ); MS ( ESI, m / z) 452 [MH]-, HRMS (ESI) calcd. For C ₁₈ H ₁₂ F ₆ NO ₄ S [MH]-: 452.0391 Found: 452.0389. 89% yield, dr = 93: 7

化合物１ｌ：（４Ｓ^＊，５Ｒ^＊）−３−（４−クロロフェニル）−５−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.60 (s, 1H), 7.47-7.50 (m, 5H), 7.68 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 6.6 Hz, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 73.1 (m), 91.5 (q, J = 29.2 Hz), 119.2 (q, J = 331.0 Hz), 123.8 (q, J = 291.2 Hz), 125.2, 125.9, 128.7, 128.9, 129.67, 129.74, 131.2, 138.6, 152.5; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 94:6) δ -78.8 (s, 0.94 × 3F), -72.7 (s, 0.94 × 3F), -71.2 (m, 0.06 × 3F), -68.9 (m, 0.06 × 3F); IR (KBr) 3081, 2909, 1716, 1600, 1495, 1452, 1388, 1332, 1206, 1111, 953, 924, 796, 752, 718, 696, 624, 535, 501 cm^-1; mp = 128.5-130.0 oC (CHCl₃); MS (ESI, m/z) 456 [M-H] -, HRMS (ESI) calcd. for C₁₇H₉ClF₆NO₃S [M-H] -: 455.9896 Found: 455.9907. 89%収率, dr = 94:6

Compound 11: (4S ^* , 5R ^* )-3- (4-chlorophenyl) -5-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.60 (s, 1H), 7.47-7.50 (m, 5H), 7.68 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 6.6 Hz, 2H) ; ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 73.1 (m), 91.5 (q, J = 29.2 Hz), 119.2 (q, J = 331.0 Hz), 123.8 (q, J = 291.2 Hz), 125.2, 125.9 , 128.7, 128.9, 129.67, 129.74, 131.2, 138.6, 152.5; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 94: 6) δ -78.8 (s, 0.94 × 3F), -72.7 (s, 0.94 × 3F), -71.2 (m, 0.06 × 3F), -68.9 (m, 0.06 × 3F); IR (KBr) 3081, 2909, 1716, 1600, 1495, 1452, 1388, 1332, 1206, 1111, 953, 924 , 796, 752, 718, 696, 624, 535, 501 cm ^-1 ; mp = 128.5-130.0 oC (CHCl ₃ ); MS (ESI, m / z) 456 [MH]-, HRMS (ESI) calcd. For C ₁₇ H ₉ ClF ₆ NO ₃ S [MH]-: 455.9896 Found: 455.9907. 89% yield, dr = 94: 6

化合物１ｍ：（４Ｓ^＊，５Ｒ^＊）−３−（４−ブロモフェニル）−５−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.60 (s, 1H), 7.47-7.51 (m, 3H), 7.59-7.67 (m, 4H), 7.75 (d, J = 6.6 Hz, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 72.6 (m), 91.1 (q, J = 29.2 Hz), 118.8 (q, J = 330.5 Hz), 123.4 (q, J = 290.2 Hz), 125.2, 125.5, 126.5, 128.3, 128.5, 129.4, 130.8, 132.3, 152.2; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 94:6) δ -78.8 (s, 0.94 × 3F), -72.6 (s, 0.94 × 3F), -71.2 (m, 0.06 × 3F), -68.9 (m, 0.06 × 3F); IR (KBr) 3080, 2908, 1586, 1490, 1387, 1329, 1217, 1111, 1011, 985, 952, 924, 885, 822, 750, 714, 695, 622, 537, 508 cm^-1; mp = 147.5-149.0 oC (CHCl₃); MS (ESI, m/z) 500 [M-H] -, HRMS (ESI) calcd. for C₁₇H₉BrF₆NO₃S [M-H] -: 499.9391 Found: 499.9402. 89%収率，dr = 94:6

Compound 1m: (4S ^* , 5R ^* )-3- (4-bromophenyl) -5-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.60 (s, 1H), 7.47-7.51 (m, 3H), 7.59-7.67 (m, 4H), 7.75 (d, J = 6.6 Hz, 2H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 72.6 (m), 91.1 (q, J = 29.2 Hz), 118.8 (q, J = 330.5 Hz), 123.4 (q, J = 290.2 Hz), 125.2, 125.5, 126.5, 128.3, 128.5, 129.4, 130.8, 132.3, 152.2; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 94: 6) δ -78.8 (s, 0.94 × 3F), -72.6 (s, 0.94 × 3F), -71.2 (m, 0.06 × 3F), -68.9 (m, 0.06 × 3F); IR (KBr) 3080, 2908, 1586, 1490, 1387, 1329, 1217, 1111, 1011, 985, 952, 924, 885, 822, 750, 714, 695, 622, 537, 508 cm ^-1 ; mp = 147.5-149.0 oC (CHCl ₃ ); MS (ESI, m / z) 500 [MH]-, HRMS (ESI) calcd. For C ₁₇ H ₉ BrF ₆ NO ₃ S [MH]-: 499.9391 Found: 499.9402. 89% yield, dr = 94: 6

化合物１ｎ：（４Ｓ^＊，５Ｒ^＊）−３−（４−ニトロフェニル）−５−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.71 (s, 1H), 7.50-7.53 (m, 3H), 7.75 (q, J = 7.2 Hz, 2H), 7.96 (q, J = 8.7 Hz, 2H), 8.36 (d, J = 8.7 Hz); ¹³C NMR (CDCl₃, 150.9 MHz) δ 72.6 (m), 91.6 (q, J = 29.2 Hz), 118.8 (q, J = 331.0 Hz), 123.3 (q, J = 290.2 Hz), 124.1, 125.1, 128.4, 129.1, 131.0, 132.3, 149.5, 151.5; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 95:5) δ -78.9 (s, 0.95 × 3F), -72.4 (s, 0.95 × 3F), -70.9 (m, 0.05 × 3F), -68.9 (m, 0.05 × 3F); IR (KBr) 3124, 2953, 1716, 1610, 1574, 1521, 1453, 1383, 1214, 1115, 982, 952, 925, 853, 748, 715, 693, 624, 592, 504 cm^-1; mp = 155.0-158.0 oC (CHCl₃); MS (ESI, m/z) 467 [M-H] -, HRMS (ESI) calcd. for C₁₇H₉F₆N₂O₅S [M-H] -: 467.0136 Found: 467.0144. 92%収率, dr = 95:5

Compound 1n: (4S ^* , 5R ^* )-3- (4-nitrophenyl) -5-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.71 (s, 1H), 7.50-7.53 (m, 3H), 7.75 (q, J = 7.2 Hz, 2H), 7.96 (q, J = 8.7 Hz, 2H) , 8.36 (d, J = 8.7 Hz); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 72.6 (m), 91.6 (q, J = 29.2 Hz), 118.8 (q, J = 331.0 Hz), 123.3 (q , J = 290.2 Hz), 124.1, 125.1, 128.4, 129.1, 131.0, 132.3, 149.5, 151.5; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 95: 5) δ -78.9 (s, 0.95 × 3F) , -72.4 (s, 0.95 × 3F), -70.9 (m, 0.05 × 3F), -68.9 (m, 0.05 × 3F); IR (KBr) 3124, 2953, 1716, 1610, 1574, 1521, 1453, 1383 , 1214, 1115, 982, 952, 925, 853, 748, 715, 693, 624, 592, 504 cm ^-1 ; mp = 155.0-158.0 oC (CHCl ₃ ); MS (ESI, m / z) 467 [MH ]-, HRMS (ESI) calcd. For C ₁₇ H ₉ F ₆ N ₂ O ₅ S [MH]-: 467.0136 Found: 467.0144. 92% yield, dr = 95: 5

化合物１ｏ：（４Ｓ^＊，５Ｒ^＊）−３−（ナフタレン−２−イル）−５−フェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.79 (s, 1H), 7.48-7.52 (m, 3H), 7.58-7.63 (m, 2H), 7.80 (d, J = 7.2 Hz, 2H), 7.86-7.97 (m, 4H), 8.17 (s, 1H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 72.8 (m), 91.1 (q, J = 29.2 Hz), 118.8 (q, J = 331.0 Hz), 123.5 (q, J = 290.7 Hz), 123.7, 123.9, 125.8, 127.2, 127.9, 128.2, 128.3, 128.6, 128.8, 128.99, 129.04, 130.7, 132.6, 134.7, 153.0; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 96:4) δ-78.6 (s, 0.96 × 3F), -72.8 (s, 0.96 × 3F), -71.3 (m, 0.04 × 3F), -68.7 (m, 0.04 × 3F); IR (KBr) 3066, 2914, 1500, 1450, 1389, 1168, 1110, 985, 956, 906, 819, 795, 760, 716, 697, 616, 538, 511, 481 cm^-1; mp = 195.5-196.5 oC (CHCl₃); MS (ESI, m/z) 472 [M-H] -, HRMS (ESI) calcd. for C₂₁H₁₂F₆NO₃S [M-H] -: 472.0442 Found: 472.0449. 99%収率, dr = 96:4

Compound 1o: (4S ^* , 5R ^* )-3- (naphthalen-2-yl) -5-phenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.79 (s, 1H), 7.48-7.52 (m, 3H), 7.58-7.63 (m, 2H), 7.80 (d, J = 7.2 Hz, 2H), 7.86- 7.97 (m, 4H), 8.17 (s, 1H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 72.8 (m), 91.1 (q, J = 29.2 Hz), 118.8 (q, J = 331.0 Hz), 123.5 (q, J = 290.7 Hz), 123.7, 123.9, 125.8, 127.2, 127.9, 128.2, 128.3, 128.6, 128.8, 128.99, 129.04, 130.7, 132.6, 134.7, 153.0; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 96: 4) δ-78.6 (s, 0.96 × 3F), -72.8 (s, 0.96 × 3F), -71.3 (m, 0.04 × 3F), -68.7 (m, 0.04 × 3F); IR ( (KBr) 3066, 2914, 1500, 1450, 1389, 1168, 1110, 985, 956, 906, 819, 795, 760, 716, 697, 616, 538, 511, 481 cm ^-1 ; mp = 195.5-196.5 oC ( CHCl ₃ ); MS (ESI, m / z) 472 [MH]-, HRMS (ESI) calcd. For C ₂₁ H ₁₂ F ₆ NO ₃ S [MH]-: 472.0442 Found: 472.0449. 99% yield, dr = 96: 4

化合物１ｐ：（４Ｓ^＊，５Ｒ^＊）−３−（４−メトキシフェニル）−５−（３，５−ジクロロフェニル）−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 3.88 (s, 3H), 5.56 (s, 1H), 7.00 (d, J = 8.7 Hz, 2H), 7.52 (s, 1H), 7.65-7.68 (m, 4H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 55.5, 72.6 (m), 89.6 (q, J = 29.7 Hz), 114.5, 118.7 (q, J = 330.5 Hz), 123.0 (q, J = 291.2 Hz), 127.2, 129.1, 129.7, 130.9, 135.1, 152.7, 162.6 ;¹⁹F NMR (CDCl₃, 282 MHz) (dr = 95:5) δ-78.5 (s, 0.95 × 3F), -72.9 (s, 0.95 × 3F), -70.9 (m, 0.05 × 3F), -68.4 (m, 0.05 × 3F); IR (KBr) 2959 1609, 1572, 1518, 1426, 1382, 1306, 1268, 1207, 1174, 1105, 1018, 868, 844, 806, 679, 621, 572, 502 cm^-1; mp = 146.0-147.5 oC (CHCl₃); MS (ESI, m/z) 520 [M-H] -, HRMS (ESI) calcd. for C₁₈H₁₀C_l2F₆NO₄S [M-H] -: 519.9612 Found: 519.9627. 98%収率, dr = 95:5

Compound 1p: (4S ^* , 5R ^* )-3- (4-methoxyphenyl) -5- (3,5-dichlorophenyl) -5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5 -Dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 3.88 (s, 3H), 5.56 (s, 1H), 7.00 (d, J = 8.7 Hz, 2H), 7.52 (s, 1H), 7.65-7.68 (m, 4H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 55.5, 72.6 (m), 89.6 (q, J = 29.7 Hz), 114.5, 118.7 (q, J = 330.5 Hz), 123.0 (q, J = 291.2 Hz), 127.2, 129.1, 129.7, 130.9, 135.1, 152.7, 162.6; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 95: 5) δ-78.5 (s, 0.95 × 3F), -72.9 (s, 0.95 × 3F), -70.9 (m, 0.05 × 3F), -68.4 (m, 0.05 × 3F); IR (KBr) 2959 1609, 1572, 1518, 1426, 1382, 1306, 1268, 1207, 1174, 1105, 1018, 868, 844, 806, 679, 621, 572, 502 cm ^-1 ; mp = 146.0-147.5 oC (CHCl ₃ ); MS (ESI, m / z) 520 [MH]-, HRMS (ESI) calcd. for C ₁₈ H ₁₀ C _l2 F ₆ NO ₄ S [MH]-: 519.9612 Found: 519.9627. 98% yield, dr = 95: 5

化合物１ｑ：（４Ｓ^＊，５Ｒ^＊）−（Ｅ）−３−フェニル−５−スチリル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CDCl₃, 300 MHz) δ 5.49 (s, 1H), 6.50 (d, J = 16.2 Hz, 1H), 7.25 (d, J = 15.6 Hz, 1H), 7.36-7.42 (m, 3H), 7.47-7.56 (m, 5H), 7.71 (d, J = 7.2 Hz, 2H); ¹³C NMR (CDCl₃, 150.9 MHz) δ 73.3 (m), 89.1 (q, J = 30.2 Hz), 113.2, 118.9 (q, J = 330.5 Hz), 123.0 (q, J = 289.7 Hz), 125.8, 127.3, 128.1, 128.9, 129.0, 129.4, 131.9, 134.8, 137.7, 151.9; ¹⁹F NMR (CDCl₃, 282 MHz) (dr = 100:0) δ -81.8 (s, 3F), -72.2 (s, 3F); IR (KBr) 3073, 2898, 1629, 1534, 1446, 1383, 1229, 1171, 1109, 964, 925, 894, 805, 753, 690, 632, 579, 532, 495 cm^-1; mp = 182.0-183.0 oC (CHCl₃); MS (ESI, m/z) 448 [M-H] -, HRMS (ESI) calcd. for C₁₉H₁₂F₆NO₃S [M-H] -: 448.0442 Found: 448.0450. 80%収率, single diastereomer
（実施例２）
表２に示す各種溶媒および各種塩基を用いて、実施例１で示した化合物１ａを製造した。各反応条件は、用いた溶媒および塩基の種類を除き、実施例１と同じである。各反応例における反応時間および収率を表２に示す。

Compound 1q: (4S ^* , 5R ^* )-(E) -3-phenyl-5-styryl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CDCl ₃ , 300 MHz) δ 5.49 (s, 1H), 6.50 (d, J = 16.2 Hz, 1H), 7.25 (d, J = 15.6 Hz, 1H), 7.36-7.42 (m, 3H) , 7.47-7.56 (m, 5H), 7.71 (d, J = 7.2 Hz, 2H); ¹³ C NMR (CDCl ₃ , 150.9 MHz) δ 73.3 (m), 89.1 (q, J = 30.2 Hz), 113.2, 118.9 (q, J = 330.5 Hz), 123.0 (q, J = 289.7 Hz), 125.8, 127.3, 128.1, 128.9, 129.0, 129.4, 131.9, 134.8, 137.7, 151.9; ¹⁹ F NMR (CDCl ₃ , 282 MHz) (dr = 100: 0) δ -81.8 (s, 3F), -72.2 (s, 3F); IR (KBr) 3073, 2898, 1629, 1534, 1446, 1383, 1229, 1171, 1109, 964, 925, 894, 805, 753, 690, 632, 579, 532, 495 cm ^-1 ; mp = 182.0-183.0 oC (CHCl ₃ ); MS (ESI, m / z) 448 [MH]-, HRMS (ESI) calcd. for C ₁₉ H ₁₂ F ₆ NO ₃ S [MH]-: 448.0442 Found: 448.0450. 80% yield, single diastereomer
(Example 2)
The compound 1a shown in Example 1 was produced using various solvents and various bases shown in Table 2. Each reaction condition is the same as in Example 1 except for the type of solvent and base used. The reaction time and yield in each reaction example are shown in Table 2.

表２に示すように、反応例１〜８のいずれにおいても、目的物を得ることができた。特に、反応例８のジメチルスルホキシド（ＤＭＳＯ）と酢酸カリウム（ＫＯＡｃ）とを用いたときでは、他の反応例よりも、短時間、かつ、高い収率で目的物を得ることができた。
（実施例３）
実施例１で製造した化合物１ａに対してハロゲン化剤を反応させて、下記式（１−２）で表される化合物３ａ〜３ｃを製造した。化合物３ａ〜３ｃは、上記一般式（１）のＲ^１およびＲ^２がそれぞれアリール基であり、Ｘがハロゲンである化合物である。

As shown in Table 2, the target product could be obtained in any of Reaction Examples 1-8. In particular, when dimethyl sulfoxide (DMSO) and potassium acetate (KOAc) in Reaction Example 8 were used, the target product could be obtained in a shorter time and with a higher yield than other reaction examples.
Example 3
The compound 1a produced in Example 1 was reacted with a halogenating agent to produce compounds 3a to 3c represented by the following formula (1-2). Compounds 3a to 3c are compounds in which R ¹ and R ^{2 in} the general formula (1) are each an aryl group and X is a halogen.

（式中のＹは、Ｆ、ＣｌまたはＢｒである。）
具体的には、（４Ｓ^＊，５Ｒ^＊）−３、５−ジフェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４、５−ジヒドロイソキサゾール（０．３０ｍｍｏｌ）、およびハロゲン化剤（０．３６ｍｍｏｌ）をアセトニトリル６．０ｍＬに溶かし、室温で１時間撹拌した。ハロゲン化剤として、Selectfluor（登録商標）、Ｎ−クロロスクシンイミド（ＮＣＳ）、Ｎ−ブロモスクシンイミド（ＮＢＳ）を用いた。その後、減圧下で溶媒を留去し、シリカゲルカラムクロマトグラフィーにて精製し、５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体である化合物３ａ〜３ｃを結晶状態で得た。

(Y in the formula is F, Cl or Br.)
Specifically, (4S ^* , 5R ^* )-3,5-diphenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole (0.30 mmol), And a halogenating agent (0.36 mmol) were dissolved in 6.0 mL of acetonitrile and stirred at room temperature for 1 hour. As the halogenating agent, Selectfluor (registered trademark), N-chlorosuccinimide (NCS), and N-bromosuccinimide (NBS) were used. Thereafter, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative compounds 3a to 3c in a crystalline state.

得られた化合物３ａ〜３ｃについて、Ｘ線結晶構造解析、ＮＭＲ、ＨＭＲＳ、ＩＲなどの各種分析を行った。その結果の詳細を以下に示す。 The obtained compounds 3a to 3c were subjected to various analyzes such as X-ray crystal structure analysis, NMR, HMRS, and IR. Details of the results are shown below.

化合物３ａ：（４Ｓ^＊，５Ｒ^＊）−４−フルオロ−３，５−ジフェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
(major isomer): white solid; ¹H NMR (CD₃CN, 300 MHz) δ 7.55-7.71 (m, 6H), 7.82-7.86 (m, 4H); ¹³C NMR (CD₃CN, 150.9 MHz) δ 91.5 (dq, J = 15.5, 28.7 Hz), 119.8 (q, J = 332.0 Hz), 123.4 (dq, J = 5.7 Hz, 291.7 Hz), 124.7, 125.3, 129.0 (d, J = 3.0 Hz), 129.5, 129.7, 130.3, 132.7, 133.7, 154.0 (d, J = 15.1 Hz); ¹⁹F NMR (CD₃CN, 282 MHz) δ -162.0 (qq, J = 8.2, 16.9 Hz, 1F), -71.6 (d, J = 16.6 Hz, 3F), -69.8 (d, J = 7.9 Hz, 3F); IR (KBr) 3068, 1601, 1496, 1450, 1393, 1332, 1215, 1113, 1028, 966, 899, 834, 759, 693, 618, 570, 528, 508 cm^-1; mp = 100.5-103.0 oC (CH₃CN); MS (ESI, m/z) 422 [M-F]⁺, HRMS calcd. for C₁₇H₁₀F₆NO₃S : 422.0286 [M-F]⁺: Found: 422.0286.
(minor isomer): white solid; ¹H NMR (CD₃CN, 300 MHz) δ 7.48-7.55 (m, 4H), 7.58-7.64 (m, 4H), 7.72 (d, J = 6.9 Hz, 2H); ¹³C NMR (CD₃CN, 150.9 MHz) δ 95.6 (m), 120.3 (q, J = 333.0 Hz), 122.8 (dq, J = 4.5, 285.2 Hz), 124.7, 126.2 (d, J = 6.0 Hz), 128.6, 129.8, 130.1, 130.3, 132.3, 133.3, 154.0 (d, J = 15.1 Hz); ¹⁹F NMR (CD₃CN, 282 MHz) δ -147.2 (q, J = 13.5 Hz, 1F), -69.0 (d, J = 13.0 Hz, 3F), -66.7 (s, 3F); IR (KBr) 3073, 2928, 1964, 1600, 1450, 1397, 1208, 1095, 1025, 925, 904, 864, 761, 743, 692, 635, 619, 563, 513, 489 cm^-1; mp = 63.0-65.0 oC (CH₃CN); MS (ESI, m/z) 422 [M-F]⁺, HRMS calcd. for C₁₇H₁₀F₆NO₃S : 422.0286 [M-F]⁺: Found: 422.0284. 89%収率, dr = 80:20

Compound 3a: (4S ^* , 5R ^* )-4-fluoro-3,5-diphenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
(major isomer): white solid; ¹ H NMR (CD ₃ CN, 300 MHz) δ 7.55-7.71 (m, 6H), 7.82-7.86 (m, 4H); ¹³ C NMR (CD ₃ CN, 150.9 MHz) δ 91.5 (dq, J = 15.5, 28.7 Hz), 119.8 (q, J = 332.0 Hz), 123.4 (dq, J = 5.7 Hz, 291.7 Hz), 124.7, 125.3, 129.0 (d, J = 3.0 Hz), 129.5 , 129.7, 130.3, 132.7, 133.7, 154.0 (d, J = 15.1 Hz); ¹⁹ F NMR (CD ₃ CN, 282 MHz) δ -162.0 (qq, J = 8.2, 16.9 Hz, 1F), -71.6 (d , J = 16.6 Hz, 3F), -69.8 (d, J = 7.9 Hz, 3F); IR (KBr) 3068, 1601, 1496, 1450, 1393, 1332, 1215, 1113, 1028, 966, 899, 834, 759, 693, 618, 570, 528, 508 cm ^-1 ; mp = 100.5-103.0 oC (CH ₃ CN); MS (ESI, m / z) 422 [MF] ⁺ , HRMS calcd. For C ₁₇ H ₁₀ F ₆ NO ₃ S: 422.0286 [MF] ⁺ : Found: 422.0286.
(minor isomer): white solid; ¹ H NMR (CD ₃ CN, 300 MHz) δ 7.48-7.55 (m, 4H), 7.58-7.64 (m, 4H), 7.72 (d, J = 6.9 Hz, 2H); ¹³ C NMR (CD ₃ CN, 150.9 MHz) δ 95.6 (m), 120.3 (q, J = 333.0 Hz), 122.8 (dq, J = 4.5, 285.2 Hz), 124.7, 126.2 (d, J = 6.0 Hz) , 128.6, 129.8, 130.1, 130.3, 132.3, 133.3, 154.0 (d, J = 15.1 Hz); ¹⁹ F NMR (CD ₃ CN, 282 MHz) δ -147.2 (q, J = 13.5 Hz, 1F), -69.0 (d, J = 13.0 Hz, 3F), -66.7 (s, 3F); IR (KBr) 3073, 2928, 1964, 1600, 1450, 1397, 1208, 1095, 1025, 925, 904, 864, 761, 743 , 692, 635, 619, 563, 513, 489 cm ^-1 ; mp = 63.0-65.0 oC (CH ₃ CN); MS (ESI, m / z) 422 [MF] ⁺ , HRMS calcd. For C ₁₇ H ₁₀ F ₆ NO ₃ S: 422.0286 [MF] ⁺ : Found: 422.0284. 89% yield, dr = 80:20

化合物３ｂ：（４Ｓ^＊，５Ｒ^＊）−４−クロロ−３，５−ジフェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CD₃CN, 300 MHz) δ 7.52-7.69 (m, 6H), 7.84-7.91 (m, 2H), 7.98 (d, J = 7.5 Hz); ¹⁹F NMR (CD₃CN, 282 MHz) δ -71.7 (s, 3F), -66.3 (s, 3F); ¹³C NMR (CD₃CN, 150.9 MHz) δ 93.2 (q, J = 27.7 Hz), 120.5 (q, J = 333.5 Hz), 123.7 (q, J = 292.7 Hz), 125.3, 126.0, 128.9, 129.80, 129.84, 129.89, 130.0, 132.5, 133.4, 156.2; ¹⁹F NMR (CD₃CN, 282 MHz) δ -71.7 (s, 3F), -66.3 (s, 3F); IR (KBr) 3070, 2925, 1964, 1898, 1763, 1600, 1497, 1450, 1388, 1309, 1204, 1105, 1011, 961, 756, 688, 616, 580, 516 cm^-1; mp = 67.0-69.0 oC (CH₃CN); MS (ESI, m/z) 422 [M-Cl]⁺, HRMS calcd. for C₁₇H₁₀F₆NO₃S : 422.0286 [M-Cl]⁺: Found: 422.0291. 94%収率, dr = 85:15

Compound 3b: (4S ^* , 5R ^* )-4-chloro-3,5-diphenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CD ₃ CN, 300 MHz) δ 7.52-7.69 (m, 6H), 7.84-7.91 (m, 2H), 7.98 (d, J = 7.5 Hz); ¹⁹ F NMR (CD ₃ CN, 282 MHz ) δ -71.7 (s, 3F), -66.3 (s, 3F); ¹³ C NMR (CD ₃ CN, 150.9 MHz) δ 93.2 (q, J = 27.7 Hz), 120.5 (q, J = 333.5 Hz), 123.7 (q, J = 292.7 Hz), 125.3, 126.0, 128.9, 129.80, 129.84, 129.89, 130.0, 132.5, 133.4, 156.2; ¹⁹ F NMR (CD ₃ CN, 282 MHz) δ -71.7 (s, 3F), -66.3 (s, 3F); IR (KBr) 3070, 2925, 1964, 1898, 1763, 1600, 1497, 1450, 1388, 1309, 1204, 1105, 1011, 961, 756, 688, 616, 580, 516 cm ^-1 ; mp = 67.0-69.0 oC (CH ₃ CN); MS (ESI, m / z) 422 [M-Cl] ⁺ , HRMS calcd. For C ₁₇ H ₁₀ F ₆ NO ₃ S: 422.0286 [M-Cl ] ⁺ : Found: 422.0291. 94% yield, dr = 85:15

化合物３ｃ：（４Ｓ^＊，５Ｒ^＊）−４−ブロモ−３，５−ジフェニル−５−（トリフルオロメチル）−４−（トリフルオロメチルスルホニル）−４，５−ジヒドロイソキサゾール
¹H NMR (CD₃CN, 300 MHz) δ 7.52-7.66 (m, 7H), 7.82 (d, J = 7.5 Hz, 1H), 7.97 (d, J = 7.5 Hz, 2H); ¹³C NMR (CD₃CN, 150.9 MHz) δ 92.9 (q, J = 27.2 Hz), 119.9 (q, J = 333.5 Hz), 123.7 (q, J = 292.7 Hz), 125.5, 126.2, 128.7, 128.9, 129.6, 129.9, 130.3, 132.3, 133.2, 157.2; ¹⁹F NMR (CD₃CN, 282 MHz) (dr = 95:5) δ -72.1 (s, 0.95 × 3F), -67.8 (s, 0.05 × 3F), -66.0 (s, 0.95 × 3F), -64.1 (s, 0.05 × 3F); IR (KBr) 3074, 2925, 1962, 1901, 1818, 1598, 1492, 1452, 1384, 1309, 1181, 1104, 1007, 932, 879, 757, 712, 616, 573, 508 cm^-1; mp = 110.0-111.5 oC (CH₃CN); MS (ESI, m/z) 422 [M-Br]⁺, HRMS calcd. for C₁₇H₁₀F₆NO₃S : 422.0286 [M-Br]⁺: Found: 422.0284.96%収率, dr = 95:5
（比較例１）
化合物１ａのトリフルオロメチルスルホニル基をニトロ基に変更した化合物である（４Ｓ^＊，５Ｒ^＊）−３、５−ジフェニル−５−（トリフルオロメチル）−４−（ニトロ）−４、５−ジヒドロイソキサゾールを用いて、実施例３と同じ反応条件で、ハロゲン化反応を試みた。その結果、ハロゲン化反応は起こらなかった。

Compound 3c: (4S ^* , 5R ^* )-4-bromo-3,5-diphenyl-5- (trifluoromethyl) -4- (trifluoromethylsulfonyl) -4,5-dihydroisoxazole
¹ H NMR (CD ₃ CN, 300 MHz) δ 7.52-7.66 (m, 7H), 7.82 (d, J = 7.5 Hz, 1H), 7.97 (d, J = 7.5 Hz, 2H); ¹³ C NMR (CD ₃ CN, 150.9 MHz) δ 92.9 (q, J = 27.2 Hz), 119.9 (q, J = 333.5 Hz), 123.7 (q, J = 292.7 Hz), 125.5, 126.2, 128.7, 128.9, 129.6, 129.9, 130.3 , 132.3, 133.2, 157.2; ¹⁹ F NMR (CD ₃ CN, 282 MHz) (dr = 95: 5) δ -72.1 (s, 0.95 × 3F), -67.8 (s, 0.05 × 3F), -66.0 (s , 0.95 × 3F), -64.1 (s, 0.05 × 3F); IR (KBr) 3074, 2925, 1962, 1901, 1818, 1598, 1492, 1452, 1384, 1309, 1181, 1104, 1007, 932, 879, 757, 712, 616, 573, 508 cm ^-1 ; mp = 110.0-111.5 oC (CH ₃ CN); MS (ESI, m / z) 422 [M-Br] ⁺ , HRMS calcd. For C ₁₇ H ₁₀ F ₆ NO ₃ S: 422.0286 [M-Br] ⁺ : Found: 422.0284.96% yield, dr = 95: 5
(Comparative Example 1)
(4S ^* , 5R ^* )-3,5-diphenyl-5- (trifluoromethyl) -4- (nitro) -4,5-dihydro is a compound obtained by changing the trifluoromethylsulfonyl group of compound 1a to a nitro group A halogenation reaction was attempted under the same reaction conditions as in Example 3 using isoxazole. As a result, no halogenation reaction occurred.

実施例３および比較例１からわかるように、特許文献７に記載の５−トリフルオロメチル−４−ニトロ−２−イソキサゾリン誘導体は、４位にハロゲンを導入できないが、本発明の５−トリフルオロメチル−４−トリフルオロメチルスルホニル−２−イソキサゾリン誘導体は、４位にハロゲンを導入することができる。 As can be seen from Example 3 and Comparative Example 1, the 5-trifluoromethyl-4-nitro-2-isoxazoline derivative described in Patent Document 7 cannot introduce a halogen at the 4-position. The methyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative can introduce a halogen at the 4-position.

Claims

5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative represented by the following general formula (1).

(In the formula, R ¹ and R ² each independently represent hydrogen, an alkyl group, an alkenyl group, an alkynyl group, or an aryl group, and X represents hydrogen or halogen.)

A method for producing the 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative according to claim 1, comprising:
Characterized in that 4-trifluoromethylsulfonylisoxazole represented by the following general formula (2) is reacted with (trifluoromethyl) trimethylsilane (CF ₃ SiMe ₃ ) in the presence of a base in a solvent. A method for producing a 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative.

(In the formula, R ¹ and R ² are the same as those in the general formula (1).)

The method for producing a 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative according to claim 2, wherein dimethyl sulfoxide is used as the solvent and potassium acetate is used as the base.

The method for producing a 5-trifluoromethyl-4-trifluoromethylsulfonyl-2-isoxazoline derivative according to claim 2 or 3, wherein a halogenating agent is reacted with the reactant after the reaction.