JP2006305558A - Catalyst composition and process for producing cross-coupled compound using same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a catalyst composition having very high activity for a cross-coupling reaction very important in organic syntheses. <P>SOLUTION: The catalyst composition for the cross-coupling reaction comprises a complex of the nickel salt represented by formula (1) (wherein R<SP>1</SP>through R<SP>4</SP>are each an alkyl group, an aryl group, a heteroaryl group or an alkenyl group; n is an integer of 1 to 6; Xs are each a halogen atom, a hydroxyl group, a nitrate group or an acetate group) with an amine compound and triphenylphosphine. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a catalyst composition that is extremely active for cross-coupling reaction in organic synthesis, and a method for producing a cross-coupling compound using the same. By using the method of the present invention, various functional compounds can be efficiently produced. For example, it is very useful as a method for efficiently synthesizing 4-hydroxy-4'-cyanobiphenyl, which is frequently used as a liquid crystal or pharmaceutical raw material.

  The coupling reaction technique is a very important technique as a technique for synthesizing electronic materials, intermediates for medical and agricultural chemicals, various functional compounds and the like. Among them, a technique for cross-coupling reaction between a boron compound and an organic halide compound in the presence of a base and a catalyst (hereinafter abbreviated as Suzuki coupling reaction technique) has attracted much attention as a useful and versatile technique. Various useful compounds can be synthesized using this technique. Particularly in recent years, it has become extremely important in the synthesis of biaryl compounds (medicine and agrochemical intermediates and liquid crystal materials) and substituted olefin compounds (raw materials for functional materials).

  Conventionally, a catalyst composed of a palladium salt and a phosphine compound (hereinafter abbreviated as a palladium-phosphine catalyst) has been frequently used as a catalyst for synthesizing a biaryl compound or a substituted olefin compound using the Suzuki coupling reaction technique. . However, palladium is very expensive, and it is difficult to use an inexpensive chloride as a coupling raw material.

  On the other hand, a catalyst (hereinafter abbreviated as a nickel-phosphine catalyst) composed of a nickel salt and a phosphine compound in which palladium is replaced with economically advantageous nickel that has been economically advantageous has been proposed (for example, Patent Documents 1 to 3). 4, see non-patent documents 1 to 3). In order to allow the reaction to proceed smoothly by these methods, a phosphine ligand that is expensive and difficult to handle such as 1,2-bis (diethylphosphino) ethane and is difficult to handle is essential. There is a problem that it is necessary to use a reducing agent such as BuLi which is expensive and difficult to handle.

  Recently, attention has been paid to a method using a catalyst composed of a nickel compound and an amine compound (hereinafter abbreviated as a nickel-amine catalyst) for these problems (for example, see Patent Document 5 and Non-Patent Document 4). In this method, in order to improve the yield, it is necessary to use an expensive amine compound such as 1,8-diazabicyclo [5.4.0] -7-undecene. Furthermore, as a nickel compound, This method is also problematic from the viewpoint of mass production because it uses bis (1,5-cyclooctadiene) nickel which is extremely sensitive and difficult to handle in the atmosphere.

  Furthermore, as a common problem in these methods using a nickel catalyst, there is a problem that an expensive strong base such as potassium phosphate is essential for the base. Since potassium phosphate has a strong basicity, it has a problem that the decomposition reaction of the boronic acid, which is a raw material, occurs at the time of the reaction, and there is a problem both economically and in process.

JP 2000-302697 A (Example) JP 2000-302720 A (Example) JP 2003-119175 A (Example) JP 2004-91467 A (Example) Japanese Patent Application Laid-Open No. 2004-91465 (Example) "Tetrahedron Letters" (UK), 1996, 37, p2993-996 (Scheme 1, Tables 1-2) “Journal of Organic Chemistry”, (USA), 1997, Vol. 62, p8024-3030 (Scheme 1, Tables 1-6) “Tetrahedron Letters” (UK), 1997, Vol. 38, p3513-3516 (Scheme 1, Tables 1-2) Tetrahedron ", (UK), 1999, Vol. 55, p11889-11894 (Figs. 1-3, Tables 1-3)

  The present invention is a catalyst composition extremely active for a cross-coupling reaction, which is a very important reaction technique for organic synthesis, which cannot be solved by conventional methods, and a method for producing a cross-coupling compound using the same. Is to provide.

  As a result of intensive studies to solve the conventional problems, the present inventors have found that a novel catalyst composition comprising a complex of a nickel salt and an amine compound and three components of triphenylphosphine is a catalyst for cross-coupling reaction. As a result, the present inventors have found that a very high activity is expressed in the Suzuki coupling reaction.

  That is, the present invention relates to a) a catalyst composition comprising a complex of a nickel salt represented by the following formula (1) and an amine compound and triphenylphosphine, and b) a boron compound represented by the following formula (2) and the following formula ( The present invention relates to a method for producing a cross-coupling compound represented by the following formula (4), wherein the compound represented by 3) is subjected to a cross-coupling reaction in the presence of a base and the catalyst composition.

（式中、Ｒ^１〜Ｒ^４は同一または異なっていてもよく、置換もしくは無置換の直線状、分岐状または環状のアルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、または置換もしくは無置換の直線状、分岐状または環状のアルケニル基を表す。ｎは１〜６の整数を表す。Ｘは各々同一または異なっていてもよく、ハロゲン原子、水酸基、硝酸基または酢酸基を表す。Ｒ^５，Ｒ^６は同一または異なっていてもよく、置換もしくは無置換の直線状、分岐状または環状のアルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、または置換もしくは無置換の直線状、分岐状または環状のアルケニル基を表す。Ｙは各々同一または異なっていてもよく、水酸基またはアルコキシ基を表す。Ｚはハロゲン原子、メタンスルホナート基またはトリフルオロメタンスルホナート基を表す。）
以下、本発明について詳細に説明する。

Wherein R ^{1 to} R ⁴ may be the same or different and are a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group Or a substituted or unsubstituted linear, branched or cyclic alkenyl group, n represents an integer of 1 to 6. X may be the same or different and each may be a halogen atom, a hydroxyl group, a nitrate group or acetic acid. R ⁵ and R ⁶ may be the same or different and are a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group. Or a substituted or unsubstituted linear, branched or cyclic alkenyl group, each Y may be the same or different, and may be a hydroxyl group or an alkoxy group. The representative .Z represents a halogen atom, methanesulfonate group or a trifluoromethanesulfonate group.)
Hereinafter, the present invention will be described in detail.

  The catalyst composition of the present invention is composed of a complex of a nickel salt and an amine compound and three components of triphenylphosphine.

  The nickel salt in the catalyst composition of the present invention refers to a compound containing nickel element as an active ingredient, for example, a 0 to divalent nickel salt. Specific examples of the nickel salt are not particularly limited. For example, nickel halides such as nickel fluoride (II), nickel chloride (II), nickel bromide (II), nickel iodide (II), etc. , Nickel (0) powder, nickel sulfate (II), nickel nitrate (II), nickel perchlorate (II), nickel sulfide (II) and other inorganic salts, nickel formate (II), nickel oxalate (II), Nickel (II) acetate, nickel (II) fumarate, nickel (II) lactate, nickel (II) gluconate, nickel (II) benzoate, nickel (II) stearate, nickel (II) sulfamate, nickel amidosulfate Examples of the organic acid nickel salt include (II), nickel carbonate (II), and nickel acetylacetonate (II).

  The above nickel salts may be used alone or as a mixture. In addition, it is preferable to use nickel halide from a viewpoint of economical efficiency, compound availability, reactivity, and stability.

  The amine compound in the catalyst composition of the present invention is a tertiary bidentate amine compound represented by the following formula (9).

（式中、Ｒ^１〜Ｒ^４は同一または異なっていてもよく、置換もしくは無置換の直線状、分岐状または環状のアルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、または置換もしくは無置換の直線状、分岐状または環状のアルケニル基を表す。ｎは１〜６の整数を表す。）
式（９）で示される第三級の二座アミン化合物の具体例としては、例えば、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルメタンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラエチルメタンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルプロピレンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルヘキサンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラエチルエチレンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラエチルプロピレンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラエチルヘキサンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラフェニルエチレンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラフェニルプロピレンジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラフェニルヘキサンジアミン、Ｎ，Ｎ−ジメチル−Ｎ’，Ｎ’−ジエチルエチレンジアミン、Ｎ，Ｎ−ジメチル−Ｎ’，Ｎ’−ジエチルプロパンジアミン、Ｎ，Ｎ−ジメチル−Ｎ’，Ｎ’−ジエチルヘキサンジアミンが挙げられる。収率及び経済性や化合物入手の観点から、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミンを用いることが好ましい。

Wherein R ^{1 to} R ⁴ may be the same or different and are a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group Or a substituted or unsubstituted linear, branched or cyclic alkenyl group, n represents an integer of 1 to 6.)
Specific examples of the tertiary bidentate amine compound represented by the formula (9) include, for example, N, N, N ′, N′-tetramethylmethanediamine, N, N, N ′, N′-tetraethylmethane. Diamine, N, N, N ′, N′-tetramethylethylenediamine, N, N, N ′, N′-tetramethylpropylenediamine, N, N, N ′, N′-tetramethylhexanediamine, N, N, N ′, N′-tetraethylethylenediamine, N, N, N ′, N′-tetraethylpropylenediamine, N, N, N ′, N′-tetraethylhexanediamine, N, N, N ′, N′-tetraphenylethylenediamine N, N, N ′, N′-tetraphenylpropylenediamine, N, N, N ′, N′-tetraphenylhexanediamine, N, N-dimethyl-N ′, N′-diethylethylenediamine, N, N— Dimethyl N ', N'-diethyl-propane diamine, N, N-dimethyl -N', N'-diethyl-hexane diamine. N, N, N ′, N′-tetramethylethylenediamine is preferably used from the viewpoints of yield, economy, and compound availability.

  The catalyst composition of the present invention is composed of a complex of a nickel salt represented by the general formula (1) and an amine compound and triphenylphosphine. Among various phosphine compounds, the catalyst composition is unique only when triphenylphosphine is used. It was found that a highly active catalyst composition was obtained. Thus, it was surprising that a highly active catalyst composition was obtained only in the case of a special combination such as general formula (1) and triphenylphosphine. The catalyst composition of the present invention is also excellent from the viewpoints of economy, availability of compounds, stability and handling.

  The catalyst composition of the present invention can be obtained by adding triphenylphosphine to the above nickel-amine complex. Moreover, even if nickel salt, an amine compound, and triphenylphosphine are added separately, a nickel-amine complex is formed in the system, and the catalyst composition of the present invention is obtained. The composition ratio of each compound can be appropriately selected from the range of 1.0 to 10.0 mol of the amine compound and 1.0 to 10.0 mol of triphenylphosphine with respect to 1.0 mol of the nickel salt. More preferably, they are 1.0-5.0 mol of amine compounds and 2.0-5.0 mol of triphenylphosphine with respect to 1.0 mol of nickel salt.

  The catalyst composition can be prepared in the presence of a solvent. The solvent used is not particularly limited as long as it is inert to nickel salts, amine compounds and triphenylphosphine. For example, ether solvents, oxygen-containing solvents, nitrogen-containing solvents, aromatic hydrocarbon solvents And aliphatic hydrocarbon solvents. Usually, these solvents can be used alone or in combination.

  The present inventors have found that the above catalyst composition has very high activity in organic synthesis reactions. In particular, it has been found that the method (Suzuki coupling reaction) in which a boron compound and a halide compound are cross-coupled in the presence of a base has extremely high activity.

  Hereinafter, the cross-coupling reaction in the method of the present invention will be described in detail.

  The Suzuki coupling reaction carried out in the method of the present invention involves cross-coupling a boron compound represented by the following formula (2) and a compound represented by the following formula (3) in the presence of a base and the catalyst composition. In this method, a ring reaction is performed to obtain a cross-coupling compound represented by the following formula (4).

（式中、Ｒ^５，Ｒ^６は同一または異なっていてもよく、置換もしくは無置換の直線状、分岐状または環状のアルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、または置換もしくは無置換の直線状、分岐状または環状のアルケニル基を表す。Ｙは各々同一または異なっていてもよく、水酸基またはアルコキシ基を表す。Ｚはハロゲン原子、メタンスルホナート基またはトリフルオロメタンスルホナート基を表す。）
本発明の方法において使用されるホウ素化合物は、上記式（２）で示される化合物である。式中、Ｒ^５は置換もしくは無置換の直線状、分岐状または環状のアルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換の直線状、分岐状または環状のアルケニル基を表す。

(In the formula, R ⁵ and R ⁶ may be the same or different, and are substituted or unsubstituted linear, branched or cyclic alkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted heteroaryl groups. Or a substituted or unsubstituted linear, branched or cyclic alkenyl group, each Y may be the same or different, and represents a hydroxyl group or an alkoxy group, and Z represents a halogen atom, a methanesulfonate group or trifluoromethane. Represents a sulfonate group.)
The boron compound used in the method of the present invention is a compound represented by the above formula (2). In the formula, R ⁵ represents a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted linear, branched or Represents a cyclic alkenyl group.

Substituted or unsubstituted linear in R ^5, it is not particularly restricted but includes branched or cyclic alkyl group, for example, linear, include branched or cyclic alkyl group of C ₁ -C _20, specifically Is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl Group, octadecyl group, nonadecyl group, eicosyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl group, cyclodecyl group, cycloundecyl group, cyclododecyl group, cyclotridecyl group Group, cyclotetradecyl group, cyclopenta Examples include a decyl group, a cyclohexadecyl group, a cycloptadecyl group, a cyclooctadecyl group, a cyclononadecyl group, a cycloeicosyl group, and the like, and polycyclic compounds such as a norbornal group and an adamantyl group are included in this category. In addition, each of any number of hydrogen atoms is a halogen atom, a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, substituted or It may be substituted with an unsubstituted linear, branched or cyclic alkenyl group, hydroxyl group, alkoxy group, amino group, cyano group, carbonyl group, carboxyl group or ester group.

Is not particularly restricted but includes substituted or unsubstituted aryl group for R ^5, for example, it includes 1-4 substituted or unsubstituted aryl group ring of C ₆ -C _18, specifically a phenyl group, a naphthyl group , Anthracenyl group, azulene group, pyrene group, phenanthrenyl group, fluorenyl group and the like. In addition, each of any number of hydrogen atoms is a halogen atom, a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, substituted or It may be substituted with an unsubstituted linear, branched or cyclic alkenyl group, hydroxyl group, alkoxy group, amino group, cyano group, carbonyl group, carboxyl group or ester group.

Is not particularly restricted but includes substituted or unsubstituted heteroaryl groups in R ^5, for example, C ₃ -C ₁₈ include 1-4 substituted or unsubstituted heteroaryl group rings, specifically a pyridyl group, Examples include pyrimidyl group, pyridazyl group, pyrazyl group, triazyl group, benzofuranyl group, indole group, benzothiophene group, quinoline group, isoquinoline group, carbazole group, acridine group, phenanthroline group, phenothiazine group and the like. In addition, each of any number of hydrogen atoms is a halogen atom, a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, substituted or It may be substituted with an unsubstituted linear, branched or cyclic alkenyl group, hydroxyl group, alkoxy group, amino group, cyano group, carbonyl group, carboxyl group or ester group.

R ⁵ substituted or unsubstituted linear in is not particularly restricted but includes branched or cyclic alkenyl group, for example, include alkenyl groups of C ₂ -C _20, specifically vinyl, propenyl, butenyl Group, pentenyl group, hexenyl group, heptenyl group, octenyl group, nonenyl group, decenyl group, undecenyl group, dodecenyl group, tridecenyl group, tetradecenyl group, pentadecenyl group, hexadecenyl group, heptadecenyl group, octadecenyl group, nonadecenyl group, eicosenyl group Cyclopropenyl group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group, cyclooctenyl group, cyclononenyl group, cyclodecenyl group, cycloundecenyl group, cyclododecenyl group, cyclotridecenyl group, Tradecenyl group, cyclopentadecenyl group, cyclohexadecenyl group, hecycloptadecenyl group, cyclooctadecenyl group, cyclononadecenyl group, cycloeicocenyl group, etc., and norbornyl Polycyclic compounds such as groups are also included in this category. In addition, each of any number of hydrogen atoms is a halogen atom, a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, substituted or It may be substituted with an unsubstituted linear, branched or cyclic alkenyl group, hydroxyl group, alkoxy group, amino group, cyano group, carbonyl group, carboxyl group or ester group.

  Y may be the same or different and each represents a hydroxyl group or an alkoxy group. When both Y are hydroxyl groups, a trimer anhydride may be formed by dehydration condensation as shown by the following formula (10). When both Y are alkoxy groups, the two alkoxy groups may form a ring.

ホウ素化合物のより好ましい例は、下記式（５）で示される芳香族ホウ素化合物または下記式（６）で示されるアルケニルホウ素化合物である。

A more preferable example of the boron compound is an aromatic boron compound represented by the following formula (5) or an alkenyl boron compound represented by the following formula (6).

（式中、Ｒ^７〜Ｒ^１０は同一または異なっていてもよく、水素原子、ハロゲン原子、置換もしくは無置換の直線状、分岐状または環状のアルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換の直線状、分岐状または環状のアルケニル基、水酸基、アルコキシ基、アミノ基、シアノ基、カルボニル基、カルボキシル基またはエステル基を表す。ａは１〜５の整数を表す。ベンゼン環の隣り合う炭素原子に結合しているＲ^７同士が、任意に結合してベンゼン環と縮合環を形成してもよい。アルケニル基上の隣接するＲ^８とＲ^１０、同一炭素上にあるＲ^９とＲ^１０はそれぞれ互いに結合して環を形成してもよい。Ｙは各々同一または異なっていてもよく、水酸基またはアルコキシ基を表す。）
特に限定されないが、上記式（５）で示される芳香族ホウ素化合物の具体例としては、例えば、フェニルボロン酸、２−メチルフェニルボロン酸、３−メチルフェニルボロン酸、４−メチルフェニルボロン酸、２，３−ジメチルフェニルボロン酸、２，４−ジメチルフェニルボロン酸、２，５−ジメチルフェニルボロン酸、２−エチルフェニルボロン酸、４−エチルフェニルボロン酸、４−ｎ−プロピルフェニルボロン酸、４−イソプロピルフェニルボロン酸、４−ｎ−ブチルフェニルボロン酸、４−ｔ−ブチルフェニルボロン酸、１−ナフチルボロン酸、２−ナフチルボロン酸、２−ビフェニルボロン酸、３−ビフェニルボロン酸、４−ビフェニルボロン酸、２−フルオロ−４−ビフェニルボロン酸、２−フルオレニルボロン酸、９−フルオレニルボロン酸、９−フェナンスレニルボロン酸、９−アントラセニルボロン酸、１−ピレニルボロン酸、２−トリフルオロメチルフェニルボロン酸、３−トリフルオロメチルフェニルボロン酸、４−トリフルオロメチルフェニルボロン酸、３，５−ビス（トリフルオロメチル）フェニルボロン酸、２−メトキシフェニルボロン酸、３−メトキシフェニルボロン酸、４−メトキシフェニルボロン酸、２，５−ジメトキシフェニルボロン酸、４，５−ジメトキシフェニルボロン酸、２，４−ジメトキシフェニルボロン酸、２−エトキシフェニルボロン酸、３−エトキシフェニルボロン酸、４−エトキシフェニルボロン酸、２−ｎ−ブトキシフェニルボロン酸、３−ｎ−ブトキシフェニルボロン酸、４−ｎ−ブトキシフェニルボロン酸、２−ｔ−ブトキシフェニルボロン酸、３−ｔ−ブトキシフェニルボロン酸、４−ｔ−ブトキシフェニルボロン酸、４−フェノキシフェニルボロン酸、３，４−メチレンジオキシフェニルボロン酸、２−フルオロフェニルボロン酸、３−フルオロフェニルボロン酸、４−フルオロフェニルボロン酸、２，４−ジフルオロフェニルボロン酸、２，５−ジフルオロフェニルボロン酸、４，５−ジフルオロフェニルボロン酸、３，５−ジフルオロフェニルボロン酸、２−クロロフェニルボロン酸、３−クロロフェニルボロン酸、４−クロロフェニルボロン酸、２−ブロモフェニルボロン酸、３−ブロモフェニルボロン酸、４−ブロモフェニルボロン酸、２−ホルミルフェニルボロン酸、３−ホルミルフェニルボロン酸、４−ホルミルフェニルボロン酸、３−ホルミル−４−メトキシフェニルボロン酸、２−（１−エトキシエトキシ）フェニルボロン酸、３−（１−エトキシエトキシ）フェニルボロン酸、４−（１−エトキシエトキシ）フェニルボロン酸、２−アセトキシフェニルボロン酸、２−アセトキシフェニルボロン酸、３−アセトキシフェニルボロン酸、４−シアノフェニルボロン酸、３−シアノフェニルボロン酸、４−シアノフェニルボロン酸、３−ニトロフェニルボロン酸、３−アセチルフェニルボロン酸、４−アセチルフェニルボロン酸、３−トリフルオロアセチルフェニルボロン酸、４−トリフルオロアセチルフェニルボロン酸、４−メチルチオフェニルボロン酸、４−ビニルフェニルボロン酸、３−カルボキシフェニルボロン酸、４−カルボキシフェニルボロン酸、３−アミノフェニルボロン酸、２−（Ｎ，Ｎ−ジメチルアミノ）フェニルボロン酸、３−（Ｎ，Ｎ−ジメチルアミノ）フェニルボロン酸、４−（Ｎ，Ｎ−ジメチルアミノ）フェニルボロン酸、２−（Ｎ，Ｎ−ジエチルアミノ）フェニルボロン酸、３−（Ｎ，Ｎ−ジエチルアミノ）フェニルボロン酸、４−（Ｎ，Ｎ−ジエチルアミノ）フェニルボロン酸、２−（Ｎ，Ｎ−ジメチルアミノメチル）フェニルボロン酸、４−ベンゼンビス（ボロン酸）、フェニルボロン酸ピナコールエステル、４−シアノフェニルボロン酸ピナコールエステルなどが挙げられる。

(Wherein R ^{7 to} R ¹⁰ may be the same or different and each represents a hydrogen atom, a halogen atom, a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or An unsubstituted heteroaryl group, a substituted or unsubstituted linear, branched or cyclic alkenyl group, a hydroxyl group, an alkoxy group, an amino group, a cyano group, a carbonyl group, a carboxyl group or an ester group, where a is 1 to 5. R ⁷ bonded to adjacent carbon atoms of the benzene ring may be arbitrarily bonded to form a condensed ring with the benzene ring, and adjacent R ⁸ and R ¹⁰ on the alkenyl group. , the R ⁹ and R ¹⁰ on the same carbon may be respectively bonded to each other to form a ring .Y may each be identical or different, a hydroxyl group or an alkoxy group It is.)
Although not particularly limited, specific examples of the aromatic boron compound represented by the above formula (5) include, for example, phenylboronic acid, 2-methylphenylboronic acid, 3-methylphenylboronic acid, 4-methylphenylboronic acid, 2,3-dimethylphenylboronic acid, 2,4-dimethylphenylboronic acid, 2,5-dimethylphenylboronic acid, 2-ethylphenylboronic acid, 4-ethylphenylboronic acid, 4-n-propylphenylboronic acid, 4-isopropylphenylboronic acid, 4-n-butylphenylboronic acid, 4-t-butylphenylboronic acid, 1-naphthylboronic acid, 2-naphthylboronic acid, 2-biphenylboronic acid, 3-biphenylboronic acid, 4 -Biphenylboronic acid, 2-fluoro-4-biphenylboronic acid, 2-fluorenylboronic acid, 9-fluro Renylboronic acid, 9-phenanthrenylboronic acid, 9-anthracenylboronic acid, 1-pyrenylboronic acid, 2-trifluoromethylphenylboronic acid, 3-trifluoromethylphenylboronic acid, 4-trifluoromethylphenylboron Acid, 3,5-bis (trifluoromethyl) phenylboronic acid, 2-methoxyphenylboronic acid, 3-methoxyphenylboronic acid, 4-methoxyphenylboronic acid, 2,5-dimethoxyphenylboronic acid, 4,5- Dimethoxyphenylboronic acid, 2,4-dimethoxyphenylboronic acid, 2-ethoxyphenylboronic acid, 3-ethoxyphenylboronic acid, 4-ethoxyphenylboronic acid, 2-n-butoxyphenylboronic acid, 3-n-butoxyphenyl Boronic acid, 4-n-butoxyphenylboronic acid, 2-t Butoxyphenylboronic acid, 3-t-butoxyphenylboronic acid, 4-t-butoxyphenylboronic acid, 4-phenoxyphenylboronic acid, 3,4-methylenedioxyphenylboronic acid, 2-fluorophenylboronic acid, 3- Fluorophenylboronic acid, 4-fluorophenylboronic acid, 2,4-difluorophenylboronic acid, 2,5-difluorophenylboronic acid, 4,5-difluorophenylboronic acid, 3,5-difluorophenylboronic acid, 2- Chlorophenylboronic acid, 3-chlorophenylboronic acid, 4-chlorophenylboronic acid, 2-bromophenylboronic acid, 3-bromophenylboronic acid, 4-bromophenylboronic acid, 2-formylphenylboronic acid, 3-formylphenylboronic acid 4-formylphenylboronic acid, 3-phospho Rumyl-4-methoxyphenylboronic acid, 2- (1-ethoxyethoxy) phenylboronic acid, 3- (1-ethoxyethoxy) phenylboronic acid, 4- (1-ethoxyethoxy) phenylboronic acid, 2-acetoxyphenylboron Acid, 2-acetoxyphenylboronic acid, 3-acetoxyphenylboronic acid, 4-cyanophenylboronic acid, 3-cyanophenylboronic acid, 4-cyanophenylboronic acid, 3-nitrophenylboronic acid, 3-acetylphenylboronic acid 4-acetylphenylboronic acid, 3-trifluoroacetylphenylboronic acid, 4-trifluoroacetylphenylboronic acid, 4-methylthiophenylboronic acid, 4-vinylphenylboronic acid, 3-carboxyphenylboronic acid, 4-carboxy Phenylboronic acid, 3-aminophen Ruboronic acid, 2- (N, N-dimethylamino) phenylboronic acid, 3- (N, N-dimethylamino) phenylboronic acid, 4- (N, N-dimethylamino) phenylboronic acid, 2- (N, N-diethylamino) phenylboronic acid, 3- (N, N-diethylamino) phenylboronic acid, 4- (N, N-diethylamino) phenylboronic acid, 2- (N, N-dimethylaminomethyl) phenylboronic acid, 4 -Benzenebis (boronic acid), phenylboronic acid pinacol ester, 4-cyanophenylboronic acid pinacol ester, and the like.

  Although not particularly limited, specific examples of the alkenyl boron compound represented by the above formula (6) include vinyl boronic acid, vinyl boronic acid / triethylamine adduct, trans-2-bromomethylvinyl boronic acid, trans-2-chloromethyl. Vinylboronic acid, cis-propenylboronic acid, trans-propenylboronic acid, 1-pentenylboronic acid, (E) -5-chloro-1-penteneboronic acid, trans-1-hexen-1-ylboronic acid, trans-2 -T-butylvinylboronic acid, trans-2-phenylvinylboronic acid, α-phenylvinylboronic acid, trans-2- (4-chlorophenyl) vinylboronic acid, trans-2- (4-fluorophenyl) vinylboronic acid, trans -1-octen-1-ylboronic acid, trans-2- [4- Trifluoromethyl) phenyl] vinylboronic acid, trans-2- (4-methylphenyl) vinylboronic acid, trans-1-nonenylboronic acid, 2-allyl-4,4,5,5-tetramethyl-1,3,2- Dioxaborene, vinylboronic acid dibutyl ester, 2- (cis-1-ethyl-1-butenyl) benzo (1,3,2) dioxaborol, trans-2- (4,4,5,5-tetramethyl-1,3 2-dioxaborolane-2-yl) styrene, methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl) -2-octenoate and the like Can be mentioned.

R ⁶ of the compound represented by the above formula (3) used in the method of the present invention can be exemplified by the same structure as R ^{5 of the} boron compound described above.

  Z represents a halogen atom, a methanesulfonate group or a trifluoromethanesulfonate group. Specific examples of the halogen atom are a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

  Further preferred examples of the compound represented by the general formula (3) are an aromatic compound represented by the following formula (7) or an alkenyl compound represented by the following formula (8).

（式中、Ｒ^１１〜Ｒ^１４は同一または異なっていてもよく、水素原子、ハロゲン原子、置換もしくは無置換の直線状、分岐状または環状のアルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換の直線状、分岐状または環状のアルケニル基、水酸基、アルコキシ基、アミノ基、シアノ基、カルボニル基、カルボキシル基またはエステル基を表す。ｂは１〜５の整数を表す。ベンゼン環の隣り合う炭素原子に結合しているＲ^１１同士が、任意に結合してベンゼン環と縮合環を形成してもよい。アルケニル基上の隣接するＲ^１２とＲ^１４、同一炭素上にあるＲ^１３とＲ^１４はそれぞれ互いに結合して環を形成してもよい。Ｚはハロゲン原子、メタンスルホナート基またはトリフルオロメタンスルホナート基を表す。）
特に限定されないが、上記式（７）で示される芳香族化合物の具体例としては、例えば、フッ化ベンゼン、塩化ベンゼン、臭化ベンゼン、ヨウ化ベンゼン、フェニルメタンスルホナート、フェニルトリフルオロメタンスルホナート、ｏ−クロロトルエン、ｍ−クロロトルエン、ｐ−クロロトルエン、ｏ−ブロモトルエン、ｍ−ブロモトルエン、ｐ−ブロモトルエン、ｏ−ヨードトルエン、ｍ−ヨードトルエン、ｐ−ヨードトルエン、２−エチルクロロベンゼン、３−エチルクロロベンゼン、４−エチルクロロベンゼン、２−エチルブロモベンゼン、３−エチルブロモベンゼン、４−エチルブロモベンゼン、２−エチルヨードベンゼン、３−エチルヨードベンゼン、４−エチルヨードベンゼン、２−プロピルクロロベンゼン、３−プロピルクロロベンゼン、４−プロピルクロロベンゼン、２−プロピルブロモベンゼン、３−プロピルブロモベンゼン、４−プロピルブロモベンゼン、２−プロピルヨードベンゼン、３−プロピルヨードベンゼン、４−プロピルヨードベンゼン、２−ブチルクロロベンゼン、３−ブチルクロロベンゼン、４−ブチルクロロベンゼン、２−ブチルブロモベンゼン、３−ブチルブロモベンゼン、４−ブチルブロモベンゼン、２−ブチルヨードベンゼン、３−ブチルヨードベンゼン、４−ブチルヨードベンゼン、１−クロロナフタレン、２−クロロナフタレン、１−ブロモナフタレン、２−ブロモナフタレン、１−ヨードナフタレン、２−ヨードナフタレン、ｏ−ジクロロベンゼン、ｍ−ジクロロベンゼン、ｐ−ジクロロベンゼン、ｏ−ジブロモベンゼン、ｍ−ジブロモベンゼン、ｐ−ジブロモベンゼン、ｏ−ブロモクロロベンゼン、ｍ−ブロモクロロベンゼン、ｐ−ブロモクロロベンゼン、ｏ−クロロフルオロベンゼン、ｍ−クロロフルオロベンゼン、ｐ−クロロフルオロベンゼン、ｏ−ブロモフルオロベンゼン、ｍ−ブロモフルオロベンゼン、ｐ−ブロモフルオロベンゼン、ｏ−クロロアニゾール、ｍ−クロロアニソール、ｐ−クロロアニソール、ｏ−ブロモアニゾール、ｍ−ブロモアニソール、ｐ−ブロモアニソール、ｏ−ヨードアニゾール、ｍ−ヨードアニソール、ｐ−ヨードアニソール、ｏ−クロロフェネトール、ｍ−クロロフェネトール、ｐ−クロロフェネトール、ｏ−ブロモフェネトール、ｍ−ブロモフェネトール、ｐ−ブロモフェネトール、ｏ−ヨードフェネトール、ｍ−ヨードフェネトール、ｐ−ヨードフェネトール、ｏ−ｎ−ブトキシクロロベンゼン、ｍ−ｎ−ブトキシクロロベンゼン、ｐ−ｎ−ブトキシクロロベンゼン、ｏ−ｎ−ブトキシブロモベンゼン、ｍ−ｎ−ブトキシブロモベンゼン、ｐ−ｎ−ブトキシブロモベンゼン、ｏ−ｎ−ブトキシヨードベンゼン、ｍ−ｎ−ブトキシヨードベンゼン、ｐ−ｎ−ブトキシヨードベンゼン、ｏ−ｔ−ブトキシクロロベンゼン、ｍ−ｔ−ブトキシクロロベンゼン、ｐ−ｔ−ブトキシクロロベンゼン、ｏ−ｔ−ブトキシフェニルブロマイド、ｍ−ｔ−ブトキシフェニルブロマイド、ｐ−ｔ−ブトキシフェニルブロマイド、ｏ−ｔ−ブトキシヨードベンゼン、ｍ−ｔ−ブトキシヨードベンゼン、ｐ−ｔ−ブトキシヨードベンゼン、２−クロロベンゾニトリル、３−クロロベンゾニトリル、４−クロロベンゾニトリル、２−ブロモベンゾニトリル、３−ブロモベンゾニトリル、４−ブロモベンゾニトリル、２−ヨードベンゾニトリル、３−ヨードベンゾニトリル、４−ヨードベンゾニトリル、ｏ−（１−エトキシエトキシ）クロロベンゼン、ｍ−（１−エトキシエトキシ）クロロベンゼン、ｐ−（１−エトキシエトキシ）クロロベンゼン、ｏ−（１−エトキシエトキシ）ブロモベンゼン、ｍ−（１−エトキシエトキシ）ブロモベンゼン、ｐ−（１−エトキシエトキシ）ブロモベンゼン、ｏ−（１−エトキシエトキシ）ヨードベンゼン、ｍ−（１−エトキシエトキシ）ヨードベンゼン、ｐ−（１−エトキシエトキシ）ヨードベンゼン、ｏ−アセチルクロロベンゼン、ｍ−アセチルクロロベンゼン、ｐ−アセチルクロロベンゼン、ｏ−アセチルブロモベンゼン、ｍ−アセチルブロモベンゼン、ｐ−アセチルブロモベンゼン、ｏ−アセチルヨードベンゼン、ｍ−アセチルヨードベンゼン、ｐ−アセチルヨードベンゼン、ｏ−アセトキシクロロベンゼン、ｍ−アセトキシクロロベンゼン、ｐ−アセトキシクロロベンゼン、ｏ−アセトキシブロモベンゼン、ｍ−アセトキシブロモベンゼン、ｐ−アセトキシブロモベンゼン、ｏ−アセトキシヨードベンゼン、ｍ−アセトキシヨードベンゼン、ｐ−アセトキシヨードベンゼン、２−トリフルオロメチルクロロベンゼン、３−トリフルオロメチルクロロベンゼン、４−トリフルオロメチルクロロベンゼン、２−トリフルオロメチルブロモベンゼン、３−トリフルオロメチルブロモベンゼン、４−トリフルオロメチルブロモベンゼン、２−トリフルオロメチルヨードベンゼン、３−トリフルオロメチルヨードベンゼン、４−トリフルオロメチルヨードベンゼン、２−クロロ安息香酸、３−クロロ安息香酸、４−クロロ安息香酸、２−ブロモ安息香酸、３−ブロモ安息香酸、４−ブロモ安息香酸、２−ヨード安息香酸、３−ヨード安息香酸、４−ヨード安息香酸、２−クロロ安息香酸メチル、３−クロロ安息香酸メチル、４−クロロ安息香酸メチル、２−ブロモ安息香酸メチル、３−ブロモ安息香酸メチル、４−ブロモ安息香酸メチル、２−ヨード安息香酸メチル、３−ヨード安息香酸メチル、４−ヨード安息香酸メチル、２−クロロアニリン、３−クロロアニリン、４−クロロアニリン、２−ブロモアニリン、３−ブロモアニリン、４−ブロモアニリン、２−ヨードアニリン、３−ヨードアニリン、４−ヨードアニリン、２−クロロホルミルベンゼン、３−クロロホルミルベンゼン、４−クロロホルミルベンゼン、２−ブロモホルミルベンゼン、３−ブロモホルミルベンゼン、４−ブロモホルミルベンゼンなどが挙げられる。

(Wherein R ^{11 to} R ¹⁴ may be the same or different and each represents a hydrogen atom, a halogen atom, a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, substituted or An unsubstituted heteroaryl group, a substituted or unsubstituted linear, branched or cyclic alkenyl group, a hydroxyl group, an alkoxy group, an amino group, a cyano group, a carbonyl group, a carboxyl group, or an ester group, and b is 1 to 5. R ¹¹ bonded to adjacent carbon atoms of the benzene ring may be arbitrarily bonded to form a condensed ring with the benzene ring, and adjacent R ¹² and R ¹⁴ on the alkenyl group. , R ¹³ and R ¹⁴ on the same carbon combined with each other may be to form a ring .Z halogen atom, methanesulfonate group or a trifluoromethyl It represents a single sulfonate group.)
Although not particularly limited, specific examples of the aromatic compound represented by the formula (7) include, for example, fluorinated benzene, chlorobenzene, bromobromide, benzene iodide, phenylmethanesulfonate, phenyltrifluoromethanesulfonate, o-chlorotoluene, m-chlorotoluene, p-chlorotoluene, o-bromotoluene, m-bromotoluene, p-bromotoluene, o-iodotoluene, m-iodotoluene, p-iodotoluene, 2-ethylchlorobenzene, 3-ethylchlorobenzene, 4-ethylchlorobenzene, 2-ethylbromobenzene, 3-ethylbromobenzene, 4-ethylbromobenzene, 2-ethyliodobenzene, 3-ethyliodobenzene, 4-ethyliodobenzene, 2-propylchlorobenzene , 3-propyl black Benzene, 4-propylchlorobenzene, 2-propylbromobenzene, 3-propylbromobenzene, 4-propylbromobenzene, 2-propyliodobenzene, 3-propyliodobenzene, 4-propyliodobenzene, 2-butylchlorobenzene, 3- Butylchlorobenzene, 4-butylchlorobenzene, 2-butylbromobenzene, 3-butylbromobenzene, 4-butylbromobenzene, 2-butyliodobenzene, 3-butyliodobenzene, 4-butyliodobenzene, 1-chloronaphthalene, 2 -Chloronaphthalene, 1-bromonaphthalene, 2-bromonaphthalene, 1-iodonaphthalene, 2-iodonaphthalene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, o-dibromobenzene, m- Bromobenzene, p-dibromobenzene, o-bromochlorobenzene, m-bromochlorobenzene, p-bromochlorobenzene, o-chlorofluorobenzene, m-chlorofluorobenzene, p-chlorofluorobenzene, o-bromofluorobenzene, m-bromo Fluorobenzene, p-bromofluorobenzene, o-chloroanisole, m-chloroanisole, p-chloroanisole, o-bromoanisole, m-bromoanisole, p-bromoanisole, o-iodoanisole, m-iodo Anisole, p-iodoanisole, o-chlorophenetole, m-chlorophenetole, p-chlorophenetole, o-bromophenetole, m-bromophenetole, p-bromophenetole, o-iodophenetole, m -Iodophene Tol, p-iodophenetole, on-butoxychlorobenzene, mn-butoxychlorobenzene, pn-butoxychlorobenzene, on-butoxybromobenzene, mn-butoxybromobenzene, pn-butoxy Bromobenzene, on-butoxyiodobenzene, mn-butoxyiodobenzene, pn-butoxyiodobenzene, ot-butoxychlorobenzene, mt-butoxychlorobenzene, pt-butoxychlorobenzene, o- t-butoxyphenyl bromide, mt-butoxyphenyl bromide, pt-butoxyphenyl bromide, ot-butoxyiodobenzene, mt-butoxyiodobenzene, pt-butoxyiodobenzene, 2-chlorobenzo Nitrile, 3-chlorobenzonite 4-chlorobenzonitrile, 2-bromobenzonitrile, 3-bromobenzonitrile, 4-bromobenzonitrile, 2-iodobenzonitrile, 3-iodobenzonitrile, 4-iodobenzonitrile, o- (1-ethoxy Ethoxy) chlorobenzene, m- (1-ethoxyethoxy) chlorobenzene, p- (1-ethoxyethoxy) chlorobenzene, o- (1-ethoxyethoxy) bromobenzene, m- (1-ethoxyethoxy) bromobenzene, p- (1 -Ethoxyethoxy) bromobenzene, o- (1-ethoxyethoxy) iodobenzene, m- (1-ethoxyethoxy) iodobenzene, p- (1-ethoxyethoxy) iodobenzene, o-acetylchlorobenzene, m-acetylchlorobenzene, p-acetylchlorobenzene o-acetylbromobenzene, m-acetylbromobenzene, p-acetylbromobenzene, o-acetyliodobenzene, m-acetyliodobenzene, p-acetyliodobenzene, o-acetoxychlorobenzene, m-acetoxychlorobenzene, p-acetoxychlorobenzene O-acetoxybromobenzene, m-acetoxybromobenzene, p-acetoxybromobenzene, o-acetoxyiodobenzene, m-acetoxyiodobenzene, p-acetoxyiodobenzene, 2-trifluoromethylchlorobenzene, 3-trifluoromethylchlorobenzene 4-trifluoromethylchlorobenzene, 2-trifluoromethylbromobenzene, 3-trifluoromethylbromobenzene, 4-trifluoromethylbromobenzene, 2-trifluoromethyliodobenzene, 3-trifluoromethyliodobenzene, 4-trifluoromethyliodobenzene, 2-chlorobenzoic acid, 3-chlorobenzoic acid, 4-chlorobenzoic acid, 2-bromobenzoic acid, 3- Bromobenzoic acid, 4-bromobenzoic acid, 2-iodobenzoic acid, 3-iodobenzoic acid, 4-iodobenzoic acid, methyl 2-chlorobenzoate, methyl 3-chlorobenzoate, methyl 4-chlorobenzoate, 2 -Methyl bromobenzoate, methyl 3-bromobenzoate, methyl 4-bromobenzoate, methyl 2-iodobenzoate, methyl 3-iodobenzoate, methyl 4-iodobenzoate, 2-chloroaniline, 3-chloroaniline 4-chloroaniline, 2-bromoaniline, 3-bromoaniline, 4-bromoaniline, 2-iodoaniline 3-iodoaniline, 4-iodoaniline, 2-chloroformyl benzene, 3-chloroformyl benzene, 4-chloroformyl benzene, 2-bromo-formyl benzene, 3-bromo-formyl benzene, 4-bromo-formyl benzene.

  Although not particularly limited, specific examples of the alkenyl compound represented by the above formula (8) include vinyl chloride, vinyl bromide, β-bromostyrene, β-chlorostyrene, β-iodostyrene, α-bromostyrene, α-chlorostyrene, α-iodostyrene, 1-bromo-1-butene, 1-chloro-1-butene, 1-iodo-1-butene, 1-bromo-1-pentene, 1-chloro-1-pentene, 1-iodo-1-pentene, 1-bromo-1-hexene, 1-chloro-1-hexene, 1-iodo-1-hexene, 1-bromo-1-heptene, 1-chloro-1-heptene, 1- Examples include iodo-1-heptene, 1-bromo-1-octene, 1-chloro-1-octene, 1-bromo-1-decene, 1-chloro-1-decene, 1-iodo-1-octene and the like. .

  In the method of the present invention, a cross-coupling reaction is carried out by reacting a boron compound represented by the general formula (2) and a compound represented by the general formula (3) in the presence of a base.

  The base used in the method of the present invention is not particularly limited as long as it is a basic compound, but usually an inorganic basic compound is exemplified. Specific examples of the inorganic base compound include, for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide and other hydroxide compounds, lithium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, carbonate Carbonate compounds such as potassium hydrogen, magnesium carbonate, calcium carbonate, barium carbonate, cesium carbonate, phosphate compounds such as lithium phosphate, sodium phosphate, potassium phosphate, lithium acetate, sodium acetate, magnesium acetate, calcium acetate, etc. And alkoxide compounds such as lithium methoxide, lithium-t-butoxide, sodium methoxide, sodium-t-butoxide, and the like. Of these, carbonate compounds are preferred from the viewpoints of economy and reaction yield.

  In addition, the usage-amount of the base to be used is normally used in 0.1-20 equivalent with respect to the aromatic boron compound mentioned above. When the amount used is less than 0.1 equivalent, the reaction does not proceed smoothly. When the amount used exceeds 20 equivalents, the yield does not improve for the amount used, but it is economically disadvantageous.

  The present inventors have found for the first time that a catalyst composition comprising a complex of a nickel salt and an amine compound and a phosphine compound is effective in the above-described cross-coupling reaction. In particular, when the catalyst composition as in the present invention is used, the reaction proceeds in a high yield even in the presence of an inexpensive base such as a carbonate. It is extremely useful as an industrial production method for reactions.

  About the usage-amount of the catalyst composition in the method of this invention, it is 0.001-0.15 equivalent as a nickel atom with respect to the compound shown by General formula (3), Preferably it is 0.005-0.10 equivalent It is. When the amount used is less than 0.001 equivalent, the reaction does not proceed smoothly, and when it exceeds 0.15 equivalent, the yield does not improve for the amount used, but it is economically disadvantageous. Become.

  The reaction temperature in the method of the present invention is usually in the range of 0 to 150 ° C.

  The reaction of the present invention can be carried out in the presence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction. For example, ether solvents, oxygen-containing solvents, nitrogen-containing solvents, aromatic hydrocarbon solvents, aliphatic hydrocarbon solvents, and the like. Can be mentioned. Usually, these solvents can be used alone or in combination. A solvent such as water can also be used as a co-solvent.

  After completion of the reaction, by appropriately combining acid washing, water washing, and alkali washing, by-product inorganic substances and unreacted raw materials are removed, and further, by a conventional purification technique such as chromatography, distillation, recrystallization, etc. A coupling compound can be obtained.

  As is clear from the above explanation, according to the method of the present invention, a highly active catalyst composition that solves the conventional problems, particularly, the present catalyst composition is used for a cross-coupling reaction such as Suzuki coupling. As a result, a cross-coupling compound can be obtained in a high yield.

  In addition, by applying the method of the present invention, 4-t-butoxy-4′-cyanobiphenyl, which is an important intermediate to 4-hydroxy-4′-cyanobiphenyl useful as a liquid crystal material, is efficiently synthesized. It became possible to do.

  EXAMPLES The method of the present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

Example 1
To a 50 ml flask substituted with nitrogen gas, 9.7 mg (0.08 mmol) of anhydrous nickel chloride (NiCl ₂ ) [Kishida Chemical], 26 mg of N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (0 .23 mmol) [Kishida Chemicals], triphenylphosphine (PPh ₃ ) 79 mg (0.30 mmol) [Wako Pure Chemicals], tetrahydrofuran 11.0 g [Kanto Chemicals], and heated and stirred for 30 minutes under solvent reflux conditions did. Then, this solution was cooled to room temperature, 0.40 g (3.3 mmol) of phenylboronic acid (PhB (OH) ₂ ) [Tokyo Chemicals], 0.38 g (3.0 mmol) of p-chlorotoluene [Tokyo Kasei Co., Ltd.] Product], potassium carbonate (K ₂ CO ₃ ) 1.24 g (9.0 mmol) [Kishida Chemical Co., Ltd.] was added, and the mixture was stirred at the solvent reflux temperature for 12 hours. After completion of the reaction, 5% aqueous HCl solution was added for post-treatment, and the organic layer obtained by the liquid separation operation was further washed with saturated aqueous NaCl solution. As a result of analyzing the obtained organic layer by gas chromatography quantitative analysis using n-dodecane [Tokyo Chemicals] as an internal standard substance, the target 4-methylbiphenyl was found to have a yield of 77% (p-chloro (Based on toluene). The results are shown in Table 1.

Example 2
In the method of Example 1, instead of 1.24 g (9.0 mmol) of potassium carbonate (K ₂ CO ₃ ), 1.91 g (9.0 mmol) [Wako Pure Chemical Industries] of potassium phosphate (K ₃ PO ₄ ) was used. When the reaction was carried out according to the method of Example 1 except that it was used, 4-methylbiphenyl, which was the target product, was produced at a yield of 74% (based on p-chlorotoluene). The results are also shown in Table 1.

Example 3
In a 50 ml flask substituted with nitrogen gas, nickel nitrate hexahydrate (Ni (NO ₃ ) ₂ .6H ₂ O) 23.3 mg (0.08 mmol) [Kishida Chemical], N, N, N ′, N'-tetramethylethylenediamine (TMEDA) 26 mg (0.23 mmol) [Kishida Chemicals], triphenylphosphine (PPh ₃ ) 79 mg (0.30 mmol) [Wako Pure Chemicals], tetrahydrofuran 11.0 g [Kanto Chemicals] The mixture was heated and stirred for 30 minutes under reflux conditions of the solvent. Then, this solution was cooled to room temperature, 0.40 g (3.3 mmol) of phenylboronic acid (PhB (OH) ₂ ) [Tokyo Chemicals], 0.38 g (3.0 mmol) of p-chlorotoluene [Tokyo Kasei Co., Ltd.] Product], potassium carbonate (K ₂ CO ₃ ) 1.24 g (9.0 mmol) [Kishida Chemical Co., Ltd.] was added, and the mixture was stirred at the solvent reflux temperature for 12 hours. After completion of the reaction, 5% aqueous HCl solution was added for post-treatment, and the organic layer obtained by the liquid separation operation was further washed with saturated aqueous NaCl solution. The obtained organic layer was analyzed by gas chromatography quantitative analysis using n-dodecane [Tokyo Kasei Co., Ltd.] as an internal standard substance. As a result, 4-methylbiphenyl as a target product was found to have a yield of 75% (p-chloro (Based on toluene). The results are shown in Table 1.

Comparative Example 1
In the method of Example 1, the reaction was performed according to the method of Example 1 except that 79 mg (0.30 mmol) of triphenylphosphine (PPh ₃ ) was not used. It was produced at a yield of 2% (based on p-chlorotoluene). The results are also shown in Table 1.

Comparative Example 2
In the method of Example 1, the reaction was conducted according to the method of Example 1 except that 26 mg (0.23 mmol) of N, N, N ′, N′-tetramethylethylenediamine (TMEDA) was not used. The product 4-methylbiphenyl was not produced at all (yield 0%). The results are also shown in Table 1.

Comparative Example 3
In the method of Example 1, 79 mg (0.30 mmol) of triphenylphosphine (PPh ₃ ) was not used, and the amount of N, N, N ′, N′-tetramethylethylenediamine (TMEDA) was 26 mg (0.23 mmol). The reaction was carried out according to the method of Example 1 except that the amount was changed from 62 to 62 mg (0.53 mmol). As a result, the target product, 4-methylbiphenyl, had a yield of 2% (based on p-chlorotoluene). It was generated with. The results are also shown in Table 1.

Comparative Example 4
In the method of Example 1, 26 mg (0.23 mmol) of N, N, N ′, N′-tetramethylethylenediamine (TMEDA) was not used, and the amount of triphenylphosphine (PPh ₃ ) was 79 mg (0.30 mmol). The reaction was carried out according to the method of Example 1 except that the amount was changed to 139 mg (0.53 mmol). As a result, 4-methylbiphenyl which was the target product was not produced at all (yield 0%). The results are also shown in Table 1.

Comparative Example 5
In the method of Example 1, instead of 79 mg (0.30 mmol) of triphenylphosphine (PPh ₃ ), 91.3 mg (0.30 mmol) [product of STREM] of tri-o-tolylphosphine was used. When the reaction was carried out according to the method of Example 1, 4-methylbiphenyl which was the target product was not produced at all (yield 0%). The results are also shown in Table 1.

Comparative Example 6
In the method of Example 1, instead of 79 mg (0.30 mmol) of triphenylphosphine (PPh ₃ ), 119.5 mg (0.30 mmol) [product of STREM] of 1,2-bis (diphenylphosphino) ethane was used. Except that, the reaction was carried out according to the method of Example 1. As a result, 4-methylbiphenyl which was the target product was not produced at all (yield 0%). The results are also shown in Table 1.

Comparative Example 7 (
(Method of “Tetrahedron”, (UK), 1999, Vol. 55, p11889-11894) In a 50 ml flask purged with nitrogen gas, 9.7 mg (0.08 mmol) of anhydrous nickel chloride (NiCl 2) [ Kishida Chemicals], 2,2′-bipyridyl (BPY) 36 mg (0.23 mmol) [Aldrich product] and tetrahydrofuran 11.0 g [Kanto Chemicals] were charged, and the mixture was heated and stirred for 30 minutes under solvent reflux conditions. Then, this solution was cooled to room temperature, 0.40 g (3.3 mmol) of phenylboronic acid (PhB (OH) 2) [Tokyo Chemicals], 0.38 g (3.0 mmol) of p-chlorotoluene [Tokyo Kasei Co., Ltd.] Product], sodium phosphate (Na3PO4) 1.48 g (9.0 mmol) [Wako Pure Chemical Industries, Ltd.] was added and stirred at the solvent reflux temperature for 12 hours. After completion of the reaction, 5% aqueous HCl solution was added for post-treatment, and the organic layer obtained by the liquid separation operation was further washed with saturated aqueous NaCl solution. As a result of analyzing the obtained organic layer by gas chromatography quantitative analysis using n-dodecane [Tokyo Chemicals] as an internal standard substance, the target 4-methylbiphenyl was found to have a yield of 41% (p-chloro (Based on toluene). The results are shown in Table 1.

Comparative Example 8
In the method of Comparative Example 7, instead of 1.48 g (9.0 mmol) of sodium phosphate (Na ₃ PO ₄ ), 1.24 g (9.0 mmol) of potassium carbonate (K ₂ CO ₃ ) [Kishida Chemical Co., Ltd.] The reaction was carried out according to the method of Comparative Example 7 except that 4-methylbiphenyl as the target product was not produced at all (yield 0%). The results are also shown in Table 1.

Comparative Example 9
In the method of Comparative Example 7, triphenylphosphine (PPh ₃ ) 79 mg (0.30 mmol) [Wako Pure Chemical Industries] was added, and instead of sodium phosphate (Na ₃ PO ₄ ) 1.48 g (9.0 mmol), The reaction was carried out according to the method of Comparative Example 7 except that 1.91 g (9.0 mmol) [Wako Pure Chemical Industries] of potassium phosphate (K ₃ PO ₄ ) was used. Was produced at a yield of 35% (based on p-chlorotoluene). The results are shown in Table 1.

Comparative Example 10
In the method of Comparative Example 9, potassium carbonate (K ₂ CO ₃ ) 1.24 g (9.0 mmol) instead of potassium phosphate (K ₃ PO ₄ ) 1.91 g (9.0 mmol) [Wako Pure Chemical Industries] Except for using Kishida Chemical Co., Ltd.], the reaction was carried out in accordance with the method of Comparative Example 9, and the target product, 4-methylbiphenyl, was produced at a yield of 27% (p-chlorotoluene basis). Was. The results are shown in Table 1.

Comparative Example 11
In the method of Example 3, the reaction was carried out according to the method of Example 3 except that 79 mg (0.30 mmol) of triphenylphosphine (PPh ₃ ) was not used. Not formed (yield 0%). The results are also shown in Table 1.

Comparative Example 12
In the method of Example 3, the reaction was conducted according to the method of Example 3 except that 26 mg (0.23 mmol) of N, N, N ′, N′-tetramethylethylenediamine (TMEDA) was not used. 4-methylbiphenyl as a product was produced at a yield of 34% (based on p-chlorotoluene). The results are also shown in Table 1.

実施例４〜１１
実施例１の方法において、フェニルボロン酸（ＰｈＢ（ＯＨ）_２） ０．４０ｇ（３．３ｍｍｏｌ）及びｐ−クロロトルエン ０．３８ｇ（３．０ｍｍｏｌ）に代えて、それぞれ表２に示した芳香族ボロン酸（３．３ｍｍｏｌ）及び芳香族ハライド（３．０ｍｍｏｌ）を用いた以外は、実施例１の方法に準じて反応を行った。結果を表２に示す。

Examples 4-11
In the method of Example 1, instead of 0.40 g (3.3 mmol) of phenylboronic acid (PhB (OH) ₂ ) and 0.38 g (3.0 mmol) of p-chlorotoluene, the aromatics shown in Table 2, respectively. The reaction was performed according to the method of Example 1 except that boronic acid (3.3 mmol) and aromatic halide (3.0 mmol) were used. The results are shown in Table 2.

Example 12
In the method of Example 1, N, N, N ′, N′-tetramethylethylenediamine (TMEDA) 26 mg (0.23 mmol) [Kishida Chemical] was replaced with N, N, N ′, N′-tetramethyl. The reaction was conducted according to the method of Example 1 except that 30 mg (0.23 mmol) [Aldrich product] of propylenediamine was used. As a result, 4-methylbiphenyl which was the target product was found to have a yield of 77% (p-chloro). (Based on toluene). The results are shown in Table 2.

実施例１３
窒素ガスで置換された５０ｍｌフラスコに、ジクロロビス（トリフェニルホスフィン）ニッケル（ＮｉＣｌ_２（ＰＰｈ_３）_２） ５２．３ｍｇ（０．０８ｍｍｏｌ）［アルドリッチ品］、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン（ＴＭＥＤＡ） ２６ｍｇ（０．２３ｍｍｏｌ）［キシダ化学品］、トリフェニルホスフィン（ＰＰｈ_３） ３９ｍｇ（０．１５ｍｍｏｌ）［和光純薬品］、テトラヒドロフラン１１．０ｇ［関東化学品］を仕込み、溶媒還流条件下にて３０分間加熱攪拌した。その後、この溶液を室温まで冷却し、フェニルボロン酸（ＰｈＢ（ＯＨ）_２） ０．４０ｇ（３．３ｍｍｏｌ）［東京化成品］、ｐ−クロロトルエン ０．３８ｇ（３．０ｍｍｏｌ）［東京化成社品］、炭酸カリウム（Ｋ_２ＣＯ_３） １．２４ｇ（９．０ｍｍｏｌ）［キシダ化学社品］を加えて、溶媒還流温度にて１２時間攪拌した。反応終了後、５％ＨＣｌ水溶液を加えて後処理し、分液操作にて得られた有機層をさらに飽和ＮａＣｌ水溶液で洗浄した。得られた有機層を、ｎ−ドデカン［東京化成品］を内部標準物質とするガスクロマトグラフィー定量分析にて分析した結果、目的物である４−メチルビフェニルが、収率７５％（ｐ−クロロトルエン基準）の割合で生成していた。

Example 13
To a 50 ml flask substituted with nitrogen gas, dichlorobis (triphenylphosphine) nickel (NiCl ₂ (PPh ₃ ) ₂ ) 52.3 mg (0.08 mmol) [Aldrich product], N, N, N ′, N′-tetra Methylethylenediamine (TMEDA) 26 mg (0.23 mmol) [Kishida Chemicals], triphenylphosphine (PPh ₃ ) 39 mg (0.15 mmol) [Wako Pure Chemicals], tetrahydrofuran 11.0 g [Kanto Chemicals] were charged, and the solvent was refluxed. The mixture was heated and stirred for 30 minutes under the conditions. Then, this solution was cooled to room temperature, 0.40 g (3.3 mmol) of phenylboronic acid (PhB (OH) ₂ ) [Tokyo Chemicals], 0.38 g (3.0 mmol) of p-chlorotoluene [Tokyo Kasei Co., Ltd.] Product], potassium carbonate (K ₂ CO ₃ ) 1.24 g (9.0 mmol) [Kishida Chemical Co., Ltd.] was added, and the mixture was stirred at the solvent reflux temperature for 12 hours. After completion of the reaction, 5% aqueous HCl solution was added for post-treatment, and the organic layer obtained by the liquid separation operation was further washed with saturated aqueous NaCl solution. The obtained organic layer was analyzed by gas chromatography quantitative analysis using n-dodecane [Tokyo Kasei Co., Ltd.] as an internal standard substance. As a result, 4-methylbiphenyl as a target product was found to have a yield of 75% (p-chloro (Based on toluene).

Complex Preparation Example 1 (Preparation of nickel chloride-TMEDA complex)
In a 200 ml flask substituted with nitrogen gas, 13.0 g (0.10 mol) of anhydrous nickel chloride (NiCl ₂ ) [Kishida Chemicals], 13.9 g of N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (0.12 mol) [Kishida Chemical Co., Ltd.] and dehydrated methanol [Kanto Chemical Co., Ltd.] 50.0 g were added and heated under reflux for 1 hour in a nitrogen atmosphere. After completion of the reaction, the reaction solution was cooled to room temperature, and the precipitated solid was collected by filtration and dried under vacuum conditions to obtain 19.7 g of a greenish yellow solid. The result of elemental analysis confirmed that the solid was a 1: 1 complex of nickel chloride and TMEDA (yield 80%).
(Elemental analysis; nickel chloride-TMEDA 1: 1 complex)
Calculated values: C = 29.3%; H = 6.6%; Cl = 28.9%; N = 11.4%; Ni = 23.9%
Found: C = 29.5%; H = 6.4%; Cl = 28.8%; N = 11.4%; Ni = 23.7%
Example 14
In a 50 ml flask substituted with nitrogen gas, 7.37 mg (0.03 mmol) of the nickel chloride-TMEDA 1: 1 complex prepared in Catalyst Preparation Example 1 and 24 mg (0.09 mmol) of triphenylphosphine (PPh ₃ ) [ Wako Pure Chemical Industries Ltd.], 11.0 g of tetrahydrofuran [Kanto Chemical Co., Ltd.] were charged, and phenylboronic acid (PhB (OH) ₂ ) 0.44 g (3.6 mmol) [Tokyo Chemicals], p-chlorotoluene 0.38 g ( 3.0 mmol) [Tokyo Kasei Co., Ltd.] and potassium carbonate (K ₂ CO ₃ ) 1.24 g (9.0 mmol) [Kishida Chemical Co., Ltd.] were added and stirred for 12 hours at the solvent reflux temperature. After completion of the reaction, 5% aqueous HCl solution was added for post-treatment, and the organic layer obtained by the liquid separation operation was further washed with saturated aqueous NaCl solution. As a result of analyzing the obtained organic layer by gas chromatography quantitative analysis using n-dodecane [Tokyo Kasei Co., Ltd.] as an internal standard substance, the target 4-methylbiphenyl was found to have a yield of 84% (p-chloro (Based on toluene). The results are also shown in Table 3.

Example 15
In the method of Example 14, the reaction was performed according to Example 14 except that 5.0 g of 1,4-dioxane [Kanto Chemical Co.] was used instead of 11.0 g of tetrahydrofuran [Kanto Chemical Co., Ltd.]. However, 4-methylbiphenyl, which was the target product, was produced at a yield of 95% (based on p-chlorotoluene). The results are also shown in Table 3.

Example 16
To a 50 ml flask substituted with nitrogen gas, 7.37 mg (0.03 mmol) of nickel chloride-TMEDA 1: 1 complex prepared in Catalyst Preparation Example 1 and 5.0 g of 1,4-dioxane [Kanto Chemical Co., Ltd.] The mixture was charged and heated at 80 ° C. for 0.5 hour to obtain a purple liquid. In a 50 ml flask substituted with separately prepared nitrogen gas, phenylboronic acid (PhB (OH) ₂ ) 0.44 g (3.6 mmol) [Tokyo Chemicals], p-chlorotoluene 0.38 g (3.0 mmol) [Tokyo Kasei Co., Ltd.], triphenylphosphine (PPh ₃ ) 24 mg (0.09 mmol) [Wako Pure Chemicals], potassium carbonate (K ₂ CO ₃ ) 1.24 g (9.0 mmol) [Kishida Chemical Co., Ltd.], 1,4 -Dioxane 10.0g [Kanto Chemical Co., Inc.] was charged and heated to the solvent reflux temperature, then the previously prepared nickel chloride-TMEDA 1: 1 complex / dioxane solution was added, and the mixture was stirred at the same temperature for 12 hours. After completion of the reaction, 5% aqueous HCl solution was added for post-treatment, and the organic layer obtained by the liquid separation operation was further washed with saturated aqueous NaCl solution. The obtained organic layer was analyzed by gas chromatography quantitative analysis using n-dodecane [Tokyo Kasei Co., Ltd.] as an internal standard substance. As a result, 4-methylbiphenyl as a target product was found to have a yield of 94% (p-chloro (Based on toluene).

Example 17
In the method of Example 14, instead of 7.37 mg (0.03 mmol) of nickel chloride-TMEDA 1: 1 complex, nickel chloride-N, N, N ′, prepared in the same manner as in Catalyst Preparation Example 1 When the reaction was carried out according to Example 14 except that 7.79 mg (0.03 mmol) of N′-tetramethylpropylenediamine 1: 1 complex was used, the target 4-methylbiphenyl was obtained in a yield of 61 % (Based on p-chlorotoluene). The results are also shown in Table 3.

Example 18
In the method of Example 14, instead of 7.37 mg (0.03 mmol) of nickel chloride-TMEDA 1: 1 complex, nickel bromide-N, N, N ′ prepared by the same method as in Catalyst Preparation Example 1 , N′-tetramethylethylenediamine 1: 1 complex, except that 10.0 mg (0.03 mmol) was used, and the reaction was carried out according to Example 14. As a result, the desired 4-methylbiphenyl was obtained in a yield of 82. % (Based on p-chlorotoluene). The results are also shown in Table 3.

Example 19
In a 50 ml flask substituted with nitrogen gas, 7.37 mg (0.03 mmol) of the nickel chloride-TMEDA 1: 1 complex prepared in Catalyst Preparation Example 1 and 24 mg (0.09 mmol) of triphenylphosphine (PPh ₃ ) [ Wako Pure Chemical Industries, Ltd.], 10.0 g of tetrahydrofuran [Kanto Chemical Co., Ltd.], tris (4-t-butoxyphenyl) boroxine 0.63 g (1.2 mmol), p-chlorobenzonitrile 0.41 g (3.0 mmol) [Tokyo Kasei Co., Ltd.] and potassium carbonate (K ₂ CO ₃ ) 1.24 g (9.0 mmol) [Kishida Chemical Co., Ltd.] were added and stirred for 12 hours at the solvent reflux temperature. After completion of the reaction, 5% aqueous HCl solution was added for post-treatment, and the organic layer obtained by the liquid separation operation was further washed with saturated aqueous NaCl solution. The obtained organic layer was analyzed by gas chromatography quantitative analysis using n-dodecane [Tokyo Chemicals] as an internal standard substance. As a result, 4-t-butoxy-4′-cyanobiphenyl, which was the target product, was recovered. It was produced at a rate of 96% (based on p-chlorobenzonitrile). The results are also shown in Table 3.

Example 20
In the method of Example 15, p-bromotoluene 0.51 g (3.0 mmol) [Tokyo Kasei Co., Ltd.] was used instead of p-chlorotoluene 0.38 g (3.0 mmol) [Tokyo Kasei Co., Ltd.]. Except for the above, the reaction was carried out according to the method of Example 15. As a result, 4-methylbiphenyl as the target product was produced at a yield of 89% (p-bromotoluene basis). The results are also shown in Table 3.

Example 21
In the method of Example 15, p-iodotoluene 0.65 g (3.0 mmol) [Tokyo Kasei Co., Ltd.] was used instead of p-chlorotoluene 0.38 g (3.0 mmol) [Tokyo Kasei Co., Ltd.]. Except for the above, the reaction was carried out according to the method of Example 15. As a result, 4-methylbiphenyl as the target product was produced at a yield of 85% (p-iodotoluene basis). The results are also shown in Table 3.

Example 22
In the method of Example 15, except that trans-β-bromostyrene 0.55 g (3.0 mmol) was used instead of p-chlorotoluene 0.38 g (3.0 mmol) [Tokyo Kasei Co., Ltd.] When the reaction was conducted according to the method of Example 15, the target product, trans-stilbene, was produced at a yield of 59% (based on trans-β-bromostyrene). The results are also shown in Table 3.

Example 23
In a 50 ml flask substituted with nitrogen gas, 7.37 mg (0.03 mmol) of the nickel chloride-TMEDA 1: 1 complex prepared in Catalyst Preparation Example 1 and 24 mg (0.09 mmol) of triphenylphosphine (PPh ₃ ) [ Wako Pure Chemicals], 1,4-dioxane 10.0 g [Kanto Chemicals], and trans-2- (4-methylphenyl) vinylboronic acid 0.58 g (3.6 mmol) [Aldrich product], bromobenzene 0.47 g (3.0 mmol) [Kanto Chemical Co., Ltd.] and potassium carbonate (K ₂ CO ₃ ) 1.24 g (9.0 mmol) [Kishida Chemical Co., Ltd.] were added and stirred at the solvent reflux temperature for 12 hours. . After completion of the reaction, 5% aqueous HCl solution was added for post-treatment, and the organic layer obtained by the liquid separation operation was further washed with saturated aqueous NaCl solution. As a result of analyzing the obtained organic layer by gas chromatography quantitative analysis using n-dodecane [Tokyo Chemicals] as an internal standard substance, the target product, trans-β- (4-methylphenyl) styrene, was collected. It was produced at a rate of 63% (based on bromobenzene). The results are also shown in Table 3.

Example 24
In the method of Example 23, except that 0.61 g (3.0 mmol) [Tokyo Kasei Co., Ltd.] was used instead of 0.47 g (3.0 mmol) [Kanto Chemical Co., Ltd.] bromobenzene When the reaction was carried out according to the method of Example 23, the desired product, trans-β- (4-methylphenyl) styrene, was produced at a yield of 61% (based on iodobenzene). The results are also shown in Table 3.

Example 25
In a 50 ml flask substituted with nitrogen gas, 7.37 mg (0.03 mmol) of the nickel chloride-TMEDA 1: 1 complex prepared in Catalyst Preparation Example 1 and 24 mg (0.09 mmol) of triphenylphosphine (PPh ₃ ) [ Wako Pure Chemical Industries, Ltd.], 1,4-dioxane 10.0 g [Kanto Chemical Co., Ltd.], trans-2-phenylvinylboronic acid 0.53 g (3.6 mmol) [Aldrich product], bromobenzene 0.47 g ( 3.0 mmol) [Kanto Chemical Co., Ltd.] and potassium phosphate (K ₃ PO ₄ ) 1.91 g (9.0 mmol) [Wako Pure Chemical Industries] were added and stirred for 12 hours at the solvent reflux temperature. After completion of the reaction, 5% aqueous HCl solution was added for post-treatment, and the organic layer obtained by the liquid separation operation was further washed with saturated aqueous NaCl solution. As a result of analyzing the obtained organic layer by gas chromatography quantitative analysis using n-dodecane [Tokyo Chemicals] as an internal standard substance, the target product, trans-stilbene, was obtained in a yield of 91% (based on bromobenzene). It was generated at a rate of The results are also shown in Table 3.

Example 26
In the method of Example 25, except that 0.61 g (3.0 mmol) [Tokyo Kasei Co., Ltd.] was used instead of 0.47 g (3.0 mmol) [Kanto Chemical Co., Ltd.] bromobenzene When the reaction was carried out according to the method of Example 25, the target product, trans-stilbene, was produced at a yield of 86% (based on iodobenzene). The results are also shown in Table 3.

Example 27
In the method of Example 25, Example 25 was used except that 0.55 g (3.0 mmol) of trans-β-bromostyrene was used instead of 0.47 g (3.0 mmol) [product of Kanto Chemical Co., Ltd.] of bromobenzene. As a result of the reaction according to the method, trans-trans-1,4-butadiene, which is the target product, was produced at a yield of 59% (based on trans-β-bromostyrene). The results are also shown in Table 3.

Claims (7)

A catalyst composition for cross-coupling reaction comprising a complex of a nickel salt represented by the following formula (1) and an amine compound and triphenylphosphine.

Wherein R ^{1 to} R ⁴ may be the same or different and are a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group Or a substituted or unsubstituted linear, branched or cyclic alkenyl group, n represents an integer of 1 to 6. X may be the same or different and each may be a halogen atom, a hydroxyl group, a nitrate group or acetic acid. Represents a group.) The catalyst composition for cross coupling reaction according to claim 1, wherein the nickel salt is nickel halide. The catalyst composition for cross coupling reaction according to claim 1 or 2, wherein the amine compound is N, N, N ', N'-tetramethylethylenediamine. A boron compound represented by the following formula (2) and a compound represented by the following formula (3) are subjected to a cross-coupling reaction in the presence of a base and the catalyst composition according to any one of claims 1 to 3. A process for producing a cross-coupling compound represented by the following formula (4):

(In the formula, R ⁵ and R ⁶ may be the same or different, and are substituted or unsubstituted linear, branched or cyclic alkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted heteroaryl groups. Or a substituted or unsubstituted linear, branched or cyclic alkenyl group, each Y may be the same or different, and represents a hydroxyl group or an alkoxy group, and Z represents a halogen atom, a methanesulfonate group or trifluoromethane. Represents a sulfonate group.) The method for producing a cross-coupling compound according to claim 4, wherein the base is a carbonate compound. 6. The method for producing a cross-coupling compound according to claim 4, wherein the boron compound is an aromatic boron compound represented by the following formula (5) or an alkenyl boron compound represented by the following formula (6). .

(Wherein R ^{7 to} R ¹⁰ may be the same or different and each represents a hydrogen atom, a halogen atom, a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, a substituted or An unsubstituted heteroaryl group, a substituted or unsubstituted linear, branched or cyclic alkenyl group, a hydroxyl group, an alkoxy group, an amino group, a cyano group, a carbonyl group, a carboxyl group or an ester group, where a is 1 to 5. R ⁷ bonded to adjacent carbon atoms of the benzene ring may be arbitrarily bonded to form a condensed ring with the benzene ring, and adjacent R ⁸ and R ¹⁰ on the alkenyl group. , the R ⁹ and R ¹⁰ on the same carbon may be respectively bonded to each other to form a ring .Y may each be identical or different, a hydroxyl group or an alkoxy group It is.) The compound represented by the formula (3) is an aromatic compound represented by the following formula (7) or an alkenyl compound represented by the following formula (8). Compound production method.

(Wherein R ^{11 to} R ¹⁴ may be the same or different and each represents a hydrogen atom, a halogen atom, a substituted or unsubstituted linear, branched or cyclic alkyl group, a substituted or unsubstituted aryl group, substituted or An unsubstituted heteroaryl group, a substituted or unsubstituted linear, branched or cyclic alkenyl group, a hydroxyl group, an alkoxy group, an amino group, a cyano group, a carbonyl group, a carboxyl group, or an ester group, and b is 1 to 5. R ¹¹ bonded to adjacent carbon atoms of the benzene ring may be arbitrarily bonded to form a condensed ring with the benzene ring, and adjacent R ¹² and R ¹⁴ on the alkenyl group. , R ¹³ and R ¹⁴ on the same carbon combined with each other may be to form a ring .Z halogen atom, methanesulfonate group or a trifluoromethyl It represents a single sulfonate group.)