JP3928197B2 - Process for producing aryl-substituted aromatics - Google Patents

Description

（式中、Tfはトリフルオロスルフォニル基を、R⁶、R⁷はそれぞれ独立に水素原子、フッ素原子、塩素原子、臭素原子、アルキル基、アリール基、アラルキル基、アルコキシ基又はアラルキルオキシ基を表す。R⁸,R⁹ はそれぞれ独立に水素原子、フッ素原子、塩素原子、臭素原子、アルキル基、アリール基、アラルキル基、アルコキシ基若しくはアラルキルオキシ基を表すか又はフェニル基と一緒になって置換基を有することもあるナフチル基を表す。）
【００１１】
またアリールグリニヤール試薬としては、例えば式（IV）で示されるグリニヤール試薬が挙げられる。

（式中、R¹⁰ 、R¹¹ はそれぞれ独立に水素原子、フッ素原子、塩素原子、臭素原子、アルキル基、アリール基、アラルキル基、アルコキシ基又はアラルキルオキシ基を表す。R¹²,R¹³ はそれぞれ独立に水素原子、フッ素原子、塩素原子、臭素原子、アルキル基、アリール基、アラルキル基、アルコキシ基若しくはアラルキルオキシ基を表か又はフェニル基と一緒になって置換基を有することもあるナフチル基を表す。ｘは塩素原子又は臭素原子を表す。）
【００１２】
ここで、式（III)で示されるトリフラート類、式（IV）で示されるグリニヤール試薬における、アルキル基としては、例えばメチル、エチル、n-プロピル、i-プロピル、n-ブチル、i-ブチル、sec-ブチル、t-ブチル、ペンチル、ヘキシル、ヘプチル、オクチル、ノニル、デシル、ウンデシル、ドデシル、トリデシル、ミリスチル、パルミチル、ステアリル等の鎖状アルキル基、シクロペンチル、シクロヘキシル等の環状アルキル基、トリフルオロメチル、2-クロロエチル、2-ブロモエチル等のハロゲン化アルキル基などが挙げられる。
アルコキシ基としては、例えばアルキル部分が上記のようなアルキル基等であるアルコキシ基などが挙げられる。
【００１３】
またアラルキル基としては、例えばベンジル、フェニルエチル、ナフチルメチルの他に、これらのフェニル、ナフチル部分にフッ素原子、塩素原子、臭素原子、前記のようなアルキル基、前記のようなアルコキシ基等が置換したものなどが挙げられる。 アラルキルオキシ基としては、例えばアラルキル部分が上記のようなアラルキル基等であるアラルキルオキシ基などが挙げられる。
アリール基としては、例えばフェニル、ナフチルの他に、フッ素原子、塩素原子、臭素原子、前記のようなアルキル基、前記のようなアルコキシ基、前記のようなアラルキル基等で置換されたフェニル及びナフチル等が挙げられる。
また、R¹⁰,R¹¹ がフェニル基と一緒になった置換基を有することもあるナフチル基としては、ナフチルの他に、フッ素原子、塩素原子、臭素原子、前記のようなアルキル基、前記のようなアルコキシ基、前記のようなアラルキル基等で置換されたナフチル等が挙げられる。
【００１４】
トリフラート類の代表例としては、例えば1-メトキシ- 2-トリフルオロメタンスルフォニルオキシベンゼン、1-クロロ- 2-トリフルオロメタンスルフォニルオキシベンゼン、1-メチル- 2-トリフルオロメタンスルフォニルオキシベンゼン、1,3-ジメチル- 2-トリフルオロメタンスルフォニルオキシベンゼン、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビフェニル、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビナフチル等が挙げられる。
またグリニヤール試薬の代表例としては、例えばフェニルグリニヤール試薬、メチルフェニルグリニヤール試薬、メトキシフェニルグリニヤール試薬、クロルフェニルグリニヤール試薬、ナフチルグリニヤール試薬、ビフェニルグリニヤール試薬等が挙げられる。
【００１５】
トリフラート類とグリニヤール試薬とを反応させるに当たり、トリフラート類に対して、パラジウム系触媒は、通常0.1 〜20モル％、好ましくは0.5 〜10モル％使用され、グリニヤール試薬は、通常１〜５モル倍、好ましくは１〜３モル倍使用される。
この反応においては、通常ジエチルエーテル等のエーテル類、ベンゼン、トルエン等の芳香族類などが使用され、反応はトリフラート類、パラジウム系触媒、溶媒からなる混合物に、-40 〜100 ℃、 好ましくは-20 〜80℃でグリニヤール試薬と溶媒の混合物を加えることにより通常実施される。
【００１６】
また本発明においては、無機塩類の共存下に反応を行うことにより、反応を効率よく進行せしめることができ、目的物の収率を向上し得る。この場合、無機塩類はパラジウム系触媒などとともに予め加えておくことが好ましい。
かかる無機塩類としては、例えば臭化リチウム、沃化リチウム、臭化マグネシウム、塩化リチウム、臭化ナトリウム、臭化カリウム、臭化セシウム、沃化ナトリウム、沃化カリウム、沃化セシウム、塩化マグネシウム、沃化マグネシウム、塩化カルシウム、臭化カルシウム、沃化カルシウム等のアルカリ金属ハライド、アルカリ土類金属ハライド等が挙げられる。
無機塩類を用いる場合、トリフラート類に対して、通常0.1 〜10当量倍、好ましくは、 １〜５当量倍である。
【００１７】
生成したアリール置換芳香族類は、例えば反応マスに希塩酸、希硫酸等の鉱酸の水溶液などを加えて、酸性にした後、必要に応じて有機溶媒で抽出、水洗、乾燥した後、溶媒を留去することにより、反応マスから取り出すことができる。
得られたアリール置換芳香族類は、必要に応じて蒸留、再結晶、各種クロマトグラフィー等の手段を施すことにより、更に精製することもできる。
【００１８】
【発明の効果】
かくして本発明の目的物であるアリール置換芳香族類が得られるが、本発明によれば、ジホスフィン系配位子及び／又はアミノ基の結合する炭素が置換されたアミノアルキルホスフィン系配位子という特定の配位子を有するパラジウム系触媒を使用することにより、グリニヤール試薬とアリールトリフラート類から目的とするアリール置換芳香族類を、高収率でしかも効率的に製造し得る。
【００１９】
【実施例】
以下、実施例により本発明を詳細に説明するが、本発明はこれら実施例に限定されるものではない。
【００２０】
参考例１( 触媒の調製例）
窒素雰囲気下、塩化パラジウム5.64mmol(1g)にアセトニトリル5ml を加えて室温で14時間攪拌した後、溶媒を2ml 留去し、濾過した。 得られた固体を乾燥することにより、塩化パラジウムビスアセトニトリル錯体1.39g を得た( 収率95％）。 窒素雰囲気下、塩化パラジウムビスアセトニトリル錯体0.385mmol(100mg)をベンゼン3ml に懸濁させ、alaphos 0.4mmol(109mg)のベンゼン溶液５mlを加えて室温で14時間攪拌した。析出した固体を濾過、ベンゼン洗浄、減圧乾燥することにより、PdCl₂(alaphos) 157mg を得た。収率91％。
尚、他の配位子も同様に調製し得る。
【００２１】
実施例１
窒素雰囲気下、エーテル4ml に乾燥させた臭化リチウム1mmol(86mg) 、PdCl₂(alaphos) 0.05mmol(22.4mg) 、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビフェニル 1mmol(305mg) を加えて懸濁させた。
次いで、氷冷攪拌下、この懸濁液に1M- フェニルマグネシウムブロミドエーテル溶液2mmol( 2ml) を加えた。30℃に昇温した後、同温度で３時間攪拌し、少量のサンプルをガスクロマトグラフィーで分析したところ、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビフェニルは完全に消失していた。
1Nの塩酸で過剰のグリニヤール試薬を分解させた後、エーテル抽出、有機層を飽和食塩水で洗浄、無水硫酸ナトリウムで乾燥、溶媒留去、得られた粗生成物をシリカゲルクロマトグラフィー( n-ヘキサン／ベンゼン＝20／１) で処理することにより、1,1':2',1"- テルフェニル 219mgを得た。 収率 95 ％
【００２２】
実施例２〜４、比較例１〜４
実施例１において、PdCl₂(alaphos)の代わりに、PdCl₂(dppp) 、PdCl₂(dppb) 、PdCl₂(dppe) 、PdCl₂(glyphos)、PdCl₂(PPh₃)₂、PdCl₂(dppf) 、Pd(PPh₃)₄ をそれぞれ0.05mmol用い、攪拌を表１に示した時間行う以外は、実施例１に準拠して実施した。結果を表１に示した。
【００２３】
【表１】

【００２４】
実施例５
実施例１において、1M- フェニルマグネシウムブロミドエーテル溶液の代わりに、1M- 4-クロロフェニルマグネシウムブロミドエーテル溶液2mmol を用い、２時間攪拌する以外は、実施例１に準拠して実施し、4-クロロ-1,1':2',1"-テルフェニルを得た。結果を表２に示した。
¹H-NMR(CDCl₃) : δ 7.03-7.43(13H,m,aromatic)
【００２５】
実施例６、比較例５
実施例５において、PdCl₂(alaphos)の代わりに、PdCl₂(dppp) 、NiBr₂(PPh₃)₂を用いる以外は実施例５に準拠して実施した。 結果を表２に示した。
【００２６】
【表２】

【００２７】
実施例７
実施例１において、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビフェニルの代わりに、1-メトキシー2- トリフルオロメタンスルフォニルオキシベンゼンを 1mmolを用い、５時間攪拌する以外は、実施例１に準拠して実施し、2-メトキシ-1,1'-ビフェニルを得た。結果を表３に示した。
¹H-NMR(CDCl₃) : δ 6.97-7.54(9H,m,aromatic) 、3.80(3H,s,CH₃)
【００２８】
実施例８、比較例６
実施例７において、PdCl₂(alaphos)の代わりに、PdCl₂(dppp) 、PdCl₂(PPh₃)₂を用いる以外は実施例５に準拠して実施した。 結果を表３に示した。
【００２９】
【表３】

【００３０】
実施例９
実施例１において、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビフェニルの代わりに、1-クロロ-2- トリフルオロメタンスルフォニルオキシベンゼンを 1mmolを用い、1M- フェニルマグネシウムブロミドエーテル溶液の代わりに、1M-2- メチルフェニルマグネシウムブロミドエーテル溶液2mmol を用い、４時間攪拌する以外は、実施例１に準拠して実施し、2-クロロ-2'-メチル-1,1'-ビフェニルを得た。結果を表４に示した。
【００３１】
比較例７、８
実施例９において、PdCl₂(alaphos)の代わりに、PdCl₂(PPh₃)₂、Nibr₂(PPh₃)₂を用いる以外は実施例９に準拠して実施した。 結果を表４に示した。
【００３２】
【表４】

【００３３】
実施例１０
実施例１において、1M- フェニルマグネシウムブロミドエーテル溶液の代わりに、1M-2- メチルフェニルマグネシウムブロミドエーテル溶液2mmol を用い、３時間攪拌する以外は、実施例１に準拠して実施し、2-メチル-1,1':2',1"-テルフェニルを得た。結果を表５に示した。
【００３４】
実施例１１
実施例１０において、PdCl₂(alaphos)の代わりに、PdCl₂(dppp) を用いる以外は実施例１０に準拠して実施した。 結果を表５に示した。
【００３５】
【表５】

【００３６】
実施例１２
実施例１において、1M- フェニルマグネシウムブロミドエーテル溶液の代わりに、1M-4- メチルフェニルマグネシウムブロミドエーテル溶液2mmol を用い、４時間攪拌する以外は、実施例１に準拠して実施し、4-メチル-1,1':2',1"-テルフェニルを得た。結果を表６に示した。
【００３７】
実施例１３
実施例１２において、PdCl₂(alaphos)の代わりに、PdCl₂(dppp) を用いる以外は実施例１２に準拠して実施した。 結果を表６に示した。
【００３８】
【表６】

【００３９】
実施例１４
実施例１において、PdCl₂(alaphos)の代わりに、PdCl₂(dppp) を用い、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビフェニルの代わりに、1,3-ジメチル-2- トリフルオロメタンスルフォニルオキシベンゼンを 1mmolを用い、1M- フェニルマグネシウムブロミドエーテル溶液の代わりに、1M-2- メチルフェニルマグネシウムブロミドエーテル溶液2mmol を用い、18時間攪拌する以外は、実施例１に準拠して実施し、2,6,2'- トリメチル-1,1'-ビフェニルを得た。収率は65％であった。
【００４０】
実施例１５
実施例１において、PdCl₂(alaphos)の代わりに、PdCl₂(dppp) を用い、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビフェニルの代わりに、1,3-ジメチル-2- トリフルオロメタンスルフォニルオキシベンゼンを 1mmolを用い、14時間攪拌する以外は、実施例１に準拠して実施し、2,6-ジメチル-1,1'-ビフェニルを得た。収率は94％であった。
【００４１】
実施例１６
実施例１において、PdCl₂(alaphos)の代わりに、PdCl₂(dppp) を用い、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビフェニルの代わりに、2-トリフルオロメタンスルフォニルオキシ-1,1'-ビナフチルを 1mmolを用い、14時間攪拌する以外は、実施例１に準拠して実施し、2-フェニル-1,1'-ビナフチルを得た。収率は91％であった。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing an aryl-substituted aromatic, and more specifically, an aryl substitution characterized by reacting an aryl triflate with an aryl Grignard reagent in the presence of a palladium-based catalyst having a specific ligand. The present invention relates to a method for producing aromatics.
[0002]
[Prior art and problems to be solved by the invention]
Aryl-substituted aromatics are important compounds as intermediates for pharmaceuticals, agricultural chemicals, etc., and as a production method using a Grignard reagent, for example, a method of reacting with aryl halides in the presence of a nickel-based catalyst or a palladium-based catalyst (Synthesis, 147, 827 (1990), J. Am. Chem. Sos., 110 8153 (1988)), a method of reacting with aryl triflates in the presence of a nickel catalyst (J. Org. Chem., 57 4066 (1992) )) Etc. have been proposed.
On the other hand, the present inventors proposed a method of reacting Grignard reagent and aryl triflates in the presence of a palladium-based catalyst having 1-N, N-dimethylamino-2-diphenylphosphinoethane as a ligand. (Tetrahedron Letters, 37 3161 (1996)), however, is not sufficiently satisfactory in terms of yield and the like, and improvement of this point has been desired.
[0003]
[Means for Solving the Problems]
As a result of intensive studies on a method for producing aryl-substituted aromatics by reacting a Grignard reagent with aryl triflates in the presence of a palladium-based catalyst, the present inventors have obtained diphosphine as a palladium-based catalyst. If a specific palladium-based catalyst having an aminoalkylphosphine-based ligand substituted with a carbon to which an amino group is bonded and / or an amino group is bonded, the desired aryl-substituted aromatics can be obtained in a high yield. Moreover, the present invention was completed by finding out that it can be efficiently produced.
[0004]
That is, in the present invention, an aryl-substituted aromatic compound is produced by reacting an aryl triflate with an aryl Grignard reagent.
Ph ₂ P- (CH ₂ ) _n -P (R ¹ ) ₂ (I)
(In the formula, n represents 2 to 4, and R ¹ represents a phenyl group which may have a substituent.)
The present invention provides an industrially excellent method for producing aryl-substituted aromatics characterized by using a palladium-based catalyst having a diphosphine-based ligand represented by formula (1).
[0005]
DETAILED DESCRIPTION OF THE INVENTION
The present invention will be described in detail below.
The present invention is characterized by using a palladium-based catalyst having the above diphosphine-based ligand (I) and / or β-aminoalkylphosphine-based ligand (II). N in the ligand (I) represents 2, 3, or 4, and R ¹ represents a phenyl group which may have a substituent.
In the aminoalkylphosphine-based ligand (II), R ² represents a phenyl group which may have a substituent, R ³ and R ⁴ each independently represents a lower alkyl group, R ⁵ represents a lower alkyl group, A phenyl group which may have a cycloalkyl group, an aralkyl group or a substituent.
[0006]
Here, examples of the lower alkyl group include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, pentyl and the like, and examples of the cycloalkyl group include Examples include cyclopentyl, cyclohexyl, cycloheptyl and the like.
Examples of the aralkyl group include phenylmethyl, phenylethyl, phenylpropyl and the like.
Examples of the phenyl group which may have a substituent include a phenyl group, a phenyl group substituted with a lower alkyl group as described above, a phenyl group substituted with a halogen atom such as a fluorine atom and a chlorine atom, methoxy, ethoxy, propoxy , Phenyl groups substituted with lower alkoxy groups such as butoxy and pentoxy.
[0007]
Representative examples of the diphosphine-based ligand (I) include, for example, 1,2-bis (diphenylphosphino) ethane (hereinafter abbreviated as dppe), 1,3-bis (diphenylphosphino) propane (hereinafter abbreviated as dppp). 1), 4-bis (diphenylphosphino) butane (hereinafter abbreviated as dppb), and the like.
Representative examples of the aminoalkylphosphine ligand (II) include, for example, 1-diphenylphosphino-2-N, N-dimethylaminopropane (hereinafter abbreviated as alphos), 1-diphenylphosphino-2- N, N-dimethylamino-3-methylbutane (hereinafter abbreviated as valphos), 1-diphenylphosphino-2-N, N-dimethylamino-3-phenylpropane (hereinafter abbreviated as phephos) and the like. The aminophosphine-based ligand (II) can be produced, for example, according to the method described in J. Org. Chem., 48 2195 (1983).
Among the ligands, dppp, dppb, alphos and the like are preferable, and dppp is particularly preferable.
[0008]
The palladium-based catalyst used in the present invention is prepared from, for example, the above-mentioned diphosphine-based ligand (I) and / or aminoalkylphosphine-based ligand (II) and a palladium compound, for example, “Experimental Chemistry Course” edited by the Chemical Society of Japan. 18 393 (1991). Examples of the palladium compound include tris (dibenzylideneacetone) palladium, allyl palladium dichloride, palladium acetate, and the like.
As the palladium-based catalyst, one prepared in advance or one prepared in a reaction system may be used.
[0009]
In the present invention, an aryl triflate is reacted with an aryl Grignard reagent in the presence of such a palladium catalyst. Examples of the aryl triflate include triflate represented by the formula (III).
[0010]

(In the formula, Tf represents a trifluorosulfonyl group, R ⁶ and R ⁷ each independently represent a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyloxy group. R ⁸ and R ⁹ each independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyloxy group, or a substituent together with a phenyl group. Represents a naphthyl group which may have
[0011]
Examples of the aryl Grignard reagent include a Grignard reagent represented by the formula (IV).

(Wherein R ¹⁰ and R ¹¹ each independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyloxy group. R ¹² and R ¹³ each represent Independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyloxy group, or a naphthyl group which may have a substituent together with a phenyl group. X represents a chlorine atom or a bromine atom.)
[0012]
Here, as the alkyl group in the triflate represented by the formula (III) and the Grignard reagent represented by the formula (IV), for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, Chain alkyl groups such as sec-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, myristyl, palmityl and stearyl, cyclic alkyl groups such as cyclopentyl and cyclohexyl, trifluoromethyl , Halogenated alkyl groups such as 2-chloroethyl and 2-bromoethyl.
As an alkoxy group, the alkoxy group etc. in which an alkyl part is the above alkyl groups etc. are mentioned, for example.
[0013]
As the aralkyl group, for example, in addition to benzyl, phenylethyl, and naphthylmethyl, the phenyl and naphthyl moieties are substituted with a fluorine atom, a chlorine atom, a bromine atom, an alkyl group as described above, and an alkoxy group as described above. And the like. Examples of the aralkyloxy group include an aralkyloxy group in which the aralkyl moiety is the aralkyl group as described above.
Examples of the aryl group include phenyl and naphthyl substituted with phenyl, naphthyl, fluorine atom, chlorine atom, bromine atom, alkyl group as described above, alkoxy group as described above, aralkyl group as described above, and the like. Etc.
In addition, naphthyl group in which R ¹⁰ and R ¹¹ may have a substituent combined with a phenyl group includes, in addition to naphthyl, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group as described above, And naphthyl substituted with an aralkyl group as described above.
[0014]
Representative examples of triflates include 1-methoxy-2-trifluoromethanesulfonyloxybenzene, 1-chloro-2-trifluoromethanesulfonyloxybenzene, 1-methyl-2-trifluoromethanesulfonyloxybenzene, 1,3-dimethyl. -2-trifluoromethanesulfonyloxybenzene, 2-trifluoromethanesulfonyloxy-1,1'-biphenyl, 2-trifluoromethanesulfonyloxy-1,1'-binaphthyl and the like.
Representative examples of Grignard reagents include phenyl Grignard reagents, methylphenyl Grignard reagents, methoxyphenyl Grignard reagents, chlorophenyl Grignard reagents, naphthyl Grignard reagents, biphenyl Grignard reagents, and the like.
[0015]
In reacting the triflate with the Grignard reagent, the palladium-based catalyst is usually used in an amount of 0.1 to 20 mol%, preferably 0.5 to 10 mol%, and the Grignard reagent is usually used in an amount of 1 to 5 mol times based on the triflate. Preferably 1 to 3 mole times is used.
In this reaction, ethers such as diethyl ether and aromatics such as benzene and toluene are usually used, and the reaction is carried out in a mixture of triflates, a palladium-based catalyst and a solvent at −40 to 100 ° C., preferably − Usually carried out by adding a mixture of Grignard reagent and solvent at 20-80 ° C.
[0016]
In the present invention, by carrying out the reaction in the presence of inorganic salts, the reaction can proceed efficiently, and the yield of the target product can be improved. In this case, it is preferable to add the inorganic salt in advance together with a palladium catalyst.
Examples of such inorganic salts include lithium bromide, lithium iodide, magnesium bromide, lithium chloride, sodium bromide, potassium bromide, cesium bromide, sodium iodide, potassium iodide, cesium iodide, magnesium chloride, iodine Examples thereof include alkali metal halides such as magnesium chloride, calcium chloride, calcium bromide and calcium iodide, and alkaline earth metal halides.
When inorganic salts are used, the amount is usually 0.1 to 10 equivalents, preferably 1 to 5 equivalents, relative to the triflate.
[0017]
The resulting aryl-substituted aromatics are made acidic by adding an aqueous solution of a mineral acid such as dilute hydrochloric acid or dilute sulfuric acid to the reaction mass, and extracted with an organic solvent, washed with water and dried as necessary. It can be removed from the reaction mass by distilling off.
The obtained aryl-substituted aromatics can be further purified by applying means such as distillation, recrystallization, and various chromatography, if necessary.
[0018]
【The invention's effect】
Thus, the aryl-substituted aromatics that are the object of the present invention can be obtained. According to the present invention, the diphosphine-based ligand and / or the aminoalkylphosphine-based ligand in which the carbon to which the amino group is bonded is substituted. By using a palladium-based catalyst having a specific ligand, the target aryl-substituted aromatics can be efficiently produced from the Grignard reagent and the aryl triflate in a high yield.
[0019]
【Example】
EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to these Examples.
[0020]
Reference Example 1 (Example of catalyst preparation)
Under a nitrogen atmosphere, 5 ml of acetonitrile was added to 5.64 mmol (1 g) of palladium chloride and stirred at room temperature for 14 hours, and then 2 ml of the solvent was distilled off and filtered. The obtained solid was dried to obtain 1.39 g of palladium chloride bisacetonitrile complex (yield 95%). Under a nitrogen atmosphere, 0.385 mmol (100 mg) of palladium chloride bisacetonitrile complex was suspended in 3 ml of benzene, 5 ml of a benzene solution of 0.4 mmol of alaphos (109 mg) was added, and the mixture was stirred at room temperature for 14 hours. The precipitated solid was filtered, washed with benzene, and dried under reduced pressure to obtain 157 mg of PdCl ₂ (alaphos). Yield 91%.
Other ligands can be prepared similarly.
[0021]
Example 1
Under a nitrogen atmosphere, add 1 mmol (86 mg) of lithium bromide dried to 4 ml of ether, 0.05 mmol (22.4 mg) of PdCl ₂ (alaphos) and 1 mmol (305 mg) of 2-trifluoromethanesulfonyloxy-1,1'-biphenyl. Suspended.
Next, 2 mmol (2 ml) of 1M-phenylmagnesium bromide ether solution was added to this suspension under ice-cooling and stirring. After raising the temperature to 30 ° C., the mixture was stirred at the same temperature for 3 hours, and a small sample was analyzed by gas chromatography. As a result, 2-trifluoromethanesulfonyloxy-1,1′-biphenyl was completely disappeared.
Excess Grignard reagent was decomposed with 1N hydrochloric acid, then extracted with ether, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting crude product was subjected to silica gel chromatography (n-hexane). / Benzene = 20/1) to give 219 mg of 1,1 ': 2', 1 "-terphenyl. Yield 95%
[0022]
Examples 2-4, Comparative Examples 1-4
In Example 1, instead of PdCl ₂ (alaphos), PdCl ₂ (dppp), PdCl ₂ (dppb), PdCl ₂ (dppe), PdCl ₂ (glyphos), PdCl ₂ (PPh ₃ ) ₂ , PdCl ₂ (dppf ), Pd (PPh ₃ ) ₄ was used in an amount of 0.05 mmol each, and stirring was performed in accordance with Example 1 except that stirring was performed for the time shown in Table 1. The results are shown in Table 1.
[0023]
[Table 1]

[0024]
Example 5
In Example 1, in place of 1M-phenylmagnesium bromide ether solution, 2 mmol of 1M-4-chlorophenylmagnesium bromide ether solution was used and stirred for 2 hours. 1,1 ': 2', 1 "-Terphenyl was obtained. The results are shown in Table 2.
¹ H-NMR (CDCl ₃ ): δ 7.03-7.43 (13H, m, aromatic)
[0025]
Example 6 and Comparative Example 5
In Example 5, instead of the _{PdCl 2 (alaphos), PdCl 2} (dppp), except using NiBr ₂ (PPh _{3) 2} was performed in conformity with Example 5. The results are shown in Table 2.
[0026]
[Table 2]

[0027]
Example 7
In Example 1, 1 mmol of 1-methoxy-2-trifluoromethanesulfonyloxybenzene was used instead of 2-trifluoromethanesulfonyloxy-1,1′-biphenyl, and the mixture was stirred for 5 hours. Then, 2-methoxy-1,1′-biphenyl was obtained. The results are shown in Table 3.
¹ H-NMR (CDCl ₃ ): δ 6.97-7.54 (9H, m, aromatic), 3.80 (3H, s, CH ₃ )
[0028]
Example 8 and Comparative Example 6
In Example 7, in place of the _{PdCl 2 (alaphos), PdCl 2} (dppp), except using PdCl ₂ (PPh _{3) 2} was performed in conformity with Example 5. The results are shown in Table 3.
[0029]
[Table 3]

[0030]
Example 9
In Example 1, 1 mmol of 1-chloro-2-trifluoromethanesulfonyloxybenzene was used instead of 2-trifluoromethanesulfonyloxy-1,1′-biphenyl, and 1M instead of 1M-phenylmagnesium bromide ether solution. 2-Chloro-2'-methyl-1,1'-biphenyl was obtained in the same manner as in Example 1 except that 2 mmol of methylphenylmagnesium bromide ether solution was used and stirred for 4 hours. The results are shown in Table 4.
[0031]
Comparative Examples 7 and 8
In Example 9, in place of the _{PdCl 2 (alaphos), PdCl 2} (PPh 3) 2, except for using Nibr ₂ (PPh _{3) 2} was performed in conformity with Example 9. The results are shown in Table 4.
[0032]
[Table 4]

[0033]
Example 10
In Example 1, in place of 1M-phenylmagnesium bromide ether solution, 2 mmol of 1M-2-methylphenylmagnesium bromide ether solution was used, except that the mixture was stirred for 3 hours. -1,1 ': 2', 1 "-terphenyl was obtained. The results are shown in Table 5.
[0034]
Example 11
In Example 10, in place of the PdCl ₂ (alaphos), except using PdCl ₂ (dppp) it was performed in conformity with Example 10. The results are shown in Table 5.
[0035]
[Table 5]

[0036]
Example 12
In Example 1, in place of 1M-phenylmagnesium bromide ether solution, 2 mmol of 1M-4-methylphenylmagnesium bromide ether solution was used, except that the mixture was stirred for 4 hours. -1,1 ': 2', 1 "-terphenyl was obtained. The results are shown in Table 6.
[0037]
Example 13
In Example 12, in place of the PdCl ₂ (alaphos), except using PdCl ₂ (dppp) it was performed in conformity with Example 12. The results are shown in Table 6.
[0038]
[Table 6]

[0039]
Example 14
In Example 1, PdCl ₂ (dppp) was used instead of PdCl ₂ (alaphos), and 1,3-dimethyl-2-trifluoromethanesulfonyl was used instead of 2-trifluoromethanesulfonyloxy-1,1′-biphenyl. 1 mmol of oxybenzene was used according to Example 1 except that 2 mmol of 1M-2-methylphenylmagnesium bromide ether solution was used instead of 1M-phenylmagnesium bromide ether solution and stirred for 18 hours. , 6,2′-Trimethyl-1,1′-biphenyl was obtained. The yield was 65%.
[0040]
Example 15
In Example 1, PdCl ₂ (dppp) was used instead of PdCl ₂ (alaphos), and 1,3-dimethyl-2-trifluoromethanesulfonyl was used instead of 2-trifluoromethanesulfonyloxy-1,1′-biphenyl. This was carried out according to Example 1 except that 1 mmol of oxybenzene was used and stirred for 14 hours to obtain 2,6-dimethyl-1,1′-biphenyl. The yield was 94%.
[0041]
Example 16
In Example 1, PdCl ₂ (dppp) was used instead of PdCl ₂ (alaphos), and 2-trifluoromethanesulfonyloxy-1,1 ′ was used instead of 2-trifluoromethanesulfonyloxy-1,1′-biphenyl. 2-Phenyl-1,1′-binaphthyl was obtained according to Example 1 except that 1 mmol of -binaphthyl was used and stirred for 14 hours. The yield was 91%.

Claims (6)

In the production of aryl-substituted aromatics by reacting aryl triflates with aryl Grignard reagents, the compound of formula (I) is used as a catalyst.
(R ¹ ) ₂ P- (CH ₂ ) _n -P (R ¹ ) ₂ (I)
(In the formula, n represents 2 to 4, and R ¹ represents a phenyl group which may have a substituent.)
A process for producing aryl-substituted aromatics, which comprises using a palladium-based catalyst having a diphosphine-based ligand represented by the formula: Aryl triflates are of formula (III)

(In the formula, Tf represents a trifluoromethanesulfonyl group, R ⁶ and R ⁷ each independently represent a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, or an aralkyloxy group. R ⁸ and R ⁹ each independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, an aralkyloxy group, or a substituent together with a phenyl group. Represents a naphthyl group which may have
The production method according to claim 1, wherein the compound is represented by the formula: Aryl Grignard reagents have the formula (IV)

(Wherein R ¹⁰ and R ¹¹ each independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyloxy group. R ¹² and R ¹³ each represent Independently represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group or an aralkyloxy group, or a naphthyl group which may have a substituent together with a phenyl group. X represents a chlorine atom or a bromine atom.)
The production method according to claim 1, wherein the compound is represented by the formula: The production method according to claim 1, wherein the reaction is carried out in the presence of an inorganic salt. The production method according to claim 4, wherein the inorganic salt is at least one selected from an alkali metal halide and an alkaline earth metal halide. The production method according to claim 4, wherein the amount of the inorganic salt used is 0.1 to 10 equivalents with respect to the aryl triflate.