JP2002187894A - 2,2-(diaryl)vinylphosphine compound, its palladium catalyst and method for producing arylamine, diaryl and arylalkyne using the catalyst - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new ligand useful for various catalytic reactions and provide a method for producing arylamines, diaryls and arylalkynes important as intermediates for pharmaceuticals and agrochemicals and as organic electronic materials by using a catalyst containing the ligand. SOLUTION: The new 2,2-(diaryl)vinylphosphine compound is expressed by general formula (1) (R1 is H, a 1-6C alkyl or the like; R2, R3, R4, R5, R6 and R7 are each a 1-6C alkyl or the like; (p), (q), (r) and (s) are each 0-5; and p+q and r+s are each within the range of 0-5). The present invention further relates to a palladium-phosphine catalyst produced by reacting the compound with a palladium compound and a method for producing arylamines, diaryls and arylalkynes in the presence of the palladium-phosphine catalyst.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel 2,2-
(Diaryl) vinylphosphine compounds, the 2,2-
The present invention relates to a palladium-phosphine catalyst obtained by reacting a (diaryl) vinylphosphine compound with a palladium compound. The present invention also relates to a method for obtaining arylamines, diaryls and arylalkynes in the presence of these palladium-phosphine catalysts.

[0002]

2. Description of the Related Art Conventionally, many transition metal complexes have been used as catalysts for organic synthesis reactions. Phosphine compounds play a very important role as ligands required for these catalysts. For example, the Tsuji-Trost reaction is a reaction between an allyl compound and a nucleophile using a palladium catalyst. (Jiro Tsuji, Palladium Reagents and Catalyst
s, JOHN WILEY & SONS, 1995, pp.125-188, pp.290-34
0).

In recent years, SL Buchwald et al. Have disclosed a method of synthesizing an arylamine by amination reaction of an aryl compound having a leaving group (US Pat. No. 5,576,460; 2000/0
2887, SL Buchwald et al, J. Org. Ch.
em. 2000, 65, pp. 1158-1174). Also, a method for producing arylamines using a catalyst comprising a trialkylphosphine and a palladium compound is disclosed (JP-A-10-139742). Also disclosed is a method for synthesizing diaryls by a coupling reaction between an arylboronic acid compound or an arylboronic ester compound and an aryl compound having a leaving group (AF Littke et al, J. Am. Chem. Soc. . 2000, 12
2, pp.4020-4028. DZ Adriano et al, Tetrahedron
Letters, 2000, 41, pp. 8199-8202. N. Miyaura and
A. Suzuki, Chem. Rev. 1995, 95, pp. 2457-2483).
Furthermore, a method for synthesizing aryl alkynes by coupling reaction between an alkyne compound and an aryl compound having a leaving group has been disclosed (HF. Chow et al, J. Org.
Chem. 2001, 66, pp. 1910-1913. Y. Nishihara et al,
J. Org. Chem. 2000, 65, pp. 1780-1787. JF. Nguef
ack et al, Tetrahedron Letters, 1996, 37, pp. 5527
-5530.NA Bumagin et al, Tetrahedron Letters, 1
996, 37, pp. 897-900.).

[0004] It is important to construct an optimum catalyst depending on the reaction or reaction substrate of interest, but combinations of metal species and phosphine ligands constituting the catalyst are various and complicated. Therefore, even if a phosphine ligand that has been developed to date is used, the catalytic activity and the like are insufficient.
There may be problems in actual industrialization, and it is important to develop new phosphine ligands.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a novel ligand useful for various catalytic reactions, and furthermore, using a catalyst containing this ligand, an intermediate for medicinal and agricultural chemicals and an organic compound. An object of the present invention is to provide a method for producing arylamines, diaryls and arylalkynes which are important as electronic materials.

[0006]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have found that a novel 2,2-
A (diaryl) vinylphosphine compound has been found.
Further, the catalyst comprising the 2,2- (diaryl) vinylphosphine compound and the palladium compound is used for an amination reaction of an aryl compound having a leaving group, an aryl compound having a leaving group and an arylboronic acid compound or an arylboronic acid. Effective in the coupling reaction with an ester compound and the coupling reaction between an aryl compound having a leaving group and an alkyne compound, and can efficiently produce arylamines, diaryls and arylalkynes in a short time. And completed the present invention.

That is, the present invention includes the following inventions. 1. The following general formula (1)

[0008]

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[0009] (In the formula, R ¹ represents a hydrogen atom, C 1 to 6 alkyl group having a carbon alicyclic group having from 5 to 7 carbon atoms, be optionally substituted phenyl group; R ² and R ³ may be the same or different, and each represents an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, or a phenyl group which may have a substituent; R ⁴ , R ⁵ , R ⁶ and R ⁷ may be the same or different and each have an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, or a substituent. An optionally substituted phenyl group, an alkoxy group having 1 to 6 carbon atoms, a dialkylamino group having 1 to 3 carbon atoms, a halogen atom, a benzyl group, a naphthyl group, a lower halogen-substituted alkyl group having 1 to 2 carbon atoms,
R ⁴ and R ⁵ and R ⁶ and R ⁷ may together form a fused benzene ring, a fused substituted benzene ring, a trimethylene group, a tetramethylene group, a methylenedioxy group;
p, q, r and s are each 0 to 5, and p + q
And r + s are in the range of 0-5. 2)
2- (diaryl) vinylphosphine compounds. 2. 2. A palladium-phosphine catalyst obtained by allowing a palladium compound to act on the 2,2- (diaryl) vinylphosphine compound according to the above item 1. 3. 3. The palladium-phosphine catalyst according to the above item 2, wherein the palladium compound is a tetravalent, divalent or zero-valent palladium salt or a palladium complex. 4. The following general formula (2) ArX ¹ (2) using an amine compound in the presence of a base (wherein, Ar is an aryl group which may have a substituent and a heteroaryl which may have a substituent Group; X ¹
Represents a halogen atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group, or a toluenesulfonyloxy group. 4. A process for producing arylamines, wherein the palladium-phosphine catalyst according to the above item 2 or 3 is used in the amination reaction with the aryl compound represented by the formula (2). 5. Aryl compounds represented by the following general formula (2) ArX ¹ (2) (where Ar and X ¹ have the same meanings as described above) using an arylboronic acid or an arylboronic ester in the presence of a base. 4. A method for producing a diaryl, wherein the palladium-phosphine catalyst described in the above item 2 or 3 is used in the carbon-carbon bonding reaction with the compound. 6. A carbon-carbon bond with an aryl compound represented by the following general formula (2) ArX ¹ (2) (wherein Ar and X ¹ have the same meanings as described above) using an alkyne compound in the presence of a base 4. A method for producing an aryl alkyne, comprising using the palladium-phosphine catalyst described in the above item 2 or 3 in the reaction.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail. In the compound (1) of the present invention, R ¹ is
A hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, and a phenyl group which may have a substituent. Desirable R ¹ is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, an alicyclic group having 6 carbon atoms, or a phenyl group. Specific examples of R ¹ include, for example, a hydrogen atom; methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, pentyl, hexyl, etc. 1 to 6 carbon atoms
Alkyl group; cyclopentyl group, cyclohexyl group,
An alicyclic group having 5 to 7 carbon atoms such as a cycloheptyl group; methyl group, ethyl group, propyl group, isopropyl group, n-
Butyl group, tert-butyl group, isobutyl group, sec
-Lower alkyl groups having 1 to 4 carbon atoms such as butyl group, lower alkoxy groups having 1 to 4 carbon atoms such as methoxy group, ethoxy group, propoxy group and butoxy group, dimethylamino group, diethylamino group, dipropylamino group, etc. And a phenyl group which may have a substituent such as a lower dialkylamino group having 1 to 3 carbon atoms, a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

R ² and R ³ may be the same or different, and each may have an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, or a substituent. A good phenyl group. Desirable R ² and R ³ may be the same or different and are each a lower alkyl group having 1 to 4 carbon atoms, an alicyclic group having 6 carbon atoms, or a phenyl group. R
Specific examples of ² and R ³ include, for example, methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, te
C1-C6 alkyl groups such as rt-butyl group, isobutyl group, sec-butyl group, pentyl group and hexyl group; C5-C7 alicyclic groups such as cyclopentyl group, cyclohexyl group and cycloheptyl group A methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group,
a lower alkyl group having 1 to 4 carbon atoms such as a tert-butyl group, an isobutyl group and a sec-butyl group, a methoxy group,
C1 such as ethoxy, propoxy, butoxy, etc.
1 to 3 carbon atoms such as lower alkoxy, dimethylamino, diethylamino, dipropylamino, etc.
And a phenyl group which may have a substituent such as a halogen atom such as a lower dialkylamino group, a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

R ⁴ , R ⁵ , R ⁶ and R ⁷ may be the same or different and each may be an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, or a substituent. A phenyl group, an alkoxy group having 1 to 6 carbon atoms, a dialkylamino group having 1 to 3 carbon atoms, a halogen atom, a benzyl group, a naphthyl group, a lower halogen-substituted alkyl group having 1 to 2 carbon atoms, R ⁴ and R ⁵ and R ⁶ and R ⁷ may be taken together to form a fused benzene ring, a fused substituted benzene ring, a trimethylene group, a tetramethylene group, a methylenedioxy group; q, r and s are each 0
To 5 and p + q and r + s are in the range of 0 to 5. Desirable R ⁴ , R ⁵ , R ⁶ and R ⁷ may be the same or different, and each is preferably a lower alkyl group having 1 to 4 carbon atoms, a lower alkoxy group having 1 to 4 carbon atoms, or 1 to 4 carbon atoms. 2, a di-lower alkylamino group and a halogen atom, wherein R ⁴ and R ⁵ and R ⁶ and R ⁷ may be taken together to form a fused benzene ring or a methylenedioxy group;
p, q, r and s are each 0 to 2. R ⁴ ,
Specific examples of R ⁵ , R ⁶ and R ⁷ include a hydrogen atom; a carbon number such as a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, a tert-butyl group, an isobutyl group and a sec-butyl group. A lower alkyl group having 1 to 4 carbon atoms; an alicyclic group having 5 to 7 carbon atoms such as a cyclopentyl group, a cyclohexyl group and a cycloheptyl group; a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group and a tert- group;
C1-C4 lower alkyl groups such as butyl group, isobutyl group and sec-butyl group; C1-C4 lower alkoxy groups such as methoxy group, ethoxy group, propoxy group and butoxy group, dimethylamino group, diethylamino A lower dialkylamino group having 1 to 3 carbon atoms such as a dipropylamino group, a fluorine atom, a chlorine atom, a bromine atom,
A phenyl group which may have a substituent such as a halogen atom such as an iodine atom; a lower alkoxy group having 1 to 4 carbon atoms such as a methoxy group, an ethoxy group, a propoxy group and a butoxy group; a dimethylamino group, a diethylamino group, C1-C3 lower dialkylamino group such as dipropylamino group; halogen atom such as fluorine atom, chlorine atom, bromine atom and iodine atom; benzyl group; naphthyl group; trifluoromethyl group, trichloromethyl group, tribromo Examples thereof include a lower halogen-substituted alkyl group having 1 or 2 carbon atoms such as methyl. Further, R ⁴ and R ⁵ and R ⁶ and R ⁷ may together form a condensed benzene ring, a condensed substituted benzene ring, a trimethylene group, a tetramethylene group, or a methylenedioxy group.

In the present invention, the compound represented by the general formula (1)
Preferred specific examples of the 2- (diaryl) vinylphosphine compound include, but are not limited to, compounds shown in Tables 1 to 17 below. Tables 1-1
The abbreviations used in 7 have the following meanings,
Abbreviations used in each compound described later in this specification have the same meaning. The numbers indicate the substituents on the phenyl group (for example, 4-Me means a methyl group substituted at the 4-position of the phenyl group).

Me methyl group Et ethyl group nPr n-propyl group iPr isopropyl group nBu n-butyl group iBu isobutyl group tButert-butyl group MeO methoxy group EtO ethoxy group F fluorine atom Cl chlorine atom Br bromine atom Me ₂ N dimethyl Group Et ₂ N diethylamino group CyPe cyclopentyl group CyHx cyclohexyl group Ph phenyl group p-Tol p-tolyl group Xy 2,4-xylyl group 2,3-benzene; condensed with a benzene ring to form α-
It means forming a naphthyl group. 3,4-benzene; condensed with a benzene ring to form β-
It means forming a naphthyl group.

[0015]

[Table 1]

[0016]

[Table 2]

[0017]

[Table 3]

[0018]

[Table 4]

[0019]

[Table 5]

[0020]

[Table 6]

[0021]

[Table 7]

[0022]

[Table 8]

[0023]

[Table 9]

[0024]

[Table 10]

[0025]

[Table 11]

[0026]

[Table 12]

[0027]

[Table 13]

[0028]

[Table 14]

[0029]

[Table 15]

[0030]

[Table 16]

[0031]

[Table 17]

The compound (1) of the present invention is produced, for example, by the method shown by the following reaction.

[0033]

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Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ ,
R ⁷ , p, q, r and s are as defined above; X
Is a halogen atom, and R is a lower alkyl group having 1 to 4 carbon atoms. )

That is, as described above, the method comprises the following five steps. First step: a) a method of reacting a diaryl ketone (3) with a Grignard reagent (5); b) an ester (4)
Reacting with a Grignard reagent (6) and / or (7) to obtain an alcohol compound (8). Second step: a step of obtaining a vinyl compound (9) by dehydrating the alcohol compound (8) using an acidic catalyst (for example, p-toluenesulfonic acid or the like). Third step: a step of obtaining a dihalide compound (10) by adding a halogen to the vinyl compound (9). Fourth step: a step of dehydrohalogenating the dihalide compound (10) using a base (for example, pyridine or the like) as necessary to obtain a vinyl halide compound (11). Fifth step: manufactured by a coupling reaction between a vinyl lithium or vinyl Grignard reagent prepared by reacting a metal lithium, alkyl lithium, or metal magnesium with a vinyl halide compound (11) and a phosphorus halide compound (12). Obtaining a 2,2- (diaryl) vinylphosphine compound (1) which is the compound of the present invention.

In compounds 3 to 10 in the above formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , p, q, r
And s have the same meaning as described above; X is a halogen atom, and R in compound 4 is a lower alkyl group having 1 to 4 carbon atoms. Specific examples of R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ are, for example, the same as those described above. Specific examples of X include, for example, halogen atoms such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Specific examples of R include methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-
Examples thereof include a lower alkyl group having 1 to 4 carbon atoms such as a butyl group.

As the diaryl ketones (3) and esters (4), commercially available ones (for example, those sold by Tokyo Chemical Industry Co., Ltd., Nacalai Tesque Co., Ltd.) can be used as they are. Or may be separately synthesized by a known method. As the Grignard reagents (5), (6), and (7), the corresponding halogen compounds which are commercially available or those prepared by a known method using a halogen compound synthesized by a known method are used. be able to.

A) a method of reacting a diaryl ketone (3) with a Grignard reagent (5) in the first step;
b) Esters (4) and Grignard reagent (6) and / or
Or alcohol compound (8) by reacting with (7)
In the step of obtaining the compound, a usual Grignard reaction can be used. In the Grignard reaction a), an alcohol compound (8) can be obtained by reacting a diaryl ketone (3) with a Grignard reagent (5). The amount of the Grignard reagent (5) to be used is preferably about 0.5 to 10 moles, particularly preferably about 0.8 to 3.0 moles, per mole of the diaryl ketone (3). Specific examples of the reaction solvent include ether solvents such as diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, dioxane, 1,3-dioxolan, and the like. Preferably, diethyl ether and tetrahydrofuran are used. The amount of the solvent to be used is preferably about 1.0 to 80 times the volume of the diaryl ketones (3), particularly preferably about 2.0 to 2.0 times.
The capacity should be 30 times. In this reaction, a suitable additive may be added to accelerate the reaction. Specific examples of additives include cesium trichloride, zinc chloride, zinc bromide,
Examples thereof include copper chloride, copper bromide, copper iodide, aluminum trichloride, and titanium tetrachloride. Preferably, cesium trichloride, copper chloride, copper bromide, and copper iodide are used. Also,
The amount of the additive used is based on the amount of the diaryl ketone (3).
The molar amount is preferably about 0.01 to 10 times, particularly preferably about 0.05 to 3.0 times. Further, this reaction is usually performed in an atmosphere of an inert gas such as nitrogen gas or argon gas. In this reaction, the reaction time is generally about 10 minutes to 30 hours, preferably 30 minutes to 1 hour.
The reaction temperature is usually about -20 to 100 ° C.
The reaction is completed at about 0 ° C., preferably about 0 ° C. to 70 ° C., and these conditions can be appropriately changed depending on the type and amount of the diaryl ketones (3) and Grignard reagent (5) used.

The method b) of the Grignard reaction is as follows:
The alcohol compound (8) can be obtained by reacting the esters (4) with the Grignard reagents (6) and / or (7). The amount of the Grignard reagents (6) and (7) to be used is preferably about 1.0- to 10-fold the molar amount of the ester (4), particularly preferably about 1.6- to 10-fold.
It may be 4.8 moles. Specific examples of the reaction solvent include diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, dioxane, 1,
Ether solvents such as 3-dioxolane are mentioned, and diethyl ether and tetrahydrofuran are preferably used. The amount of the solvent used is preferably about 1.0 to 50 times, more preferably about 4.0 to 10 times the volume of the ester (4). Also,
In this reaction, an appropriate additive may be added to accelerate the reaction. Specific examples of additives include cesium trichloride,
Zinc chloride, zinc bromide, copper chloride, copper bromide, copper iodide, aluminum trichloride, titanium tetrachloride, but preferably, cesium trichloride, copper chloride, copper bromide, using copper iodide Good. The amount of the additive to be used is preferably about 0.01 to 10 mol, particularly preferably about 0.05 to 3.0 mol, per mol of the ester (4).
Further, this reaction is usually performed in an atmosphere of an inert gas such as nitrogen gas or argon gas. In this reaction, the reaction time is generally about 10 minutes to 30 hours, preferably about 30 minutes to 8 hours, and the reaction temperature is usually -20.
The reaction is completed at about 100 ° C to about 100 ° C, preferably about 0 ° C to 70 ° C. These conditions are appropriately determined depending on the type and amount of the esters (4) and Grignard reagents (6) and (7) used. Can be changed. In the above a) and b), after completion of the reaction, the target compound can be obtained by performing ordinary post-treatment.

In the second step, the alcohol compound (8) is
In the step of obtaining a vinyl compound (9) by dehydration using an acidic catalyst (for example, p-toluenesulfonic acid), a usual dehydration reaction can be used. Specific examples of the acidic catalyst include hydrochloric acid, sulfuric acid, camphorsulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and the like. Preferably, p-toluenesulfonic acid is used. The amount of the acidic catalyst used is preferably about 0.0001 to about the alcohol compound (8).
0.2 times mol, particularly preferably about 0.005 to 0.05
It is good to make it twice the mole. Specific examples of the reaction solvent include aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; and ether solvents such as diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, dioxane, and 1,3-dioxolan. Preferably, benzene, toluene, or xylene is used. The amount of the solvent to be used is preferably about 1.0 to 50 times, more preferably about 2.0 to 20 times the volume of the alcohol compound (8). Further, this reaction is usually performed in an atmosphere of an inert gas such as nitrogen gas or argon gas. In this reaction,
The reaction time is usually about 10 minutes to 30 hours, preferably 3 minutes.
The reaction temperature is usually about 20 to 18 hours.
The reaction is completed at about 0 ° C., preferably about 70 to 140 ° C., and these conditions can be appropriately changed depending on the type and amount of the alcohol compound (8) and the acidic catalyst used. After completion of the reaction, the desired compound can be obtained by performing ordinary post-treatment.

In the third step, by adding a halogen to the vinyl compound (9), the dihalide compound (1
In the step of obtaining 0), a usual halogen addition reaction to an olefin can be used. Specific examples of halogen include chlorine, bromine, and iodine, and bromine is preferably used. The amount of the halogen used is preferably about 0.5 to 2.0 with respect to the vinyl compound (9).
The molar ratio is particularly preferably about 0.8 to 1.2 times. Specific examples of the reaction solvent include aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene;
Diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, dioxane, 1,3-
Ether solvents such as dioxolane; dichloromethane,
Chloroform, carbon tetrachloride, dichloroethane, dibromomethane, halogenated solvents such as dibromoethane, and the like, preferably dichloromethane, dichloroethane,
Halogen solvents such as chloroform and carbon tetrachloride are preferably used. The amount of the solvent used is the vinyl compound (9)
On the other hand, the capacity is preferably about 0.2 to 50 times, particularly preferably about 0.5 to 20 times. Further, this reaction is usually performed in an atmosphere of an inert gas such as nitrogen gas or argon gas. In this reaction, the reaction time is generally about 10 minutes to 24 hours, preferably 30 minutes to 8 hours.
The reaction is usually carried out at a temperature of about -60 to 100 ° C., preferably about -30 to 50 ° C., and the reaction is completed. These conditions are based on the vinyl compound (9) and halogen used. Can be appropriately changed depending on the type and amount of After completion of the reaction, the desired compound can be obtained by performing ordinary post-treatment.

The dihalide compound (10) in the fourth step
Is subjected to dehydrohalogenation using a base, if necessary, to obtain a vinyl halide compound (11), by using a usual dehydrohalogenation reaction. Specific examples of the base include triethylamine, dimethylaniline, diethylaniline, pyridine, picoline, lutidine, ethylpyridine, quinoline, and isoquinoline. Preferably, pyridine is used. The amount of the base to be used is preferably about 0.5 to 30 moles, particularly preferably about 1.0 to 10 moles, per mole of the dihalide compound (10). Specific examples of the reaction solvent include aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; and ether solvents such as diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, dioxane, and 1,3-dioxolan. Preferably, benzene, toluene, or xylene is used. The amount of solvent used is
Preferably about 0.2 to the dihalide compound (10)
The volume is preferably 30 to 30 times, particularly preferably about 0.5 to 10 times. Further, this reaction is usually performed in an atmosphere of an inert gas such as nitrogen gas or argon gas. In this reaction, the reaction time is generally about 10 minutes to 30 hours, preferably about 30 minutes to 16 hours, and the reaction temperature is usually about 20 to 140 ° C, preferably 60 to 110 ° C.
The reaction is completed at about ° C, and these conditions can be appropriately changed depending on the type and amount of the dihalide compound (10) and the base used. After completion of the reaction, the desired compound can be obtained by performing ordinary post-treatment.

In the fifth step, the vinyl halide compound (1
1) The compound of the present invention, which is produced by a coupling reaction between a vinyl lithium or vinyl Grignard reagent prepared by reacting a metal lithium, alkyl lithium or metal magnesium with a phosphorus halide compound (12), In the step of obtaining the 2- (diaryl) vinyl phosphine compound (1), a conventional binding reaction between a lithium reagent or a Grignard reagent and a phosphorus halide compound can be used. The amount of the metal lithium, alkyl lithium and metal magnesium used is preferably about 0.5 to 0.5 with respect to the vinyl halide compound (11).
The molar ratio is preferably 3.0 times, particularly preferably about 0.8 to 1.5 times. The amount of the phosphorus halide compound (12) to be used is preferably about 0.5 to 3.0 times mol, particularly preferably about 0.1 mol, per mol of the vinyl halide compound (11).
It is good to be 7 to 1.5 times mol. Specific examples of the reaction solvent include diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, dioxane,
Ether solvents such as 1,3-dioxolane are exemplified, and diethyl ether and tetrahydrofuran are preferably used. The amount of the solvent used is preferably about 1.0 to 50 with respect to the vinyl halide compound (11).
The capacity is doubled, particularly preferably about 4.0 to 30 times. In this reaction, a suitable additive may be added to accelerate the reaction. Specific examples of additives include copper chloride, copper bromide, copper iodide, copper triflate, copper cyanide,
Examples thereof include copper iodide dimethylsulfide complex, copper iodide triphenylphosphine complex, and copper iodide tributylphosphine complex. Copper chloride, copper bromide, and copper iodide are preferably used. The amount of the additive used is preferably about 0.01 to about the vinyl halide compound (11).
The molar ratio is preferably 10-fold, particularly preferably about 0.05 to 3.0-fold. Further, this reaction is usually performed in an atmosphere of an inert gas such as nitrogen gas or argon gas. Also,
In this reaction, the reaction time is generally about 10 minutes to 40 hours, preferably about 30 minutes to 24, and the reaction temperature is
Usually about -100 to 120 ° C, preferably -80 to 80
The reaction is completed at about ℃, and these conditions can be appropriately changed depending on the kind and amount of the vinyl halide compound (11) and the phosphorus halide compound (12) used. After completion of the reaction, the desired compound can be obtained by performing ordinary post-treatment.

The compound (1) of the present invention thus obtained forms a palladium-phosphine catalyst together with a palladium compound as a ligand. The palladium compound used as a catalyst precursor for forming the palladium-phosphine catalyst is not particularly limited, but tetravalent, divalent and zero-valent palladium salts and palladium complexes are mainly used. Specific examples of the palladium compound include tetravalent palladium compounds such as sodium hexachloropalladium (IV) tetrahydrate, potassium hexachloropalladium (IV), palladium (II) chloride,
Palladium (II) bromide, palladium (II) acetate, palladium acetylacetonate (II), dichlorobis (benzonitrile) palladium (II), dichlorobis (acetonitrile) palladium (II), dichlorobis (triphenylphosphine) palladium (II) , Dichlorotetraamminepalladium (II), dichloro (cycloocta-1,5-diene) palladium (II), palladium trifluoroacetate (II), π-allylpalladium chloride dimer (II) and other trivalent palladium compounds, Zero-valent palladium compounds such as dibenzylideneacetone) dipalladium (0), tris (dibenzylideneacetone) dipalladium-chloroform complex (0), tetrakis (triphenylphosphine) palladium (0), etc. It is below.

A palladium-phosphine catalyst obtained by reacting a novel 2,2- (diaryl) vinylphosphine compound (1) with a palladium compound is described, for example, in the literature (Y. Uozumi and T. Hayashi, J. Am. Chem. . So
c., 1991, 113, 9887).
2,2- (diaryl) vinylphosphine compound (1)
And π-allylpalladium chloride dimer (II).

As described above, the novel 2,2 of the present invention
A palladium-phosphine catalyst obtained by reacting a-(diaryl) vinylphosphine compound (1) with a palladium compound reacts with a reaction substrate (amine compound, arylboronic acid, arylboronic ester, alkyne compound) in the presence of a base. It can be used as a catalyst in an amination reaction or a carbon-carbon bonding reaction with an aryl compound having a leaving group.

The aryl compound having a leaving group in the present invention is represented by the general formula (2): ArX ¹ (2) (wherein, Ar represents an aryl group which may have a substituent and a substituent An optionally substituted heteroaryl group; X ¹
Represents a halogen atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group, or a toluenesulfonyloxy group. ).

The aryl compound (2) used in the present invention is not particularly limited, but specific examples include the following aryl bromides, aryl chlorides,
Compounds such as aryl iodides, aryl fluorides, aryl trifluoromethanesulfonates, arylmethanesulfonates, aryl p-toluenesulfonates, and aryl halides having two or more halogen atoms can be exemplified. .

That is, bromobenzene, o-bromoanisole, m-bromoanisole, p-bromoanisole, o-bromotoluene, m-bromotoluene, p-bromotoluene, o-bromophenol, m-bromophenol, p-bromophenol Bromophenol, 2-bromobenzotrifluoride, 3-bromobenzotrifluoride, 4-bromobenzotrifluoride, 1-bromo-2,4-dimethoxybenzene, 1-bromo-2,5-dimethoxybenzene,
2-bromophenethyl alcohol, 3-bromophenethyl alcohol, 4-bromophenethyl alcohol, 5-
Bromo-1,2,4-trimethylbenzene, 2-bromo-m-xylene, 2-bromo-p-xylene, 3-bromo-o-xylene, 4-bromo-o-xylene, 4-bromo-m-xylene , 5-bromo-m-xylene, 1-
Bromo-3- (trifluoromethoxy) benzene, 1-
Bromo-4- (trifluoromethoxy) benzene, 2-
Bromobiphenyl, 3-bromobiphenyl, 4-bromobiphenyl, 4-bromo-1,2- (methylenedioxy) benzene, 1-bromonaphthalene, 2-bromonaphthalene, 1-bromo-2-methylnaphthalene, 1-bromo -4-methylnaphthalene, 1,4-dibromonaphthalene, 4,4′-dibromobiphenyl, 2-bromothiophene, 3-bromothiophene, 2-bromopyridine,
-Bromopyridine, 4-bromopyridine, 9-bromophenanthrene, 2-bromofuran, 3-bromofuran,
Aryl bromides such as

Chlorobenzene, o-chloroanisole,
m-chloroanisole, p-chloroanisole, o-chlorotoluene, m-chlorotoluene, p-chlorotoluene, o-chlorophenol, m-chlorophenol, p
-Chlorophenol, 2-chlorobenzotrifluoride,
3-chlorobenzotrifluoride, 4-chlorobenzotrifluoride, 1-chloro-2,4-dimethoxybenzene,
1-chloro-2,5-dimethoxybenzene, 2-chlorophenethyl alcohol, 3-chlorophenethyl alcohol, 4-chlorophenethyl alcohol, 5-chloro-
1,2,4-trimethylbenzene, 2-chloro-m-xylene, 2-chloro-p-xylene, 3-chloro-o-
Xylene, 4-chloro-o-xylene, 4-chloro-m
-Xylene, 5-chloro-m-xylene, 1-chloro-
3- (trifluoromethoxy) benzene, 1-chloro-
4- (trifluoromethoxy) benzene, 2-chlorobiphenyl, 3-chlorobiphenyl, 4-chlorobiphenyl, 1-chloronaphthalene, 2-chloronaphthalene, 1
-Chloro-2-methylnaphthalene, 1-chloro-4-methylnaphthalene, 1,4-dichloronaphthalene, 4,
4'-dichlorobiphenyl, 2-chlorothiophene, 3
Aryl chlorides such as -chlorothiophene, 2-chloropyridine, 3-chloropyridine, 4-chloropyridine, 9-chlorophenanthrene, 2-chlorofuran, 3-chlorofuran;

Iodobenzene, o-iodoanisole,
m-iodoanisole, p-iodoanisole, o-iodotoluene, m-iodotoluene, p-iodotoluene, o-iodophenol, m-iodophenol, p
-Iodophenol, 2-iodobenzotrifluoride,
3-iodobenzotrifluoride, 4-iodobenzotrifluoride, 1-iodo-2,4-dimethoxybenzene,
1-iodo-2,5-dimethoxybenzene, 2-iodophenethyl alcohol, 3-iodophenethyl alcohol, 4-iodophenethyl alcohol, 5-iodo-
1,2,4-trimethylbenzene, 2-iodo-m-xylene, 2-iodo-p-xylene, 3-iodo-o-
Xylene, 4-iodo-o-xylene, 4-iodo-m
-Xylene, 5-iodo-m-xylene, 1-iodo-
3- (trifluoromethoxy) benzene, 1-iodo-
4- (trifluoromethoxy) benzene, 2-iodobiphenyl, 3-iodobiphenyl, 4-iodobiphenyl, 1-iodonaphthalene, 2-iodonaphthalene, 1
-Iodo-2-methylnaphthalene, 1-iodo-4-methylnaphthalene, 1,4-diiodonaphthalene, 4,
4'-diiodobiphenyl, 2-iodothiophene, 3
Aryl iodides such as -iodothiophene, 2-iodopyridine, 3-iodopyridine, 4-iodopyridine, 9-iodophenanthrene, 2-iodofuran, and 3-iodofuran;

Fluorobenzene, o-fluoroanisole, m-fluoroanisole, p-fluoroanisole, o-fluorotoluene, m-fluorotoluene, p
-Fluorotoluene, o-fluorophenol, m-fluorophenol, p-fluorophenol, 2-fluorobenzotrifluoride, 3-fluorobenzotrifluoride, 4-fluorobenzotrifluoride, 1-fluoro-2,4 -Dimethoxybenzene, 1-fluoro-2,5
-Dimethoxybenzene, 2-fluorophenethyl alcohol, 3-fluorophenethyl alcohol, 4-fluorophenethyl alcohol, 5-fluoro-1,2,4-
Trimethylbenzene, 2-fluoro-m-xylene, 2
-Fluoro-p-xylene, 3-fluoro-o-xylene, 4-fluoro-o-xylene, 4-fluoro-m-
Xylene, 5-fluoro-m-xylene, 1-fluoro-3- (trifluoromethoxy) benzene, 1-fluoro-4- (trifluoromethoxy) benzene, 2-fluorobiphenyl, 3-fluorobiphenyl, 4-fluorobiphenyl , 4-fluoro-1,2- (methylenedioxy) benzene, 1-fluoronaphthalene, 2-fluoronaphthalene, 1-fluoro-2-methylnaphthalene,
1-fluoro-4-methylnaphthalene, 1,4-difluoronaphthalene, 4,4′-difluorobiphenyl, 2
-Fluorothiophene, 3-fluorothiophene, 2-
Aryl fluorides such as fluoropyridine, 3-fluoropyridine, 4-fluoropyridine, 9-fluorophenanthrene, 2-fluorofuran, and 3-fluorofuran;

Trifluoromethanesulfonyloxybenzene, o-trifluoromethanesulfonyloxyanisole, m-trifluoromethanesulfonyloxyanisole, p-trifluoromethanesulfonyloxyanisole, o-trifluoromethanesulfonyloxytoluene, m-trifluoromethanesulfonyloxytoluene, p -Trifluoromethanesulfonyloxytoluene, o-trifluoromethanesulfonyloxyphenol, m-trifluoromethanesulfonyloxyphenol, p-trifluoromethanesulfonyloxyphenol, 2-trifluoromethanesulfonyloxybenzotrifluoride, 3-trifluoromethanesulfonyloxybenzotrif Chloride, 4-trifluoromethanesulfonyloxybenzotrif Lido, 1-trifluoromethanesulfonyloxy 2,4-dimethoxybenzene, 1-trifluoromethanesulfonyloxy 2,5-dimethoxybenzene, 2-trifluoromethanesulfonyloxyphenethyl alcohol, 3-trifluoromethanesulfonyloxyphenethyl alcohol, 4-trifluoromethane Sulfonyloxyphenethyl alcohol, 5-trifluoromethanesulfonyloxy 1,2,4-trimethylbenzene, 2-trifluoromethanesulfonyloxym
-Xylene, 2-trifluoromethanesulfonyloxy p-xylene, 3-trifluoromethanesulfonyloxy o-xylene, 4-trifluoromethanesulfonyloxy o-xylene, 4-trifluoromethanesulfonyloxy m-xylene, 5-trifluoromethanesulfonyloxym -Xylene, 1-trifluoromethanesulfonyloxy 3- (trifluoromethoxy) benzene, 1
-Trifluoromethanesulfonyloxy 4- (trifluoromethoxy) benzene, 2-trifluoromethanesulfonyloxybiphenyl, 3-trifluoromethanesulfonyloxybiphenyl, 4-trifluoromethanesulfonyloxybiphenyl, 4-trifluoromethanesulfonyloxy1,2- (methylene Dioxy) benzene, 1-trifluoromethanesulfonyloxynaphthalene, 2-trifluoromethanesulfonyloxynaphthalene, 1-trifluoromethanesulfonyloxy 2-methylnaphthalene, 1-trifluoromethanesulfonyloxy 4-methylnaphthalene, 1,4-ditrifluoromethane Sulfonyloxynaphthalene, 4,4'-ditrifluoromethanesulfonyloxybiphenyl, 2-trifluoromethanesulfonyl Oxythiophene, 3-trifluoromethanesulfonyloxythiophene, 2-trifluoromethanesulfonyloxypyridine, 3-trifluoromethanesulfonyloxypyridine, 4-trifluoromethanesulfonyloxypyridine, 9-trifluoromethanesulfonyloxyphenanthrene, 2-trifluoromethanesulfonyloxyfuran Aryltrifluoromethanesulfonates such as, 3-trifluoromethanesulfonyloxyfuran;

Methanesulfonyloxybenzene, o-methanesulfonyloxyanisole, m-methanesulfonyloxyanisole, p-methanesulfonyloxyanisole, o-methanesulfonyloxytoluene, m-methanesulfonyloxytoluene, p-methanesulfonyloxytoluene, o-methanesulfonyloxyphenol, m-methanesulfonyloxyphenol, p-methanesulfonyloxyphenol, 2-methanesulfonyloxybenzotrifluoride, 3-methanesulfonyloxybenzotrifluoride, 4-methanesulfonyloxybenzotrifluoride , 1-methanesulfonyloxy 2,4
-Dimethoxybenzene, 1-methanesulfonyloxy 2,5-dimethoxybenzene, 2-methanesulfonyloxyphenethyl alcohol, 3-methanesulfonyloxyphenethyl alcohol, 4-methanesulfonyloxyphenethyl alcohol, 5-methanesulfonyloxy 1,2,4 -Trimethylbenzene, 2-methanesulfonyloxy m-xylene, 2-methanesulfonyloxy p
-Xylene, 3-methanesulfonyloxy o-xylene, 4-methanesulfonyloxy o-xylene, 4-methanesulfonyloxy m-xylene, 5-methanesulfonyloxy m-xylene, 1-methanesulfonyloxy 3- (trifluoromethoxy ) Benzene, 1-methanesulfonyloxy 4- (trifluoromethoxy) benzene, 2-methanesulfonyloxybiphenyl, 3-methanesulfonyloxybiphenyl, 4-methanesulfonyloxybiphenyl, 4-methanesulfonyloxy 1,2
-(Methylenedioxy) benzene, 1-methanesulfonyloxynaphthalene, 2-methanesulfonyloxynaphthalene, 1-methanesulfonyloxy 2-methylnaphthalene, 1-methanesulfonyloxy 4-methylnaphthalene, 1,4-dimethanesulfonyloxy Naphthalene,
4,4'-dimethanesulfonyloxybiphenyl, 2-
Methanesulfonyloxythiophene, 3-methanesulfonyloxythiophene, 2-methanesulfonyloxypyridine, 3-methanesulfonyloxypyridine, 4-methanesulfonyloxypyridine, 9-methanesulfonyloxyphenanthrene, 2-methanesulfonyloxyfuran, 3-methane Arylmethanesulfonates such as sulfonyloxyfuran; and

P-toluenesulfonyloxybenzene,
o- (p-toluenesulfonyloxy) anisole, m
-(P-toluenesulfonyloxy) anisole, p-
(P-toluenesulfonyloxy) anisole, o-
(P-toluenesulfonyloxy) toluene, m- (p
-Toluenesulfonyloxy) toluene, p- (p-toluenesulfonyloxy) toluene, o- (p-toluenesulfonyloxy) phenol, m- (p-toluenesulfonyloxy) phenol, p- (p-toluenesulfonyloxy) phenol , 2- (p-toluenesulfonyloxy) benzotrifluoride, 3- (p-toluenesulfonyloxy) benzotrifluoride, 4- (p-
Toluenesulfonyloxy) benzotrifluoride, 1-
(P-toluenesulfonyloxy) -2,4-dimethoxybenzene, 1- (p-toluenesulfonyloxy)
2,5-dimethoxybenzene, 2- (p-toluenesulfonyloxy) phenethyl alcohol, 3- (p-toluenesulfonyloxy) phenethyl alcohol, 4-
(P-toluenesulfonyloxy) phenethyl alcohol, 5- (p-toluenesulfonyloxy) -1,2,2
4-trimethylbenzene, 2- (p-toluenesulfonyloxy) -m-xylene, 2- (p-toluenesulfonyloxy) -p-xylene, 3- (p-toluenesulfonyloxy) -o-xylene, 4- ( p-toluenesulfonyloxy) -o-xylene, 4- (p-toluenesulfonyloxy) -m-xylene, 5- (p-toluenesulfonyloxy) -m-xylene, 1- (p-toluenesulfonyloxy) -3 -(Trifluorotrifluoromethoxy) benzene, 1- (p-toluenesulfonyloxy) -4- (trifluoromethoxy) benzene, 2-
(P-toluenesulfonyloxy) biphenyl, 3-
(P-toluenesulfonyloxy) biphenyl, 4-
(P-toluenesulfonyloxy) biphenyl, 4-
(P-toluenesulfonyloxy) -1,2- (methylenedioxy) benzene, 1- (p-toluenesulfonyloxy) naphthalene, 2- (p-toluenesulfonyloxy) naphthalene, 1- (p-toluenesulfonyloxy) -2-methylnaphthalene, 1- (p-toluenesulfonyloxy) -4-methylnaphthalene, 1,4-di (p-toluenesulfonyloxy) naphthalene, 4,
4′-di (p-toluenesulfonyloxy) biphenyl, 2- (p-toluenesulfonyloxy) thiophene, 3- (p-toluenesulfonyloxy) thiophene, 2- (p-toluenesulfonyloxy) pyridine,
3- (p-toluenesulfonyloxy) pyridine, 4-
(P-toluenesulfonyloxy) pyridine, 9- (p
-Toluenesulfonyloxy) phenanthrene, 2-
(P-toluenesulfonyloxy) furan, 3- (p-
Aryl p-toluenesulfonates such as toluenesulfonyloxy) furan; and the like.

Further, 1,2-dibromobenzene, 1,3
-Dibromobenzene, 1,4-dibromobenzene, 9,
10-dibromoanthracene, 9,10-dichloroanthracene, 1-bromo-2-fluorobenzene, 1-bromo-3-fluorobenzene, 1-bromo-4-fluorobenzene, 2-bromochlorobenzene, 3-bromochlorobenzene, -Bromochlorobenzene, 2-bromo-5-chlorotoluene, 3-bromo-4-chlorobenzotrifluoride, 5-bromo-2-chlorobenzotrifluoride, 1-bromo-2,3-dichlorobenzene, 1- Bromo-2,6-dichlorobenzene, 1-bromo-3,5
-Dichlorobenzene, 2-bromo-4-fluorotoluene, 2-bromo-5-fluorotoluene, 3-bromo-
Aryl halides having two or more halogen atoms, such as 4-fluorotoluene, 4-bromo-2-fluorotoluene and 4-bromo-3-fluorotoluene, can also be exemplified as the aryl halide used in the present invention.

The amine compound used in the present invention includes primary amines, secondary amines, imines, amides and the like. Although it does not specifically limit as primary amines, For example, ethylamine, propylamine, butylamine, isobutylamine, tert-
Aliphatic primary amines such as butylamine, pentylamine, cyclopentylamine, hexylamine, cyclohexylamine, heptylamine, octylamine, aniline, o-fluoroaniline, m-fluoroaniline,
p-fluoroaniline, o-anisidine, m-anisidine, p-anisidine, o-toluidine, m-toluidine, p-toluidine, 2-naphthylamine, 2-aminobiphenyl, 4-aminobiphenyl, 3,4-methylenedioxy Aromatic primary amines such as aniline, m-xylidine, p-xylidine and the like can be mentioned.

The secondary amines are not particularly restricted but include, for example, piperazine, 2-methylpiperazine, homopiperazine, N-methylhomopiperazine,
6-dimethylpiperazine, N-methylpiperazine, N-
Ethyl piperazine, N-ethoxycarbonylpiperazine, N-benzylpiperazine, morpholine, 2,6-dimethylmorpholine, piperidine, 2,6-dimethylpiperidine, 3,3-dimethylpiperidine, 3,5-dimethylpiperidine, 2-ethylpiperidine , 4-piperidone, pyrrolidine, 2,5-dimethylpyrrolidine, carbazole, indole, indoline, and other cyclic secondary amines, dimethylamine, diethylamine, N-methylaniline optionally having a substituent on an aromatic ring, N- Non-cyclic secondary amines such as ethylaniline, N-methylbenzylamine, N-methylphenethylamine, diphenylamine derivatives and the like.

The imines are not particularly limited, but include, for example, benzophenone imine and 4,4'-dimethoxybenzophenone imine. The amides are not particularly limited, for example,
2-azetidinone (β-propiolactam), γ-butyrolactam, δ-valerolactam, ε-caprolactam, acetamide, propioamide, cyclohexylcarboxamide, benzamide, N-methylformamide, N-methylacetamide, N-ethylacetamide, N-methylcyclohexylcarboxamide, N-
Methylbenzamide and the like. The arylboronic acid compound or arylboronic ester compound used in the present invention is not particularly limited. For example, phenylboronic acid, 4-methylphenylboronic acid, 2-thienylboronic acid, 2-furanylboron Acid, 2,3,4,5,6-pentafluorophenylboronic acid, 2-fluorophenylboronic acid, 3-fluorophenylboronic acid, 4-fluorophenylboronic acid, 2-
Chlorophenylboronic acid, 3-chlorophenylboronic acid, 4-chlorophenylboronic acid, 2-bromophenylboronic acid, 3-bromophenylboronic acid, 4-bromophenylboronic acid, 2-iodophenylboronic acid, 3-iodophenylboronic acid , 4-iodophenylboronic acid,
2,4-difluorophenylboronic acid, 2,5-difluorophenylboronic acid, 2,6-difluorophenylboronic acid, 3,4-difluorophenylboronic acid, 3,5
-Difluorophenylboronic acid, 4-trifluoromethylphenylboronic acid, 3,5-bis (trifluoromethyl) phenylboronic acid, 3-cyanophenylboronic acid,
Arylboronic acids such as 4-formylphenylboronic acid, 4-methoxyphenylboronic acid, 1-naphthylboronic acid, 2-naphthylboronic acid, ferrocenylboronic acid, 4-hydroxyphenylboronic acid and esters of the above-mentioned boronic acids (Eg, dimethyl ester, diethyl ester, dipropyl ester, pinacol ester, etc.). The alkyne compound used in the present invention is not particularly limited, but includes, for example, acetylene, propyne, 1-butyne, 1-pentyne, 1-hexyne, 1-heptin, 1-octyne, phenylacetylene, -Propyn-1-ol, 3-butyn-1-ol, 2-methyl-3-butyn-2-ol, 1-ethynylcyclohexanol, trimethylsilylacetylene and the like.

In the present invention, the amine compound is used in an amount of 0.1 mol to 50 mol per mol of the aryl compound (2), or 0 to 1 mol of the leaving group on the ring of the aryl compound (2). The compound may be present in the reaction system in a range of 0.1 mol to 50 times mol, but it is more preferable to remove the unreacted amine compound.
It may be present in the reaction system in a range of 0.2 mol to 30 mol per mol, or in a range of 0.2 mol to 60 mol per mol of the leaving group on the ring of the aryl compound (2). . In the present invention, the arylboronic acid compound or the arylboronic ester compound is used in an amount of 0.1 mol to an excess relative to 1 mol of the aryl compound (2), or 1 mol of a leaving group on the ring of the aryl compound (2). May be present in the reaction system in an amount of from 0.1 mol to an excess, but more preferably the aryl compound (2) because the recovery of unreacted arylboronic acid or arylboronic ester compound becomes complicated. In the range of 0.2 to 30 moles per mole,
Alternatively, it may be present in the reaction system in a range of 0.2 mol to 60 mol per 1 mol of the leaving group on the ring of the aryl compound (2). In the present invention, the alkyne compound is used in an amount of 0.1 mol to excess based on 1 mol of the aryl compound (2), or 0.1 mol per 1 mol of the leaving group on the ring of the aryl compound (2).
It is sufficient that the alkyne compound is present in the reaction system in a range of 1 mol to an excess, but it is more preferable to use 0.1 mol per mol of the aryl compound (2) since recovery of the unreacted alkyne compound becomes complicated.
In the range of 2 mol to 30 mol, or the aryl compound (2)
May be present in the reaction system in the range of 0.2 mol to 60 mol per 1 mol of the leaving group on the ring.

The base used in the present invention includes:
It may be selected from an inorganic base and / or an organic base, and is not particularly limited, but is more preferably an alkali metal such as lithium fluoride, sodium fluoride, potassium fluoride, rubidium fluoride, cesium fluoride and the like. Alkali metal or alkaline earth metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, barium carbonate; sodium-methoxide, sodium-ethoxide , Sodium-phenoxide, potassium-methoxide, potassium-ethoxide, potassium-phenoxide, lithium-phenoxide, lithium-tert-butoxide, sodium-t
alkali metal alkoxides such as tert-butoxide, potassium-tert-butoxide and the like; phosphates of alkali metals such as lithium phosphate, potassium phosphate and sodium phosphate; triethylamine, tributylamine,
Tertiary amines such as tripropylamine, triisopropylamine, and tricyclohexylamine; secondary amines such as diethylamine, dipropylamine, diisopropylamine, dibutylamine, and dicyclohexylamine; Even if you add it as it is,
Alternatively, it may be prepared in situ from an alkali metal, an alkali metal hydride, an alkali metal hydroxide, an alkali metal phosphate and an alcohol, and then supplied to a reaction site.

The amount of the base used is preferably at least 0.5 times the mol of the leaving group of the aryl compound (2). If the amount of the base is less than 0.5 mol, the yield of arylamines, diaryls and arylalkynes may be low. Even if a large excess of the base is added, the yield of the arylamines, diaryls and arylalkynes is hardly affected.
It is in the range of ~ 5 times mol.

The reaction in the present invention is usually performed in the presence of an inert solvent. The solvent used is not particularly limited as long as it does not significantly inhibit this reaction, and is not particularly limited. Aliphatic organic solvents such as pentane, hexane, heptane, and octane; alicyclic rings such as cyclohexane and methylcyclohexane Formula organic solvents; Aromatic organic solvents such as benzene, toluene and xylene; Ether organic solvents such as diethyl ether, diisopropyl ether, dimethoxyethane, tetrahydrofuran, dioxane, and dioxolane; acetonitrile, dimethylformamide, dimethyl sulfoxide, hexa Methyl phosphotriamide and the like can be mentioned. Of these, aromatic organic solvents such as benzene, toluene, and xylene, and ether organic solvents such as diethyl ether, dimethoxyethane, tetrahydrofuran, and dioxane are more preferable.

The catalyst used in this reaction includes a) the above-mentioned palladium compound, base, reaction substrate (amine compound, arylboronic acid, arylboronic ester compound or alkyne compound), aryl compound having a leaving group, and 2 , 2- (diaryl) vinylphosphine compound (1), and b) reacting the palladium compound with a 2,2- (diaryl) vinylphosphine compound (1) and a reaction substrate alone in the presence of a base. The method of charging, c) a palladium compound and a 2,2- (diaryl) vinylphosphine compound (1) are previously mixed in a reaction system to prepare a catalyst, and then, in the presence of a base,
A method in which a reaction substrate and an aryl compound having a leaving group are charged, d) a catalyst prepared in advance by mixing a palladium compound and a 2,2- (diaryl) vinylphosphine compound (1) with a reaction substrate, Equivalent results can be obtained by any of the methods of independently charging an aryl compound having a leaving group.

The amount of the palladium compound used in the amination reaction or the carbon-carbon bonding reaction is 0.001 to 20 mol% based on the amine compound, the arylboronic acid or the arylboronic ester compound or the alkyne compound, Preferably, it is 0.01 to 5 mol%. The amount of the 2,2- (diaryl) vinyl phosphine compound used in this reaction is 0.1 to 10 moles per mole of the palladium compound, and is preferably
It is 1 to 5 times mol.

In the present invention, the palladium compound and the 2,2- (diaryl) vinylphosphine compound (1)
Is required. The present invention can be carried out under normal pressure, in an atmosphere of an inert gas such as nitrogen or argon, or under pressure. The present invention is carried out at a reaction temperature in the range of 10 ° C to 300 ° C, more preferably in the range of 20 ° C to 200 ° C. In the present invention, the reaction time depends on the amount and the amount of the aryl compound (2), the amine compound, the arylboronic acid or the arylboronic acid ester compound or the alkyne compound, the base, the palladium compound and the 2,2- (diaryl) vinylphosphine compound (1). It is not fixed depending on the reaction temperature, but may be selected from a range of several minutes to 72 hours. After the completion of the reaction, the desired compound can be obtained by treating with a conventional method.

[0067]

The novel 2,2- (diaryl) of the present invention
When used together with a palladium compound, the vinyl phosphine compound exhibits excellent performance as a catalyst for the amination reaction of an aryl compound having a leaving group or a carbon-carbon bonding reaction. It is possible to produce amines, diaryls and arylalkynes, which are excellent as industrial catalysts.

[0068]

EXAMPLES The present invention will be described in detail with reference to the following examples, but the present invention is not limited to these examples. The devices used for measuring the physical properties in the examples are as follows. 1) ¹ H-NMR spectrum: GEMINI2000 type device (manufactured by Varian) or DRX-500 type device (manufactured by Bruker) Internal standard substance: tetramethylsilane 2) ³¹ P-NMR spectrum: DRX-500 type device (manufactured by Bruker) External standard substance: 85% phosphoric acid 3) ¹⁹ F-NMR spectrum: DRX-500 type apparatus (manufactured by Bruker) Internal standard substance: trifluoroacetic acid 4) Melting point: Yanaco MP-500D (manufactured by Yanagimoto Co., Ltd.) 5 ) Gas chromatography equipment: GC 353 (GL Sc
ience) Column: NB-1 (30m x 0.25mm) (GL Sci
internal standard substance: o-terphenyl or tridecane 6) Mass spectrum (MS): M-80 mass spectrometer: ionization voltage 20 eV (manufactured by Hitachi, Ltd.)

[0069]

Example 1 Synthesis of 1,1-diphenyl-2- (diphenylphosphino) propene (Exemplified Compound 20) (1) Synthesis of 1-diphenylpropene 96.0 g of magnesium in a reaction vessel under a nitrogen atmosphere.
(3.95 mol) and tetrahydrofuran (hereinafter T
500 mL (abbreviated as HF) was added. Then, after confirming the start of the reaction by adding trace amounts of iodine and benzene bromide, 677 g of benzene bromide was added while maintaining the temperature in the system at about 40 ° C.
A mixture of (4.31 mol) and 1500 mL of THF was slowly dropped, and the mixture was refluxed for 1 hour. While maintaining the temperature in the system at about 40 ° C., 140 g of methyl propionate (1.5 g
9 mol) was slowly added dropwise, and the mixture was further stirred at 60 ° C. for 3 hours. The reaction solution was washed with 0.1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Concentrate with toluene 8
The solution was dissolved in 00 mL, and 3.8 g of p-toluenesulfonic acid monohydrate was added, followed by azeotropic dehydration for 1.5 hours under reflux of toluene. After cooling, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from methanol to obtain 230 g (75%) of the title compound as white crystals. Melting point: 48-49 ° C. ¹ H-NMR (CDCl ₃ ) δ 1.76 (d, J = 7.
1 Hz, 3H), 6.17 (q, J = 7.1 Hz, 1
H), 7.08-7.44 (m, 10H)

(2) Synthesis of 2-bromo-1,1-diphenylpropene 19.4 g (100 mmol) of 1,1-diphenylpropane and 78 mL of 1,2-dichloroethane were added to a reaction vessel under a nitrogen atmosphere. And cooled to 0 ° C., and 15.9 g of bromine
(100 mmol) was slowly added dropwise, followed by stirring at room temperature for 1 hour. Then, 32.4 mL of pyridine (400 m
mol) and 156 mL of toluene.
For 3 hours. After cooling, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was purified by column chromatography and recrystallized from methanol to give 14.5 g (53%) of the title compound as white crystals. Melting point: 46-47 ° C. ¹ H-NMR (CDCl ₃ ) δ 2.43 (s, 3H),
7.14 to 7.38 (m, 10H)

(3) Synthesis of 1,1-diphenyl-2- (diphenylphosphino) propene (exemplary compound 20). Under a nitrogen atmosphere, 1.37 g (5.00 mmol) of 2-bromo-1,1-diphenylpropane and T
HF (14 mL) was added and the mixture was cooled to −70 ° C., and butyllithium (3.4 mL, 1.6 M hexane solution, 5.5 mmol) was added.
After l) was slowly added dropwise, the mixture was stirred for 30 minutes. afterwards,
Chlorodiphenylphosphine 1.1 mL (6.0 mmol
After adding l), the mixture was heated to room temperature and stirred for 13 hours. Water was added to the reaction solution, and the organic layer was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol to give 1.08 g (60%) of the title compound as white crystals. Melting point: 128-130 ° C ¹ H-NMR (CDCl ₃ ) δ 1.70 (d, J = 2.
8 Hz, 3H), 7.12 to 7.47 (m, 20H) ³¹ P-NMR (CDCl ₃ ) δ -4.68

[0072]

Example 2 Synthesis of 1,1-diphenyl-2- (dicyclohexylphosphino) propene (Exemplified Compound 19) Under a nitrogen atmosphere, 2-bromo-1,1-1- obtained in Example 1 (2) was placed in a reaction vessel. 8.50 g of diphenyl propylene (31.
1 mmol) and 85 mL of THF, and the mixture was cooled to -70 ° C.
Stirred for 0 minutes. Thereafter, 8.25 mL (37.3 mmol) of chlorodicyclohexylphosphine was added, and the mixture was stirred for 75 minutes, heated to room temperature, and further stirred for 15.5 hours. Water was added to the reaction solution, and the organic layer was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol to give 8.80 g (72%) of the title compound as white crystals. Melting point: 128-130 ° C ¹ H-NMR (CDCl ₃ ) δ 1.06-1.94
(M, 25H), 7.04~7.36 ( m, 10H) 31 P-NMR (CDCl 3) δ -3.68

[0073]

Example 3 1,1-Diphenyl-2- (di-ter)
Synthesis of t-butylphosphino) propene (Exemplified Compound 17) Under a nitrogen atmosphere, 1.37 g (5.0) of 2-bromo-1,1-diphenylpropene obtained in Example 1 (2) was placed in a reaction vessel.
mmol), 0.134 g of magnesium (5.5 mmol)
l) and 11 mL of THF were added. Then, after confirming the start of the reaction by adding trace amounts of iodine and benzene bromide, the mixture was refluxed for 2 hours. After cooling, 0.520 g of copper chloride (5.3 mmo
l) and 1.1 mL of chlorodi-t-butylphosphine
After adding (5.5 mmol), the mixture was refluxed for 18 hours. The reaction solution was cooled to room temperature, and 14 mL of heptane was added, and the generated crystals were filtered. The crystals were dissolved in 40 mL of ethyl acetate, washed with 28% aqueous ammonia and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol to give the title compound as white crystals.
736 g (43%) were obtained. Melting point: 130-133 ° C ¹ H-NMR (CDCl ₃ ) δ 1.21 (S, 9H),
1.26 (S, 9H), 2.06 (d, J = 1.4H
z, 3H), 7.08-7.36 (m, 10H) ³¹ P-NMR (CDCl ₃ ) δ 30.13

[0074]

Example 4 Synthesis of 1,1-bis (4-dimethylaminophenyl) -2- (diphenylphosphino) propene (Exemplary Compound 105) (1) 1,1-bis (4-dimethylaminophenyl)
Synthesis of propene Ethyl magnesium bromide 10 in a reaction vessel under nitrogen atmosphere
2 mL (0.80 M THF solution, 82.0 mmol)
And cooled to 0 ° C. Thereafter, 20.0 g of 4,4'-bis (dimethylamino) benzophenone (74.5 m
mol) and THF (40 mL) were slowly added dropwise, and the mixture was stirred at room temperature for 5 hours. After adding a saturated aqueous ammonium chloride solution to the reaction solution, the generated metal salt was removed by celite filtration. Then, the organic layer was extracted from the filtrate with toluene, and the solvent was removed under reduced pressure. The concentrate was dissolved in 150 mL of toluene, and 0.1 g of p-toluenesulfonic acid monohydrate was added, followed by azeotropic dehydration under reflux of toluene. After cooling, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. This was purified by column chromatography to obtain 13.6 g (65%) of pale yellow crystals. ¹ H-NMR (CDCl ₃ ) δ 1.77 (d, J = 7.
0 Hz, 3H), 2.92 (s, 6H), 2,98
(S, 6H), 5.94 (q, J = 7.0 Hz, 1
H), 6.58 to 6.79 (m, 4H), 7.02 to
7.18 (m, 4H)

(2) Synthesis of 1,1-bis (4-dimethylaminophenyl) -2-bromopropene Under a nitrogen atmosphere, 13.6 g (48) of 1,1-bis (4-dimethylaminophenyl) propene was added to a reaction vessel. .5mmo
l) and 54 mL of 1,2-dichloroethane were added to
After cooling to ℃ and slowly dropping 7.76 g (48.5 mmol) of bromine, the mixture was stirred at room temperature for 2.5 hours. Thereafter, 15.7 mL (194 mmol) of pyridine and 109 mL of toluene were added, and the mixture was stirred at 80 ° C. for 3 hours. After cooling, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. After the concentrate was purified by column chromatography, it was crystallized from methanol to obtain 12.0 g (69%) of the title compound as green-yellow crystals. Melting point: 119-122 ° C ¹ H-NMR (CDCl ₃ ) δ 2.46 (s, 3H),
2.94 (s, 12H), 6.58 to 6.70 (m, 4
H), 6.96 to 7.20 (m, 4H)

(3) Synthesis of 1,1-bis (4-dimethylaminophenyl) -2- (diphenylphosphino) propene (exemplary compound 105) 1,1-bis (4-dimethyl) was placed in a reaction vessel under a nitrogen atmosphere. Aminophenyl) -2-bromopropyl 3.0 g (8.
3 mmol) and 10 mL of THF were added, and the mixture was cooled to −60 ° C., and 5.2 mL of butyllithium (1.6 M hexane solution, 8.3 mmol) was slowly added dropwise, followed by stirring for 30 minutes. And chlorodiphenylphosphine 1.1
After adding mL (6.0 mmol), the temperature was raised to room temperature and 1 mL
Stir for 6 hours. Water was added to the reaction solution, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized twice from hexane / ethanol to give 1.9 g (60%) of the title compound as white crystals. Melting point: 95-97 ° C ¹ H-NMR (CDCl ₃ ) δ 1.73 (d, J = 2.
8Hz, 3H), 2.91 (s, 6H), 2.95
(S, 6H), 6.52 to 6.69 (m, 4H), 6.
97-7.10 (m, 4H), 7.18-7.49
(M, 10H). ³¹ P-NMR (CDCl ₃ ) δ -2.79

[0077]

Example 5 Synthesis of 1,1-bis (4-dimethylaminophenyl) -2- (dicyclohexylphosphino) propene (Exemplified Compound 120) 1 , 1
-Bis (4-dimethylaminophenyl) -2-bromopropane (1.44 g, 4.00 mmol) and THF1
Add 4 mL and cool to -60 ° C.
After 8 mL (1.6 M hexane solution, 4.4 mmol) was slowly added dropwise, the mixture was stirred at the same temperature for 1 hour. afterwards,
0.97 mL of chlorodicyclohexylphosphine (4.
After stirring for 30 minutes, the temperature was raised to room temperature, and the mixture was further stirred for 17 hours. Water was added to the reaction solution, and the organic layer was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol and hexane to give 0.44 g of the title compound as white crystals.
(23%). Melting point: 159-164 ° C ¹ H-NMR (CDCl ₃ ) δ 1.04-2.15
(M, 25H), 2.91 (s, 6H), 2.92
(S, 6H), 6.50-6.75 (m, 4H), 6.
85-7.08 (m, 4H) ³¹ P-NMR (CDCl ₃ ) δ-2.19

[0078]

Example 6 Synthesis of 1,1-bis (4-dimethylaminophenyl) -2- (di-t-butylphosphino) propene (exemplary compound 118) Example 4 (2) in a reaction vessel under a nitrogen atmosphere. 1,1 obtained in
-Bis (4-dimethylaminophenyl) -2-bromopropane 1.44 g (4.00 mmol), magnesium 0.107 g (4.4 mmol) and THF 11.5
mL was added. Then, after confirming the start of the reaction by adding a small amount of iodine, the mixture was refluxed for 2 hours. After cooling, copper chloride 0.416
g (4.2 mmol) and 0.91 mL (4.4 mmol) of chlorodi-tert-butylphosphine were added, and the mixture was refluxed for 18 hours. The reaction solution was cooled to room temperature, and 22.5 mL of heptane and 7.5 mL of diethyl ether were added, and the generated crystals were filtered. The crystals were converted to ethyl acetate 30m.
L, washed with 28% aqueous ammonia and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol to give the title compound as white crystals, 0.34 g (20%). Melting point: 133-135 ° C ¹ H-NMR (CDCl ₃ ) δ 1.21 (s, 9H),
1.26 (s, 9H), 2.21 (d, J = 1.6H)
z, 3H), 2.91 (s, 6H), 2.92 (s, 6
H), 6.50-6.69 (m, 4H), 6.91-
7.04 (m, 4H) ³¹ P-NMR (CDCl ₃ ) δ 31.68

[0079]

Example 7 Synthesis of 2,2-diphenyl-1- (diphenylphosphino) ethylene (Exemplified Compound 10) (1) Synthesis of 1,1-diphenylethylene 31.6 g of magnesium was placed in a reaction vessel under a nitrogen atmosphere.
(1.30 mol) and 50 mL of THF were added. Then, after confirming the start of the reaction by adding trace amounts of iodine and ethyl bromide, 600 mL of THF was added, and methyl chloride gas was blown in while controlling the blowing amount and temperature so as to keep the temperature at 30 to 40 ° C. After confirming that the heat generation had subsided and the magnesium metal had disappeared, the mixture was stirred at the same temperature for 1 hour. Next, 182 g (1.10 mol) of benzophenone and THF3
64 mL of the mixture was slowly added dropwise at 35 to 40 ° C., and the mixture was further stirred for 15 hours. After cooling, the mixture was poured into a 10% aqueous ammonium chloride solution and stirred for 30 minutes. After liquid separation, the mixture was washed with brine and dried over anhydrous magnesium sulfate. Then, the product concentrated under reduced pressure, 400 mL of toluene and 1 g of p-toluenesulfonic acid monohydrate were added, and azeotropic dehydration was performed for 2 hours under reflux of toluene. After cooling, the mixture was washed with 2% aqueous sodium carbonate and water, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was purified by distillation to give 174 g (97%) of the title compound.
%). Boiling point: 103 ° C / 134Pa (1mmHg)

(2) Synthesis of 1-bromo-2,2-diphenylethylene Under a nitrogen atmosphere, 110 g (0.60 mol) of 1,1-diphenylethylene and 1098 g of carbon tetrachloride were added to a reaction vessel, and 95.9 g of bromine was added. A mixed solution of 0.60 mol) and 288 g of carbon tetrachloride was added dropwise over 1 hour under ice cooling. After completion of the dropwise addition, the mixture was stirred at the same temperature for 7 hours. 119 g of pyridine and 500 mL of toluene were added to the residue obtained by concentrating the reaction solution, and the mixture was refluxed for 3 hours. After cooling, the mixture was washed with 5% hydrochloric acid and water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. After distillation, recrystallization from methanol gave 126 g of the title compound as white crystals (8
1%). Melting point: 45 ° C. ¹ H-NMR (CDCl ₃ ) δ 6.77 (s, 1H),
7,15 to 7,47 (m, 10H)

(3) Synthesis of 2,2-diphenyl-1- (diphenylphosphino) ethylene (exemplified compound 10) 2-Bromo-1,1-diphenylpropene was converted to 2-bromo-1,1-diphenylethylene 1. 30g (5.00m
mol), and the same operation as in Example 1 (3) was performed.
1.03 g (57%) of the title compound was obtained as white crystals. Melting point: 116-118 ° C ¹ H-NMR (CDCl ₃ ) δ 6.85 (d, J = 3.
4 Hz, 1 H), 7.16 to 7.50 (m, 20 H) ³¹ P-NMR (CDCl ₃ ) δ-23.01

[0082]

Example 8 1,1-Diphenyl-2- (dicyclohexylphosphino) -3-methylbutene (Exemplified Compound 4)
Synthesis of 9) (1) Synthesis of 1,1-diphenyl-3-methylbutene In a nitrogen atmosphere, 2.92 g of magnesium (1
20 mmol) and 100 mL of THF were added. Then, after confirming the start of the reaction by adding trace amounts of iodine and benzene bromide, 17.3 g (110 mmol) of benzene bromide was slowly dropped, and the mixture was refluxed for 10 minutes. Then 40
While maintaining the temperature at about 105 ° C., 6.51 g of ethyl isovalerate (5
(0.0 mmol) was added dropwise slowly, and the mixture was refluxed for 3 hours. The reaction solution was washed with 0.1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Concentrate 50mL toluene
And p-toluenesulfonic acid monohydrate 0.05 g
Was added and azeotropic dehydration was performed for 2 hours under toluene reflux. After cooling, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 8.81 g (79%) of a transparent oil. ¹ H-NMR (CDCl ₃ ) δ 1.01 (d, J = 6.
6Hz, 6H), 2.29 to 2.58 (m, 1H),
5.89 (d, J = 10.2 Hz, 1H), 7.13-
7.43 (m, 10H)

(2) Synthesis of 2-bromo-1,1-diphenyl-3-methylbutene Under a nitrogen atmosphere, 8.81 g (39.6 mmol) of 1,1-diphenyl-3-methylbutene and 1,1
35 mL of 2-dichloroethane was added, the mixture was cooled to 0 ° C, and 6.33 g (39.6 mmol) of bromine was slowly added dropwise, followed by stirring at room temperature for 1 hour. The reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol and ethyl acetate to give 8.64 g (72%) of the title compound as white crystals. Melting point: 112-114 ° C ¹ H-NMR (CDCl ₃ ) δ 1.11 (d, J = 6.
6 Hz, 6 H), 2.87 (septet, J = 6.6)
Hz, 1H), 7.13-7.38 (m, 10H)

(3) Synthesis of 1,1-diphenyl-2- (dicyclohexylphosphino) -3-methylbutene (Exemplified Compound 49) Under a nitrogen atmosphere, 2-bromo-1,1-diphenyl-3-methylbutene was placed in a reaction vessel. 1.20g (4.00mmo
l) and 12 mL of THF are added and cooled to -70 ° C.
2.8 mL of butyllithium (1.6 M hexane solution,
4.4 mmol) was slowly added dropwise at the same temperature.
Minutes. Then, 1.1 mL (4.8 mmol) of chlorodicyclohexylphosphine was added, and the mixture was stirred at the same temperature for 3 hours, and then heated to room temperature over 13 hours. Water was added to the reaction solution, and the organic layer was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol and toluene to give 0.72 g (43%) of the title compound as white crystals. Melting point: 162 to 163 ° C. ¹ H-NMR (CDCl ₃ ) δ 0.86 to 2.18
(M, 22H), 1.23 (d, J = 7.0 Hz, 6
H) 2.63-2.92 (m, 1H), 7.05-
7.33 (m, 10H) ³¹ P-NMR (CDCl ₃ ) δ -1.46

[0085]

Example 9 1,2,2-Triphenyl-1- (dicyclohexylphosphino) ethylene (Exemplified Compound 99)
(1) Synthesis of 1,1,2-triphenylethylene Under a nitrogen atmosphere, benzylmagnesium chloride
7 mL (1.06 M-THF solution, 55 mmol) was added, and the mixture was cooled to 0 ° C. Then, benzophenone 9.11
g (50.0 mmol) and a mixed solution of THF (18 mL) were slowly added dropwise, and the mixture was stirred at room temperature for 1 hour. The reaction solution was washed with 0.1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated saline, and then dried over anhydrous magnesium sulfate.
The solvent was removed under reduced pressure. The concentrate was dissolved in 46 mL of toluene, and 0.18 g of p-toluenesulfonic acid monohydrate was added, followed by azeotropic dehydration for 2 hours under reflux of toluene. After cooling, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 12.5 g (98%) of a transparent oil. ¹ H-NMR (CDCl ₃ ) 6.94 to 7.37 (m, 1
6H)

(2) Synthesis of 1-bromo-1,2,2-triphenylethylene Under a nitrogen atmosphere, 12.5 g (48.8 mmol) of 1,1,2-triphenylethylene and 1,2-
50 mL of dichloroethane was added, the mixture was cooled to 0 ° C., and 7.80 g (48.8 mmol) of bromine was slowly added dropwise, followed by stirring at room temperature for 1 hour. The reaction solution was washed with saturated aqueous sodium hydrogen carbonate, saturated aqueous sodium thiosulfate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol and ethyl acetate to give the title compound as white crystals (11.3 g, 69%). Melting point: 116-118 ° C ¹ H-NMR (CDCl ₃ ) δ 6.91-7.42
(M, 15H).

(3) 1,2,2-triphenyl-1-
Synthesis of (dicyclohexylphosphino) ethylene (Exemplified Compound 99) Under a nitrogen atmosphere, 1.68 g (5.0 mmol) of 1-bromo-1,2,2-triphenylethylene and 0.134 g (5.5 mmol) of magnesium were placed in a reaction vessel. ) And TH
F13mL was added. After confirming the start of the reaction by adding trace amounts of iodine and benzene bromide, the mixture was refluxed for 2 hours. After cooling, 0.520 g (5.3 mmol) of copper chloride and 1.2 mL of chlorodicyclohexylphosphine (5.5 m
mol), and the mixture was refluxed for 17 hours. The reaction solution was cooled to room temperature, and 17 mL of heptane was added, and the generated crystals were filtered. Dissolve the crystals in 40 mL of ethyl acetate and add 28%
The extract was washed with aqueous ammonia and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol to give 1.34 g of the title compound as white crystals (5.
9%). Melting point: 121-123 ° C ¹ H-NMR (CDCl ₃ ) δ 0.94-2.00
(M, 22H), 6.84~7.40 ( m, 15H) 31 P-NMR (CDCl 3) δ -0.79

[0088]

Example 10 Synthesis of 1,1-bis (4-methoxyphenyl) -2- (diphenylphosphino) propene (Exemplified Compound 103) (1) Synthesis of 1,1-bis (4-methoxyphenyl) propanol Nitrogen Under an atmosphere, add ethyl magnesium chloride 3 to the reaction vessel.
1.9 mL (0.97 M THF solution, 30.9 mmol
1) and 20 mL of THF were added, and the mixture was cooled to 4 ° C. Then, 5.00 g of 4,4'-dimethoxybenzophenone
(20.6 mmol) and a mixed solution of THF (20 mL) were slowly added dropwise, followed by stirring at room temperature for 1 hour. After adding a saturated aqueous ammonium chloride solution to the reaction solution, the organic layer was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. This was purified by column chromatography to obtain 3.06 g (55%) of the title compound as a pale yellow oil. ¹ H-NMR (CDCl ₃ ) δ 0.86 (t, J = 7.
4 Hz, 3H), 1.96 (br-s, 1H), 2.2
2 (q, J = 7.4 Hz, 2H), 3.79 (s, 6
H), 6.80-6.89 (m, 4H), 7.25-
7.33 (m, 4H)

(2) Synthesis of 1,1-bis (4-methoxyphenyl) propene. Under a nitrogen atmosphere, 2.86 g (10.5 mmol) of 1,1-bis (4-methoxyphenyl) propanol was added to the reaction vessel.
l), 40 mL of toluene and 28 mg of p-toluenesulfonic acid monohydrate were added, and azeotropic dehydration was performed for 2 hours under reflux of toluene. After cooling, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and then 2.60 g of the title compound as pale yellow crystals.
(97%). Melting point: 99-100 ° C. ¹ H-NMR (CDCl ₃ ) δ 1.75 (d, J = 7.
0 Hz, 3H), 3.79 (s, 3H), 3.84
(S, 3H), 6.03 (q, J = 7.0 Hz, 1
H), 6.78-6.81 (m, 2H), 6.90-
6.92 (m, 2H), 7.09 to 7.11 (m, 2H)
H), 7.13 to 7.16 (m, 2H)

(3) Synthesis of 1,1-bis (4-methoxyphenyl) -2-bromopropene In a nitrogen atmosphere, 1.50 g (9.82 mmol) of 1,1-bis (4-methoxyphenyl) propene was added to a reaction vessel. ) And 25 mL of 1,2-dichloroethane, and add -20 ° C.
And 1.57 g (9.82 mmol) of bromine and 1,
After slowly dropping a mixture of 13 mL of 2-dichloroethane, the mixture was stirred at room temperature overnight. The reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to obtain 3.26 g (100%) of the title compound as a pale yellow oil. ¹ H-NMR (CDCl ₃ ) δ 2.43 (s, 3H),
3.78 (s, 6H), 6.81 to 6.84 (m, 4
H), 7.05-7.09 (m, 2H), 7.16-
7.19 (m, 2H)

(4) Synthesis of 1,1-bis (4-methoxyphenyl) -2- (diphenylphosphino) propene (Exemplified Compound 103) 1,1-bis (4-methoxyphenyl) ) -2-Bromopropyl 2.00 g (6.00
mmol) and THF (30 mL), and the mixture was cooled to −65 ° C., and butyllithium (4.0 mL, 1.5 M hexane solution, 6.0 mmol) was slowly added dropwise, followed by stirring for 30 minutes. Then, chlorodiphenylphosphine 0.90
After adding mL (5.0 mmol), at the same temperature for 1 hour,
The temperature was raised to room temperature and stirred for 1 hour. Saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol to give the title compound as white crystals, 1.45.
g (66%). Melting point: 123-125 ° C ¹ H-NMR (CDCl ₃ ) δ 1.71 (d, J = 2.
9Hz, 3H), 3.76 (s, 3H), 3.79
(S, 3H), 6.74-6.77 (m, 2H), 6.
82 to 6.85 (m, 2H), 7.05 to 7.10
(M, 4H), 7.32~7.40 ( m, 10H) 31 P-NMR (CDCl 3) δ -3.73

[0092]

Example 11 Synthesis of 1,1-bis (4-fluorophenyl) -2- (diphenylphosphino) propene (Exemplary Compound 107) (1) Synthesis of 1,1-bis (4-fluorophenyl) propanol Nitrogen Under an atmosphere, 10.0 g of cerium chloride (4
0.6 mmol) and 80 mL of THF, and the mixture was stirred at room temperature for 20 hours. The mixture was cooled to 0 ° C. and 25.1 mL of ethylmagnesium chloride (0.97M-THF)
Solution, 24.3 mmol) was added dropwise over 30 minutes. Then 3.54 g of 4,4'-difluorobenzophenone
(16.2 mmol) and 20 mL of THF
After dropwise addition over 0 minutes, the mixture was stirred for 1 hour. 10
After adding an aqueous solution of acetic acid, the organic layer extracted with ethyl acetate was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. This was purified by column chromatography to obtain 3.12 g (78%) of the title compound as a pale yellow oil. ¹ H-NMR (CDCl ₃ ) δ 0.85 (t, J = 7.
4 Hz, 3H), 2.05 (s, 1H), 2.26
(Q, J = 7.4 Hz, 2H), 6.95-7.00
(M, 4H), 7.32 to 7.37 (m, 4H)

(2) Synthesis of 1,1-bis (4-fluorophenyl) propene Under a nitrogen atmosphere, 2.80 g (11.3 mmol) of 1,1-bis (4-fluorophenyl) propanol was placed in a reaction vessel.
l), 60 mL of toluene and 14 mg of p-toluenesulfonic acid monohydrate were added, and azeotropic dehydration was performed for 1 hour under reflux of toluene. After cooling, the reaction solution was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and then 2.39 g of the title compound as white crystals (9.
2%). Melting point: 43-44 ° C. ¹ H-NMR (CDCl ₃ ) δ 1.74 (d, J = 7.
0 Hz, 3H), 6.09 (q, J = 7.0 Hz, 1
H), 6.91 to 6.96 (m, 2H), 7.04 to
7.08 (m, 2H), 7.10 to 7.17 (m, 4
H)

(3) Synthesis of 1,1-bis (4-fluorophenyl) -2-bromopropene In a nitrogen atmosphere, 2.00 g (8.69 mmol) of 1,1-bis (4-fluorophenyl) propene was added to a reaction vessel. ) And 25 mL of 1,2-dichloroethane, and add -20 ° C.
And 1.39 g (8.69 mmol) of bromine and 1,
After a mixture of 12 mL of 2-dichloroethane was added dropwise over 1 hour, the mixture was stirred at the same temperature for 1 hour and at room temperature for 16 hours.
Next, a mixed solution of 0.703 mL (8.69 mmol) of pyridine and 20 mL of toluene was added dropwise over 15 minutes.
Stirred at 00 ° C. for 2 hours. After cooling, the reaction mixture was added with saturated aqueous sodium hydrogen carbonate, and the organic layer extracted with toluene was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol to give 1.21 g (45%) of the title compound as white crystals. Melting point: 53-54 ° C ¹ H-NMR (CDCl ₃ ) δ 2.42 (s, 3H),
6.98 to 7.03 (m, 4H), 7.11 to 7.13
(M, 2H), 7.19 to 7.23 (m, 2H)

(4) Synthesis of 1,1-bis (4-fluorophenyl) -2- (diphenylphosphino) propene (exemplified compound 107) 1,1-bis (4-fluorophenyl) was placed in a reaction vessel under a nitrogen atmosphere. ) -2-Bromopropyl 0.907 g (2.9
3 mL) and THF (20 mL) were added, the mixture was cooled to -65 ° C, and butyl lithium (2.0 mL, 1.5 M hexane solution, 2.9 mmol) was slowly added dropwise, followed by stirring for 40 minutes. And chlorodiphenylphosphine 0.5
After adding a mixed solution of 8 mL (3.2 mmol) and 5 mL of THF, the mixture was stirred at the same temperature for 2 hours, and then heated to room temperature. Saturated aqueous ammonium chloride was added to the reaction solution, and the organic layer extracted with ethyl acetate was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was recrystallized from methanol to give 0.687 g (57%) of the title compound as white crystals. Melting point: 88-90 ° C. ¹ H-NMR (CDCl ₃ ) δ 1.63 (d, J = 2.
8 Hz, 3H), 6.81 to 6.87 (m, 2H),
6.90 to 6.96 (m, 2H), 7.00 to 7.08
(M, 4H), 7.25~7.32 ( m, 10H) 31 P-NMR (CDCl 3) δ -4.40 19 F-NMR (CDCl 3) δ -115.0, -11
4.9

[0096]

Example 12 Under a nitrogen atmosphere, 0.85 g (5.0 mmol) of diphenylamine and 0.76 g of o-terphenyl as an internal standard substance were added to a reaction vessel and 10 mL of toluene was added.
And dissolved. 0.53 g (5.5 mmol) of sodium t-butoxide and 1-bromo-4-te were added to this mixture.
rt-butylbenzene 0.95 mL (5.5 mmol
l), 2.8 mg of palladium acetate (0.25 mol% /
Amine), and 23.2 mg (1.0 mol% / amine) of 1,1-bis (4-dimethylaminophenyl) -2- (diphenylphosphino) propene obtained in Example 4.
After stirring, the mixture was stirred at 100 ° C. for 8 hours. The reaction solution was cooled, and the target diphenyl (4-tert-butylphenyl) amine was quantified by an internal standard substance quantitative method by gas chromatography. Table 18 shows the results. ¹ H-NMR (CDCl ₃ ) δ 1.31 (s, 9H),
6.92 to 7.30 (m, 14H)

[0097]

EXAMPLE 13 2.3 mg (0.25 mol) of the palladium of Example 12 was converted to (π-allyl) palladium chloride.
% / Amine), and the same operation as in Example 12 was carried out, and the target diphenyl (4-tert-butylphenyl) amine was quantified by an internal standard substance quantitative method by gas chromatography. Table 18 shows the results.

[0098]

EXAMPLE 14 The palladium of Example 12 was replaced with 4.8 mg (0.25 m) of dichlorobis (benzonitrile) palladium.
ol% / amine), except that the desired diphenyl (4-tert-amine) was obtained.
(Butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 1 shows the results.
FIG.

[0099]

Example 15 The same operation as in Example 12 was carried out except that palladium in Example 12 was changed to 3.8 mg of palladium acetylacetonate (0.25 mol% / amine), and the desired diphenyl (4-tert) was obtained. -Butylphenyl) amine was quantified by gas chromatography internal standard substance determination method. Table 18 shows the results.

[0100]

EXAMPLE 16 The palladium of Example 12 was replaced with 14.4 mg of tetrakis (triphenylphosphine) palladium.
(0.25 mol% / amine), except that the target diphenyl (4
-Tert-Butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 18 shows the results.

[0101]

Example 17 The palladium of Example 12 was converted to 5.7 mg (0.2 mg) of tris (dibenzylideneacetone) dipalladium.
Except for changing to 5 mol% / amine, the same operation as in Example 12 was performed to obtain the desired diphenyl (4-ter
(t-Butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 18 shows the results.

[0102]

[Table 18]

[0103]

Example 18 The phosphine of Example 12 was replaced with 1,1-bis (4-dimethylaminophenyl) -2 obtained in Example 4.
-(Diphenylphosphino) propene 20.7mg
(1.0 mol% / amine), and the same operation as in Example 12 was carried out.
(tert-Butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0104]

Example 19 The phosphine of Example 12 was replaced with 18.9 mg (1.0 mol% / amine) of 1,1-diphenyl-2- (diphenylphosphino) propene obtained in Example 1.
The same operation as in Example 12 was carried out, except that the target diphenyl (4-tert-butylphenyl) was used.
The amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0105]

Example 20 The phosphine of Example 12 was combined with 19.5 mg (1.0 mol% / amine) of 1,1-diphenyl-2- (dicyclohexylphosphino) propene obtained in Example 2 and the reaction time was reduced to 3 hours. Except for the change, the same operation as in Example 12 was performed to obtain the desired diphenyl (4-
(tert-Butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0106]

Example 21 The phosphine of Example 12 was replaced with 19.5 mg (1.0 mol% / amine) of 1,1-diphenyl-2- (di-t-butylphosphino) propene obtained in Example 3, palladium acetate Was changed to 2.3 mg (1.0 mol% / amine) of (π-allyl) palladium chloride and the reaction time was changed to 3 hours, and the same operation as in Example 12 was carried out to obtain the desired diphenyl (4-tert- (Butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0107]

Example 22 The phosphine of Example 12 was replaced by 18.2 mg (1.0 mol% / amine) of 2,2-diphenyl-1- (diphenylphosphino) ethylene obtained in Example 7.
The same operation as in Example 12 was carried out, except that the target diphenyl (4-tert-butylphenyl) was used.
The amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0108]

Example 23 The phosphine of Example 12 was replaced with 1,1-bis (4-dimethylaminophenyl) -2 obtained in Example 5.
-(Dicyclohexylphosphino) propene 23.8 m
g (1.0 mol% / amine) and the reaction time were changed to 3 hours.
The amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0109]

Example 24 The phosphine of Example 12 was replaced with 1,1-bis (4-dimethylaminophenyl) -2 obtained in Example 6.
-(Di-t-butylphosphino) propene 21.2 mg
(1.0 mol% / amine), and the same operation as in Example 12 was carried out.
(tert-Butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0110]

Example 25 The phosphine of Example 12 was replaced with 20.9 mg (1.0 mol) of 1,1-diphenyl 2- (dicyclohexylphosphino) -3-methylbutene obtained in Example 8.
% / Amine), and the same operation as in Example 12 was carried out, and the target diphenyl (4-tert-butylphenyl) amine was quantified by an internal standard substance quantitative method by gas chromatography. Table 19 shows the results.

[0111]

EXAMPLE 26 The phosphine of Example 12 was replaced with 22.6 mg (1.0 mol%) of 1,2,2-triphenyl-1- (dicyclohexylphosphino) ethylene obtained in Example 9.
/ Amine), and the same operation as in Example 12 was carried out, and the target diphenyl (4-tert-butylphenyl) amine was quantified by an internal standard substance quantitative method by gas chromatography. Table 19 shows the results.

[0112]

Comparative Example 1 The same operation as in Example 12 was carried out except that phosphine in Example 12 was changed to 13.1 mg (1.0 mol% / amine) of triphenylphosphine. (Butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0113]

Comparative Example 2 The same operation as in Example 12 was carried out except that the phosphine of Example 12 was changed to 15.2 mg (1.0 mol% / amine) of tris (o-tolyl) phosphine, and the target diphenyl ( 4-tert-butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0114]

Comparative Example 3 The phosphine of Example 12 was replaced with BINAP
(2,2-bis (diphenylphosphino) -1,1′-
Binaphthyl) 11.7 mg (1.0 mol% / amine)
The same operation as in Example 12 was carried out, except that the target diphenyl (4-tert-butylphenyl) was used.
The amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0115]

Comparative Example 4 The same operation as in Example 12 was carried out except that the phosphine in Example 12 was changed to 14.0 mg (1.0 mol% / amine) of triscyclohexylphosphine, to thereby obtain the desired diphenyl (4-tert-amine). (Butylphenyl) amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0116]

Comparative Example 5 The phosphine of Example 12 was 10.6 mg (1.0 mol% / amine) of vinyldiphenylphosphine.
The same operation as in Example 12 was carried out, except that the target diphenyl (4-tert-butylphenyl) was used.
The amine was quantified by an internal standard substance determination method by gas chromatography. Table 19 shows the results.

[0117]

[Table 19]

As is clear from Table 19, the present invention
2- (diaryl) vinylphosphine compound (Example 1
When the amination reaction was carried out by using the compounds of Examples 8 to 26), the desired arylamine could be obtained in good yield. On the other hand, triphenylphosphine (Comparative Example 1), tris (o-tolyl) phosphine (Comparative Example 2), BINAP (Comparative Example 3), replacing phosphine with the 2,2- (diaryl) vinylphosphine compound of the present invention. When the reaction was carried out using triscyclohexylphosphine (Comparative Example 4) and vinyldiphenylphosphine (Comparative Example 5), the yield of the target arylamine was at most 37%. As described above, the 2,2- (diaryl) vinyl phosphine compound of the present invention is a very useful phosphine for completing the amination reaction of the present invention.

[0119]

Example 27 Np-methoxyphenyl-Np-
Synthesis of tolylamine 0.214 g of p-toluidine in a reaction vessel under a nitrogen atmosphere
(2.00 mmol) and 4 mL of dioxane were added and dissolved. 0.515 g of p-iodoanisole was added to this mixture.
(2.2 mmol), sodium t-butoxide 0.
231 g (2.4 mmol), 4.5 m of palladium acetate
g (1 mol% / amine) and 1,1 obtained in Example 2
After adding 15.6 mg (2 mol% / amine) of -diphenyl 2- (dicyclohexylphosphino) propene,
Stirred at 100 ° C. for 8 hours. The reaction solution was cooled, saturated aqueous ammonium chloride was added, extracted with toluene, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was purified by column chromatography to obtain 0.351 g of Np-methoxyphenyl-Np-tolylamine as yellow crystals.
(82%). The results are shown in Table 20. Melting point: 81-82 ° C ¹ H-NMR (CDCl ₃ ) δ 2.74 (s, 3H),
3.79 (s, 3H), 5.38 (br-s, 1H),
6.78-6.91 (m, 4H), 6.96-7.09
(M, 4H)

[0120]

Example 28 Np-methoxyphenyl-Np-
Synthesis of tolylamine Under a nitrogen atmosphere, p-tolyl bromide 0.3 was added to the reaction vessel.
30 g (1.93 mmol) and 4 mL of toluene were added and dissolved. 0.266 g of p-anisidinin was added to this mixture.
(2.16 mmol), 0.226 g (2.35 mmol) of sodium-t-butoxide, 8.5 mg (1 mol% / amine) of tris (dibenzylidene) dipalladium and 1,1-diphenyl-2 obtained in Example 2. −
(Dicyclohexylphosphino) propene 32.3mg
(2 mol% / amine) and then stirred at 100 ° C. for 5 hours. The reaction solution was cooled, saturated aqueous ammonium chloride was added, extracted with toluene, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was purified by column chromatography to give 0.366 g (89%) of Np-methoxyphenyl-Np-tolylamine. Table 2 shows the results
0 is shown.

[0121]

Example 29 Synthesis of N- (diphenylmethylene) -4-aminobiphenyl 0.4-bromobiphenyl 0.4 was added to a reaction vessel under a nitrogen atmosphere.
66 g (2.00 mmol) and 4 mL of toluene were added and dissolved. Benzophenone imine 0.39 was added to this mixture.
9 g (2.2 mmol), sodium tert-butoxide 0.231 g (2.4 mmol), palladium acetate 1
After adding 3.5 mg (3 mol% / amine) and 46.9 mg (6 mol% / amine) of 1,1-diphenyl-2- (dicyclohexylphosphino) propene obtained in Example 2, the mixture was stirred at 100 ° C. for 16 hours. did. The reaction solution was cooled, saturated aqueous ammonium chloride was added, extracted with toluene, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was purified by column chromatography to obtain 0.409 g (61%) of N- (diphenylmethylene) -4-aminobiphenyl as a yellow oil. The results are shown in Table 20. ¹ H-NMR (CDCl ₃ ) 6.74 to 7.88 (m, 1
9H).

[0122]

Example 30 Synthesis of N- (4-cyanophenyl) morpholine Under a nitrogen atmosphere, 0.275 g (2.00 mmol) of 4-chlorobenzonitrile and 4 mL of toluene were added and dissolved in a reaction vessel. 0.192 g of morpholine is added to this mixture.
(2.2 mmol), sodium t-butoxide 0.
231 g (2.4 mmol), 4.5 m of palladium acetate
g (1 mol% / amine) and 1,1 obtained in Example 2
After adding 15.6 mg (2 mol% / amine) of -diphenyl-2- (dicyclohexylphosphino) propene, the mixture was stirred at 100 ° C for 14 hours. The reaction solution was cooled, saturated aqueous ammonium chloride was added, extracted with toluene, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was purified by column chromatography, and N
-(4-cyanophenyl) morpholine 0.304 g (8
1%). The results are shown in Table 20. Melting point: 80-81 ° C ¹ H-NMR (CDCl ₃ ) δ 3.23-3.33
(M, 4H), 3.80-3.90 (m, 4H), 6.
81 to 6.92 (m, 2H), 7.47 to 7.57
(M, 2H)

[0123]

Example 31 Synthesis of ditolylamine Under a nitrogen atmosphere, p-tolyl triflate was added to a reaction vessel in an amount of 0.1 mL.
503 g (2.10 mmol) and 4 mL of dioxane were added and dissolved. To this mixture was added p-toluidine 0.246.
g (2.29 mmol), potassium phosphate 0.658 g
(3.10 mmol), 19.9 mg (2.1 mol% / triflate) of tris (dibenzylideneacetone) dipalladium and 1,1-diphenyl- obtained in Example 2.
2- (dicyclohexylphosphino) propene 58.7
mg (7.2 mol% / triflate),
Stirred at 00 ° C. for 12 hours. The reaction solution was cooled, saturated aqueous ammonium chloride was added, extracted with toluene, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was purified by column chromatography and ditolylamine 0.2
68 g (65%) were obtained. The results are shown in Table 20. Melting point: 78-82 ° C ¹ H-NMR (CDCl ₃ ) δ 2.32 (s, 6H),
5.51 (br-s, 1H), 6.88 to 7.17
(M, 8H)

[0124]

Example 32 N- (3-thiophenyl) -N, N-
Synthesis of diphenylamine Under a nitrogen atmosphere, add 3-bromothiophene 0.3 to a reaction vessel.
58 g (2.20 mmol) and 4 mL of toluene were added and dissolved. 0.343 g of diphenylamine was added to this mixture.
(2.03 mmol), sodium tert-butoxide 0.229 g (2.39 mmol), palladium acetate 4.4 mg (1 mol% / amine) and 1,1-diphenyl-2- (dicyclohexylphosphino) obtained in Example 2. ) After adding 30.6 mg (2 mol% / amine) of propene, the mixture was stirred at 100 ° C for 10 hours. The reaction solution was cooled, saturated aqueous ammonium chloride was added, extracted with toluene, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The concentrate was purified by column chromatography and N-
(3-thiophenyl) -N, N-diphenylamine
257 g (50%) were obtained. The results are shown in Table 20. Melting point: 79-82 ° C ¹ H-NMR (CDCl ₃ ) δ 6.66 (d / d, J =
1.4, 3.1 Hz, 1H), 6.88 (d / d, J =
1.4, 5.1 Hz, 1H), 6.94-7.36
(M, 11H)

[0125]

Comparative Example 6 Synthesis of Np-methoxyphenyl-Np-tolylamine Same as Example 27 except that the phosphine of Example 27 was changed to 4.2 mg (1.0 mol% / amine) of vinyldiphenylphosphine. Perform the operation to obtain the desired Np-
When methoxyphenyl-Np-tolylamine was quantified by an internal standard substance quantification method by gas chromatography, the quantitative value was 5%. Table 20 shows the results.

[0126]

Comparative Example 7 Synthesis of Np-methoxyphenyl-Np-tolylamine Same as Example 28 except that the phosphine of Example 28 was changed to 4.2 mg (1.0 mol% / amine) of vinyldiphenylphosphine. Perform the operation to obtain the desired Np-
When methoxyphenyl-Np-tolylamine was quantified by an internal standard substance quantification method by gas chromatography, the quantitative value was 5%. Table 20 shows the results.

[0127]

[Table 20]

As is clear from Table 20, the present invention
2- (diaryl) vinylphosphine compound (Example 2
7-32), the desired arylamine could be obtained in good yield. On the other hand, when the phosphine is reacted with vinyl diphenylphosphine (Comparative Examples 6 to 7) instead of the 2,2- (diaryl) vinylphosphine compound of the present invention, the yield of the target arylamine is 5%. Met. Thus, the 2,2- (diaryl) vinylphosphine compound of the present invention
It is a very useful phosphine for completing the amination reaction of the present invention.

[0129]

Example 33 1,1-Diphenyl-2- (di-te)
Synthesis of (rt-butylphosphino) propene] (π-allyl) palladium chloride 0.183 g (0.5 mmol) of (π-allyl) palladium chloride dimer in a reaction vessel under a nitrogen atmosphere. -Diphenyl-2- (di-t-butylphosphino) propene 0.338 g (1.0 mmol)
l) and 3 mL of toluene were stirred at room temperature for 62 hours.
After adding 3 mL of heptane to the reaction solution and stirring for 30 minutes,
The generated crystals are filtered and dried to give 0.25 g of the title compound.
(48%). _{^{31 P-NMR (CDCl 3)}} δ 63.83 MS (EI): 519,521

[0130]

EXAMPLE 34 The palladium and phosphine of Example 12 were converted to the 1,1-diphenyl-2- (di-
tert-butylphosphino) propene] (π-allyl) palladium chloride (palladium-phosphine catalyst), except that the same operation as in Example 12 was carried out to obtain the desired diphenyl (4-tert-butylphenyl) amine Was determined by gas chromatography using the internal standard substance determination method. As a result, the quantitative value of the target substance was 90%.
Met.

[0131]

Example 35 Synthesis of 4-methylbiphenyl Under a nitrogen atmosphere, 4-bromotoluene 0.12 was added to a reaction vessel.
3 mL (1.0 mmol), phenylboronic acid 0.18
29 g (1.5 mmol), 87.2 mg of KF (1.
5 mmol), 4.5 mg of palladium acetate (0.02 m
mol), 11.7 mg of 1,1-diphenyl 2- (dicyclohexylphosphino) propene obtained in Example 2.
(0.03 mmol) and 3 mL of dioxane were added, followed by stirring at room temperature for 20 hours. As a result of quantifying the reaction solution with an internal standard, the title compound was obtained in a yield of 70%. ¹ H-NMR (CDCl ₃ ) δ 2.39 (s, 3H),
7.19 to 7.65 (m, 9H)

[0132]

Example 36 Synthesis of 4-methylbiphenyl Under a nitrogen atmosphere, 4-bromotoluene 0.12 was added to a reaction vessel.
3 mL (1.0 mmol), phenylboronic acid 0.18
29 g (1.5 mmol), 87.2 mg of KF (1.
5 mmol), 4.5 mg of palladium acetate (0.02 m
mol), 11.7 mg of 1,1-diphenyl 2- (dicyclohexylphosphino) propene obtained in Example 2.
(0.03 mmol) and 3 mL of dioxane were added, and the mixture was stirred at 80 ° C for 4 hours. As a result of quantifying the reaction solution with an internal standard, the title compound was obtained in a yield of 95%.

[0133]

Example 37 Synthesis of 2-phenylpyridine 0.79 of 2-bromopyridine was placed in a reaction vessel under a nitrogen atmosphere.
g (5.0 mmol), 0.73 g of phenylboronic acid
(6.0 mmol), 1.38 g of K ₂ CO ₃ (10.0 g)
mmol), 11.2 mg of palladium acetate (0.05 m
mol), 39.1 mg of 1,1-diphenyl 2- (dicyclohexylphosphino) propene obtained in Example 2.
(0.1 mmol), water 5 mL and toluene 15 mL
Was added and stirred at 80 ° C. for 4 hours. The concentrate was purified by column chromatography to give the title compound 0.66.
g, yield 85%. ¹ H-NMR (CDCl ₃ ) δ 7.15 to 7.29
(M, 1H), 7.34 to 7.55 (m, 3H), 7.
68 to 7.80 (m, 2H), 7.92 to 8.04
(M, 2H), 8.65 to 8.74 (m, 1H)

[0134]

Example 38 Synthesis of 4- (4-cyanophenyl) -2-methyl-3-butyn-2-ol In a nitrogen atmosphere, 1.38 g (10.0 mmol) of 4-chlorobenzonitrile was added to a reaction vessel under a nitrogen atmosphere. 1.68 g (20.0 mmol) of methyl-3-butyn-2-ol, 2.7 mg (0.015 mmol) of palladium chloride, 1.4 mg (0.0075 mmol) of copper iodide, 1,1 obtained in Example 2 -Diphenyl 2- (dicyclohexylphosphino) propene 17.6 mg (0.045 mmol),
After adding 4 mL of diisopropylamine and 4 mL of dimethylformamide, the mixture was stirred at 100 ° C. for 23 hours. The solvent was removed under reduced pressure and the concentrate was purified by column chromatography to give 1.56 g (84%) of the title compound as white crystals. ¹ H-NMR (CDCl ₃ ) δ 1.63 (s, 6H),
2.23 (br-s, 1H), 7.44 to 7.65
(M, 4H)

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 211/54 C07C 211/54 4H050 213/02 213/02 217/92 217/92 249/02 249/02 251/24 251/24 253/30 253/30 255/53 255/53 C07D 213/06 C07D 213/06 213/127 213/127 295/14 295/14 Z 333/36 333/36 C07F 15/00 C07F 15/00 C // C07B 37/04 C07B 37/04 BC 43/04 43/04 61/00 300 61/00 300 (72) Inventor Takenobu Nishikawa 1-4-11 Nishi-Hachiman, Hiratsuka-shi, Kanagawa Takasago International Corporation (72) Inventor Yoji Hori 1-4-11 Nishihachiman, Hiratsuka-shi, Kanagawa Prefecture Takasago International Corporation (72) Inventor Toshimitsu Hagiwara Nishi, Hiratsuka-shi, Kanagawa 1-4-11 Yawata Takasago International Corporation F term (reference) 4C023 GA01 4C055 AA01 BA02 BA08 CA01 DA01 FA01 FA31 FA37 4G069 BA27A BA27B BC72A BC72B BE02B BE03B BE16B BE26B BE27A BE27B BE46B CB25 DA02 4H006 AA02 AC22 AC24 AC52 BA25 BA48 BJ40 CD40 BP30 CD4 WB21

Claims (6)

[Claims] [Claim 1] The following general formula (1) (Wherein, R ¹ is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, or an optionally substituted phenyl group; R ² and R ³ are R ⁴ , an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, and a phenyl group which may have a substituent; R ⁵ , R ⁶ and R ⁷ may be the same or different, and each may have an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, or a substituent. A phenyl group, an alkoxy group having 1 to 6 carbon atoms, a dialkylamino group having 1 to 3 carbon atoms, a halogen atom, a benzyl group, a naphthyl group, a lower halogen-substituted alkyl group having 1 to 2 carbon atoms, and R ⁴ R ⁵ and R
⁶ and R ⁷ may together form a fused benzene ring, a fused substituted benzene ring, a trimethylene group, a tetramethylene group, a methylenedioxy group; p, q, r and s
Are 0 to 5, respectively, and p + q and r + s are 0
-5. 2,2- (diaryl) vinylphosphine compounds represented by the formula: 2. The 2,2- (diaryl) according to claim 1.
A palladium-phosphine catalyst obtained by reacting a palladium compound with a vinyl phosphine compound. 3. The palladium compound is tetravalent, divalent and zero-valent.
A palladium salt or a palladium complex having a valence of 3.
A palladium-phosphine catalyst as described. 4. An amine compound in the presence of a base, which is represented by the following general formula (2): ArX ¹ (2) (wherein, Ar has an aryl group which may have a substituent and a substituent An optionally substituted heteroaryl group; X ¹
Represents a halogen atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group, or a toluenesulfonyloxy group. A process for producing arylamines, wherein the palladium-phosphine catalyst according to claims 2 to 3 is used in the amination reaction with the aryl compound represented by the formula (3). 5. An arylboronic acid or an arylboronic ester in the presence of a base, represented by the following general formula (2): ArX ¹ (2) (wherein, Ar and X ¹ have the same meanings as described above). A process for producing diaryls, wherein the palladium-phosphine catalyst according to claim 2 is used in a carbon-carbon bond reaction with the represented aryl compound. 6. An aryl compound represented by the following general formula (2) ArX ¹ (2) (wherein Ar and X ¹ have the same meanings as described above) using an alkyne compound in the presence of a base. A method for producing an aryl alkyne, comprising using the palladium-phosphine catalyst according to claim 2 in the carbon-carbon bonding reaction of the above.