JP5544756B2 - Phosphine compound and catalyst comprising the phosphine compound and a transition metal compound - Google Patents

Description

  The present invention relates to a novel phosphine compound. More specifically, the present invention relates to a phosphine compound useful as a ligand in a transition metal complex catalyst serving as a catalyst for various reactions, and a catalyst for synthesizing aromatic amine, biaryl, and substituted styrene derivatives composed of the phosphine compound and a transition metal compound.

  Conventionally, it is known that transition metal complexes such as palladium serve as catalysts for various reactions (for example, Palladium Reagents and Catalysts, 1995). The transition metal complex is a compound composed of a transition metal compound and a ligand, and the ligand has an extremely important role in controlling the activity and selectivity of the catalytic reaction. Examples of ligands that have been reported so far in carbon-carbon (or heteroelement) bonding reactions include tri (tert-butyl) phosphine (see, for example, Patent Document 1 and Non-Patent Document 1), and dialkylphosphino groups. Phosphorus ligands such as substituted ferrocene derivatives (see, for example, Patent Document 2 and Non-Patent Document 2), 2-dicyclohexylphosphino-1,1′-biphenyl derivatives (for example, see Patent Document 3), 1,3 Carbene-based ligands such as -bis- (2,6-diisopropylphenyl) imidazolinium salt (see, for example, Non-Patent Document 3) are known.

  On the other hand, in a reaction other than a carbon-carbon (or heteroelement) bonding reaction, a linking group having 2,2′-bis (diphenylphosphino) -1,1′-binaphthyl (commonly known as BINAP) and 6,6′-position A bidentate ligand having a 1,1′-biphenyl structure bonded through a ligand has been reported as a ligand for asymmetric synthesis reaction (particularly asymmetric hydrogenation reaction) (see, for example, Patent Documents 4 and 5).

JP 10-139742 A JP 2000-247990 A US2002 / 156295 Japanese Patent No. 4167899 JP 2000-154156 A

Journal of American Chemical Society, 122 (17), 4020-4028 (2000) Journal of American Chemical Society, 130, 6586-6596 (2008) Angew. Chem. Int. Ed. , 46, 2768-2813 (2007)

  Although transition metal catalysts having tri (tert-butyl) phosphine as a ligand are known to have extremely high activity, tri (tert-butyl) phosphine itself has a characteristic of being easily oxidized with oxygen. It has a drawback that is difficult to handle. On the other hand, other ligands have a defect that the reaction activity is lower than that of a transition metal catalyst having tri (tert-butyl) phosphine as a ligand, although it is relatively stable to oxygen. In particular, in the synthesis of triarylamines, especially triarylamines from aryl chloride raw materials, and the synthesis of biphenyl compounds, it has been desired to develop catalysts that are stable in air and oxygen and that are highly active. .

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have obtained the general formula (1), which is a biphenyl monodentate ligand in which a ring structure is formed by bonding the 6,6 ′ positions to each other. The present inventors have found that the represented phosphine compound is extremely excellent as a ligand of a transition metal complex, and have completed the present invention.

  That is, the present invention relates to a phosphine compound represented by the following general formula (1) and a catalyst comprising the phosphine compound and a transition metal compound.

(Wherein R ¹ and R ² each independently represents a hydrogen atom, a linear, branched or cyclic alkyl group, an alkoxy group, an amino group, a substituted or unsubstituted phenyl group, and R represents a linear, Represents a branched or cyclic alkyl group, a substituted or unsubstituted phenyl group, and M represents a linear or branched alkylene group having 1 to 8 carbon atoms which may have a substituent, or -CH. _{2 CH 2 -O-CH 2 CH} 2 - represents a group).
Hereinafter, the present invention will be described in more detail.

The linear, branched or cyclic alkyl group as R ¹ and R ² in the general formula (1) is not particularly limited, and examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and an n-butyl group. , Sec-butyl group, tert-butyl group, n-pentyl group, n-hexyl group, cyclohexyl group, n-heptyl group, 2-ethylhexyl group, adamantyl group and the like, and the like. be able to.

  Examples of the alkoxy group include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, sec-butoxy group, n-pentoxy group, n-hexyloxy group, n-heptyloxy group, 2 -An ethylhexyloxy group etc. are mentioned.

  Examples of the amino group include a dimethylamino group, a diethylamino group, and a diphenylamino group.

  Examples of the substituted or unsubstituted phenyl group include phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, and condensed naphthyl. Groups and the like.

R in the general formula (1) is a linear, branched or cyclic alkyl group, a substituted or unsubstituted phenyl group, and examples thereof include the substituents exemplified for R ¹ and R ² . Among them, bulky and electron donating substituents such as tert-butyl group, cyclohexyl group, and adamantyl group are more preferable because of high catalytic activity.

  The phosphine compound represented by the general formula (1) is a novel phosphine compound in which the 6,6′-position forms a ring via —O—M—O—.

The substituent M represents a linear or branched alkylene group having 1 to 8 carbon atoms which may have a substituent, or a —CH ₂ CH ₂ —O—CH ₂ CH ₂ — group. Specific examples of the linear or branched alkylene group having 1 to 8 carbon atoms which may have a substituent include a methylene group, a propylene group, a butylene group, a pentylene group, a hexylene group, a heptylene group, Linear alkylene group such as octylene group, and 2-hydroxypropane-1,3-diyl group, hexane-2,5-diyl group, 2,3-methylenedioxybutane-1,4-diyl group, etc. A branched alkylene group is mentioned.

  The phosphine compound represented by the above general formula (1) is combined with a transition metal compound to produce various arylamine synthesis, biaryl synthesis, carbon-carbon bond reactions such as substituted styrene derivatives, and catalysts for carbon-heteroelement bonding reactions. As very effective. Among these, phosphine compounds described in the following L1 to L14 are more preferable in terms of catalytic activity.

  Below, the manufacturing method of the compound of this invention is demonstrated.

  For example, according to Japanese Patent Application Laid-Open No. 2004-10583, 2-iodo-3-bromo-anisole is synthesized from 3-bromoanisole, and Suzuki-Miyaura coupling with 2-methoxyphenylboronic acid is performed. -6,6'-dimethoxy-1,1'-biphenyl is synthesized. Next, 2-dialkylphosphino (or diarylphosphino) -6,6′-dimethoxy-1,1′-biphenyl is synthesized by treatment with n-butyllithium / chlorodialkylphosphine (or chlorodiarylphosphine). can do. Thereafter, the methyl group is deprotected by treating with boron tribromide, and subsequently reacting with the desired dibromoalkane, bis (2-chloroethyl) ether, etc., to give a phosphine represented by the general formula (1). Compounds can be synthesized.

  The phosphine compound represented by the general formula (1) thus obtained becomes a catalyst for various reactions by being combined with a transition metal compound as a ligand. For example, reactions such as synthesis of arylamines from aryl halides and amines, synthesis of biaryls by coupling of aryl halides with aryl boron reagents, etc., or synthesis of substituted styrenes by reaction of aryl halides with olefins, etc. Can be mentioned. In these reactions, an aryl sulfonate can be used in place of the aryl halide.

  The conditions for these catalytic reactions are not particularly limited, but the transition metal compound is 0.001 to 10 mol% with respect to the substrate such as aryl halide, and the ligand is 0.8 with respect to the transition metal compound. In a solvent inert to the reaction (for example, an aromatic solvent such as toluene and xylene, an ether solvent such as tetrahydrofuran, dimethoxyethane, 1,4-dioxane, cyclopentylmethyl ether, dimethyl) Nonpolar solvents such as sulfoxide and dimethylformamide), a reaction temperature of 20 to 160 ° C., a reaction time of 0.5 to 48 hours, and usually carried out in an inert gas atmosphere such as nitrogen or argon.

  Although there is no restriction | limiting in particular as a transition metal compound, For example, tetravalent palladium compounds, such as sodium hexachloro palladium (IV) acid tetrahydrate and hexachloro palladium (IV) potassium, palladium (II) chloride, palladium bromide (II ), Palladium (II) acetate, palladium (II) acetylacetonate, dichlorobis (benzonitrile) palladium (II), dichlorobis (acetonitrile) palladium (II), dichlorobis (triphenylphosphine) palladium (II), dichlorotetraamminepalladium ( II), divalent palladium compounds such as dichloro (cycloocta-1,5-diene) palladium (II), palladium (II) trifluoroacetate, tris (dibenzylideneacetone) dipalladium (0), tris ( ) Dipalladium (0) chloroform complex, tetrakis (triphenylphosphine) palladium (0) 0-valent palladium compounds such as and the like. Also, nickel acetate, nickel chloride, (N, N, N ′, N′-tetramethylethylenediamine) nickel dichloride, [1,1′-bis (diphenylphosphino) ferrocene] nickel dichloride, [1,3-bis ( And nickel compounds such as [diphenylphosphino) propane] nickel dichloride, [1,4-bis (diphenylphosphino) butane] nickel dichloride, bis (cyclopentadienyl) nickel. Of these, palladium compounds are preferred from the viewpoint of activity and selectivity.

Since the phosphine compound represented by the general formula (1) has C ₂ point group axial asymmetry, an optically active substance of (R) form or (S) form exists. When the phosphine compound is used in the reaction, it may be a racemate or any one of the optically active substances.

  Further, the phosphine compound represented by the general formula (1) may be immobilized on polystyrene or the like by a known method, or may be immobilized on a polymer carrier by microencapsulation (for example, JP-A No. 2002-253972). Absent. Moreover, you may use what was fix | immobilized using the silane coupling agent to inorganic supports, such as a silica gel (for example, Journal of American Chemical Society, 125, 4688-4690 (2003)).

  The phosphine compound of the present invention is an excellent ligand for transition metal compounds such as palladium, and exhibits high selectivity and high activity in various catalytic reactions such as arylamine synthesis, biaryl synthesis, and substituted styrene derivative synthesis. It is.

¹ H-NMR chart (CDCl ₃ ) of Compound A is shown. ¹ H-NMR chart (acetone-d ₆ ) of Compound B is shown. ¹ H-NMR chart (CDCl ₃ ) of Compound C is shown. ¹ H-NMR chart (Methanol-d ₄ ) of Compound D is shown. ¹ H-NMR chart (CDCl ₃ ) of Compound L3 is shown.

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited to these. In addition, the identification of the compound obtained in the Example was performed by ¹ H-NMR measurement and FDMS measurement. ¹ H-NMR measurement was performed using Gemini 200 manufactured by Varian, and FDMS measurement was performed using Hitachi M-80B.

Synthesis example 1
(1) Synthesis of Compound A After adding 3.01, 2,6,6, -tetramethylpiperidine (3.01 g) and 30 ml of dehydrated tetrahydrofuran to a 50 ml Schlenk tube under a nitrogen atmosphere, The solution was cooled to −78 ° C. in a dry ice-methanol bath, and 12.6 ml of 1.6 M n-butyllithium / hexane solution was added. Thereafter, the mixture was stirred at the same temperature for 30 minutes and further at 0 ° C. for 30 minutes (reaction liquid A). Next, 2.86 g (21.0 mmol) of zinc chloride and 50 ml of tetrahydrofuran are added to a 100 ml Schlenk tube to dissolve the zinc chloride (slightly cloudy), and then the reaction solution is cooled to −78 ° C. did. Thereafter, 27 ml (42.9 mmol) of 1.6 M tert-butyllithium / heptane solution was added, and subsequently stirred at the same temperature for 30 minutes (reaction solution B).

Next, the previously prepared reaction solution A was added to a 300 ml eggplant-shaped flask, and the reaction solution was cooled to -78 ° C in a dry ice-methanol bath. The reaction liquid B was dripped there, and also it stirred at the same temperature for 30 minutes and 0 degreeC for 2 hours. Next, a solution consisting of 1.89 g (10.2 mmol) of 3-methoxyanisole / 15 ml of tetrahydrofuran was added at −78 ° C., and the mixture was further stirred at −30 ° C. for 14 hours. Next, a solution consisting of 17.69 g (69.7 mmol) of iodine / 60 ml of tetrahydrofuran was added at the same temperature. Then, after stirring at room temperature for 1 hour, 85 ml of 21% sodium thiosulfate aqueous solution was added to terminate the reaction. 100 ml of chloroform was added to the obtained reaction solution, and the organic layer was extracted. The obtained organic layer was dried over magnesium sulfate and purified by silica gel chromatography (eluent: hexane / ethyl acetate = 10/1 volume ratio). The target fraction was concentrated and further recrystallized with hexane to isolate 1.3 g of Compound A. The compound was identified by ¹ H-NMR (CDCl ₃ ) (see FIG. 1).

(2) Synthesis of Compound B In a 50 ml Schlenk tube, under a nitrogen atmosphere, Compound A 1.21 g (3.6 mmol), o-methoxyphenylboronic acid 0.596 g (3.942 mmol), 20% aqueous sodium carbonate solution 6.3 g (12.2 mmol), 0.182 g (0.158 mmol) of tetrakis (triphenylphosphine) palladium and 25 ml of dimethoxyethane were added, and the mixture was heated and stirred at 90 ° C. for 48 hours. After cooling to room temperature, chloroform was added to extract the organic layer, and the organic layer was treated with saturated brine and then dried over magnesium sulfate. After concentration, 0.77 g (yield 66%, colorless oil) of the desired compound B was isolated by purification with silica gel chromatography (eluent: toluene / ethyl acetate = 10/1 volume ratio). . The compound was identified by ¹ H-NMR (see FIG. 2).

(3) Synthesis of Compound C In a nitrogen atmosphere, 1.40 g (4.78 mmol) of Compound B and 25 ml of tetrahydrofuran were added to a 100 ml Schlenk tube, and then the reaction solution was cooled to −78 ° C. To the reaction solution, 3.6 ml of n-butyllithium / hexane solution (1.6 mol / l) was dropped and aged at the same temperature, and further a chlorodicyclohexylphosphine / tetrahydrofuran solution (11.7 wt% solution) was added to 12. 0 ml (5.95 mmol) was added dropwise. After stirring overnight at room temperature, 25 ml of saturated aqueous ammonium chloride solution was added dropwise to terminate the reaction. The organic layer was separated, dried over magnesium sulfate, and purified by silica gel chromatography (eluent: hexane / ethyl acetate = 10/1 volume ratio) to give 880 mg of compound C as colorless crystals (yield 45). %) Isolated. The compound was identified by ¹ H-NMR (see FIG. 3).

Example 1 (Synthesis of Compound L3)
After 0.83 g (2.0 mmol) of Compound C obtained in Synthesis Example 1 was dissolved in 18 ml of dehydrated dichloromethane, the reaction solution was cooled to −78 ° C. Next, 6.1 ml (6.1 mmol) of a 1 mol / l boron tribromide dichloromethane solution was added dropwise with a syringe, and the mixture was stirred at the same temperature for 1 hour and further at room temperature for 48 hours. The reaction was terminated.

The produced precipitate was filtered and washed, and then the obtained precipitate was purified by silica gel chromatography (eluent: hexane / ethyl acetate = 2/1 volume ratio, subsequently methanol) to obtain dihydroxy compound D as a white powder. 590 mg (yield 76%) was isolated. The compound was identified by ¹ H-NMR (see FIG. 4).

  Next, 560 mg (1.47 mmol) of Compound D, 1.02 g (7.38 mmol) of potassium carbonate and 15 ml of dimethylformamide were added to a 50 ml eggplant-shaped flask under a nitrogen atmosphere, and the mixture was stirred at room temperature for 30 minutes. Thereafter, 190 μl of 1-bromo-4-chlorobutane was dropped with a syringe, followed by stirring at the same temperature for 24 hours and further at 60 ° C. for 47 hours.

The reaction was terminated by adding 20 ml of water, and extracted with 30 ml of diethyl ether. The obtained organic layer was treated in a conventional manner and then concentrated. The obtained residue was purified by silica gel chromatography (eluent: hexane / ethyl acetate = 20/1 volume ratio) to isolate 0.18 g (yield 28%) of Compound L3 as a colorless powder. The compound was identified by ¹ H-NMR (see FIG. 5) and FDMS.

  FDMS (m / e): 436

In addition, although the toluene solution (0.5 wt%) of compound L3 was stirred in air at room temperature for 2 days, no oxidized peak was detected on ³¹ P-NMR.

Example 2
Under a nitrogen atmosphere, 6.24 g (40 mmol) of bromobenzene, 7.32 g (40 mmol) of 3-methyldiphenylamine, 4.99 g (52 mmol) of sodium tert-butoxide, and 45 ml of toluene were added to a 200 ml eggplant type flask. Next, in a 20 ml Schlenk tube, 6.6 mg of palladium acetate, 26 mg of compound L3 (compound L3 / palladium = 2/1 molar ratio) as a ligand, and 5 ml of toluene were heated and stirred at 60 ° C. for 30 minutes. A solution was prepared. Among them, 1.6 ml (palladium corresponds to 0.025 mol% with respect to bromobenzene) was dropped into the previously prepared reaction solution with a syringe, and the mixture was heated and stirred at 100 ° C. for 3 hours. After cooling to room temperature, 25 ml of water was added to separate the organic layer. The organic layer was analyzed for yield and turnover number of 3-methyltriphenylamine (product-mol / Pd-mol / hr) by gas chromatography analysis using triphenylamine as an internal standard. . The results are shown in Table 1.

Comparative Examples 1-2
The ligand is 2-dicyclohexylphosphino-1,1′-biphenyl (described in Patent Document 3), 2-dicyclohexylphosphino-2 ′, 6′-dimethoxy-1,1′-biphenyl (Patent Document) The amination was carried out in accordance with Example 2 instead of (also called SPhos). The results are shown in Table 1.

Example 3 (Synthesis of Compound L2)
Except that 1-bromo-4-chlorobutane was replaced with 1-bromo-3-chloropropane, the same reaction as in Example 1 was performed, and 123 mg (yield 19.8%) of compound L2 was isolated.

Example 4
The same reaction as in Example 2 was carried out except that bromobenzene was replaced with 4.48 g (40 mmol) of chlorobenzene. As a result of analysis, the yield of 3-methyltriphenylamine was 29.4%. The results are shown in Table 1.

Example 5
The reaction was conducted according to Example 2, replacing Compound L3 with Compound L2 synthesized in Example 3. As a result of gas chromatography analysis, the yield of 3-methyltriphenylamine was 52.2%.

Example 6 (Synthesis of 4-methyl-1,1'-biphenyl)
To a 100 ml eggplant-shaped flask, 1.0 g (8.93 mmol) of chlorobenzene, 1.28 g (9.41 mmol) of 4-tolylboronic acid, 20 ml of dimethoxyethane and 14.1 g (26.6 mmol) of 20 wt% sodium carbonate were added. Next, in a 20 ml Schlenk tube, 6.6 mg of palladium acetate, 26 mg of compound L3 (compound L3 / palladium = 2/1 molar ratio) as a ligand, and 5 ml of toluene were heated and stirred at 60 ° C. for 30 minutes. A solution was prepared. Among them, 1.6 ml (palladium corresponds to 0.16 mol% with respect to bromobenzene) was dropped into the previously prepared reaction solution with a syringe, and the mixture was heated and stirred for 6 hours under reflux. After cooling to room temperature, the organic layer was separated. As a result of analyzing the organic layer by gas chromatography, the yield of 4-methyl-1,1′-biphenyl was 99% or more.

Claims (7)

A phosphine compound represented by the following general formula (1).

(Wherein R ¹ and R ² each independently represents a hydrogen atom, a linear, branched or cyclic alkyl group, an alkoxy group, an amino group, a substituted or unsubstituted phenyl group, and R represents a linear, Represents a branched or cyclic alkyl group, a substituted or unsubstituted phenyl group, and M represents a linear or branched alkylene group having 1 to 8 carbon atoms which may have a substituent, or -CH. _{2 CH 2 -O-CH 2 CH} 2 - represents a group). The R is a cyclohexyl group, tert-butyl group, 1-adamantyl group, phenyl group, o-tolyl group, 2,6-dimethylphenyl group, 2,4,6-trimethylphenyl group. 1. The phosphine compound according to 1. The phosphine compound according to claim 1 or 2, wherein in the general formula (1), the 2'-position is a hydrogen atom. It is the following L1-L14, The phosphine compound of Claim 1 characterized by the above-mentioned.

(Cy represents a cyclohexyl group.) Synthesis of arylamines from aryl halides or aryl sulfonates and amines , comprising the phosphine compounds and transition metal compounds according to any one of claims 1 to 4 , aryl halides or aryl sulfonates and aryl boron reagents; Catalysts for the synthesis of biaryls by coupling and the synthesis of substituted styrenes by reaction of aryl halides or aryl sulfonates with olefins . 6. The catalyst for synthesis according to claim 5, wherein the transition metal compound is a palladium compound. A process for producing arylamines , biaryls, and substituted styrenes using the catalyst according to claim 5 or 6, wherein the aryl halide as a substrate thereof is an aryl chloride.

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