JP2003261584A - Solid-phase carried bidentate chelate phosphine and solid-phase supported bidentate chelate phosphine catalyst - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a solid-phase carried phosphine catalyst useful for producing medicines, agrochemicals and intermediates therefor. <P>SOLUTION: The solid-phase carried bidentate chelate phosphine is represented by the formula XN-(CH<SB>2</SB>PR<SP>1</SP>R<SP>2</SP>)<SB>2</SB>[wherein, X means a resin; and R<SP>1</SP>and R<SP>2</SP>mean each independently a 6-14C aryl group (the aryl group may optionally be substituted with a 1-6C alkyl group or a 3-6C cycloalkyl group) or the 1-6C alkyl group or the 3-6C cycloalkyl group]. A solid-phase carried bidentate chelate phosphine palladium complex catalyst or solid-phase carried bidentate chelate phosphine rhodium complex catalyst is produced from the solid-phase carried bidentate chelate phosphine and a palladium compound or a rhodium compound. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a solid phase supported bidentate chelate phosphine-palladium complex catalyst and a solid phase supported bidentate chelate phosphine-rhodium complex catalyst, which are useful for producing various pharmaceuticals and agricultural chemicals and their intermediates. And a solid phase supported bidentate chelate phosphine which is a ligand thereof.

Further, solid-state supported bidentate chelating phosphine-palladium complex catalysts and solid-state supported bidentate chelating phosphine-rhodium complex catalysts and solid phase which are ligands thereof are useful in high-speed synthesis by combinatorial chemistry and automatic synthesizers. The present invention relates to a supported bidentate chelate phosphine.

[0003]

2. Description of the Related Art Solid-phase supported catalysts in which transition metals are supported on organic polymers have been actively researched and developed because of the necessity for high-speed organic synthesis such as combinatorial chemistry. .

Further, solid-phase supported catalysts which can be used in an aqueous solution have been attracting attention because of the efficiency of production and consideration of the environment.

J. Am. Chem. Soc. 2001, 123 (12) 2889-2890,
The solid-phase supported phosphine catalysts described in J. Org. Chem. 2000, 65, 1881-1885 and US 5777062 are shown to be useful only in an organic solvent, and are shown to be useful in an aqueous solution. Was not done.

Tetrahedron Letters 38 (1997) 3703-3706
And, the solid-phase supported phosphine catalyst described in J. Am. Chem. Soc. 1998, 120, 1466-1468 can be used in an aqueous solution, but the production method is complicated, and there are problems in production. Had.

Tetrahedron 55 (1999) 14341-14352, Tetrah
edron Lett. 1997,38,3557-3560, Tetrahedron Lett.199
8,39,8303-8306, J.Org.Chem.1999.64,3384-3388 and J. Org.
The solid-phase supported phosphine catalyst described in Org. Chem, 1999.64, 6921-6823 can be used in an aqueous solution and the production method is easy, but the solid-phase supported phosphine having high catalytic activity and reaction selectivity is also available. A catalyst was desired.

[0008]

Means for Solving the Problems As a result of intensive investigations by the present inventors, a solid-phase-supported phosphine catalyst which is easy to produce, has excellent catalytic activity and reaction selectivity, and can be used in an aqueous solution has been obtained. The invention was discovered.

That is, the present invention provides the formula XN- (CH ₂ PR ¹ R ² ) ₂ (wherein X represents a resin, and R ¹ and R ² are each independently C _6-14. aryl group (the aryl group may be optionally substituted with C _1-6 alkyl or C _3-6 cycloalkyl group.), refers to a C _1-6 alkyl group or a C _3-6 cycloalkyl group The solid-state supported bidentate chelate phosphine represented by the formula, XN- (CH ₂ PR ¹ R ² ) ₂ (wherein X represents a resin, and R ¹ and R 2 ² are each independently a C _6-14 aryl group (the aryl group may be optionally substituted with a C _1-6 alkyl group or a C _3-6 cycloalkyl group), C _1-6 means an alkyl group or a C _3-6 cycloalkyl group.) is produced from the solid supported bidentate chelate phosphine and palladium compound or a rhodium compound represented by the solid-phase supported bidentate Kiretohosu Fin - palladium complex catalyst or a solid supported bidentate chelating phosphines - relates rhodium complex catalyst.

The present invention will be described in more detail below.

In the present invention, "n" is normal, "i" is iso, "s" is secondary, "t" is tertiary, "c" is cyclo, "o" is ortho and "m" is meta. "P" means para.

First, the terms in each substituent of the substituents R ¹ , R ² and X will be described.

The C _1-6 alkyl group may be linear or branched, and may be methyl, ethyl, n-propyl, i-
Propyl, n-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methyl Pentyl, 1-methylpentyl, 3,
3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,
Examples thereof include 3-dimethylbutyl and 2-ethylbutyl.

Examples of the C _3-6 cycloalkyl group include c-propyl, c-butyl, c-pentyl and c-hexyl.

Examples of the C _6-14 aryl group include phenyl, naphthyl, biphenylyl and anthryl.

Next, specific examples of the substituents of R ¹ , R ² and X will be described.

Specific examples of R ¹ and R ² are, independently of each other, phenyl, o-methylphenyl, m-methylphenyl,
p-methylphenyl, α-naphthyl, β-naphthyl, o-biphenylyl, m-biphenylyl, p-biphenylyl, 1-anthryl, 2-anthryl, 9-anthryl, methyl, ethyl,
n-propyl, i-propyl, i-butyl, s-butyl, t-butyl, n-pentyl, n-hexyl, c-propyl, c-butyl,
c-pentyl and c-hexyl and the like, and preferably,
For example, phenyl, o-methylphenyl, α-naphthyl,
Examples thereof include β-naphthyl, o-biphenylyl, t-butyl and c-hexyl, and preferably phenyl.

Specific examples of preferred combinations of R ¹ and R ² include the following.

R ¹ and R ² are each independently a C _6-14 aryl group (wherein the aryl group may be optionally substituted with a C _1-6 alkyl group or a C _3-6 cycloalkyl group). .) In which R ¹ and R ² are the same C _6-14 aryl group (the aryl group may be optionally substituted with a C _1-6 alkyl group or a C _3-6 cycloalkyl group). .) and is a combination, R ¹ and R ² are the same phenyl group (said phenyl group is optionally in may be substituted by C _1-6 alkyl or C _{3 -6} cycloalkyl group.) A combination, R ¹ is o-biphenylyl and R ² is t-butyl, R ¹ is
A combination of o-biphenylyl and R ² is c-hexyl, a combination of R ¹ is α-naphthyl and R ² is phenyl, a combination of R ¹ is β-naphthyl and R ² is phenyl, and R ¹ is Examples include a combination of o-methylphenyl and R ² is o-methylphenyl, a combination of R ¹ is phenyl and R ² is phenyl, and R ¹ is o-for reasons such as easiness of raw material procurement. A combination of methylphenyl and R ² is o-methylphenyl and a combination of R ¹ is phenyl and R ²
More preferred is the combination where is phenyl.

Specific examples of X are not particularly limited as long as they are resins having an affinity for water, but polystyrene resins,
Examples thereof include polyethylene glycol-polystyrene resin and PEGA resin.

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION A method for producing a solid-supported bidentate chelate phosphine will be described below.

The solid-supported bidentate chelating phosphine is prepared by stirring paraformaldehyde and secondary phosphine (HPR ¹ R ² ) in an organic solvent under an inert atmosphere, and then adding a resin (amino resin) having an amino group at the end to this reaction solution. X-NH ₂ ) can be added and reacted. (R ¹ , R ² and X have the same meanings as above.) First, paraformaldehyde and secondary phosphine (HP
The conditions for stirring R ¹ R ² ) in an organic solvent under an inert atmosphere will be described.

The reaction can be carried out under a nitrogen atmosphere or an argon atmosphere as the inert atmosphere.

The organic solvent is not particularly limited as long as it is stable under the reaction conditions and is inert and does not interfere with the reaction. For example, the following solvents can be used.

Specifically, alcohols (eg, methanol, ethanol, propanol, butanol, octanol, etc.), cellosolves (eg, methoxyethanol, ethoxyethanol, etc.), aprotic polar organic solvents (eg, dimethylformamide, dimethylsulfoxide). , Dimethylacetamide, tetramethylurea, sulfolane, N-methylpyrrolidone and N, N-dimethylimidazolidinone), ethers (eg diethyl ether,
Diisopropyl ether, t-butyl methyl ether,
Tetrahydrofuran, dioxane, etc.), aliphatic hydrocarbons (eg pentane, hexane, c-hexane, octane, decane, decalin, petroleum ether, etc.), aromatic hydrocarbons (benzene, chlorobenzene, o-dichlorobenzene, nitrobenzene, toluene) , Xylene, mesitylene, tetralin, etc.), halogenated hydrocarbons (eg, chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc.), ketones (acetone, methyl ethyl ketone, etc.)
Methyl butyl ketone, methyl isobutyl ketone, etc.), lower aliphatic acid esters (eg methyl acetate, ethyl acetate,
Solvents such as butyl acetate and methyl propionate), alkoxyalkanes (eg dimethoxyethane and diethoxyethane) and nitrites (eg acetonitrile, propionitrile and butyronitrile) are mentioned.

These solvents are appropriately selected according to the easiness of reaction, and may be used alone or in combination of two or more. If necessary, the water content may be removed with a suitable dehydrating agent or desiccant and used as a non-aqueous solvent.

Preferred examples include alcohol solvents such as methanol, ethanol and propanol. The solvent described above is an example for carrying out the present invention, and the present invention is not limited to these conditions.

The reaction temperature is in the range of 0 ° C. to solvent reflux temperature, preferably room temperature to solvent reflux temperature.

The reaction time is in the range of 10 minutes to 24 hours, preferably 1 hour to 10 hours.

The amount of paraformaldehyde used is in the range of 0.5 to 2 molar equivalents with respect to the amount of secondary phosphine (HPR ¹ R ² ) used, preferably 0.8 to.
It is in the range of 1.3 molar equivalents.

Next, the conditions for producing a solid-phase supported bidentate chelate phosphine by adding a resin (X-NH ₂ ) having an amino group at the terminal to the reaction solution prepared above will be described.

Examples of the resin having an amino group at the terminal include polystyrene resin having an amino group at the terminal, polyethylene glycol-polystyrene resin having an amino group at the terminal (PEG-PS resin), and PEGA resin having an amino group at the terminal. Can be mentioned.

More specifically, Low cross-linked polysty
3000-4000MW polyethyle with rene and amino group at the end
Polyethylene-grafted polys made of ne glycol
tyrene resin, aminomethyl copolystyrene-1% DVB resin,
1% Cross-linked polystyrene resin, Macroporous pol
ystyrene resin, dimethylacrylamide and mono-2-acrylamid
oprop-1-yl [2-Aminopropy-1-yl] polyetyrene glycol resin, Bis 2-acrylaminoprop-1-yl polyethylene
Resin cross-linked with glycol and Aminomethylcopolyst
An example of the resin is rene-1% DVB. (DV
B means divinylbenzene. The above resin can be manufactured and used, but a commercially available product may be used.

Commercially available resins, preferably Ar,
ArgoGel-NH commercially available from gonaut₂, PS-NH₂And A
rgoPore-NH₂Nova commercially available from Novabiochem
Syn TG amino resin LL, Nova Syn TG amino resin H
L, Amino methyl Nova Ge, AminoPEGA resin, Amino me
thylated polystyrene, Amino methylated polystyrene
 HL and Amino methylated polystyrene VHL
Be done.

The reaction can be carried out in the air, but it is preferably carried out in a nitrogen atmosphere or an argon atmosphere.

When a resin (X-NH ₂ ) having an amino group at the terminal is added, it can be added as it is or after adding a solvent.

The solvent to be added is not particularly limited as long as it is a reaction solvent which is stable under the reaction conditions and is inert and does not interfere with the reaction, as the reaction solvent used for producing the compound of the present invention. For example, the following solvents can be used.

Specifically, alcohols (eg, methanol, ethanol, propanol, butanol, octanol, etc.), cellosolves (eg, methoxyethanol, ethoxyethanol, etc.), aprotic polar organic solvents (eg, dimethylformamide, dimethylsulfoxide). , Dimethylacetamide, tetramethylurea, sulfolane, N-methylpyrrolidone and N, N-dimethylimidazolidinone), ethers (eg diethyl ether,
Diisopropyl ether, t-butyl methyl ether,
Tetrahydrofuran, dioxane, etc.), aliphatic hydrocarbons (eg pentane, hexane, c-hexane, octane, decane, decalin, petroleum ether, etc.), aromatic hydrocarbons (benzene, chlorobenzene, o-dichlorobenzene, nitrobenzene, toluene) , Xylene, mesitylene, tetralin, etc.), halogenated hydrocarbons (eg, chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc.), ketones (acetone, methyl ethyl ketone, etc.)
Methyl butyl ketone, methyl isobutyl ketone, etc.), lower aliphatic acid esters (eg methyl acetate, ethyl acetate,
Solvents such as butyl acetate and methyl propionate), alkoxyalkanes (eg dimethoxyethane and diethoxyethane) and nitrites (eg acetonitrile, propionitrile and butyronitrile) are mentioned.

These solvents are appropriately selected according to the easiness of reaction, and may be used alone or in combination of two or more. If necessary, the water content may be removed with a suitable dehydrating agent or desiccant and used as a non-aqueous solvent.

Preferably, aromatic hydrocarbons (benzene,
Examples thereof include chlorobenzene, o-dichlorobenzene, nitrobenzene, toluene, xylene, mesitylene, tetralin, etc.) and halogenated hydrocarbons (eg, chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc.).

The solvent described above is an example for carrying out the present invention, and the present invention is not limited to these conditions.

The amount of the resin (X-NH ₂ ) having an amino group used is in the range of 0.01 to 5 equivalents, preferably 0.0, with respect to paraformaldehyde in terms of moles of the amino group of the resin.
It is in the range of 5 to 0.5 equivalent.

The reaction temperature is in the range of 0 ° C. to the solvent reflux temperature, preferably room temperature to the solvent reflux temperature.

The reaction time is in the range of 10 minutes to 24 hours, preferably 1 hour to 10 hours.

Next, a solid-phase supported bidentate chelate phosphine (XN- (CH ₂ PR ¹ R ² ) ₂ ) and a palladium compound or a rhodium compound are used to solid-phase supported bidentate chelate phosphine-palladium complex catalyst or solid-state supported bidentate. A method for producing the chelate phosphine-rhodium complex catalyst will be described.

Solid-state supported bidentate chelate phosphine (XN- (CH
₂ PR ¹ R ² ) ₂ ) to an organic solvent, and then a palladium compound or a rhodium compound is added and the reaction is carried out with stirring to carry out a stirring reaction. Complex catalysts can be produced. (R ¹ , R ² and X have the same meanings as described above.) Examples of the organic solvent used include water, alcohols (eg, methanol, ethanol, propanol, butanol, octanol, etc.), cellosolves (eg, methoxyethanol, ethoxy, etc.). Ethanol etc.), aprotic polar organic solvents (eg dimethylformamide, dimethylsulfoxide, dimethylacetamide, tetramethylurea, sulfolane, N-methylpyrrolidone and N, N-dimethylimidazolidinone), ethers (eg diethyl ether) , Diisopropyl ether, t-
Butyl methyl ether, tetrahydrofuran, dioxane, etc., aliphatic hydrocarbons (eg pentane, hexane, c-hexane, octane, decane, decalin, petroleum ether, etc.), aromatic hydrocarbons (benzene, chlorobenzene, o-dichlorobenzene) , Nitrobenzene, toluene, xylene, mesitylene, tetralin, etc.), halogenated hydrocarbons (eg chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc.), ketones (acetone, methyl ethyl ketone, methyl butyl ketone, methyl isobutyl ketone, etc.), lower Aliphatic acid esters (such as methyl acetate, ethyl acetate, butyl acetate and methyl propionate), alkoxyalkanes (such as dimethoxyethane and diethoxyethane) and nitrites (such as acetonitrile and propylene) Solvent Onitoriru and butyronitrile), and the like.

These solvents are appropriately selected according to the easiness of reaction, and may be used alone or in combination of two or more. If necessary, the water content may be removed with a suitable dehydrating agent or desiccant and used as a non-aqueous solvent.

Aromatic hydrocarbons (benzene, chlorobenzene, o-dichlorobenzene, nitrobenzene, toluene, xylene, mesitylene, tetralin, etc.), halogenated hydrocarbons (eg chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc.) are preferable. ) Is given.

The solvent described above is an example for carrying out the present invention, and the present invention is not limited to these conditions.

The palladium compound is not particularly limited as long as it generally coordinates with phosphine. For example, PdCl ₂ (MeCN) ₂ , PdCl ₂ (PhCN) ₂ , Li ₂ PdCl ₄ , Na ₂ PdC.
l ₄ , [Pd (MeCN) ₄ ] (BF ₄ ) ₂ , [Pd (η ³ -C ₃ H ₅ ) Cl] ₂ , [Pd (η
³ -C ₃ H ₅ )] ₂ , PdCl ₂ (PMe ₃ ) ₂ , PdCl ₂ (PPh ₃ ) ₂ and Pd (OAc) ₂
And the like, preferably Pd (OAc) ₂ and [Pd (η ³ -C ₃ H ₅ ) C
l] ₂ etc.

The rhodium compound is not particularly limited as long as it generally coordinates with phosphine. For example, [RhCl (CO) ₂ ] ₂ , [RhCl (C ₂ H ₄ ) ₂ ] ₂ , [RhCl ( C ₈ H ₁₂ )] ₂ ,
[RhI ₂ (CO) ₂ ] ₂ and Dicarbonylacetylacetonato rhodium
And the like, and preferably [RhCl (CO) ₂ ] _{2 and the} like.

The amount of the palladium compound or rhodium compound used depends on the amount of solid-phase supported bidentate chelate phosphine (XN- (CH ₂ PR
¹ R ² ) ₂ ) 0.1 to 5 molar equivalents, preferably 0.3 to 1.5 molar equivalents, relative to the total loading amount (the number of moles of phosphorus atoms introduced into the solid-phase supported bidentate chelate phosphine). Is.

The reaction temperature is in the range of 0 ° C. to solvent reflux temperature, preferably 10 ° C. to solvent reflux temperature.

The reaction time is 5 minutes to 24 hours, preferably 1
It is in the range of 0 minutes to 10 hours.

Specific examples of the preferable solid phase supported bidentate chelate phosphine-palladium complex catalyst or solid phase supported bidentate chelate phosphine-rhodium complex catalyst include the following compounds. (1) Formula, XN- (CH ₂ PR ¹ R ² ) ₂ (In the formula, X represents a resin, and R ¹ and R ² are each independently a C _6-14 aryl group (the aryl group). is, C _1-6 alkyl or C _3-6 may be optionally substituted with a cycloalkyl group.), expressed in means C _1-6 alkyl group or a C _3-6 cycloalkyl group.) A solid phase supported bidentate chelate phosphine-palladium complex catalyst or a solid phase supported bidentate chelate phosphine-rhodium complex catalyst produced from a solid phase supported bidentate chelate phosphine and a palladium compound or a rhodium compound. (2) R ¹ and R ² are the same C _6-14 aryl group (the aryl group may be optionally substituted with a C _1-6 alkyl group or a C _3-6 cycloalkyl group), C _1-6 alkyl group or C
The solid-state supported bidentate chelate phosphine-palladium complex catalyst or the solid-state supported bidentate chelate phosphine-rhodium complex catalyst according to (1), which is a _3-6 cycloalkyl group. (3) R ¹ and R ² are each independently, C _6-14 aryl group (the aryl group may be optionally substituted with C _1-6 alkyl group or a C _3-6 cycloalkyl group The solid phase supported bidentate chelate phosphine-palladium complex catalyst or the solid phase supported bidentate chelate phosphine-rhodium complex catalyst according to (1). (4) R ¹ and R ² are the same C _6-14 aryl group (the aryl group may be optionally substituted with a C _1-6 alkyl group or a C _3-6 cycloalkyl group). (3) The solid-state supported bidentate chelate phosphine-palladium complex catalyst or the solid-state supported bidentate chelate phosphine-rhodium complex catalyst. (5) R ¹ and R ² are identical phenyl groups (the phenyl group may be. Which is optionally substituted with C _1-6 alkyl or C _{3 -6} cycloalkyl group) (4) The solid-state supported bidentate chelate phosphine-palladium complex catalyst or the solid-state supported bidentate chelate phosphine-rhodium complex catalyst. (6) The solid-state supported bidentate chelate phosphine-palladium complex catalyst or the solid-state supported bidentate phosphine-rhodium complex catalyst according to (5), wherein R ¹ and R ² are phenyl groups. (7) The solid-supported bidentate chelate phosphine-palladium complex catalyst according to (6), which uses Pd (OAc) ₂ as the palladium compound. (8) Use of [Pd (η ³ -C ₃ H ₅ ) Cl] ₂ as the palladium compound (6) Solid-phase supported bidentate chelate phosphine-
Palladium complex catalyst. (9) The solid-state supported bidentate chelate phosphine-rhodium complex catalyst according to (6), wherein [RhCl (CO) ₂ ] ₂ is used as the rhodium compound.

Next, solid phase supported bidentate chelate phosphine-
A reaction using a palladium complex catalyst or a solid-state supported bidentate chelate phosphine-rhodium complex catalyst will be described.

As the reaction that can be used, any reaction can be applied as long as it is an organic reaction involving a phosphine-palladium catalyst and a phosphine-rhodium catalyst.

Examples thereof are organometallic compounds-synthesis method and utilization method- (Tokyo Kagaku Dojin), Metal-catalyzed Cross-co.
uppling Reaction (WILLY-VCH), Handbook of Palladium
-The reactions introduced in the books such as Catalyzed Organic Reactions (Academic Press).

For example, cross-coupling reaction, carbonylation reaction of aryl halide, nucleophilic reaction to allyl ligand, oxidation of allyl ligand to aldehyde and ketone, esterification by CO insertion, hydrogenation , Hydrosilylation, decarbonylation of acid halides and aldehydes.

More specifically, Suzuki-Miyaura coupling represented by the following formula, conversion of aryl halide by CO insertion to arylcarboxylic acid by CO insertion, substitution reaction at allyl position via π-allyl palladium, etc. can give.

[0061]

[Chemical 1]

As the reaction conditions and the like, the reaction conditions described in the above-mentioned textbooks and their references can be used.

In particular, the Suzuki-Miyaura coupling reaction will be described in detail below.

Specific examples of the solvent used include water,
Alcohols (eg, methanol, ethanol, propanol, butanol, octanol, etc.), cellosolves (eg, methoxyethanol, ethoxyethanol, etc.), aprotic polar organic solvents (eg, dimethylformamide, dimethylsulfoxide, dimethylacetamide, tetramethylurea, etc.) Sulfolane, N-methylpyrrolidone and N, N-dimethylimidazolidinone), ethers (eg diethyl ether, diisopropyl ether, t-butylmethyl ether, tetrahydrofuran and dioxane), aliphatic hydrocarbons (eg pentane,
Hexane, c-hexane, octane, decane, decalin, petroleum ether, etc.), aromatic hydrocarbons (benzene, chlorobenzene, o-dichlorobenzene, nitrobenzene, toluene, xylene, mesitylene, tetralin, etc.), halogenated hydrocarbons ( For example, chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc.), ketones (acetone, methyl ethyl ketone, methyl butyl ketone, methyl isobutyl ketone, etc.), lower aliphatic acid esters (eg methyl acetate, ethyl acetate, butyl acetate, methyl propionate, etc.) ), Alkoxyalkanes (eg, dimethoxyethane, diethoxyethane, etc.) and nitriles (eg, acetonitrile, propionitrile, butyronitrile, etc.) and the like.

These solvents are appropriately selected according to the easiness of reaction and can be used alone or in combination of two or more. If necessary, the water content may be removed with a suitable dehydrating agent or desiccant and used as a non-aqueous solvent.

The base to be used may be either an inorganic base or an organic base. Illustrative examples of the inorganic base include alkali metal carbonates such as cesium carbonate, potassium carbonate and sodium carbonate, and alkaline earth metal carbonates. Examples thereof include alkali metal hydroxides and alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide and barium hydroxide. Examples of the organic base include triethylamine, diisopropylethylamine, butylamine, piperidine, pyridine and the like.

The number of equivalents is 0.1 to 10 equivalents, preferably 0.5 to 5 equivalents. The reaction temperature is −20 ° C. to 200 ° C., preferably 0 ° C. to solvent reflux temperature.

The equivalent number of boronic acid to the aryl halide is 0.1 to 5 equivalents, preferably 0.5 to 3
Equivalent. The palladium catalyst used is 0.001 equivalent to 5 equivalents, preferably 0.01 equivalent to 1 equivalent relative to the aryl halide.

[0069]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 Synthesis of compound (1)

[0071]

[Chemical 2]

Paraformaldehyde 213 mg (7.0
9 mmol) and 1.35 ml (7.76 mmol) of diphenylphosphine
Was heated in methanol at 70 ° C. for 1 hour with slow stirring under an argon atmosphere. After cooling to room temperature, ArgoGelNH ₂ (A
2.00 g (0.37 mmol / g) (manufactured by rgonaut) and 30 ml of toluene were added, and the mixture was stirred at room temperature for 3 hours. Then, the reaction solution was filtered and the resin was washed with 30 ml of methanol three times and with dichloromethane three times. The target compound was obtained by drying the resin under reduced pressure. Total loading (number of moles of phosphorus atom introduced into solid-phase supported bidentate chelate phosphine) 1.48 mmol. ³¹ P { ¹ H} NMR (SRMAS NMR (Swelling Resin Magic Angle S
pining NMR), 162MHz, CDCl ₃ ) δ -28.7ppm (s)

Example 2 Synthesis of compound (2)

[0074]

[Chemical 3]

The solid phase-supported phosphine (compound (1)) obtained in Example 1 (total loading 1.48 mmol) and 30 ml of dichloromethane were placed in a reaction vessel (Merrifield vessel), and [Pd (η ³ -C ₃ H ₅ ) Cl] ₂ 142 mg
(0.39 mmol) was added at room temperature, and the mixture was stirred at 25 ° C for 15 minutes. After filtration, the resin was washed with dichloromethane three times and dried under reduced pressure to obtain the target compound. ³¹ P { ¹ H} NMR (SRMAS NMR (Swelling Resin Magic Angle S
pining NMR), 162MHz, CDCl ₃ ) δ 2.20ppm (s)

Example 3 Synthesis of compound (2 ')

[0077]

[Chemical 4]

The solid phase-supported phosphine (compound (1)) obtained in Example 1 (total loading 1.48 mmol) and 30 ml of dichloromethane were placed in a reaction vessel (Merrifield vessel), and Pd (OAc) ₂ 175 mg ( (0.78 mol)
Was added at room temperature and stirred at 25 ° C for 15 minutes. After filtration, the resin was washed with dichloromethane three times and dried under reduced pressure to obtain the target compound. ³¹ P { ¹ H} NMR (SRMAS NMR (Swelling Resin Magic Angle S
pining NMR), 162MHz, CDCl ₃ ) δ + 7.0ppm (s)

Example 4 Representative Reaction Example: Suzuki-Miyaura Reaction 1 mmol of iodobenzene and 1.2 phenylboronic acid were placed in a reaction vessel.
mmol, 54 mg (0.02 mmol in terms of Pd) of compound (2) and 5.0 mmol of potassium carbonate were stirred in 3.3 ml of water at 50 ° C. for 12 hours. The reaction solution was filtered, washed with 50 ml of diethyl ether, the filtered solution was dried over anhydrous sodium sulfate, and the obtained product was analyzed by GC-MS. Biphenyl was obtained with a yield of 99% and a purity of 99%. I found out that

Example 5 When the same reaction as in Example 4 was carried out using the compound (2) recovered by filtration in Example 4, the yield of biphenyl was 99.
%, Purity 99%. Similar results were obtained when the reaction was charged again using the compound (2) recovered again at this time.

Example 6 Aryl halide ArX 0.06 mmol and boronic acid R were placed in a reaction vessel.
(OH) ₂ 0.072 mmol, compound (2) 3.2 mg (Pd conversion 1.2 μ
mol), 0.3 mmol of potassium carbonate and 200 μl of water were heated and stirred at 50 ° C. for 12 hours. After filtering the reaction mixture, diethyl ether
After washing with 10 ml and drying the filtered solution with anhydrous sodium sulfate, the obtained product was analyzed by GC-MS (HP6890 Series GasChromatograp
h and 5973 Network Mass Selective Detector (YOKOGAW
As a result of analysis by A ANALYTICAL SYSTEMS)), products were obtained in a high yield and high purity as shown in the table below.

[0082]

[Table 1]

[0083]

INDUSTRIAL APPLICABILITY According to the present invention, solid-phase loading, which is easy to produce, has excellent catalytic activity and reaction selectivity, and can be used in an aqueous solution, is useful for producing pharmaceuticals and agricultural chemicals and their intermediates. A phosphine catalyst can be provided.

Claims (10)

[Claims] 1. The formula, XN- (CH ₂ PR ¹ R ² ) ₂ (wherein X represents a resin, and R ¹ and R ² are each independently a C _6-14 aryl group ( The aryl group may be optionally substituted with a C _1-6 alkyl group or a C _3-6 cycloalkyl group.), C _1-6
It means an alkyl group or a C _3-6 cycloalkyl group. ) A solid-phase-supported bidentate chelate phosphine represented by 2. R ¹ and R ² are each independently C _6-14.
Aryl group (the aryl group is a C _1-6 alkyl group or a C _3-6
It may be optionally substituted with a cycloalkyl group. The solid-state supported bidentate chelate phosphine according to claim 1. Wherein R ¹ and R ² are identical C _6-14 aryl group (the aryl group may be optionally substituted by C _1-6 alkyl group or a C _3-6 cycloalkyl group. The solid-phase supported bidentate chelate phosphine according to claim 2. 4. R ¹ and R ² are the same phenyl group (the phenyl group may be optionally substituted with a C _1-6 alkyl group or a C _3-6 cycloalkyl group). Item 3. A solid-phase-supported bidentate chelate phosphine according to Item 3. 5. The method according to claim 4, wherein R ¹ and R ² are phenyl groups.
The solid-phase supported bidentate chelating phosphine described. 6. The formula, XN- (CH ₂ PR ¹ R ² ) ₂ (wherein X represents a resin, and R ¹ and R ² are each independently a C _6-14 aryl group ( The aryl group may be optionally substituted with a C _1-6 alkyl group or a C _3-6 cycloalkyl group.), C _1-6
It means an alkyl group or a C _3-6 cycloalkyl group. ) A solid-state supported bidentate chelating phosphine-palladium complex catalyst or a solid-state supported bidentate chelating phosphine-rhodium complex catalyst produced from a solid-state supported bidentate chelating phosphine and a palladium compound or a rhodium compound. 7. R ¹ and R ² are each independently C _6-14.
Aryl group (the aryl group is a C _1-6 alkyl group or a C _3-6
It may be optionally substituted with a cycloalkyl group. ) Is a solid phase-supported bidentate chelate phosphine-
Palladium complex catalyst or solid-state supported bidentate chelate phosphine-rhodium complex catalyst. 8. R ¹ and R ² are identical C _6-14 aryl group (the aryl group may be optionally substituted by C _1-6 alkyl group or a C _3-6 cycloalkyl group. The solid-state supported bidentate chelating phosphine-palladium complex catalyst or the solid-state supported bidentate chelating phosphine-rhodium complex catalyst according to claim 7. 9. R ¹ and R ² are the same phenyl group (the phenyl group may be optionally substituted with a C _1-6 alkyl group or a C _3-6 cycloalkyl group). Item 9. A solid phase supported bidentate chelate phosphine-palladium complex catalyst or a solid phase supported bidentate chelate phosphine-rhodium complex catalyst. 10. The method according to claim 9, wherein R ¹ and R ² are phenyl groups.
The solid-state supported bidentate chelate phosphine-palladium complex catalyst or the solid-state supported bidentate chelate phosphine-rhodium complex catalyst.