JP2003260365A - Coupling reaction catalyst and method for manufacturing coupling compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a coupling reaction catalyst having high catalytic activity for the coupling reaction between an organic compound having a leaving group and a reaction agent. <P>SOLUTION: An organic compound having a leaving group (such as an aromatic halide) is subjected to the coupling reaction with a reacting agent (such as alkenes) in the presence of the coupling reaction catalyst composed of a transition metal compound (A) such as palladium and a ligand (B). The ligand (B) has a coordination group (a coordination group having a nitrogen atom or a phosphorus atom) to the transition metal compound (A) and has at least one organic group having a negative charge or capable of producing the negative charge (such as an aromatic alcoholate such as phenolate). Further, the catalyst may contain a base (in particular, an inorganic base capable of producing the negative charge of the ligand (B)). <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a catalyst (or catalyst system) useful for a coupling reaction such as a Heck reaction, and a method for producing a coupling compound using this catalyst.

[0002]

2. Description of the Related Art In the field of organic synthesis, transition metal catalysts have been proposed for use in the production of many key intermediates such as pharmaceuticals and functional substances. For example, regarding the Heck reaction between alkenes and halides, J. Organomet. Chem., 1
999,576,23-41, a reaction in which a new olefin is produced by a reaction between an organic halogen compound and an olefin compound with a palladium catalyst is reported. In the Heck reaction, the coupling reaction is usually performed in the presence of a palladium catalyst and a base such as amines.

However, many conventional methods require a high temperature of over 100 ° C. as a reaction condition. for that reason,
In order to carry out the above reaction industrially, a large amount of energy is consumed, the load on the environment is high, and safety is also a problem. In addition, in general, the organic reaction at high temperature has low selectivity and the activity of the catalyst is likely to decrease, and the operation of recovering an expensive precious metal catalyst is complicated.

In Chem. Commun., 2000, 1895-1896, diphenylphosphinophenolate was used as a ligand of a palladium catalyst in the reaction of reacting an aryl halide with hexamethyldisilane to produce a trimethylsilylaryl compound. Have been reported to be useful.

[0005]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a coupling reaction catalyst having high catalytic activity, and to use this catalyst,
It is intended to provide a method capable of producing an unsaturated compound safely and economically.

Another object of the present invention is a coupling reaction catalyst having a ligand having a strong σ-donor ability and a high π-acceptor ability and capable of efficiently carrying out a coupling reaction with a high selectivity. And a method for producing a coupling compound (coupling reaction product) using this catalyst.

[0007]

Means for Solving the Problems As a result of intensive studies for achieving the above-mentioned object, the present inventors have found that in the presence of a transition metal catalyst, in a coupling reaction between an alkene and a halide, a specific catalyst is present in a reaction system. The inventors have found that the coexistence of a ligand significantly improves the activity of the transition metal catalyst and can efficiently produce an organic compound under milder conditions, and completed the present invention.

That is, the coupling reaction catalyst of the present invention comprises a transition metal compound (A) and a ligand (B), and the ligand (B) is a ligand for the transition metal compound (A). It has a position group and an organic group having at least one negative charge or an organic group capable of generating the negative charge. The transition metal compound (A) is a group 8 element of the periodic table, a first group of the periodic table.
It contains a transition metal element selected from Group B elements and the like. The coordinating group of the ligand (B) may contain a Group 5B element of the periodic table. Further, the organic group of the ligand (B) may be at least one (anionic group) selected from alcoholate (oxide such as phenolate and naphtholate), thiolate (sulfide) and acylamide group. In the ligand (B), the organic group having a negative charge or capable of being generated and the coordinating group are usually bonded to the conjugated position. That is, in the ligand (B), the organic group having a negative charge and the coordinating group are directly bonded or
Alternatively, it may be bonded to a conjugated position. Examples of such ligands include aromatic compounds.
More specifically, in the catalyst of the present invention, the transition metal compound (A) may be a palladium compound, and the ligand (B) is, for example, at least 1 selected from a nitrogen atom and a phosphorus atom. It may be an aromatic compound (compound having a phenolic hydroxyl group) that has a coordinating group composed of two elements and is capable of forming an aromatic alcoholate.

The coupling reaction catalyst of the present invention may be a catalyst (or catalyst system) composed of a base in addition to the transition metal compound (A) and the ligand (B).
The base may be an inorganic base capable of generating a negative charge (anion) of the ligand (B).

In the method of the present invention, a compound having a leaving group and an unsaturated compound are subjected to a coupling reaction in the presence of the above coupling reaction catalyst to produce a coupling compound. In this method, a halogen atom, a sulfonyloxy group or a sulfonyl halide group, a diazonium group, a carbonyl halide group or the like can be used as the leaving group. The method of the present invention may be used to react an aromatic halide with a reactant (alkene or the like).

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The coupling reaction catalyst of the present invention comprises a transition metal compound (or transition metal catalyst) (A) and a ligand (B) capable of coordinating to this transition metal compound. Has been done.

[(A) Transition metal compound or transition metal catalyst]
As the transition metal element constituting the transition metal compound (or transition metal catalyst), elements of Group 3A to 7A, Group 8 element, Group 1B of the periodic table, for example, Group 3A element of the periodic table (S
c, Y and rare earth elements), Periodic Table Group 4A elements (Ti,
Zr, Hf), periodic table group 5A element (V, Nb, T
a), periodic table group 6A elements (Cr, Mo, W), periodic table group 7A elements (Mn, Tc, Re), periodic table group 8 elements (Fe, Ru, Os, Co, Rh, Ir, Ni, Pd,
Pt) and the periodic table 1B group element (Cu, Ag, Au) can be illustrated.

Of these transition metal elements, periodic table 4A
At least one member selected from Group 7 element to Group 7A element of the periodic table, Group 8 element of the periodic table and Element 1B of the periodic table, in particular, Group 8 element of the periodic table (iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium, Platinum) and at least one element selected from Group 1B elements (copper, silver, gold) of the periodic table are preferable. More preferable transition metal elements include nickel, palladium, and platinum of the Group 8 elements of the periodic table (IUPAC Inorganic Chemistry Nomenclature Revised Edition (1989)
Element which is classified as a Group 10 element in the periodic table), especially palladium.

The oxidation number of the element is not particularly limited and may be 0, +1, +2, +3, + depending on the type of the element.
It may be 4 or the like.

The transition metal compound may be a simple metal, but is usually a compound containing a transition metal element. The compound of the transition metal element is, for example, an inorganic acid salt (for example, nitrate, sulfate, phosphoric acid, perhalogenate, hydrochloric acid,
Hydrohalic acid salts such as hydrobromic acid), organic acid salts (for example, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, sulfonic acid salts such as p-toluenesulfonic acid, phosphonic acid salts, formic acid, acetic acid) , Carboxylic acid salts such as propionic acid), halides (eg, chloride, bromide, iodide, etc.), complexes (or complex salts), and the like. Also, a transition metal compound (or transition metal catalyst)
The solid catalyst may be a solid catalyst in which these metal compounds are fixed on a carrier (support such as activated carbon, silica, alumina, titania). Furthermore, iron oxide, cobalt oxide,
It may be a metal oxide such as nickel oxide.

The ligand constituting the complex is, for example, O.
H (hydroxo), C _1-4 alkoxy, C _l-4 acyl, C _1-4 alkoxy - carbonyl group, acetylacetonato, cycloalkadiene (cyclopentadienyl group,
Cyclooctadienyl group, cyclooctadiene, etc.),
Benzylidene group, benzylideneacetone, benzylideneacetylacetonato, benzylideneacetophenone, halogen atom, CO, CN, oxygen atom, H ₂ O (aco),
Phosphine (eg, triarylphosphine such as triphenylphosphine), phosphite (eg, triarylphosphite such as triphenylphosphite), NH ₃ (ammine), NO, NO ₂ (nitro), N
O ₃ (nitrato), nitrogen-containing compounds (ethylenediamine, diethylenetriamine, pyridine, phenanthroline, bipyridyl, etc.) and the like can be mentioned. In the complex or complex salt, the same kind or different kinds of ligands may coordinate one kind or two or more kinds.

The transition metal compound is often used as an inorganic acid salt, an organic acid salt, a halide or a complex which may be a complex salt. More specifically, as the complex or complex salt,
For example, among palladium (II) acetate, palladium (II) acetylacetonato, tris (dibenzylideneacetone) dipalladium (O), and other palladium complexes or complex salts, and corresponding Group 8 metal sources of the periodic table, Compounds of Group 8 metal elements, especially complexes or complex salts, are often used.

[(B) Ligand] The ligand (B) comprises a coordinating group (or a coordinable site) for the transition metal compound (or transition metal catalyst) (A) and at least one negative group. It has an organic group having a charge or an organic group capable of generating the negative charge. Such ligands can be used alone or in combination of two or more. The ligand (B) may form a coupling catalyst in the reaction system in association with the transition metal compound (transition metal catalyst) (A), and is free from the transition metal catalyst (A). It may be present in the reaction system in a form, or may be present in the reaction system as a complex coordinated with the transition metal catalyst (A). Further, the ligand (B) may be a chelate type ligand.

The coordinating group is not particularly limited as long as it is capable of coordinating with the transition metal compound (or transition metal catalyst) (A), and corresponds to, for example, the ligand of the complex or complex salt. Atoms or organic groups such as hydroxyl groups, C
_1-4 alkoxy, C _l-4 acyl, C _1-4 alkoxy -
Carbonyl group, acetylacetonato group, benzylideneacetylacetonato group, cycloalkadienyl group (cyclopentadienyl group, cyclooctadienyl group, etc.), benzylidene group, halogen atom, cyano group, nitro group, amino group or substituted Amino group (C _1-6 alkylamino group such as dimethylamino, diethylamino, dibutylamino group), nitrogen-containing heterocyclic group (5- or 6-membered heterocyclic group containing at least one nitrogen atom as a hetero atom, for example, pyrrolyl group , 5-membered ring groups such as imidazolyl groups, 6-membered ring groups such as pyridyl groups, bipyridyl groups, pyrazinyl groups, pyrimidinyl groups, condensed heterocyclic groups such as phenanthrolinyl groups), phosphino groups (eg, methylphosphino) , dimethylphosphino, diethylphosphino, C _1-6 a, such as dibutyl phosphino group Kiruhosufino group, a mono C _1-6 alkyl such as methyl phenyl phosphino, butylphenyl phosphino group - mono C _6-12 aryl phosphino group, a phenyl phosphino, diphenylphosphino, such as ditolyl phosphino group C _{6- 12} arylphosphino groups), and the arsino (arsino) corresponding to these phosphino groups.
no), stibino, bismuth
ino) group and the like.

The preferred coordinating group is usually the periodic table 5B.
It is composed of a group element such as at least one element selected from nitrogen atom, phosphorus atom, arsenic, antimony, and bismuth, particularly at least one element selected from nitrogen atom and phosphorus atom. Examples of such a coordinating group include the cyano group, nitro group, amino group or substituted amino group, nitrogen-containing heterocyclic group, phosphino group, arsino group corresponding to these phosphino groups, and stibino group. ) Group, a bismuthino group and the like.

The organic group of the ligand (B) is only required to generate a negative charge in the reaction system, and is generally weaker acidic than a carboxyl group or a sulfonic acid group, and further an organic group which generates a negative charge. (Anionic group or group capable of generating anionic group by dissociation). As such an organic group,
For example, a hydroxyl group (particularly a phenolic hydroxyl group), an alcoholate (oxide) corresponding to this hydroxyl group (particularly an alcoholate formed from a phenolic hydroxyl group such as phenolate or naphtholate), a mercapto group (particularly a phenolic mercapto group), A thiolate (sulfide) corresponding to a mercapto group, an organic group capable of generating a negative charge (anion), for example, an acylamide group (a C _1-6 alkyl-carbonylamide group such as an acetamide group, a C _6-12 such as a benzoylamide group). aryl - carbonyl amide group, methanesulfonyl amide group, ethanesulfonyl amide group, C _6-12 arylsulfonyl such as C _1-6 alkanesulfonyl amide groups, p- toluenesulfonyl amido group such as trifluoromethyl sulfonyl amide group ami Group, etc.), and others. The ligand may have these organic groups individually or in combination. The negative charge (anion) is
It may be in the form of a salt in which a proton is partially or completely substituted with a cationic species.

The ligand (B) may be a non-aromatic compound or an aromatic compound. In order to enhance the catalytic activity, an aromatic compound, particularly a compound that forms a conjugated structure with an organic group (anionic group) having a negative charge or generating a negative charge is preferable. The aromatic compound may be a hydrocarbon cyclic aromatic compound, and is a heterocyclic aromatic compound having at least one hetero atom selected from a nitrogen atom, an oxygen atom and a sulfur atom as a ring-constituting atom. It may be.

When it is assumed that the coordinating group does not influence the acid dissociation index, the ligand (B) is usually weaker in acidity than carbonic acid (acid dissociation index pKa = 6.35). ,
At an ionic strength of 0.1 mol / dm ³ , the acid dissociation index pKa in the aqueous solution was 6.8 to 1 regardless of the number of dissociation steps.
5, preferably about 7.5-12. The ligand (B) having such an acid dissociation index (as a compound having no coordinating group) is described in “Revised 3rd Edition Chemical Handbook Basic Edition II”.
(Maruzen Co., Ltd., issued January 25, 1988) can be referred to.

Such a ligand (B) has, for example, the formula:
(cd) _m -Ar- (A) _n (In the formula, Ar represents an aromatic ring,
cd represents the coordinating group, A represents an organic group having a negative charge or an organic group capable of generating a negative charge (anionic group), and m and n each represent an integer of 1 or more). .

The aromatic ring has a C _6-12 arene ring such as a benzene ring or a naphthalene ring, and at least one hetero atom selected from a nitrogen atom, an oxygen atom and a sulfur atom as a ring-constituting atom. Alternatively, a 6-membered heterocycle, a condensed heterocycle of an aromatic or non-aromatic 5- or 6-membered heterocycle and a hydrocarbon ring (such as a benzene ring) can be exemplified.
Examples of the heterocycle include sulfur-containing heterocycles such as thiophene, oxygen-containing heterocycles such as furan and benzofuran, pyrrole, imidazole, pyridine, pyrazine, pyrimidine, indole, quinoline, carbazole, acridine, phenazine, phenanthroline, and other nitrogen-containing heterocycles. Examples include heterocycles.

In the above formula, m = 1 to 3 (especially 1 to
2), n = 1 to 3 (particularly 1 to 2), and m + n = 2 to 6 (preferably 2 to 4).

Further, in the aromatic ring, the substitution position of the organic group with respect to the coordinating group is not particularly limited, and for example, 5
In a membered ring or a 6-membered ring (for example, a benzene ring), the o-position,
It may be either m-position or p-position, but is preferably m-position, especially p-position. Further, the naphthalene ring may have 3-position, 4-position, 5-position, 6-position (particularly 4-position and / or 5-position).

A typical compound of the ligand (B) having an organic group is an aromatic compound (compound having a phenolic hydroxyl group) capable of forming or forming an aromatic alcoholate, for example, phenols [ For example, monohydric phenols (alkylphenols such as phenol, cresol, xylenol, halogenated phenols, nitrophenols, aminophenols, phenolsulfonic acids), dihydric phenols (catechol,
Resorcin, hydroquinone, orcin, etc.), trihydric phenols (pyrogallol, oxyhydroquinone, phloroglucin, etc.)], naphthols and the like.

The ligand (B) will be described by taking a phosphino group as a coordinating group. For example, tris (hydroxyaryl) phosphines such as tris (p-hydroxyphenyl) phosphine and tris (m).
-Hydroxyphenyl) phosphine and the like; bis (hydroxyphenyl) arylphosphine, such as bis (p-hydroxyphenyl) phenylphosphine, bis (m-hydroxyphenyl) phenylphosphine and the like;
Bis (hydroxyphenyl) alkylphosphines such as bis (hydroxy C _6-12 aryl) C _1-10 alkylphosphines such as bis (p-hydroxyphenyl) methylphosphine and bis (m-hydroxyphenyl) _{ethylphosphine} ; diaryl Phosphinophenols, for example, m-hydroxyphenyl (diphenyl) phosphine, p-hydroxyphenyl (diphenyl) phosphine, p-hydroxyphenyl (ditolyl) phosphine, p-hydroxyphenylbis (nitrophenyl) phosphine, p-hydroxyphenylbis. (Chlorophenyl) phosphine, 4-diphenylphosphino-1-naphthol, 5-diphenylphosphino-1-naphthol,
6-diphenylphosphino-1-naphthol, 5-diphenylphosphino-2-naphthol, 6-diphenylphosphino-1-naphthol and the like; dialkylphosphinophenols such as m-hydroxyphenyl (dimethyl) phosphine, p- Hydroxyphenyl (dimethyl) phosphine, p-hydroxyphenyl (diethyl)
Examples thereof include hydroxyphenyl (diC _1-6 alkyl) phosphine such as phosphine, p-hydroxyphenyl (dibutyl) phosphine, p-hydroxyphenyl (di-t-butyl) phosphine, and naphthols corresponding to these. The ligand is a compound having the other coordinating group (for example, a cyano group, a nitro group, an amino group or a substituted amino group, a coordinating group having a nitrogen atom such as a pyridyl group) in place of the phosphino group. May be

The amount of the ligand (B) used is an effective amount for enhancing the activity of the transition metal compound (A), for example, 0.01 mol or more (for example, 1 mol of the transition metal compound (A)). , 0.01 to 50 mol, preferably 0.05 to 20
Mol, more preferably about 0.1 to 10 mol,
Usually, it is often about 0.5 to 5 mol (for example, 1 to 3 mol).

[Base] When the acid component is by-produced by the reaction, the catalyst of the present invention is preferably used in combination with a base to remove the deoxidized component from the reaction system. Further, in order to enhance the activity of the catalyst, it is preferable that the transition metal compound, the ligand and the base constitute a catalyst system. As the deoxidizing component and the base constituting the catalyst system, organic bases (trialkylamines such as trimethylamine, triethylamine and tributylamine, alkanolamines such as triethanolamine and dimethylaminoethanol, N, N-dimethylaminocyclohexane and the like) Alicyclic amines, aromatic amines such as N, N-dimethylaminobenzene, pyridine,
Morpholine, 1,4-diazabicyclo [2.2.2] octane, 1,5-diazabicyclo [3.2.1] octane, 1,5-diazabicyclo [3.3.0] octane,
1,4-diazabicyclo [4.2.0] octane, 1,
5-diazabicyclo [3.3.1] nonane, 1,5-diazabicyclo [5.3.0] decane, 1,5-diazacyclo [3.3.0.0 ^2,6 ] octane, 1,8-diazabicyclo [5.4.0] Undeca-7-ene, 1,5-
Cyclic amines such as diazabicyclo [4.3.0] nonane-5-ene and hexamethylenetetramine), inorganic bases (alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide, sodium carbonate, carbonic acid) In addition to alkali metal carbonates such as potassium and sodium hydrogen carbonate, alkaline earth metal hydroxides such as calcium hydroxide and magnesium hydroxide, alkaline earth metal carbonates such as calcium carbonate, etc., a base can be generated. Ingredients [eg metal alkoxides (sodium methoxide,
Examples thereof include alkali metal alkoxides such as sodium ethoxide and potassium methoxide), salts of weak acids and strong alkalis (for example, alkali metal salts of organic carboxylic acids such as sodium acetate and potassium acetate).
These bases can be used alone or in combination of two or more. Organic bases are commonly used as tertiary amines.

The preferred base is an inorganic base or a component capable of forming an inorganic base, particularly an inorganic base capable of forming an anionic group of the ligand (B). As such an inorganic base, an alkali metal compound (especially an alkali metal hydroxide such as sodium hydroxide) capable of forming an alcoholate (especially phenolic alcoholate) such as a phenolate or a naphtholate is preferable, and an alkali metal compound can be formed. Alkali metal alkoxides and alkali metal salts of organic carboxylic acids are also useful.

A base is not always necessary, but when a base is used, the amount of the base used can be selected from a wide range as long as it does not adversely affect the reaction. When a negative charge is generated from the organic group of the ligand (B), the ratio of the base to the ligand (B) is usually 0. 5 to 1000 mol, preferably 1 to 5
00 mol, more preferably 1 to 100 mol (for example,
It can be selected from the range of about 1 to 50 mol). Furthermore, the amount of the base used can be selected according to the type of reaction component, and may be an excess amount with respect to the reaction component. In particular, if the base is a liquid at the reaction temperature, the base may be used as a solvent or an excess amount of the base may be used. For example, when an acid component is by-produced by elimination of an organic compound, it is usually 1 mol or more per 1 mol of the organic compound (for example, 1 to 50 mol, preferably 1 to 20 mol, more preferably 1 to 10 mol). , Especially 1
~ 5 mol). In the reaction system in which the acid component is by-produced, when a negative charge is generated from the organic group of the ligand (B), the base has two types of neutralization of the acid component and generation of a negative charge from the organic group. Perform a function. Therefore, in such a reaction system, usually 1 mol or more (for example, 1 to 1000 mol, preferably 1 to 5 mol) relative to 1 mol of the organic compound.
00 mol, more preferably about 1 to 100 mol).

Depending on the reaction system (such as a reaction system using a solvent for separating the aqueous phase and the organic phase into two phases), a phase transfer catalyst (onium salt such as tetrabutylammonium bromide or tetrabutylammonium chloride) may be used together with the base. Or a halotetraalkylammonium such as tetrabutylammonium fluoride or tetrabutylammonium bromide; a phosphonium salt or the like), and the phase transfer catalyst may be used instead of the base. In addition, in order to increase the reaction rate, silver salts (inorganic acid salts (silver nitrate, silver sulfate, silver carbonate, etc.),
Organic acid salt) may coexist in the reaction system. further,
Inorganic salts (for example, lithium halide (lithium chloride,
A lithium salt) such as lithium bromide) may coexist in the reaction system. These components can be used alone or in combination of two or more.

[Method for producing coupling compound] In the present invention, in the presence of the coupling reaction catalyst or catalyst system,
Compounds having a leaving group L with (organic compound) R ^a -L, (such as an unsaturated compound) reactant and H-R ^b is coupling reaction, with the elimination of the leaving group L, coupling compound the production of R ^a -R ^b. The coupling reaction also includes a cross coupling reaction.

[(C) Organic compound ^Ra- L] The leaving group L of the organic compound is not particularly limited as long as it can be eliminated by a coupling reaction, and examples thereof include a halogen atom (fluorine, fluorine,
Chlorine, bromine, iodine atom), sulfonyloxy group (benzenesulfonyloxy group, tosyl group such as p-toluenesulfonyloxy group, arenesulfonyloxy group such as OTs, methanesulfonyloxy group OMs, trifluoromethanesulfonyloxy group (triflate group) OT
f, trichloromethanesulfonyloxy group, alkanesulfonyloxy group such as ethanesulfonyloxy group) or sulfonyl halide group (sulfonyl chloride,
Sulfonyl bromide group), diazonium group, carbonyl halide group (carbonyl chloride group, etc.) and the like. The organic compound may have these leaving groups alone or may have a plurality of the same or different leaving groups. Of these leaving groups, usually a halogen atom (particularly a bromine atom or an iodine atom), an arenesulfonyloxy group (OTs
Etc.), alkanesulfonyloxy groups (OMs, OTf
Etc.) is used.

Organic compound R having such a leaving group L
^a- L can be selected according to the target compound by the coupling reaction and is not particularly limited. Examples of the organic compound include halides (haloalkanes, haloalkenes, halocycloalkanes, haloarenes, halogenated arylalkanes, haloheterocyclic compounds, etc.), sulfonic acids or their derivatives (vinyl triflate, allyl triflate, etc.). C _2-10 alkenyl triflate; C _4-10 alkenyl triflate such as cyclohexenyl triflate), aromatic diazonium salt (benzenediazonium chloride, naphthalenediazonium chloride, p-aminoazobenzene, azoxybenzene, hydrazobenzene, etc.), organic Acid halides (alkylcarbonyl halides optionally having substituents such as acetyl chloride, propionyl chloride, butyryl chloride, valeryl chloride, lactoyl chloride, maloyl chloride; Methacryloyl chloride, methacryloyl chloride, alkenylcarbonyl halides such as crotonyl chloride;
Arylcarbonyl halides such as benzoyl chloride, chlorobenzoyl chloride, toluoyl chloride, salicyloyl chloride, anisoyl chloride, vanilloyl chloride, naphthoyl chloride, phthaloyl chloride;
Aralkylcarbonyl halides such as cinnamoyl chloride; heterocyclic carbonyl halides such as furoyl chloride, tenoyl chloride, nicotinoyl chloride, isonicotinoyl chloride, etc.) and the like.

The preferred organic compound is a halide. Examples of the haloalkanes include bromomethane, bromoethane, methylene bromide, ethylene dibromide, and other brominated alkanes, and their corresponding iodide alkanes. Examples of haloalkenes include vinyl bromide, vinylidene bromide, tetrabromoethylene, allyl bromide, propenyl bromide, crotyl bromide and other C bromides.
Examples include _2-10 alkenes, aromatic vinyl bromides such as α-bromostyrene, bromophenylethylene, and iodides corresponding to these. Examples of the halocycloalkanes include bromo C _3-10 cycloalkanes such as bromocyclohexane and bromocyclooctane, bridged cyclic bromocycloalkanes such as bromoisobornyl, bromonorbornane, bromonorbornene, and bromoadamantane. Examples thereof include corresponding iodocycloalkanes and bridged cyclic iodocycloalkanes.

Examples of the haloarenes include bromobenzene, bromonaphthalene, bromotoluene, bromotrichloromethylbenzene, bromotrifluoromethylbenzene, bromoxylene, bromophenol, bromoanisole, bromonitrobenzene, bromoaniline,
Examples thereof include mono- or di-alkylamino bromobenzene, bromobenzoic acid, bromobenzene sulfonic acid, bromobenzaldehyde and the like, which may have a substituent, and corresponding iodide arenes. Examples of the halogenated aryl alkanes include benzyl bromide and phenethyl bromide. Examples of the haloheterocyclic compound include bromothiophene, bromofuran, bromobenzofuran, bromopyrrole, bromoimidazole, bromopyridine, bromopyrimidine, bromoindole, bromoquinoline, bromoisoquinoline, bromophthalazine, bromocarbazole, bromoacridine, bromophenanthroline and the like 5, or Examples thereof include bromides of compounds having a 6-membered heterocycle (and condensed heterocycles with a hydrocarbon ring such as a benzene ring) and iodides corresponding to these bromides.

Of these organic compounds having a leaving group, aromatic halides (for example, haloarenes) are usually used in many cases.

[(D) Reactant] The reagent H- ^Rb is not particularly limited as long as it can be coupled with the organic compound ^Ra- L together with the elimination of the leaving group. As such a reaction agent, a compound having a carbon-hydrogen (HC) bond at a reaction site with a leaving group (for example, an unsaturated compound, an organometallic compound, a compound having an active methylene group or a methine group, etc.) And a compound having a nucleophilic HX group (wherein X represents a hetero atom).

(I) Unsaturated compounds Unsaturated hydrocarbons have at least one carbon atom in the molecule.
As long as it has a carbon unsaturated bond (carbon-carbon double bond, carbon-carbon triple bond), various olefin compounds (alkenes or their derivatives) and acetylene compounds (alkynes or their derivatives) can be used. Representative unsaturated hydrocarbons can be represented by, for example, the following formula (1).

[0043]

[Chemical 1]

(In the formula, R ¹ , R ² , R ³ and R ⁴ are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, an aryl group or an aralkyl group, and these groups are substituted. R ³ and R ⁴ may have a group and R ³ and R ⁴ may be directly bonded to each other to form a carbon-carbon triple bond) R ¹ , R ² , R ³ and halogen represented by R ^4. Atoms include fluorine, chlorine, bromine and iodine atoms. Examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl,
Examples thereof include C _1-20 alkyl groups such as hexyl and octyl groups (preferably C _1-10 alkyl groups, especially C _1-6 alkyl groups). Examples of the alkenyl group include C _2-20 alkenyl groups such as vinyl, propenyl, isopropenyl, allyl and butenyl groups (preferably C _2-10 alkenyl groups, especially C _2-6 alkylene groups). Aryl groups include phenyl,
C _6-14 aryl groups such as naphthyl groups are included, and aralkyl groups include C _6-10 aryl-C _1-4 alkyl groups such as benzyl and phenethyl groups.

Substituent R¹~ R^FourIs usually a hydrogen atom, halo
Gen atom, alkyl group (for example, C _1-10Alkyl group, special
To C_1-6Alkyl group), alkenyl group (eg C_2-6A
Lucenyl group, especially C_2-4Alkenyl group), aryl group
(For example, C_6-10Aryl group). In equation (2)
By the way, R³And R^FourAnd are directly bonded to each other by carbon-carbon
Forming a heavy bond to form an alkyne or its derivative
Good.

R ^{1 to} R ⁴ may have a substituent depending on the kind. As a substituent, a halogen atom (fluorine, chlorine, bromine, iodine atom), an alkyl group (methyl,
C _1-20 alkyl group such as ethyl, propyl, butyl group, etc., preferably C _1-10 alkyl group, especially C _1-6 alkyl group), alkenyl group (vinyl, propenyl, isopropenyl, butenyl group, etc.) the above-exemplified C _2-10 alkenyl group, preferably a C _2-6 alkenyl group), the above-exemplified C _6-14 aryl group such as an aryl group (phenyl group), an aralkyl group (benzyl, C such as phenethyl _{6- 10} aryl -C _1-4 alkyl group), a hydroxyl group, an alkoxy group (methoxy, ethoxy, butoxy, t-C _1-6 alkoxy group such as butoxy), C _1-6 thioalkoxy groups corresponding to the alkoxy group , (such as phenoxy group) an aryloxy group, a carbonyl group (or keto group), an acyl group (acetyl, aliphatic C _1-6 acyl group such as propionyl group, Fang, such benzoyl group Such as family acyl group), a carboxyl group, an alkoxycarbonyl group (methoxycarbonyl, ethoxycarbonyl, C _1-6 alkoxy such as butoxycarbonyl group - carbonyl group), aryloxycarbonyl group (phenoxycarbonyl group), an amino group, N- Substituted amino groups (N-mono C _1-4 alkylamino groups such as methylamino and butylamino groups, N, N- such as dimethylamino, diethylamino and dibutylamino groups)
Examples thereof include diC _1-4 alkylamino group, acylamino group such as acetylamino group), nitro group and cyano group.

(A) Olefin-based compound Among the unsaturated hydrocarbons, the olefin-based compound may be any compound having at least one carbon-carbon double bond in the molecule, and enones are also included. Examples of the olefin compound include α-olefins (α-C _2-10 olefins such as ethylene, propylene, and 1-butene, aromatic vinyl compounds such as styrene, vinyltoluene, and vinylxylene), and carbon inside. Compounds having a carbon double bond (C _4-10 olefins such as 2-butene, 3-hexene and 4-octene, aromatic vinyl compounds such as stilbene), C having two or more double bonds in the molecule
_5-20 alkadienes (1,4-decadiene, dihydromyrcene, myrcene, etc.), C _5-20 alkadienes having a double bond at the conjugated position (1,3-butadiene, isoprene, 4,6-decadiene, etc.) , Cyclic compounds (cyclopentene, cyclopentadiene, dicyclopentadiene,
Cyclohexene, 1,3-cyclohexadiene, 1,8
-Cyclic olefins such as cyclopentadecadiene, bridged cyclic olefins such as bornene, norbornene and limonene) and the like.

The olefinic compound includes carbon-
Also included are enyne compounds containing a carbon double bond and a carbon-carbon triple bond (2-methyl-1-hexen-3-yne, 2-methyl-1-octen-3-yne, etc.), and a carbon-carbon triple bond. May be located in a conjugated position with respect to the carbon-carbon double bond. Further, the olefin-based compound includes a compound having an oxygen-containing functional group [a compound having a hydroxyl group (such as allyl alcohol), a compound having a carboxyl group or a derivative thereof (acrylic acid, methacrylic acid, an acrylic ester (methyl acrylate, Acrylic acid C such as ethyl acrylate and butyl acrylate
_1-20 alkyl ester, 2-hydroxyethyl acrylate, hydroxyalkyl acrylate such as 3-hydroxypropyl acrylate, glycidyl acrylate, etc.), methacrylic acid esters corresponding to these acrylic esters, acrolein, fumaric acid, maleic acid ,
Maleic acid diester, etc.), a compound having an alkoxy group (such as ethoxyethylene), a compound having a carbonyl group (3-butene-2-one, cyclopentenone, cyclohexenone, isophorone, diketene, ketene, furan, benzofuran, nootkatone, Benzoquinone etc.)
Etc.], compounds having a nitrogen-containing functional group [compounds having an amino group (eg, allylamine), acrylonitrile,
Pyrrole, etc.], halogen-containing compounds (allyl chloride, 3,3,3-trifluoro-1-propylene, etc.), compounds containing heteroatoms such as phosphorus, tin, boron, silicon (phosphonium salts such as allyltriphosphonium bromide) , Tin compounds such as allyltin, boron compounds such as allylborane, and silicon compounds such as (trimethylsilyl) ethylene). Further, allene compounds (1,2-propadiene and the like) are also included.

(B) Acetylene Compound Among the unsaturated hydrocarbons, the acetylene compound is not particularly limited as long as it is a compound containing at least one carbon-carbon triple bond in the molecule. Examples of the acetylene compound (acetylenes) include α-C _2-20 acetylenes (acetylene, methylacetylene, 1-butyne and the like 1
-Alkynes (C _2-16 acetylene, etc.), especially C _2-10 acetylene, C _2-20 having a carbon-carbon triple bond inside
Acetylenes (C _2-16 acetylene such as 2-butyne, 3-hexyne, 4-octyne and tolan, especially C _2-10 acetylene), C _5-20 alkadynes having two or more triple bonds in the molecule (1 , 4 Dekajiin C _5-16, such as alkadiynes, especially C _5-10 alkadiynes), C _5-20 alkadiynes compound having a triple bond conjugated position (4,6 Dekajiin C _5-16, such as alkadiynes, especially C _{5 -10} arcaziin),
Cyclic compounds (C such as 1,8-cyclopentadecadiyne
_4-16 cycloalkyne or cycloalkadiyne, especially C
_5-10 cycloalkyne or cycloalkadiyne) and the like.

The acetylene compound is an enyne compound containing a carbon-carbon triple bond and a carbon-carbon double bond in the molecule (for example, 2-methyl-1-hexene-3-yne, 2
C _5-16 alkaeneins such as -methyl-1-octen-3-yne, especially C _5-10 alkaeneins) are also included,
The carbon-carbon double bond may be located in a conjugated position with respect to the carbon-carbon triple bond. Furthermore, the acetylene-based compound includes a compound having an oxygen-containing functional group [for example, a compound having a hydroxyl group (propargyl alcohol, etc.), a compound having a carbonyl group (3-butyne-2).
-One), a compound having a carboxyl group or a derivative thereof (acetylenedicarboxylic acid, acetylenedicarboxylic acid diester, etc.), a compound having an alkoxy group (ethoxyacetylene, etc.), and a halogen-containing compound [propargyl chloride, 3,3,3] 3-trifluoro-
1-propyne and the like], compounds containing heteroatoms such as phosphorus, tin, boron and silicon [phosphonium salts such as propargyltriphenylphosphonium bromide, tin compounds such as alkynyltin, boron compounds such as alkynylborane, (trimethylsilyl ) Silicon compounds such as acetylene] and the like are also included.

It is also possible to isomerize an allene compound such as 1,2-propadiene into an acetylene compound in the reaction system for use in the reaction. It can also be used by generating benzynes in the system.

(Ii) Organometallic compound The organometallic compound is not particularly limited as long as the carbon atom and the metal atom are bonded, and various compounds can be used. Representative organometallic compounds include compounds containing a Group 1B element of the periodic table (copper compounds, etc.), compounds containing a Group 2B element of the periodic table (zinc compounds, etc.), compounds containing a Group 3B element of the periodic table (boron). Compounds, aluminum compounds, thallium compounds, etc.), compounds containing Group 4B elements of the Periodic Table (silicon compounds, tin compounds, etc.), compounds containing Group 5B elements of the Periodic Table (bismuth compounds, etc.), Group 8 elements of the Periodic Table. Compounds containing, compounds containing Group 1A elements of the periodic table (lithium compounds, potassium compounds, lead compounds, etc.), compounds containing Group 2A elements of the periodic table (beryllium compounds, calcium compounds, magnesium compounds that may be Grignard reagents, etc.) ), Compounds containing Group 3A elements of the periodic table (lanthanum compounds, samarium compounds, etc.), compounds containing Group 4A elements of the periodic table (Titanium compounds, zirconium compounds, etc.) can be exemplified.

Examples of the compound containing a Group 1B element of the periodic table include phenyl copper (I), alkenyl copper such as lithium dipropenyl copper (I), phenyl acetylene copper, and the like.
Examples thereof include copper acetylide such as phenylacetylene copper. The compound containing a Group 1B element of the periodic table also includes an organic Group 1B metal compound corresponding to the copper compound.

Examples of the compound containing a Group 2B element of the periodic table include organic zinc compounds (alkyl zinc such as diethyl zinc and dibutyl zinc, aryl zinc such as diphenyl zinc and ditolyl zinc), and organometallic compounds corresponding to these compounds. Can be illustrated.

Of the compounds containing Group 3B elements of the periodic table,
Examples of the boron compound include trialkylboranes (tri-C _1-6 alkylboranes such as trimethylborane, triethylborane, tributylborane) and trialkenylboranes (triC such as trivinylborane, tripropenylborane, triallyborane). _2-6 alkenylborane, etc.), triarylborane ( _{triC 6-10 arylborane} which may have a substituent such as an alkyl group and a methoxy group, for example, triphenylborane, tritoluylborane, etc.), triaralkyl borane (tribenzylidene Ruboran, tri phenethyl Ruboran), (such as mono-C _1-6 alkyl di C _6-10 aryl borane) monoalkyl diaryl borane, dialkyl monoaryl borane (di-C _1-6 alkyl mono- C _6-10 aryl borane , Boronic acid (boronic acid, phenylboronic acid, etc.) Any arylboronic acid, alkylboronic acid such as ethylboronic acid) or its derivatives (boronic acid ester, boronic anhydride, etc.), compounds having a hydrogen atom on the boron atom (dicyclohexylborane, (Ipc) ₂ BH (diisopino) Camphenylborane), 9-BBN (9-borabicyclo [3.3.1] nonane, IpcBH ₂ (monoisocamphenylborane), etc.), compounds having a halogen atom on the boron atom (B
-Bromo-9-borabicyclo [3.3.1] nonane, dicyclohexylchloroborane, etc.) and the like.

Examples of the organoaluminum compound include trialkylaluminums such as trimethylaluminum, triethylaluminum and triisobutylaluminum,
Dialkyl aluminum halide, alkenyl dialkyl aluminum, alkynyl dialkyl aluminum,
Examples thereof include aryl aluminum such as triphenyl aluminum and tritolyl aluminum, and diaryl aluminum halide. Examples of the organic thallium compound include compounds corresponding to the above aluminum compounds. Further, the Group 3B element-containing compound of the periodic table also includes an organic Group 3B metal compound corresponding to the above compound.

Of the compounds containing Group 4B elements of the periodic table,
The organic silicon compound, for example, alkyl silanes (for example, tetramethylsilane, trimethylethyl silane, C _1-6 alkylsilanes such as tetraethyl silane, C _1-6, such as methyltrichlorosilane, dimethyldichlorosilane, trimethylchlorosilane Alkylhalosilanes), alkenylsilanes (vinylsilane, 2-
Puropenirushiran, C _2-6 alkenyl silanes such as allylsilanes), C _2-6 alkynyl silanes such as alkynyl silanes (2-propynyl silane), arylalkyl silanes (phenylmethyl silane, phenyl dimethylchlorosilane) , Arylsilanes (arylhalosilanes such as diphenylsilane, trichlorophenylsilane, diphenyldichlorosilane), silanols, acylsilanes, and other organosilicon compounds.

Examples of the organic tin compound include alkyltin (C _1-10 alkyltins such as dialkyltin, tetraalkyltin and tetraoctyl), alkenyltin (C _2-10 alkenyltins such as vinyltin and allyltin), aryltin (diaryl). tin, C _6-10 aryl tin such as tetraaryltin), C _1-6 alkyl C _6-10 aryl tin such as alkylaryl tin (tributylphenyl stannane), alpha-heteroatom-substituted tin compounds, these halides Examples thereof include hydroxide and hydroxide.

Examples of the organic tin compound include dialkyltin halides [eg, dimethyltin dichloride,
Di-C _1-10 alkyltin dichloride such as diethyltin dichloride and dibutyltin dichloride], trialkyltin halide [eg, tri-C _1-10 alkyltin chloride such as trimethyltin chloride, triethyltin chloride, tributyltin chloride], tetraalkyl Tin [for example, tetramethyltin, tetraethyltin, tetrabutyltin, and other tetra C _1-10 alkyltin], diaryltin dihalide [diphenyltin dichloride, etc.], triaryltin halide [triphenyltin chloride, etc.], tetraaryltin [tetra Phenyl tin, etc.], alkylaryl tin [methyl phenyl tin, dimethyl phenyl tin, butyl diphenyl tin, methyl triphenyl tin, etc.] and the like. In addition,
The above substituents (halogen atom, alkyl group, alkoxy group, etc.) may be substituted on these aryl groups.

Further, the organotin compound has a tin atom
A compound having a hydrogen atom (for example, dibutyl (ethinyl)
Le) J C such as Chin hydride_1-10Alkyl (C_2-10
Alkynyl) Chin hydride etc.), halo on tin atom
A compound having a gen atom (for example, dibutyl (ethinyl)
Le) di-C such as tin chloride_1-10Alkyl (C_2-10Al
Kinyl) Chin halide) etc. are also included. Furthermore, organic
Among the acetylene-based compounds described below, the tin compounds include α
-Hydrogen source for acetylenes and acetylenes with functional groups
It also includes compounds in which the child is replaced by a tin atom. In addition, organic
Examples of the compounds include trialkyl (alkynyl
Ru) tin [eg trimethyl (ethynyl) tin, tri
Methyl (propynyl) tin, Trimethyl (octynyl)
Tin, tributyl (ethynyl) tin, tributyl (pro
Pinyl) tin, tributyl (octynyl) tin, etc.
Re-C_1-10Alkyl (C_2-16Alkynyl) tin, preferably
Is a bird C _1-6Alkyl (C_2-10Alkynyl) tin, sara
And preferably Tri-C_1-4Alkyl (C_2-10Alkynyl)
Tin], trialkyl (arylalkynyl) tin [example
For example, trimethyl (phenylethynyl) tin, tributy
Tri-C such as ru (phenylethynyl) tin_1-10Alkyl
(C_6-10Aryl-C_2-16Alkynyl) tin, preferably
Is a bird C_1-6Alkyl (phenyl-C_2-10Alkynyl)
Tin, more preferably Tri-C_1-4Alkyl (phenyl
-C_2-10Alkynyl) tin], dialkyldi (alkynyl)
Ru) tin [eg dibutyldi (ethynyl) tin, dibu
Tilldi (propynyl) tin, dibutyldi (octynyl)
Di C such as tin_1-10Alkyldi (C_2-16Alkynyl)
, Preferably C_1-6Alkyldi (C_2-10Alkini
Ru) tin], dialkyldi (arylalkynyl) tin
[For example, dibutyldi (phenylethynyl) tin, etc.
The C_1-10Alkyldi (C_6-14Aryl-C_2-16Alkini
Le) tin, preferably di-C_1-6Alkyldi (phenyl-
C_2-10Alkynyl) tin], alkyltri (alkynyl)
Ru) tin [butyltri (ethynyl) tin, butyltri
(Propynyl) tin, butyltri (octynyl) tin
Which C_1-10Alkyl tri (C_2-16Alkynyl) tin, good
More preferably C_1-6Alkyl tri (C_2-10Alkynyl)
], Alkyltri (arylalkynyl) tin [eg
For example, C such as butyltri (phenylethynyl) tin_1-10
Alkyl tri (C_6-14Aryl-C_2-16Alkynyl)
, Preferably C_1-6Alkyltri (phenyl-C_2-10
Alkynyl) tin], tetraalkynyltin [tetrae
Tinyl tin, tetrapropynyl tin, tetraoctynyl
Tetra CC such as tin_2-16Alkynyl tin, preferably
Tetra C _2-10Alkynyltin], tetra (arylal)
Quinyl) tin [eg tetraphenylethynyltin
Which tetra (C_6-14Aryl-C_2-16Alkynyl)
, Preferably tetra (phenyl-C)_2-10Alkynyl)
Tin)] and the like. In addition, these aryl groups
Is a substituent (halogen atom, alkyl group, alkoxy group
Etc.) may be substituted. Including elements of Group 4B of the periodic table
The compounds include organic group 4B metallizations corresponding to the above compounds.
Compounds are also included.

Among the compounds containing Group 1A elements of the periodic table,
Examples of the organic lithium compound include methyl lithium and butyl lithium (n-butyl lithium, s-butyl lithium,
Examples thereof include alkyl lithium (e.g., t-butyl lithium, etc.), alkenyl lithium, aryl lithium (e.g., phenyl lithium), and the like.
Examples include potassium butoxide and potassium triphenylmethyl. Lead compounds include alkyl lead (trialkyl lead such as tributyl lead, tetraalkyl lead such as tetraethyl lead), aryl lead triacetate (phenyl lead triacetate, etc.), alkenyl lead triacetate (styryl lead triacetate, etc.), etc. It can be illustrated. The compound containing a Group 1A element of the periodic table also includes an organic Group 1A metal compound corresponding to the above compound.

Of the compounds containing Group 2A elements of the periodic table,
As the organomagnesium compound, a Grignard reagent,
For example, alkyl magnesium halide (C _1-20 alkyl magnesium halide such as methyl magnesium chloride, ethyl magnesium bromide and butyl magnesium bromide), alkenyl magnesium halide (C _2-16 alkenyl magnesium halide such as vinyl magnesium bromide and propenyl magnesium bromide) ), Cycloalkyl magnesium halide (C _4-10 such as cyclohexyl magnesium bromide, etc.), aryl magnesium halide (phenyl magnesium bromide, naphthyl magnesium bromide, tolyl phenyl magnesium bromide, C _6-18 such as trimethylphenyl magnesium bromide) Aryl magnesium halide, etc.), aralkyl magnesium halide Id (such as C _6-10 aryl C _1-4 alkyl magnesium halide such as benzyl bromide), and other Grignard reagent can be exemplified. The compound containing a Group 2A element of the periodic table,
Organic Group 2A metal compounds such as beryllium compounds (eg, diphenyl beryllium) and calcium compounds (eg, phenyl calcium iodide) are also included.

Examples of the compound containing a Group 3A element of the periodic table include lanthanum compounds (eg, tetraphenyllanthanum (III) lithium salt) and samarium compounds (eg, tetra (t-butyl) lithium samarium (III)).
-THF adduct, etc.) and corresponding organic Group 3A metal compounds.

Examples of the compound containing a Group 4A element of the periodic table include titanium compounds (dichlorodimethyltitanium (IV), trichloromethyltitanium, alkyltitanium compounds such as methyltriisopropoxytitanium, aralkyltitanium compounds such as allyltitanium compounds and crotyltitanium compounds). , Alkynyl titanium compounds such as propargyl titanium compounds,
(Trimethyl) pentamethylcyclopentadienyl titanium, aralkyl titanium compounds such as tetrabenzyl titanium, etc.), organic group 4A metal compounds corresponding to these titanium compounds [eg, zirconium compounds (eg, tetraallyl zirconium (IV), phenyl] Tributoxy zirconium (IV) and the like].

(Iii) Compound Having Active Methylene Group or Methine Group As the above compound, for example, an electron-withdrawing group (for example,
Adjacent α of sulfonyl group, carbonyl group, nitro group, etc.
A compound having a hydrogen atom (methylene group or methine group) at the position (particularly a compound having a methylene group or a methine group between a plurality of carbonyl groups), for example, acetylacetone, acetoacetic acid ester (methyl acetoacetate, ethyl acetoacetate, etc.), Malonates (dimethyl malonate, diethyl malonate, etc.), β-keto acids such as triacetylmethane or derivatives thereof; aryl ketones such as phenylacetone, dibenzoylmethane; alkyl ketones such as acetone, methyl ethyl ketone; acetophenone, propio Examples thereof include alkyl aryl ketones such as phenone; vinyl ketones such as methyl vinyl ketone and butyl vinyl ketone.

(Iv) Compound having a nucleophilic HX group (wherein X represents a hetero atom) In the above formula, the hetero atom is at least a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom. It contains a type of heteroatom. Examples of such compounds include amines having active hydrogen atoms (alkylamines such as methylamine, dimethylamine, diethylamine, dibutylamine, alkanolamines such as ethanolamine, cycloalkylamines such as cyclohexylamine, Aryl amines such as aniline, toluidine, nitroaniline, and phenylenediamine,
Aralkylamines such as benzylamine and phenylethylamine, heterocyclic compounds such as pyrrolidine, piperidine, aminopyrimidine, and indole), imines (alkylimines (hexaneimine, ethylidenemethylamine, etc.) and other aliphatic imines, aromatics Imines), alcohols (alkyl alcohols such as methanol, ethanol, butanol, cycloalkyl alcohols such as cyclohexanol, aralkyl alcohols such as benzyl alcohol), thiols corresponding to the alcohols, phosphines ( Mono- or dialkylphosphines such as dimethylphosphine, ethylphosphine, diethylphosphine, and dibutylphosphine; cycloalkylphosphines such as dicyclohexylphosphine; Le phosphine, diphenyl phosphine, aryl phosphines such as ditolyl phosphine, etc.), and others.

Of these reactants, unsaturated hydrocarbons or derivatives thereof (particularly alkenes or derivatives thereof) are often used.

The transition metal compound (or transition metal catalyst)
May be at least a catalytic amount, and for example, 0.000001 to 1 mol, preferably 0.0001 to 0.5 mol, and more preferably 0.0005 to 0.2 mol with respect to 1 mol of the organic compound. It is about 0.001
It is often about 0.1 mole times.

The ratio of the reaction agent is, for example, 0.0001 to 100 with respect to 1 mol of the organic compound (particularly 1 mol of the leaving group).
0 mol, preferably 0.001 to 100 mol, more preferably about 0.005 to 10 mol, 0.2 to 5
Mol (for example, 0.5 to 3 mol, particularly 0.8 to 2 mol)
It is often about double.

The above reaction can be carried out in the absence or presence of a solvent. For example, a solution reaction system using a solvent,
The reaction can be carried out using a solventless reaction system which does not use a solvent, a gas phase flow reaction or the like. In the solution reaction system, it is easy to control the reaction temperature. The solvent of the reaction system may be an aqueous solution (homogeneous or heterogeneous aqueous solution) or a mixed solvent of a plurality of solvents. Furthermore, the solvent of the reaction system is
It may be a biphasic solvent of an aqueous phase and an organic phase. In such a two-phase solvent, a component capable of forming a base in an aqueous phase (alkali metal alkoxide, alkali metal salt of organic carboxylic acid, etc.) can be effectively used as the base.

The solvent is not particularly limited as long as it is inert to the reaction, and examples thereof include ethers (diethyl ether, dibutyl ether, tetrahydrofuran, dioxane, dimethoxyethane, etc.) and aliphatic hydrocarbons (normal hexane, heptane). , Octane, cyclohexane, cyclopentane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), halogenated hydrocarbons (dichloroethane, dichloromethane, chloroform, chlorine-containing hydrocarbons such as carbon tetrachloride, trifluoromethyl) Benzene, hexafluorobenzene, perfluorooctane,
Fluorine-containing hydrocarbons such as perfluorocyclohexane), sulfur-containing solvents (dimethyl sulfoxide, sulfolane, etc.) and the like. Also, a component that is liquid in the reaction system (for example, a liquid component in a supercritical state, for example, a supercritical fluid such as carbon dioxide, ethane, or fluorocarbon) may be used even if it is not a liquid at room temperature and atmospheric pressure. further,
The following nitrogen-containing solvent may be used.

The nitrogen-containing solvent is not particularly limited as long as it is a compound having a nitrogen atom in the molecule. For example, amines such as triethylamine, tripropylamine, tributylamine, triethanolamine and dimethylaminoethanol, nitrogen-containing heterocyclic compounds such as pyridine, α-picoline and N-methylpyrrolidone, N, N-dimethylformamide, N, Examples include amides such as N-dimethylacetamide and N-methylpyrrolidinone, ureas such as N, N-dimethylpropyleneurea, phosphoric acid amides such as hexamethylphosphoramide, and nitriles such as acetonitrile and benzonitrile.

The amount of the solvent used is not particularly limited as long as it does not impair the reaction operation, and is, for example, 0 to 10000 parts by weight, preferably 0 to 100 parts by weight, and more preferably 0 to 50 parts by weight relative to 1 part by weight of the organic compound. It is about part by weight.

The reaction temperature is, for example, -100 to 300.
C, preferably -50 to 200 C, more preferably 0.
It is about 150 to 150 ° C., and usually about 50 to 150 ° C. The reaction time can be appropriately selected in consideration of, for example, economic efficiency.

The atmosphere of the reaction system is not particularly limited, except that the concentration range of the combustion-supporting gas (such as oxygen) is within a safe range, and components capable of forming a gaseous atmosphere in the reaction system, such as carbonization. Hydrogen compounds (methane, ethane, etc.), nitrogen compounds (ammonia, nitrogen dioxide, nitric oxide, hydrogen cyanide, etc.), sulfur compounds (hydrogen sulfide, carbon disulfide, sulfur dioxide, etc.), carbon monoxide, carbon dioxide, etc. Good. A preferable atmosphere is an inert gas (a rare gas such as argon or helium or a nitrogen gas). The reaction pressure is
It can be selected according to the type of reaction components and the like. For example, as the total pressure in the reactor at the reaction temperature, for example,
0001 to 100 MPa, preferably 0.001 to 10
MPa, and more preferably 0.01 to 1 MPa.

In the present invention, the coupling reaction product can be efficiently produced with a high selectivity by the coupling reaction. Therefore, the present invention can be utilized in various coupling reactions, for example, production of olefins by reaction of aromatic halides and alkenes.

[0077]

INDUSTRIAL APPLICABILITY In the present invention, since the transition metal compound and the specific ligand are combined, the catalytic activity of the coupling reaction catalyst can be greatly improved. Therefore, the target compound can be produced safely and economically by a coupling reaction between an organic compound having a leaving group and a reactant. further,
Since the catalyst or the catalyst system is used, the target compound can be efficiently produced with high selectivity.

[0078]

The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited by these examples.

Example 1 Palladium (II) acetate was added to a 20 mL glass reaction vessel.
(0.90 mg, 4.0 μmol), p-diphenylphosphinophenol (2.2 mg, 7.9 μmol),
Tetrabutylammonium bromide (2.6mg, 8.1μ
mol) and toluene (1 mL) were added, and sodium hydroxide (19.2 mg, 480 μmol) was added to this mixture.
And a solution of water (1 mL), 4-bromo (trifluoromethyl) benzene (90 mg, 400 μmol), and styrene (45.8 mg, 440 μmol) were added, and the mixture was stirred at 100 ° C. for 6 hours under a nitrogen atmosphere. ) -4
-(Trifluoromethyl) stilbene was produced in 100% yield. The yield was determined by gas chromatographic analysis using dimethoxybenzene as an internal standard, in mol% based on 4-bromo (trifluoromethyl) benzene.

Example 2 A reaction was conducted in the same manner as in Example 1 except that m-hydroxyphenyl (diphenyl) phosphine was used instead of p-hydroxyphenyl (diphenyl) phosphine, and the reaction solution was analyzed by gas chromatography. (E)
-4- (trifluoromethyl) stilbene yield 26%
Obtained in.

Example 3 Palladium (II) acetate was added to a 20 mL glass reaction vessel.
(0.90 mg, 4.0 μmol), p-diphenylphosphinophenol (2.2 mg, 7.9 μmol),
Tetrabutylammonium bromide (2.6mg, 8.1μ
mol), sodium acetate (39.4 mg, 480 μm)
ol), and N, N-dimethylacetamide (2 mL)
4-Bromo (trifluoromethyl) benzene (90 mg, 400 μmol) and styrene (45.8 mg, 440 μmol) were added to this mixture, and the mixture was stirred at 100 ° C. for 6 hours in a nitrogen atmosphere, and (E) -4 −
(Trifluoromethyl) stilbene was produced with a yield of 88%.

Example 4 Instead of 4-bromo (trifluoromethyl) benzene,
The reaction was performed in the same manner as in Example 1 except that 3′-bromoacetophenone was used and the reaction time was 11 hours, and the corresponding product (E) -3-acetylstilbene was 76%. Was produced in a yield of.

Comparative Example 1 When a reaction was carried out in the same manner as in Example 1 without using p-hydroxyphenyl (diphenyl) phosphine,
Almost no target compound was obtained. That is, when the reaction liquid was analyzed by gas chromatography,
The yield of (E) -4- (trifluoromethyl) stilbene was 1%.

Comparative Example 2 p-hydroxyphenyl (diphenyl) phosphine (2
mol%) instead of triphenylphosphine (2mo
(1%) was used, the reaction was carried out in the same manner as in Example 1, but almost no product was obtained. That is, when the reaction liquid was analyzed by gas chromatography,
The yield of (E) -4- (trifluoromethyl) stilbene was 1% or less.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) // C07B 61/00 300 C07B 61/00 300

Claims (11)

[Claims] 1. A transition metal compound (A) and a ligand (B)
In the coupling reaction catalyst, the ligand (B) is capable of generating a coordinating group for the transition metal compound (A), an organic group having at least one negative charge, or the negative charge. Coupling reaction catalyst having various organic groups. 2. The coupling reaction catalyst according to claim 1, wherein the transition metal compound (A) contains at least one element selected from an element belonging to Group 8 of the periodic table and an element belonging to Group 1B of the periodic table. 3. The coordination group of the ligand (B) is represented by the group 5 of the periodic table.
The coupling reaction catalyst according to claim 1, containing a Group B element. 4. The coupling reaction catalyst according to claim 1, wherein the organic group of the ligand (B) is at least one selected from alcoholate, thiolate and acylamide groups. 5. The coupling reaction catalyst according to claim 4, wherein the ligand (B) is an aromatic compound. 6. The transition metal compound (A) is a palladium compound, and the ligand (B) has a coordinating group composed of at least one element selected from a nitrogen atom and a phosphorus atom, The coupling reaction catalyst according to claim 1, which is an aromatic compound capable of forming an aromatic alcoholate. 7. The coupling reaction catalyst according to claim 1, further comprising a base. 8. The coupling reaction catalyst according to claim 7, wherein the base is an inorganic base capable of generating a negative charge of the ligand (B). 9. A method for producing a coupling compound by causing a coupling reaction between an organic compound having a leaving group and a reactant in the presence of the coupling reaction catalyst according to claim 1. 10. The leaving group is a halogen atom, a sulfonyloxy group or a sulfonyl halide group, a diazonium group,
The production method according to claim 9, which is at least one selected from carbonyl halide groups. 11. The production method according to claim 9, wherein the aromatic halide is reacted with an alkene.