JP2013056852A - Method of producing coupling compound and coupling catalyst - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of efficiently producing a coupling compound of an aromatic compound and boronic acids without using any noble metal catalyst.SOLUTION: In the presence of a catalyst including a peroxide and a non-noble metal transition metal element, an aromatic compound is reacted with organic boronic acids. In this way, a coupling compound, wherein intermolecular elimination occurs between a hydrogen atom bonded to an aromatic ring of the aromatic compound and an optionally derivatized dihydroxyboryl group of the organic boronic acids to form a carbon-carbon bond, is obtained.

Description

  The present invention relates to a method for producing a compound in which an aromatic compound and an organic boronic acid are coupled, and a catalyst (coupling catalyst) used in this production method.

  As a representative method for obtaining a coupling compound by coupling an aromatic boronic acid and an aromatic compound, a Suzuki coupling reaction (Suzuki-Miyaura coupling reaction) is known. In the Suzuki coupling reaction, a coupling compound (cross-coupling compound) can be obtained by reacting an aromatic boronic acid with a halogenated aromatic compound in the presence of a base and a palladium catalyst. Thus, in the Suzuki coupling reaction, a palladium catalyst is essential, and the reaction substrate is limited to a halogenated aromatic compound.

  Various methods are being developed as such a coupling method of the Suzuki coupling reaction. For example, Non-Patent Document 1 (J. Org. Chem, 2003, 68 (2), pages 578-580) discloses an aromatic boronic acid and a large excess of benzene, and a manganese compound with respect to the aromatic boronic acid. A method is disclosed in which 3 equivalents of (manganese acetate) are reacted under reflux to obtain a coupling compound. In the method of this document, since a manganese compound is used as an oxidizing agent for oxidizing boronic acid, a large amount of manganese compound is required.

  Non-Patent Document 2 (Angew. Chem. Int. Ed., 2008, 47, 8897-8900 pages) discloses that aromatic boronic acid and benzene are mixed in a stoichiometric amount of an iron compound (base, oxidant). A method for obtaining a coupling compound by reacting in the presence of iron sulfate or the like and a polyfunctional nitrogen-containing ligand (1,5,7,10-tetraazacyclopentadecane) is disclosed. However, also in this document, since an iron compound is used as an oxidizing agent, a large amount of an iron compound is required, and a large amount of a nitrogen-containing ligand is also required.

Non-Patent Document 3 (J. Am. Chem. Soc, 2010, 132 (38), pages 13194-13196) describes an aromatic heterocyclic compound (such as pyridine) and an aromatic boronic acid as 1 equivalent of trifluoromethane. A method for obtaining a coupling compound by reacting in a water / methylene chloride mixed solvent in the presence of acetic acid, 3 equivalents of K ₂ S ₂ O ₈ as an oxidizing agent and 0.2 equivalents of silver nitrate is disclosed. However, the method of this document requires an expensive silver compound, although a catalytic amount is sufficient. Further, the substrate is limited to an electron-deficient aromatic heterocyclic compound such as pyridine.

  Non-Patent Document 4 (Org. Lett., 2010, 12 (12), pages 2694-2697) describes an aromatic heterocyclic compound (such as pyrrole) and an aromatic boronic acid as a quantifier. A method of reacting in the presence of an amount of an iron compound (such as iron sulfate) and a polyfunctional nitrogen-containing ligand (1,5,7,10-tetraazacyclopentadecane) to obtain a coupling compound is disclosed. This document also discloses that the iron compound can be reduced to a catalytic amount by using oxygen in the air as an oxidizing agent.

  However, even in the method of this document, the substrate is limited to an electron-deficient aromatic heterocyclic compound such as pyrrole or pyridine.

J. et al. Org. Chem, 2003, 68 (2), 578-580. Angew. Chem. Int. Ed. , 2008, 47, 8897-8900 pages J. et al. Am. Chem. Soc, 2010, 132 (38), 13194-13196. Org. Lett. 2010, 12 (12), pages 2694-2697.

  Accordingly, an object of the present invention is to provide a method capable of efficiently producing a coupling compound of an aromatic compound and a boronic acid, and a catalyst used in this method.

  Another object of the present invention is to provide a method capable of producing a coupling compound in a combination of a wide range of aromatic compounds and boronic acids, and a catalyst used in this method.

  Still another object of the present invention is to provide a method capable of efficiently producing a coupling compound of an aromatic compound and a boronic acid without using a noble metal catalyst and a catalyst used in this method.

  As a result of intensive studies to achieve the above-mentioned problems, the present inventors have found that when a peroxide as a specific oxidant and a non-noble metal transition element (for example, iron) as a catalyst are combined, a Suzuki coupling reaction is performed. As described above, it is possible to efficiently produce a coupling compound of an aromatic compound and a boronic acid without using a noble metal catalyst, and in this method, the aromatic compound as a substrate must be halogenated or triflated. It is not necessary to be a specific aromatic heterocyclic compound such as pyridine, and a coupling compound can be obtained by combining a wide range of aromatic compounds and boronic acids, and further, a non-noble metal transition element is used as a catalyst. It is possible to obtain a coupling compound efficiently even in a catalyst amount (that is, a system using a small amount of metal). However, the present invention has been completed.

  That is, in the method of the present invention, an aromatic compound and an organic boronic acid are reacted (oxidatively coupling reaction) in the presence of a peroxide and a catalyst containing a non-noble metal-based transition metal element, and the aromatic compound and An organic boronic acid (for example, an aromatic boronic acid) is bonded between a hydrogen atom bonded to the aromatic ring of the aromatic compound and a dihydroxyboryl group (or boronic acid group) that may be derivatized of the organic boronic acid. A coupling compound in which a carbon-carbon bond is formed by intermolecular elimination is produced.

  The peroxide may be an organic peroxide (for example, dialkyl peroxide). The ratio of the peroxide may be 1 mol or more with respect to 1 mol of dihydroxyboryl group which may be derivatized organic boronic acids.

  In addition, the non-noble metal-based transition metal element may particularly contain iron. In addition, the said catalyst may contain the non noble metal type | system | group transition metal element normally by making a non noble metal type | system | group transition metal element into a metal of positive ionic valence.

  The catalyst may further contain a nitrogen-containing organic compound as a ligand. Such a nitrogen-containing organic compound may typically contain an aromatic polyamine, and in particular, may contain at least one selected from bipyridines, terpyridines, and phenanthrolines.

  In the reaction, the ratio of the catalyst may be 0.8 mol or less with respect to 1 mol of a dihydroxyboryl group that may be derivatized with an organic boronic acid, in terms of a non-noble metal-based transition metal element.

  In the present invention, the catalyst used in the above-mentioned method, that is, an aromatic compound and an organic boronic acid are reacted, the aromatic compound and the organic boronic acid are bonded to the aromatic ring of the aromatic compound, and the organic boronic acid. A catalyst for producing a coupling compound in which a carbon-carbon bond is formed by intermolecular elimination with an optionally derivatized dihydroxyboryl group, which is used in combination with a peroxide, A catalyst containing a noble metal-based transition metal element is included.

In the present specification, “organic boronic acids” means an organic group and a dihydroxyboryl group (—B (OH)) which may be bonded to the organic group (or a carbon atom of the organic group) and derivatized. ₂ ) means a compound having at least one. In the present specification, the “aromatic compound” means a compound having at least one hydrogen atom bonded to an aromatic ring.

  In the present invention, a coupling compound of an aromatic compound and a boronic acid can be efficiently produced by combining a specific oxidizing agent and a catalyst containing a specific metal element. In particular, in the method of the present invention, the aromatic compound is not limited to a halide or an aromatic heterocyclic compound, and a coupling compound can be produced in a wide range of combinations of aromatic compounds and boronic acids. Further, in the method of the present invention, a non-noble metal-based transition element can be used as a catalyst. Therefore, even if a noble metal-based catalyst is not used, and even if the amount of metal catalyst used is a catalyst amount, aromatics can be efficiently used. A coupling compound of a compound and a boronic acid can be produced.

  In the present invention, an aromatic compound and an organic boronic acid (boronic acid) are reacted in the presence of a peroxide and a catalyst containing a non-noble metal-based transition metal element (non-noble metal-based transition metal catalyst), and the aromatic compound and Between the hydrogen atom in which the organic boronic acid is bonded (directly bonded) to the aromatic ring of the aromatic compound (or the carbon atom constituting the aromatic ring) and the dihydroxyboryl group which may be derivatized of the organic boronic acid A coupling compound (oxidation coupling compound) in which a carbon-carbon bond is formed by elimination between molecules [or an aromatic compound and an organic residue of an organic boronic acid are bonded] is produced.

[Aromatic compounds]
If the aromatic compound (compound having an aromatic ring) has a hydrogen atom (hydrogen atom involved in intermolecular elimination) bonded (or substituted) to the aromatic ring (or the carbon atom constituting the aromatic ring) It may be a monocyclic aromatic compound or a polycyclic aromatic compound, and may be an aromatic hydrocarbon compound (arene compound) or a heteroatom-containing aromatic compound (heterocyclic aromatic compound). .

The aromatic rings constituting the aromatic compound can be broadly classified into aromatic hydrocarbon rings and aromatic heterocyclic rings. As the aromatic hydrocarbon ring (or arene ring), for example, a benzene ring, a polycyclic aromatic hydrocarbon ring {for example, a condensed polycyclic aromatic hydrocarbon ring (for example, a naphthalene ring, an anthracene ring, a phenanthrene ring, Fluorene ring, pyrene ring, fluoranthene ring, triphenylene ring, naphthacene ring, perylene ring, benzo [a] pyrene ring, benzo [e] pyrene ring and other condensed 2- to 6-ring aromatic hydrocarbon rings), multiple aromatics A hydrocarbon group such as an alkylene group (for example, a C _1-10 alkylene group (or an alkylidene group) such as a methylene group, an ethylene group or a 2-propylidene group); an ether group; (—O—), carbonyl group (—CO—), oxycarbonyl group (—OCO—), imino group (—NH—), amide group (—NHCOO) -), a thio group (-S-), a sulfonyl group _(-SO 2 -), a sulfinyl group (-SO-), oxyalkylene group (e.g., oxymethylene group, an oxy _{C 1-4} alkylene group such as oxyethylene group Aromatic hydrocarbon rings linked via a heteroatom-containing linking group such as)] (for example, aromatics in which 2 to 6 C _6-10 arene rings such as biphenyl ring, phenylnaphthalene ring, and terphenyl ring are directly bonded. Group hydrocarbon ring).

  The aromatic heterocycle (or heteroarene ring) is an aromatic ring containing a heteroatom (in particular, at least one heteroatom selected from a nitrogen atom, an oxygen atom and a sulfur atom) as an atom constituting the aromatic ring. For example, monocyclic aromatic heterocycle [or monocyclic heteroarene ring such as pyrrole ring, pyridine ring, furan ring, thiophene ring, azole ring (for example, diazole ring, oxazole ring, thiazole ring, etc.) , Pyrazine ring, etc.], condensed polycyclic aromatic heterocycle [or condensed polycyclic heteroarene ring such as thieno [2,3-b] thiophene ring, indole ring, benzo [b] furan ring, 3,4 -Ethylenedioxythiophene ring, benzo [b] thiophene ring, benzopyran ring, quinoline ring, carbazole ring, phenanthridine ring, acridine ring, A condensed 2- to 6-ring aromatic heterocycle such as a Santen ring or a thianthrene ring], or a plurality of aromatic rings (including aromatic hydrocarbon rings) including at least an aromatic heterocycle are directly bonded or linking groups (linkage exemplified above) An aromatic ring bonded via a group [for example, an aromatic ring in which a plurality of aromatic heterocycles are bonded to each other (for example, 2 to 6 rings such as a bipyridyl ring, a bifuryl ring, a terpyridine ring, a bithiophene ring, a terthiophene ring, etc. An aromatic ring in which an aromatic heterocycle is directly bonded, and the like].

As long as the aromatic compound has an aromatic ring (aromatic ring skeleton), the aromatic compound may have a substituent (a substituent substituted on the aromatic ring). Examples of the substituent (substituent which is not optionally derivatized dihydroxyboryl group) include, for example, a hydrocarbon group [eg, C _1-10 such as alkyl group (methyl, ethyl, butyl, t-butyl group, pentyl group, etc.). Alkyl group, preferably C _1-6 alkyl group, more preferably C _1-4 alkyl group), haloalkyl group (halo C _1-4 alkyl group such as trichloromethyl, trifluoromethyl, tetrafluoropropyl group, etc.), alkenyl Groups (C _2-6 alkenyl groups such as vinyl, propenyl, isopropenyl, butenyl groups, preferably C _2-4 alkenyl groups), aryl groups (C _6-14 aryl groups such as phenyl groups), aralkyl groups (benzyl, such as _{C 6-10} aryl _{-C 1-4} alkyl group), such as a phenethyl group, a halogen atom (e.g., Tsu atom, a chlorine atom, a bromine atom, an iodine atom), a hydroxyl group, a mercapto group, (thio) ether group [e.g., alkoxy group (methoxy, ethoxy, butoxy, C _1-6 alkoxy group such as t- butoxy ), An alkylthio group (eg, a C _1-6 alkylthio group corresponding to the above alkoxy group such as a methylthio group), an aryloxy group (C _6-10 aryloxy group such as a phenoxy group), etc.], a hydroxyalkyl group (eg, , Hydroxy C _1-10 alkyl group such as hydroxymethyl group, hydroxyethyl group), acyl group [formyl group, alkylcarbonyl group (eg, C _1-6 alkyl-carbonyl group such as acetyl, propionyl group), aroyl group ( For example, benzoyl group etc.)], carboxyl group, ester group [ For example, alkoxy-carbonyl groups (C _1-6 alkoxy-carbonyl groups such as methoxycarbonyl, ethoxycarbonyl, and butoxycarbonyl groups), aryloxycarbonyl groups (such as phenoxycarbonyl groups)], amino groups, substituted amino groups (for example, Alkylamino groups such as dimethylamino groups), carbamoyl groups, nitro groups, cyano groups, halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), substituents in which these substituents are bonded to each other [for example, alkoxy Aryl group (for example, C _1-4 alkoxy C _6-10 aryl group such as methoxyphenyl group) and the like]. The aromatic compound (or aromatic ring) may have these substituents alone or in combination of two or more.

  In the aromatic compound having such a substituent, the number of substituents is, for example, 1 to 8, preferably 1 to 6, more preferably about 1 to 4, although it depends on the type of the aromatic skeleton. Also good. In particular, in a monocyclic aromatic ring having a substituent (benzene ring or monocyclic aromatic heterocycle), the number of substitutions of the substituent is 1 to 4, preferably 1 to 3, and more preferably about 1 to 2. There may be.

  The aromatic compound has at least one hydrogen atom directly bonded to the aromatic ring as described above, but the number of such hydrogen atoms is not particularly limited, and is, for example, 1 or more (for example, 1 to 1 30), preferably 2 to 25 (eg 2 to 22), more preferably about 3 to 20 (eg 3 to 18), usually about 2 to 15 (eg 3 to 12). May be. Note that even if the aromatic compound has a plurality of hydrogen atoms, it is not necessary for all hydrogen atoms to participate in intermolecular desorption, and at least one hydrogen atom may be deintercalated.

Typical aromatic compounds include aromatic hydrocarbon compounds and aromatic heterocyclic compounds. Examples of the aromatic hydrocarbon compound (or the aromatic hydrocarbon which may have a substituent) include, for example, a monocyclic aromatic hydrocarbon compound {or a monocyclic aromatic which may have a substituent. Hydrocarbons such as benzene, substituted benzenes [eg alkylbenzenes (eg, mono to tetra C _1-10 alkyl benzenes such as toluene, ethyl benzene, isopropyl benzene, xylene, trimethyl benzene, preferably mono to tetra C _1-6 Alkylbenzene, more preferably mono to tri C _1-4 alkyl benzene), alkoxy benzene (eg mono to tetra C _1-10 alkoxy benzene such as anisole, ethoxybenzene, dimethoxybenzene, trimethoxybenzene, etc., preferably mono to tetra C _{1 -6} Arukokishiben Emissions, more preferably mono- to _{tri-C 1-4} alkoxy benzene), acyl benzene (e.g., _{C 1-10} acyl benzene and acetophenone), halobenzenes (e.g., fluorobenzene, chlorobenzene, bromobenzene, dichlorobenzene, tribromobenzene ), Haloalkylbenzene (eg, mono, di or tri (trifluoromethyl) benzene), halo-alkylbenzene (eg, chlorotoluene), hydroxybenzene (eg, phenol, dihydroxybenzene, trihydroxybenzene, etc.), alkyl - hydroxybenzene (e.g., cresol, _{C 1-10} alkyl, such as xylenol - hydroxybenzene), halo - alkoxy benzene (e.g., halo _{-C 1-10} such chloroanisole Turkey carboxymethyl benzene), and carboxymethyl benzene (benzoic acid), alkoxycarbonyl benzene (e.g., methyl benzoate, _{C 1-10} alkoxy, such as ethyl benzoate - carbonyl benzene), acyl benzene (e.g., _{C 1-10,} such as acetophenone Acyl-benzene), benzonitrile, aniline, anilide (for example, N—C _1-10 acylaniline such as acetanilide), etc.], a polycyclic aromatic hydrocarbon compound {or optionally having a substituent. Polycyclic aromatic hydrocarbons such as condensed polycyclic aromatic hydrocarbons (eg naphthalene, anthracene, phenanthrene, fluorene, pyrene, fluoranthene, triphenylene, naphthacene, perylene, benzo [a] pyrene, benzo [e] pyrene Condensed 2- to 6-ring aromatic hydrocarbons such as A compound in which 2 to 6 C _6-10 arenes such as biphenyl, phenylnaphthalene and terphenyl are directly bonded (for example, biphenyl, phenylnaphthalene, terphenyl, etc.) Bis to tetrakisaryl etc.)], a polycyclic aromatic hydrocarbon having a substituent [for example, a condensed polycyclic aromatic hydrocarbon having a substituent (for example, an alkoxy condensed polycyclic arene (eg, methoxynaphthalene, etc.) C _1-10 alkoxy-fused 2 to 6-ring aromatic hydrocarbons, etc.), halo-fused polycyclic arenes (for example, halo-fused 2 to 6-ring aromatic hydrocarbons such as chloronaphthalene) Etc.] and the like.

As the aromatic heterocyclic compound, for example, a monocyclic aromatic heterocyclic compound {or a monocyclic heteroarene which may have a substituent, for example, pyrrole, pyridine, pyrimidine, furan, thiophene, azole (for example, , Diazoles, oxazoles, thiazoles, etc.), monocyclic heterocyclic arenes such as pyrazines; alkylfurans (eg C _1-10 alkylfurans such as 2 or 3-methylfuran, 2 or 3-pentylfuran), alkylthiophenes (Eg C _1-10 alkylthiophene such as 2 or 3-methylthiophene), alkoxythiophene (eg C _1-10 alkoxythiophene such as 2 or 3-methoxythiophene), halothiophene (eg 2 or 3-chloro Thiophene, 2 or 3-bromothiophene), acylthio Fen (e.g., 2 or 3-thiophene-carbaldehyde, _{C 1-10} acyl such as 2 or 3-acetyl-thiophene - thiophene), thiophene carboxylic acid, alkoxycarbonyl thiophene (e.g., such as 2 or 3-thiophenecarboxylate), etc. A monocyclic heteroarene having a substituent of the above-mentioned examples, a polycyclic aromatic heterocyclic compound {or a polycyclic heteroarene optionally having a substituent, for example, a condensed polycyclic aromatic heterocycle Compound [eg, thieno [2,3-b] thiophene, indole, benzo [b] furan, 3,4-ethylenedioxythiophene, benzo [b] thiophene, benzopyran, quinoline, carbazole, phenanthridine, acridine, xanthene Condensed 2- to 6-ring heterocyclic arenes such as thianthrene; N-al Le indole (e.g., N-N-C _1-4 alkyl indoles, such as methyl indole) such fused 2-6 bicyclic heterocyclic arene having the exemplary substituents such as, ring assembly aromatic heterocyclic compound ( For example, a compound in which 2 to 6 aromatic heterocyclic compounds such as bipyridyl, bifuryl, terpyridine, bithiophene, terthiophene and the like are directly bonded; a compound in which the above substituent is substituted on these compounds, and the like}.

  In the present invention, a wide range of aromatic compounds can be used as a substrate (reaction substrate), but a relatively active (or activated) aromatic compound [for example, an aromatic heterocyclic compound or an aromatic ring is strongly activated. Even if it is not an aromatic compound having a substituent (for example, an amino group, a substituted amino group, an amide group, a hydroxyl group, an alkoxy group, etc.), a coupling compound with an organic boronic acid can be obtained efficiently.

  In the present invention, a compound substituted with a halogen atom can also be used as the aromatic compound, but the elimination of the halogen atom directly bonded to the aromatic ring as in the Suzuki coupling reaction does not occur, and the hydrogen atom The coupling compound is formed by the elimination of. Therefore, a coupling compound having a halogen atom as a substituent can be obtained.

[Organic boronic acids]
The organic boronic acid includes, in addition to the organic boronic acid, a derivative of organic boronic acid [or an organic boronic acid in which a dihydroxyboryl group (—B (OH) ₂ ) of the organic boronic acid is derivatized] and the like. That is, the organic boronic acids are dihydroxyboryl groups (simply dihydroxyboryl groups, boronic acid groups, derivatized) which may be derivatized (directly bonded) to an organic group (aliphatic group or aromatic group). Or a compound having a good boronic acid group). In organic boronic acids, even if the number of such boronic acid groups is one, it is plural (for example, 2 to 6, preferably 2 to 4, more preferably about 2 to 3). (Ie may be polyboronic acids), in particular one (ie monoboronic acid).

The derivative of the organic boronic acid is not particularly limited as long as it can be coupled with the aromatic compound. For example, organic boronic acid ester {for example, dialkyl ester (for example, dimethyl ester, diethyl ester, diisopropyl ester, dibutyl) di _{C 1-6} alkyl ester such as an ester), a diol [for example, alkane diols (e.g., ethylene glycol, propylene glycol, 1,3-propanediol, pinacol (2,3-dimethyl-2,3-butanediol), Aliphatic diols such as C _2-10 alkanediols such as 2,2-dimethyl-1,3-propanediol), diesters with aromatic diols such as dihydroxyarene (eg, 1,2-dihydroxybenzene), etc. , Cyclic 3 amount of organic boronic acid (Or boroxine), and the like. In the diester with diol, the two hydroxy groups of the organic boronic acid form a boronic ester (boronate) with the two hydroxyl groups of the diol. For example, in the diester with pinacol, the dihydroxyboryl group of the organic boronic acid Is derivatized to a group represented by the following formula.

Organic boronic acids are aliphatic boronic acids {or non-aromatic boronic acids such as saturated aliphatic boronic acids [eg alkyl boronic acids (eg methyl boronic acid, n-butyl boronic acid, isobutyl boronic acid, hexyl boronic acid, tetra Deshiruboron acid, octadecyl boronic acid, such as C _1-20 alkyl boronic acids, such as bromomethyl boronic acid), cycloalkyl boronic acids (e.g., C _4-10 cycloalkyl boronic acid such as cyclohexyl boronic acid), etc.], unsaturated Aliphatic boronic acids [e.g., alkenyl boronic acids (e.g., C _2-20 alkenyl boronic acids such as vinyl boronic acid), etc., derivatives thereof (e.g., boronic esters), etc.], and aromatic boronic acids, Any of these may be used, but aromatic boronic acids are particularly preferably used. It may be.

  Aromatic boronic acids are compounds having a boronic acid group directly bonded to an aromatic ring (or aromatic group), and include aromatic boronic acids and derivatives of aromatic boronic acids (the derivatives exemplified above). Examples of the aromatic ring constituting the aromatic boronic acid include the aromatic rings exemplified in the paragraph of the aromatic compound.

  Aromatic boronic acids may have a substituent on the aromatic ring. Examples of the substituent (a substituent that is not a boronic acid group) include the substituents exemplified in the paragraph of the aromatic compound. The number of substituents can also be selected from the same range as described above. The positional relationship between the boronic acid group substituted on the aromatic ring and the substituent is not particularly limited. For example, as long as it is a benzene ring, it may be in the ortho position, the meta position, or the para position.

Representative aromatic boronic acids include areneboronic acids (aromatic hydrocarbon boronic acids), heteroarene boronic acids (aromatic heterocyclic boronic acids), and the like. Examples of the areneboronic acids (or arylboronic acids) include monocyclic areneboronic acids {for example, phenylboronic acid, phenylboronic acid having a substituent [for example, alkylphenylboronic acid (for example, methylphenylboronic acid (2,3 Or 4-methylphenylboronic acid), ethylphenylboronic acid, isopropylphenylboronic acid, butylphenylboronic acid, t-butylphenylboronic acid, pentylboronic acid, dimethylphenylboronic acid, etc. mono to tetra C _1-10 alkylphenyl boronic acid), alkoxyphenyl acid (e.g., methoxyphenyl boronic acid, ethoxyphenyl boronic acid, isopropoxyphenyl boronic acid, mono- to tetra-C _1-10 alkoxyphenyl acid such dimethoxyphenyl boronic acid), alkyl Oh phenylboronic acid (e.g., 2, 3 or 4-methyl mono- to tetra C _1-10 alkyl thio boronic acid, such as thiophenyl boronic acid), acyl phenylboronic acid (e.g., formyl phenyl boronic acid, such as acetyl phenylboronic acid C _1-10 acylphenylboronic acid), halophenylboronic acid (eg, fluorophenylboronic acid, chlorophenylboronic acid, bromophenylboronic acid, dichlorophenylboronic acid, difluorophenylboronic acid, trifluorophenylboronic acid, etc.), haloalkylphenyl Boronic acids (eg, mono, di or tri (trifluoromethyl) phenylboronic acid, bromomethylboronic acid, etc.), halo-alkylphenylboronic acids (eg, fluoro-methylphenylboronic acid, etc.), hydroxyphen Ruboron acid (such as 2, 3 or 4-hydroxyphenyl boronic acid), hydroxyalkyl phenylboronic acid (e.g., hydroxy C _1-10 alkyl phenyl boronic acids, such as hydroxymethylphenyl boronic acid), carboxyphenyl boronic acid (e.g. , 2, 3 or 4-carboxyphenylboronic acid), halo-alkoxyphenylboronic acid (eg halo-C _1-10 alkoxyphenylboronic acid such as chloro-methoxyphenylboronic acid), alkoxycarbonylphenylboronic acid (eg , methoxycarbonylphenyl boronic acid, C _1-10 alkoxy, such as ethoxycarbonyl-phenyl boronic acid - carbonyl phenyl boronic acid), cyanophenyl boronic acid (e.g., 2, 3 or 4- cyanophenyl boronic acid), cyano - Le Kill phenylboronic acid (cyano - cyano -C _1-10 alkyl boronic acid, such as methyl phenyl boronic acid), cyano - halo phenyl boronic acid (cyano - such fluorophenylboronic acid), nitrophenyl boronic acid (e.g., 2, 3 or 4-nitrophenylboronic acid), nitro-carboxyphenylboronic acid, aminophenylboronic acid, substituted aminophenylboronic acid (for example, N, N-dialkylaminophenylboronic acid such as N, N-dimethylaminophenylboronic acid) N, N-diarylaminophenylboronic acids such as N, N-diphenylaminophenylboronic acid, etc.], derivatives thereof, etc.}, polycyclic areneboronic acids {eg, condensed polycyclic areneboronic acids (eg, Naphthaleneboronic acid, anthraceneboronic acid, phen A polycyclic compound in which a plurality of arene rings are bonded via a direct bond or a linking group), a condensed 2- to 6-cyclic areneboronic acid such as toltenboronic acid, pyreneboronic acid, fluoreneboronic acid, 9,9-dimethylfluoreneboronic acid, etc. Arene boronic acids [e.g., arene boronic acids in which 2 to 6 _C6-10 arenes such as biphenylboronic acid, terphenylboronic acid, naphthylphenylboronic acid, bromobiphenylboronic acid, etc. are directly bound], these Derivatives, etc.}, polyboronic acids corresponding to these {eg arene diboronic acid (eg benzene diboronic acid etc.), polycyclic arene diboronic acid [eg biphenyl diboronic acid (4,4′-biphenyldiboron, etc.) Acid, etc.)], derivatives thereof etc.}.

Examples of the heteroarene boronic acids include monocyclic heteroarene boronic acids {for example, pyridine boronic acid, pyrimidine boronic acid, furan boronic acid, thiophene boronic acid; alkoxypyridine boronic acid (for example, C _{1- 10} alkoxypyridine boronic acids), halopyridine boronic acids (eg, fluoropyridine boronic acid, chloropyridine boronic acid, bromopyridine boronic acid, difluoropyridine boronic acid, etc.), acylfuran boronic acids (eg, formylfuran boronic acid, etc. _1-10 acyl furan boronic acid), alkyl-thiophene boronic acid (e.g., C _1-10 alkylthiophene acid such as methyl thiophene boronic acid), acyl thiophene boronic acid (e.g., formyl thiophene boronic acid, acetate C _1-10 acyl such as Le thiophene boronic acid - thiophene boronic acid), halo thiophene boronic acid (e.g., chloro thiophene boronic acid, monocyclic heteroarene boron having the exemplary substituents etc. bromothiophene boronic acid) Acid, derivatives thereof, etc.}, polycyclic heteroarene boronic acids {eg, condensed polycyclic heteroarene boronic acids [eg, benzofuran boronic acid, benzothiophene boronic acid, dibenzothiophene boronic acid, 3,4- (methylenedi] Oxy) fused 2- to 6-ring heterocyclic arene boronic acids such as phenylboronic acid and quinoline boronic acid], ring-assembled heteroarene boronic acids (for example, 2 to 6 heteroarenes such as bithiophene boronic acid are directly bonded Arene boronic acids), their derivatives etc.}, this Etc. corresponding polyboronic acids in the like.

  In the reaction, the ratio between the aromatic compound and the organic boronic acid depends on the number of hydrogen atoms in the aromatic compound, the number of boronic acid groups in the organic boronic acid, the number of organic boronic acids to be coupled with the aromatic compound, etc. You can choose according to your needs. For example, when one hydrogen atom of an aromatic compound is mainly used for coupling, the use ratio of the aromatic compound is 1 mol or more (for example, 1.2 mol) with respect to 1 mol of the boronic acid group of the organic boronic acid. To 500 mol), preferably an excess mol [eg, 1.5 mol or more (eg, 1.5 to 300 mol), more preferably 2 mol or more (eg, 3 to 200 mol)]. Moreover, you may use an excess aromatic compound as a solvent.

[Peroxide]
In the present invention, at least a peroxide is used as the oxidizing agent. Examples of the peroxide include hydrogen peroxide, peroxo compounds [for example, peroxide salts (for example, alkali peroxides or alkaline earth metal salts such as sodium peroxide, magnesium peroxide, calcium peroxide, potassium peroxide) Peracids (for example peracids of oxo acids such as persulfuric acid, perphosphoric acid), peracid salts (for example alkali metal salts or alkaline earth metal salts of peracids such as sodium persulfate, potassium persulfate, An ammonium salt of a peracid such as ammonium sulfate), etc.], and an organic peroxide.

The organic peroxide (or peroxide), for example, hydroperoxide [for example, an alkyl hydroperoxide (t-butyl hydroperoxide, such as 1,1,3,3-tetramethylbutyl hydroperoxide _{C 1- 10} alkyl hydroperoxides), alkane dihydroperoxides (eg 2,5-dimethylhexane-2,5-dihydroperoxide etc.), aralkyl hydroperoxides (eg cumene hydroperoxide etc.)], dialkyl peroxides (For example, di-C _1-10 alkyl peroxides such as diethyl peroxide, di-t-butyl peroxide, di-t-amyl peroxide; diaralkyl peroxides such as dicumyl peroxide; t-butyl-cumyl peroxide Alkyl-aralkyls such as oxides Kishido), diacyl peroxides [e.g., diacetyl peroxide, di-alkanoylamino peroxide (di C _1-18 alkanoyl peroxide such as lauroyl peroxide, etc.); benzoyl peroxide, 4-chlorobenzoyl peroxide, benzoyl toluyl peroxide, Diaroyl peroxides such as toluyl peroxide (such as di-C _7-12 aroyl peroxide), di (alkylperoxy) alkanes [for example, 2,2-di (t-butylperoxy) butane, 2,5 -Di (C _1-10 alkylperoxy) C _1-10 alkanes such as dimethyl-2,5-di (t-butylperoxy) hexane, 2,2-bis (t-butylperoxy) octane], di (Alkylperoxy) cycloalkane [for example, 1,1-bis (t- Chirupaokishi) cyclohexane, 1,1-bis (t-butylperoxy) 3,3,5-di _{(C 1-10} alkyl peroxy such _{trimethylcyclohexane) C 5-10} cycloalkane, di (alkyl peroxy alkyl ) Arenes [e.g., di (C _1-10 alkylperoxy C _1-4 alkyl such as 1,3-bis (t-butylperoxyisopropyl) benzene, 1,4-bis (t-butylperoxyisopropyl) benzene] ) C _6-10 arene], di (alkylperoxy) alkyne [eg, 2,5-dimethyl-2,5-di (t-butylperoxy) hexyne-3, etc.], di (acylperoxy) alkane ( For example, 2,5-dimethyl-2,5-dibenzoylperoxyhexane etc.), peracid [eg peralkanoic acid (eg If, performic acid, C _1-18 over alkanoic acids such as peracetic acid), peracetic arene carboxylic acid (e.g., perbenzoic acid, perphthalic acid), etc.], peresters [e.g., peracetic acid alkyl ester (e.g., Peralkanoic acid alkyl esters such as t-butyl peracetate, t-butyl peroxyoctoate, t-butyl peroxydecanoate, t-butyl _{peroxylaurate} (C _1-18 peralkanoic acid C _1-6 alkyl) Esters, etc .; perarene carboxylic acid alkyl esters (C _1-6 alkyl esters, etc.) such as t-butyl peroxybenzoate, di-t-butyl peroxyphthalate, di-t-butyl peroxyisophthalate, etc.], ketones Peroxides (eg methyl isobutyl ketone peroxide, methyl ethyl ketone peroxide, Hexanone peroxide, etc.), peroxycarbonate [for example, dialkyl peroxycarbonates such as diisopropylperoxydicarbonate and di-2-ethylhexylperoxydicarbonate; dialkoxyalkylperoxides such as di-2-ethoxyethylperoxydicarbonate Oxydicarbonate; dicycloalkyl peroxycarbonate such as bis- (4-t-butylcyclohexyl) peroxycarbonate] and the like.

  Peroxides may be used alone or in combination of two or more.

Of these, preferred peroxides include organic peroxides (eg, alkyl hydroperoxides, dialkyl peroxides, etc.), especially branched alkyl peroxides [eg, branched alkyl hydroperoxides (t-butyl). Branched C _3-6 alkyl hydroperoxides such as hydroperoxide), dibranched alkyl peroxides (dibranched C _3-6 alkyl peroxides such as di-t-butyl peroxide) and the like] are preferable.

  The ratio of the peroxide (or oxidizing agent) may be a theoretical amount or more, and for example, 1 mol or more (for example, 1.1 to 10 mol), preferably 1 mol of the boronic acid group of the organic boronic acid. May be about 1.2 mol or more (for example, 1.3 to 8 mol), more preferably about 1.5 mol or more (for example, 1.7 to 5 mol).

  Note that the oxidizing agent may be composed only of a peroxide, and within the range that does not impair the effects of the present invention, the peroxide is the main component of the oxidizing agent and other oxidizing agents [for example, nitric acid, sulfuric acid, etc. , Perhalogenic acid or its salt (perchloric acid, periodic acid, sodium perchlorate, sodium periodate, potassium periodate, etc.), metal acid or its salt (permanganic acid, sodium permanganate, permanganate) Potassium acid, potassium chromate, potassium dichromate, etc.), Lewis acids (boron trifluoride, aluminum chloride, antimony pentachloride, etc.), oxygen, nitric oxide (dinitrogen tetroxide, etc.), etc.] May be.

[catalyst]
The catalyst contains at least a non-noble metal-based transition metal element (or a non-noble metal-based transition metal catalyst) as a catalyst component. That is, the catalyst (non-noble metal-based transition metal catalyst) is composed of a non-noble metal-based transition metal element (or transition metal component). Examples of non-noble metal-based transition metal elements (sometimes simply referred to as transition metal elements) include, for example, Group 3 elements of the periodic table [or Group 3 metals of the periodic table; Sc, Y, lanthanoids (La, Ce, Pr, Nd, Sm, etc.), actinides], periodic table group 4 elements (Ti, Zr, Hf, etc.), periodic table group 5 elements (V, Nb, Ta, etc.) , Periodic Table Group 6 elements (Cr, Mo, W, etc.), Periodic Table Group 7 elements (Mn, Tc, Re, etc.), Iron (Fe), Cobalt (Co), Nickel (Ni), Copper (Cu) And Group 12 elements of the periodic table (such as Zn). The catalyst may contain these transition metal elements alone or in combination of two or more.

  Of these transition metal elements, iron is particularly preferable. Therefore, the catalyst may contain at least iron.

In addition, the oxidation number (or valence or ionic value) of the transition metal element contained in the catalyst is not particularly limited, and may be, for example, 0 (or 0 valence), +1 (or 1 valence), depending on the type of element, It may be +2 (or divalent), +3 (or trivalent), +4 (or tetravalent), etc., and the catalyst is usually in the form of a positive oxidation number (or valence or ionic value) (or transition) Often contains transition metal elements (as metal compounds or ion binding compounds). For example, the oxidation number of iron is often divalent or trivalent, and trivalent iron (Fe ³⁺ ) may be particularly preferably used. In addition, the valence of the transition metal element used as a raw material or a precursor is not particularly limited as long as it can be converted (oxidized or reduced) into a desired valence in the reaction system. For example, iron having a lower valence (for example, iron of 0 valence, 2 valence, etc.) used as a raw material or a precursor may be oxidized in the reaction system to produce trivalent iron.

  The transition metal element constituting the catalyst may be a single metal, but may be usually contained in the catalyst in the form of a transition metal compound (a compound containing a transition metal element). A transition metal compound (such as a complex) may be generated in the reaction system.

Examples of the transition metal compound include inorganic salts [or inorganic compounds such as inorganic acid salts (for example, perhalogenates such as nitrates, sulfates, sulfites, phosphates, phosphonates, perchlorates, Chromate, etc.), halides (eg, chloride, bromide, iodide, etc.), oxides, sulfides, hydroxides, etc.], organic acid salts {eg, sulfonates [eg, methanesulfonate, Alkane sulfonates such as ethane sulfonate (such as C _1-10 alkane sulfonate); haloalkane sulfonates such as trifluoromethane sulfonate (such as halo C _1-4 alkane sulfonate); benzene sulfonate , _p-(such as _{C 6-10} arene sulfonate) toluene arene sulfonates such as sulfonates, carboxylates [e.g., formate, acetate Carboxylate _{(C 1-12} alkanoate etc), such as propionate; dichloroacetic acid, trifluoroacetic acid salt, (such as halo _{C 1-4} alkanoates) haloalkanes salts such as tribromo acetate, etc.], etc.} Etc. are included. In addition, the transition metal compound used as a raw material or a precursor and its valence will not be specifically limited if a transition metal compound can be produced in a reaction system. For example, trifluoromethane sulfonate may be generated from other transition metal compounds other than trifluoromethane sulfonate in the reaction system in the presence of trifluoromethane sulfonic acid.

Moreover, the transition metal element may be contained in the catalyst in the form of a complex (or complex salt). Examples of the ligand constituting the complex include OH (hydroxo), alkoxy groups (C _1-4 alkoxy groups, etc.), acyl groups (C _1-4 acyl groups, etc.), alkoxycarbonyl groups (C _1-4 alkoxy), and the like. Carbonyl acetonato, cycloalkadienyl (cyclopentadienyl, cyclooctadienyl, etc.), benzylidene, vinylidene, benzylideneacetone, benzylideneacetylacetonato, benzylideneacetophenone, cycloalkadiene ( Cyclooctadiene, etc.), aromatic compounds (benzene, toluene, cymene, cumene, xylene, naphthalene, etc.), halogen atoms, CO, CN, oxygen atoms, H ₂ O (aco), phosphine (triphenylphosphine, etc.), phos Fight (Triphenylphosphite Etc.), NH ₃ (ammine), NO, NO ₂ (nitro), NO ₃ (nitrato), nitrogen-containing organic compounds, nitriles (acetonitrile, benzonitrile), and the like.

Examples of nitrogen-containing organic compounds include amines and imines (Schiff bases). The amine may be any of primary to tertiary amines, but preferred amines include amines in which the nitrogen atom constituting the amine is sp ² nitrogen. Such amines having sp ² nitrogen include aromatic nitrogen ring compounds (aromatic compounds in which the hetero atom constituting the aromatic hetero ring is a nitrogen atom) and the like, as will be described later.

  The amine may be an amine having one amino group (that is, a monoamine) or an amine having a plurality of amino groups (or imino groups) (that is, a polyamine). A preferred amine is a polyamine. Particularly preferred polyamines include those polyamines classified as multidentate ligands in the complex (or coordination compound).

  The imine may also have one carbon-nitrogen double bond or an imine (polyimine) having a plurality of carbon-nitrogen double bonds (or imino groups). A preferred imine is polyimine, and particularly preferred polyimines include polyimines classified as multidentate ligands in complexes (or coordination compounds).

Typical amines are roughly classified into aliphatic amines and aromatic amines. Examples of the aliphatic amine include aliphatic monoamines [eg, aliphatic primary monoamines such as alkylamines (eg, C _1-10 alkylamines such as ethylamine); dialkylamines (eg, diC ₁ such as dimethylamine). _-10 alkylamines), aliphatic secondary monoamines such as azacycloalkanes (eg piperidine, morpholine, etc.); trialkylamines (eg triethylamine), tricycloalkylamines (eg tricyclohexylamine), alkyldicycloalkyls amines (e.g., such as methyl dicyclohexylamine) aliphatic tertiary monoamines, such as, aliphatic polyamines [e.g., (C _2-10 alkane diamines such as, for example, ethylenediamine) alkane diamine, poly alkane diamines (e.g., di Chirentoriamin, aliphatic primary polyamines such as triethylene tetramine, etc.); N, N'- dialkyl alkane diamines (e.g., N, N, such as N'- dimethylethylenediamine, N'- di _{C 1-4} alkyl _{C 2 -10} alkanediamine), polyazacycloalkanes (for example, di- to tetraazacycloalkanes such as piperazine, 1,4,7-triazacyclononane, 1,4,8,11-tetraazacyclotetradecane; etc.) Aliphatic secondary polyamines; N, N, N ′, N′-tetraalkylalkanediamines (for example, N, N, N ′, N′-tetra, such as N, N, N ′, N′-tetramethylethylenediamine) C _1-4 alkyl _{C 2-10} alkane diamine), N, N, N ' , N'',N''- penta-alkyl dialkylene triamine (e.g., N, , N ', N'',N''- N , such as pentamethyldiethylenetriamine, N, N', N '', N '' - penta _{C 1-4} alkyl di _{C 2-4} alkylene triamines), N, N ' , N '' - tri-alkyl triazacycloalkane (e.g., 1,4,7-trimethyl-1,4,7-triazacyclononane N, such as, N ', N''- tri _{C 1-4} alkyl thoria Aliphatic tertiary polyamines such as zacycloalkane) and the like.

The aromatic amine may be an aromatic monoamine (for example, pyridine and the like), but may usually be an aromatic polyamine. Aromatic polyamines include aromatic tertiary polyamines, such as ring-aggregated aromatic nitrogen ring compounds {eg bipyridines [or bipyridines optionally having substituents, eg bipyridine (2,2′-bipyridine). Alkyl bipyridines (eg, C _1-4 alkyl bipyridines such as 4,4′-dimethyl-2,2′-bipyridine), aryl bipyridines (eg, 4,4′-diphenyl-2,2′-bipyridine, etc.) C _6-10 arylbipyridine), alkoxybipyridine (eg, _C1-4 alkoxybipyridine such as 4,4′-dimethoxy-2,2′-bipyridine), bipyridine having a halogen atom [eg, haloalkylbipyridine (eg, , Halo _C1-4 alkylbipyridines such as 4,4'-ditrifluoromethyl-2,2'-bipyridine) Etc.], nitrobipyridine (eg, 4,4′-dinitro-2,2′-bipyridine, etc.), carboxybipyridine (eg, 4,4′-dicarboxy-2,2′-bipyridine, etc.), dialkylaminobipyridine ( For example, substitution of C _1-4 alkylaminobipyridine such as 4,4′-dimethylamino-2,2′-bipyridine), hydroxybipyridine (eg, 4,4′-dihydroxy-2,2′-bipyridine, etc.) A bipyridine having a group (such as the substituents exemplified above), a terpyridine [or a terpyridine optionally having a substituent such as terpyridine (2,2 ′: 6 ′, 2 ″ -terpyridine, etc.), Terpyridine having a group (terpyridine corresponding to bipyridine having the substituent)], quaterpyridines [or optionally having a substituent Quaterpyridine, for example, quaterpyridine (2,2 ′: 6 ′, 2 ″: 6 ″, 2 ′ ″-quaterpyridine, etc.), quaterpyridine having a substituent (having the above-mentioned substituent) Terpyridine corresponding to bipyridine)] and the like, etc.}, condensed polycyclic aromatic nitrogen ring compounds {for example, phenanthrolines [or phenanthrolines optionally having substituents, for example, Phenanthroline (such as 1,10-phenanthroline); alkylphenanthroline (for example, 4,7-dimethyl-1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 5,6-dimethyl-1,10-) C _1-4 alkylphenanthrolines such as phenanthroline), arylphenanthrolines (eg, 4,7-diphenyl-1 , 10-phenanthroline, 2,9-diphenyl-1,10-phenanthroline, C _6-10 arylphenanthroline such as 5,6-diphenyl-1,10-phenanthroline), phenanthroline having a halogen atom [for example, haloalkylarylphenanthroline ( For example, halo C _1-4 alkyl C _6-10 aryl phenanthroline such as 4,7-di (4-trifluoromethylphenyl) -1,10-phenanthroline)], alkyl-aryl phenanthroline (eg, 2,9- _{C 1-4} alkyl _{-C 6-10} aryl phenanthroline such as dimethyl-4,7-diphenyl-1,10-phenanthroline), alkoxy phenanthroline (e.g., 3,4,7,8-tetramethoxy-1,10-phenanthroline Which C _1-4 alkoxy-phenanthroline) 2 or more carbon atoms constituting the aromatic ring of the fused polycyclic aromatic compounds such as phenanthroline] having a substituent (such as the above-exemplified substituents) such as has been substituted with a nitrogen atom Compound} and the like.

Examples of the imine include bis (N-substituted imino) acenaphthenes {eg, bis (arylimino) acenaphthene [eg, bis (phenylimino) acenaphthene (1,2-bis (phenylimino) acenaphthene)]. And (C _6-10 arylimino) acenaphthene] and the like.

  Among these amines, aromatic polyamines such as bipyridines, terpyridines, and phenanthrolines are preferable. Particularly, aromatic polyamines having an electron deficiency (or having an electron-withdrawing substituent) [for example, halogen atoms (particularly, And a condensed polycyclic aromatic nitrogen compound having a fluorine atom (such as phenanthroline)].

  The ligands may be used alone or in combination of two or more (or in the complex or complex salt, one or two or more of the same or different ligands may be coordinated).

  The catalyst containing a ligand only needs to contain a transition metal element (or transition metal compound) and a ligand (or a compound that can be a ligand), and as described above, before being subjected to a reaction system or reaction. May be generated. For example, in the reaction, the transition metal complex may be used as it is as the transition metal compound, and the catalyst forms a complex with the transition metal compound (eg, inorganic salt, organic acid salt, etc.) and the transition metal constituting the transition metal compound. A transition metal complex may be formed in the reaction system or before being subjected to the reaction.

  When the transition metal complex is formed in the reaction system, the proportion of the ligand depends on the type and coordination number of the transition metal element constituting the transition metal compound, and the type of ligand (monodentate ligand). Depending on whether it is a polydentate ligand or the like, and usually at least one equivalent of a ligand can be used for the transition metal element.

  The catalysts may be used alone or in combination of two or more.

  The catalyst may be supported (fixed) on a carrier (activated carbon or the like).

  In the reaction, the ratio of the catalyst is usually 1 mol or less, for example, 0.8 mol or less [for example, 0.001 to 1 mol] per 1 mol of the boronic acid group of the organic boronic acid in terms of non-noble metal-based transition metal element. 0.7 mol (for example, 0.005 to 0.6 mol)], preferably 0.5 mol or less (for example, 0.01 to 0.4 mol), more preferably 0.3 mol or less [for example, 0 0.02 to 0.3 mol (for example, 0.03 to 0.25 mol)], particularly 0.2 mol or less [for example, 0.04 to 0.2 mol (for example, 0.05 to 0.15 mol). ] Degree.

  The ratio of the oxidizing agent (or peroxide) to the catalyst is the former / the latter (molar ratio) = 1/1 to 100/1, preferably 2/1 to 80/1 (for example, 3/1 to 60/1). ), More preferably about 5/1 to 50/1.

  The reaction can be performed in the presence or absence of a solvent. The solvent is not particularly limited as long as it is inert in the reaction (a solvent that is not oxidized or hardly oxidized by an oxidizing agent). For example, ethers (for example, chain ethers such as diethyl ether and dibutyl ether, tetrahydrofuran, and dioxane) Cyclic ethers), hydrocarbons (eg, aliphatic hydrocarbons such as hexane, heptane, octane, decane, alicyclic hydrocarbons such as cyclohexane, cyclopentane, etc.), halogenated hydrocarbons (eg, Haloalkanes such as methylene chloride and chloroform), sulfur-containing solvents (dimethylsulfoxide, sulfolane, etc.) and the like. Moreover, you may use an aromatic compound as a solvent in excess. These solvents may be used alone or in combination of two or more.

  Although reaction temperature is not specifically limited, For example, 30-200 degreeC (for example, 40-180 degreeC), Preferably it is 50-160 degreeC, More preferably, it is about 60-150 degreeC (for example, 70-130 degreeC), Usually, it may be about 50 to 120 ° C. (for example, 60 to 100 ° C.). The reaction time can be appropriately selected according to the type of substrate (aromatic compound) used, the type of peroxide (peroxide decomposition temperature, etc.), and the reaction temperature. You may adjust, confirming the grade of the production | generation of a ring compound.

  The reaction may be performed under normal pressure, increased pressure, or reduced pressure, or may be performed under reflux. Note that the reaction may be performed in an oxidizing atmosphere or in a non-oxidizing atmosphere [for example, in a nitrogen gas or a rare gas (such as helium or argon)].

  After completion of the reaction, the product may be isolated using a conventional separation and purification means such as concentration, drying, crystallization, recrystallization, filtration, extraction, distillation, chromatography and the like.

[Coupling compound]
As described above, intermolecular elimination occurs between the hydrogen atom bonded to the aromatic ring of the aromatic compound and the boronic acid group of the organic boronic acid, and the corresponding coupling compound is obtained. That is, at least one carbon is produced between the aromatic compound (1) and the organic boronic acid (2) (or a derivative thereof) by a coupling reaction (oxidative coupling reaction) represented by the following formula (I). -A coupling compound (3) in which a carbon bond is formed is obtained.

[In the formula, Z represents an aromatic compound (or a residue obtained by removing a hydrogen atom bonded to an aromatic ring from an aromatic compound), and R represents an organic group (or a residue obtained by removing a dihydroxyboryl group from an organic boronic acid). . ]
The coupling compound only needs to have at least one carbon-carbon bond formed by intermolecular elimination between the hydrogen atom of the aromatic compound and the boronic acid group of the organic boronic acid. A carbon-carbon bond may be formed. For example, if intermolecular detachment is possible, (Ia) when the aromatic compound has a plurality of hydrogen atoms, one aromatic compound (compound (1a) is represented by the following formula (Ia): )) And a plurality of organic boronic acids (compound (2a) or a derivative thereof) may be subjected to intermolecular elimination to obtain a coupling compound (compound (3a)), which is represented by the following formula (Ib): As shown, when the organic boronic acid has a plurality of boronic acid groups, it is desorbed between one organic boronic acid and a plurality of aromatic compounds to form a coupling compound (compound (3b)) may be obtained.

[Wherein, m, n and p each represents an integer of 2 or more, and Z and R are the same as defined above. However, m> = n and p are below the number of the hydrogen atoms couple | bonded with the aromatic ring of the aromatic compound. ]
The number of carbon-carbon bonds can be adjusted by adjusting the types of aromatic compounds, organic boronic acids, the reaction ratio thereof, and the like. For example, it is easy to reduce the number of carbon-carbon bonds per aromatic compound by using an excess of aromatic compounds relative to organic boronic acids. In the present invention, typically, a coupling compound in which one carbon-carbon bond is formed between an aromatic compound and an organic boronic acid (an organic boronic acid having one boronic acid group) may be obtained. Many. In addition, when the aromatic compound has a plurality of hydrogen atoms, which hydrogen atom is eliminated is determined according to the type, size, substitution position, and the like of the substituent substituted on the aromatic ring. In many cases, the coupling compound proceeds regioselectively to obtain a coupling compound having a single structure, or the coupling compound may be obtained as a regioisomer.

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

Example 1
To a 20 mL Schlenk tube, FeCl ₂ (iron (II) chloride) 0.012 mmol (10 mol% of boronic acid), 4-bromophenylboronic acid 0.12 mmol, benzene 1.1 mL (1.2 mmol, based on boronic acid) 100 equivalents), 0.24 mmol of di-t-butyl peroxide (2 equivalents relative to boronic acid) was added.

And it was made to react by heating at 80 degreeC for 12 hours under stirring in nitrogen atmosphere. The reaction solution was poured into 20 mL of brine and extracted three times with 25 mL of diethyl ether. The obtained organic layer (ether layer) was dried over magnesium sulfate, filtered, and the obtained filtrate was concentrated. The concentrated residue was subjected to silica gel chromatography (PTLC) to obtain the corresponding coupling compound (4-bromobiphenyl). The conversion of 4-bromophenylboronic acid was 23%, and the conversion of di-t-butyl peroxide was 33%. The conversion rate of 4-bromophenylboronic acid was a value measured by ¹ H-NMR, and the conversion rate of di-t-butyl peroxide was measured by gas chromatography on the basis of 4-bromophenylboronic acid. Value. The table summarizes the structure and yield of the product (coupling compound).

(Example 2)
In Example 1, instead of FeCl ₂ , FeCl ₃ (iron chloride (III)) 0.012 mmol (10 mol% of boronic acid) was used in the same manner as in Example 1, and the corresponding coupling compound Got. The conversion of 4-bromophenylboronic acid was 29%, and the conversion of di-t-butyl peroxide was 50%. The table summarizes the structure and yield of the product (coupling compound).

(Example 3)
In Example 1, instead of FeCl ₂ , Fe (CF ₃ SO ₃ ) ₃ (iron (III) trifluoromethanesulfonate, iron (III) triflate, Fe (OTf) ₃ ) 0.012 mmol (10 mol% of boronic acid) ) And the corresponding coupling compound was obtained in the same manner as in Example 1 except that the reaction time was 2 hours. The conversion of 4-bromophenylboronic acid was 76%, and the conversion of di-t-butyl peroxide was more than 199%. The table summarizes the structure and yield of the product (coupling compound).

Example 4
In Example 3, a corresponding coupling compound was prepared in the same manner as in Example 3 except that 0.012 mmol of 2,2′-bipyridine (ligand L5) was used and the reaction time was 48 hours. Obtained. The conversion of 4-bromophenylboronic acid was 64%, and the conversion of di-t-butyl peroxide was 112%. The table summarizes the structure and yield of the product (coupling compound).

(Example 5)
In Example 3, the corresponding coupling compound was obtained in the same manner as in Example 3 except that 0.012 mmol of 1,10-phenanthroline (ligand L1) was used and the reaction time was 48 hours. It was. The conversion of 4-bromophenylboronic acid was 99%, and the conversion of di-t-butyl peroxide was 171%. The table summarizes the structure and yield of the product (coupling compound).

(Example 6)
In Example 3, except that 0.012 mmol of 4,7-diphenyl-1,10-phenanthroline (ligand L2) was used and the reaction time was 12 hours, the same procedure as in Example 3 was followed. A coupling compound was obtained. The conversion of 4-bromophenylboronic acid was over 99%, and the conversion of di-t-butyl peroxide was 180%. The table summarizes the structure and yield of the product (coupling compound).

(Example 7)
In Example 3, except that 0.012 mmol of 4,7-bis [4- (trifluoromethyl) phenyl] -1,10-phenanthroline (ligand L3) was used and the reaction time was 12 hours. Gave the corresponding coupling compound as in Example 3. The conversion of 4-bromophenylboronic acid was over 99%, and the conversion of di-t-butyl peroxide was 169%. The table summarizes the structure and yield of the product (coupling compound).

(Example 8)
In Example 3, 0.012 mmol of 4,7-bis [4- (trifluoromethyl) phenyl] -1,10-phenanthroline (ligand L3) was used, and the amount of benzene used was 0.36 mmol. Instead of (30 equivalents to boronic acid), the corresponding coupling compound was obtained in the same manner as in Example 3 except that the reaction time was 12 hours. The conversion of 4-bromophenylboronic acid was over 99%, and the conversion of di-t-butyl peroxide was 173%. The table summarizes the structure and yield of the product (coupling compound).

Example 9
In Example 7, the corresponding coupling compound was obtained in the same manner as in Example 7 except that the reaction time was 3 hours. The conversion of 4-bromophenylboronic acid was 80%, and the conversion of di-t-butyl peroxide was 134%. The table summarizes the structure and yield of the product (coupling compound).

(Example 10)
In Example 7, a corresponding cup was prepared in the same manner as in Example 7 except that 0.012 mmol of 4,7-diphenyl-1,10-phenanthroline (ligand L2) was used in place of the ligand L3. A ring compound was obtained. The conversion of 4-bromophenylboronic acid was 67%, and the conversion of di-t-butyl peroxide was 102%. The table summarizes the structure and yield of the product (coupling compound).

(Example 11)
In Example 7, Example 7 was used except that 0.012 mmol of 4,7-bis (4-methoxyphenyl) -1,10-phenanthroline (ligand L4) was used in place of the ligand L3. Similarly, the corresponding coupling compound was obtained. The conversion of 4-bromophenylboronic acid was 49%, and the conversion of di-t-butyl peroxide was 84%. The table summarizes the structure and yield of the product (coupling compound).

(Comparative Example 1)
In Example 1, the corresponding coupling compound was obtained in the same manner as in Example 1 except that FeCl ₂ was not used and the reaction time was changed to 12 hours. The conversion of 4-bromophenylboronic acid was 5%, and the conversion of di-t-butyl peroxide was 12%. The table summarizes the structure and yield of the product (coupling compound).

(Comparative Example 2)
In Example 8, the corresponding coupling compound was obtained in the same manner as in Example 8 except that di-t-butyl peroxide was not used. The conversion of 4-bromophenylboronic acid was 9%. The table summarizes the structure and yield of the product (coupling compound).

(Example 12)
To a 20 mL Schlenk tube, 0.020 mmol of Fe (OTf) ₃ (10 mol% of boronic acid), 4,7-bis [4- (trifluoromethyl) phenyl] -1,10-phenanthroline (ligand L3) 0.020 mmol (10 mol% of boronic acid), phenylboronic acid 0.20 mmol, benzene 1.79 mL (2.0 mmol, 100 equivalents to boronic acid), di-t-butyl peroxide 0.40 mmol (in boronic acid) 2 equivalents) was added.

  And it was made to react by heating at 80 degreeC for 24 hours under stirring in nitrogen atmosphere. The reaction solution was poured into 20 mL of brine and extracted three times with 25 mL of diethyl ether. The obtained organic layer (ether layer) was dried over magnesium sulfate, filtered, and the obtained filtrate was concentrated. The concentrated residue was subjected to silica gel chromatography (PTLC) to obtain the corresponding coupling compound. The table summarizes the structure and yield of the product (coupling compound).

(Example 13)
In Example 12, the corresponding coupling compound was obtained in the same manner as in Example 12 except that 0.20 mmol of 4-methylphenylboronic acid was used instead of phenylboronic acid. The table summarizes the structure and yield of the product (coupling compound).

(Example 14)
In Example 12, the corresponding coupling compound was obtained in the same manner as in Example 12 except that 0.20 mmol of 4-chlorophenylboronic acid was used instead of phenylboronic acid. The table summarizes the structure and yield of the product (coupling compound).

(Example 15)
In Example 12, the corresponding coupling compound was obtained in the same manner as in Example 12 except that 0.20 mmol of 3-bromophenylboronic acid was used instead of phenylboronic acid. The table summarizes the structure and yield of the product (coupling compound).

(Example 16)
In Example 12, instead of phenylboronic acid, 0.20 mmol of 2-chlorophenylboronic acid was used, and the reaction temperature was changed to 90 ° C. In the same manner as in Example 12, the corresponding coupling compound was obtained. It was. The table summarizes the structure and yield of the product (coupling compound).

(Example 17)
Example 12 corresponds to Example 12 except that 0.20 mmol of 4- (trifluoromethyl) phenylboronic acid is used instead of phenylboronic acid, and the reaction time is changed to 12 hours. A coupling compound was obtained. The table summarizes the structure and yield of the product (coupling compound).

(Example 18)
In Example 12, the corresponding coupling compound was obtained in the same manner as in Example 12 except that 0.20 mmol of 4-cyanophenylboronic acid was used instead of phenylboronic acid. The table summarizes the structure and yield of the product (coupling compound).

(Example 19)
In Example 12, the corresponding coupling compound was obtained in the same manner as in Example 12 except that 0.20 mmol of 4- (ethoxycarbonyl) phenylboronic acid was used instead of phenylboronic acid. The table summarizes the structure and yield of the product (coupling compound).

(Example 20)
In Example 12, 0.20 mmol of 4-methoxyphenylboronic acid was used instead of phenylboronic acid, the reaction temperature was changed to 90 ° C., and the reaction time was changed to 22 hours. The corresponding coupling compound was obtained. The table summarizes the structure and yield of the product (coupling compound).

(Example 21)
In Example 12, the corresponding coupling compound was obtained in the same manner as Example 12 except that 0.20 mmol of 3-methoxyphenylboronic acid was used instead of phenylboronic acid. The table summarizes the structure and yield of the product (coupling compound).

(Example 22)
In Example 12, the corresponding coupling compound was obtained in the same manner as in Example 12 except that 0.20 mmol of 3-chloro-4-methoxyphenylboronic acid was used instead of phenylboronic acid. The table summarizes the structure and yield of the product (coupling compound).

(Example 23)
In Example 12, instead of phenylboronic acid, 0.20 mmol of 3-thiopheneboronic acid was used, the reaction temperature was changed to 90 ° C., and the reaction time was changed to 20 hours. A coupling compound was obtained. The table summarizes the structure and yield of the product (coupling compound).

(Example 24)
To a 20 mL Schlenk tube, 0.020 mmol of Fe (OTf) ₃ (10 mol% of boronic acid), 4,7-bis [4- (trifluoromethyl) phenyl] -1,10-phenanthroline (ligand L3) 0.020 mmol (10 mol% of boronic acid), 0.20 mmol of 4-fluorophenylboronic acid, 2.0 mmol of chlorobenzene (100 equivalents based on boronic acid), 0.40 mmol of di-t-butyl peroxide (based on boronic acid) 2 equivalents) was added.

  And it was made to react by heating at 80 degreeC for 24 hours under stirring in nitrogen atmosphere. The reaction solution was poured into 20 mL of brine and extracted three times with 25 mL of diethyl ether. The obtained organic layer (ether layer) was dried over magnesium sulfate, filtered, and the obtained filtrate was concentrated. The concentrated residue was subjected to silica gel chromatography (PTLC) to obtain the corresponding coupling compound. The table summarizes the structure and yield of the product (coupling compound). In the table, o-, m-, and p- mean an ortho isomer, a meta isomer, and a para isomer, respectively.

(Example 25)
Example 24 is the same as Example 24 except that 2.0 mmol of 1,4-difluorobenzene is used instead of chlorobenzene and 0.20 mmol of 4-ethoxycarbonylphenylboronic acid is used instead of 4-fluorophenylboronic acid. To give the corresponding coupling compound. The table summarizes the structure and yield of the product (coupling compound).

(Example 26)
In Example 24, 2.0 mmol of 1,3,5-trifluorobenzene was used instead of chlorobenzene, 0.20 mmol of 4-ethoxycarbonylphenylboronic acid was used instead of 4-fluorophenylboronic acid, and the reaction time was 48 hours. The corresponding coupling compound was obtained in the same manner as in Example 24 except that. The table summarizes the structure and yield of the product (coupling compound).

(Example 27)
In Example 24, Example 24 was used except that 2.0 mmol of thiophene was used instead of chlorobenzene, 0.20 mmol of 4-bromophenylboronic acid was used instead of 4-fluorophenylboronic acid, and the reaction time was 4 hours. In the same manner as above, the corresponding coupling compound was obtained. The table summarizes the structure and yield of the product (coupling compound). In the table, 2- and 3-mean a 2-position (substitution) and a 3-position (substitution), respectively.

(Example 28)
In Example 27, the corresponding coupling compound was obtained in the same manner as in Example 27 except that thiophene was 0.6 mmol and the reaction time was 2 hours. The table summarizes the structure and yield of the product (coupling compound).

(Example 29)
Example 24 In the same manner as in Example 24, except that 2.0 mmol of 3-bromothiophene was used instead of chlorobenzene and 0.20 mmol of 3-methoxyphenylboronic acid was used instead of 4-fluorophenylboronic acid A coupling compound was obtained. The table summarizes the structure and yield of the product (coupling compound). In the table, 2- and 5-mean a 2-position (substitution) and a 5-position (substitution), respectively.

  The results are shown in the table. In the table, the yield is a value calculated on the basis of boronic acid from the yield of the product obtained by purification by silica gel column chromatography on the basis of boronic acid.

  In the present invention, since coupling can be performed with elimination of a hydrogen atom of an aromatic compound and a boronic acid group of an organic boronic acid, a coupling compound can be obtained in a wide range of combinations of aromatic compounds and organic boronic acids. it can. Moreover, since the aromatic compound does not need to be an activated aromatic compound such as a halide, and it is not necessary to use a noble metal catalyst, the aromatic compound and the organic boronic acid can be used in a simple reaction system. Can be efficiently obtained. Such a method of the present invention (or a coupling compound obtained by the method of the present invention) can be used for various chemical products (liquid crystal materials, organic EL materials, etc.), chemicals, pharmaceuticals and the like.

Claims (10)

  A hydrogen atom in which an aromatic compound and an organic boronic acid are bonded to an aromatic ring of the aromatic compound by reacting the aromatic compound with the organic boronic acid in the presence of a peroxide and a catalyst containing a non-noble transition metal element. And a coupling compound in which a carbon-carbon bond is formed by intermolecular elimination between an organic boronic acid and an optionally derivatized dihydroxyboryl group.   The process according to claim 1, wherein the organic boronic acid is an aromatic boronic acid.   The method according to claim 1 or 2, wherein the peroxide is an organic peroxide.   The production method according to any one of claims 1 to 3, wherein the ratio of the peroxide is 1 mol or more with respect to 1 mol of the dihydroxyboryl group which may be derivatized with an organic boronic acid.   The production method according to claim 1, wherein the non-noble metal-based transition metal element contains iron.   The production method according to claim 1, wherein the catalyst further contains a nitrogen-containing organic compound as a ligand.   The production method according to claim 6, wherein the nitrogen-containing organic compound contains an aromatic polyamine.   The production method according to claim 6 or 7, wherein the nitrogen-containing organic compound contains at least one selected from bipyridines, terpyridines, and phenanthrolines.   The ratio of the catalyst is 0.8 mol or less based on 1 mol of a dihydroxyboryl group which may be derivatized with an organic boronic acid, in terms of a non-noble metal-based transition metal element. The manufacturing method as described.   An aromatic compound and an organic boronic acid are reacted, and the aromatic compound and the organic boronic acid are bonded to a hydrogen atom bonded to the aromatic ring of the aromatic compound and a dihydroxyboryl group which may be derivatized from the organic boronic acid. A catalyst for producing a coupling compound in which a carbon-carbon bond is formed by desorption between molecules, and is used in combination with a peroxide and contains a non-noble metal-based transition metal element.