JP5700624B2 - Cross coupling catalyst composed of ultrafine transition metal particles and cross coupling method using the same - Google Patents

Description

  The present invention relates to a cross-coupling catalyst comprising ultrafine transition metal particles and a cross-coupling method using the same. Specifically, a cross-coupling catalyst comprising ultrafine transition metal particles containing at least one transition metal selected from Group 8 to Group 11 transition metals and a coordinating organic solvent, and a high catalyst using the same The present invention relates to an active cross-coupling method.

  Currently, large amounts of chemical substances are consumed in modern society in plastics, pharmaceuticals, agricultural chemicals, etc., and developing new production methods using catalysts to produce these substances is an efficient resource and energy. It is extremely important from the viewpoint of utilization of the environment and global environmental conservation.

  In particular, the cross-coupling reaction between different kinds of molecules accompanied by carbon-carbon bond formation is used for the synthesis of various organic compounds as the most important catalytic reaction process.

  However, although the catalytic cross-coupling reaction has made remarkable progress academically, it is necessary to use a considerable amount of a noble metal as a catalyst, and many of them have not yet been industrialized. For this reason, also from the viewpoint of effective utilization of rare metal resources, development of a long-life and high-activity catalytic reaction process using a very small amount of metal catalyst is strongly desired.

  In recent years, attempts have been made to improve the catalytic activity by increasing the ratio of the surface exposed atoms of the metal by making the metal simple particles (nanoparticles). However, since these metal particles usually aggregate with each other in a solution and are bulked, the original activity of the catalyst is impaired.

  Conventional techniques for nano-sizing by preventing bulk formation of metal particles include stabilization by a ligand (for example, pincer-type phosphorus ligand) (Non-patent Documents 1 and 2), polymer compounds such as dendrimers (Non-Patent Documents 3-5), polymer support (Non-Patent Documents 6-10), or protection with an ionic protective agent (Non-Patent Documents 11-12) are reported. However, the conventional fine metal particles need to be stabilized, for example, using a ligand or a protective agent in the process of synthesis, or supporting them on a polymer or the like.

  Recently, by reducing metal chlorides and the like in dimethylformamide (DMF), it is possible to synthesize nanoparticle phosphors such as gold, platinum and palladium having nanosizes of about 2 nm or less easily and in large quantities. It has been reported (see Patent Literature 1 and Non-Patent Literature 13-14). The production of these nanoparticles does not require the use of a ligand or a protective agent as described above, or support on a polymer or the like, and the obtained nanoparticles are stable and have a uniform particle size. Furthermore, the nanoparticles are unexpectedly highly dispersible in various media without being subjected to a separate surface treatment, and can be uniformly dispersed in the media.

Japanese Patent Application No. 2009-154932

By K. Takenaka and Y. Uozumi, Adv. Synth. Catal., 2004, 346, 1693-1696 C. Rocaboy and J.A. Gladysz et al., Organic Letters, 2002, Vol.4. No.12, 1993-1996 E.H.Rahim and J.B.Christensen et al., Nano Letters, 2001, Vol.1, No.9, 499-501 K. Yamamoto and A. Sonoi et al., Nature Chemistry, 1, 397-402 (2009) K.R.Gopidas and M.A.Fox et al., Nano Letters, 2003, Vol.3, No.12, 1757-1760 By Z. Zhang and Z. Wang, J. Org. Chem., 2006, 71, 7485-7487 T. Mizugaki and K. Kaneda et al., Chemistry Letters., Vol. 38, No. 11 (2009), 1118-1119 G. Wei and M. Zhang et al., J. Phys. Chem. C 2008, Vol. 112, No. 29, 10827-10832 K. Okamoto and S. Kobayashi et al., J. Am. Chem. Soc., 2005, Vol. 127, No. 7, 2125-2135 By Z. Yinghurai and R.A. Kemp. Et al., Adv. Synth. Catal., 2007, 349, 1917-1922 By Z. Zhang, Z. Wang and M-M. Zhou, J. Org. Chem., 2006, 71, 4339-4342 G. Zhang and Y. Kuang et al., Green Chem., 2009, 11, 1428-1432 H. Kawasaki et al., Chem. Commun 46, 3759 (2010) H. Kawasaki et al., Langmuir 26, 5926 (2010)

  In the conventional catalytic cross-coupling reaction including a palladium complex, there are the following problems, and many problems to be improved remain from the viewpoint of industrialization process. i) A relatively large amount of catalyst is used (in many reports, it is academically conducted with a catalyst amount of 1 to 5 mol%); ii) In order to prevent deactivation of the metal catalyst, a catalyst comprising a phosphorus compound or the like It is stabilized using a ligand; iii) In order to prevent catalyst deactivation due to aggregation of the metal catalyst, it must be stabilized with a protective agent, or a metal must be supported on silica, an organic polymer or the like.

  The present invention uses a transition metal ultrafine particle composed of a transition metal and a coordinating organic solvent, which does not contain a component such as a ligand, a protective agent, or a polymer, so that the metal surface on the catalyst is cross-linked. An object of the present invention is to provide a cross-coupling reaction catalyst that can be used efficiently and maximally and has a catalytic activity significantly improved as compared with conventional catalysts, and a cross-coupling reaction using the catalyst.

  As a result of intensive studies by the present inventors, when the nanoparticles obtained in Japanese Patent Application No. 2009-154932 were used for the cross-coupling reaction, the transition metal ultrafine particle catalyst of the present invention was a metal species that did not contain a ligand and a protective agent. It is found that the metal surface on the catalyst can be used efficiently and maximally in the cross-coupling reaction, and the catalytic activity can be dramatically improved as compared with the conventional reaction system. It was. In particular, the Mizorogi-Heck reaction using haloarenes and olefins having electron-withdrawing groups as reaction substrates, and the Suzuki-Miyaura reaction using haloarenes and organic boronic acids were performed. It has been found that the process proceeds efficiently with a good yield and a high catalyst rotation speed. That is, the present invention is as follows.

[1] A catalyst for cross-coupling reaction comprising transition metal ultrafine particles containing at least one transition metal selected from the group consisting of Group 8 to Group 11 transition metals and a coordinating organic solvent.

[2] Formula: AX
(Where
A is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted alkenyl group; and
X is a halogen, a mesylate group, a tosylate group, a triflate group, or a carboxylic acid halide group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group, or an unsubstituted or substituted alkynyl group;
Y is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR ¹ ) ₂ , ZnX ¹ , AlR ² ₂ , SnR ³ ₃ , MgX ² , or SiR ⁴ _3, wherein, ^{X 1} and ^{X 2} is halogen and ^{R 1,} R 2, ^{R 3} and ^{R 4} are each independently hydrogen or alkyl)
By reacting with a compound represented by
Formula: AB
(In the formula, A and B are as described above.)
The catalyst for cross-coupling reactions according to [1], which is used for a cross-coupling reaction to obtain a product represented by

[3] Formula: AX
(Where
A is an unsubstituted or substituted aryl group or an unsubstituted or substituted heteroaryl group; and
X is a halogen, a mesylate group, a tosylate group, or a triflate group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted alkenyl group or an unsubstituted or substituted aryl group;
Y is an alkoxycarbonyl group or B (OR ¹ ) ₂ and R ¹ is hydrogen)
By reacting with a compound represented by
Formula: AB
(In the formula, A and B are as described above.)
The catalyst for a cross coupling reaction according to any one of [1] or [2], which is used for a cross coupling reaction to obtain a product represented by:

[4] The catalyst for cross-coupling reaction according to any one of [1] to [3], wherein the transition metal is a Group 10 transition metal.

[5] The catalyst for cross coupling reaction according to any one of [1] to [4], wherein the transition metal is palladium.

[6] The coordinating organic solvent is N, N-dimethylformamide (DMF), N-methylformamide, N, N-dimethylacetamide (DMA), N-methylacetamide, 1,3-dimethyl-2-imidazolide. Any one of [1] to [5], which is an amide solvent selected from the group consisting of non- (DMI), N-methyl-2-pyrrolidone (NMP), and hexamethylphosphoric triamide (HMPA) The catalyst for cross-coupling reaction as described.

[7] The catalyst for cross coupling reaction according to any one of [1] to [6], wherein the coordinating organic solvent is N, N-dimethylformamide (DMF).

[8] The catalyst for cross-coupling reaction according to any one of [1] to [7], wherein the transition metal ultrafine particles have an average particle size of 2 nm or less.

[9] The catalyst for cross-coupling reaction according to any one of [1] to [8], wherein the transition metal ultrafine particles are phosphors.

[10] The catalyst for cross coupling reaction according to any one of [1] to [9], wherein the turnover number (TON) is 1.0 × 10 ⁴ or more.

[11] Prepared by heating and refluxing at least one transition metal chloride selected from the group consisting of Group 8 to Group 11 transition metals in a coordinating organic solvent. The manufacturing method of the catalyst for cross coupling reactions of any one of Claims 1.

[12] The production method according to [11], wherein the heating and refluxing is performed while irradiating microwaves.

[13] The production method according to any one of [11] and [12], wherein the reaction solution after the reflux with heating is appropriately evaporated, and then diluted with a coordinating organic solvent to prepare a desired concentration.

[14] The production method according to [13], wherein dilution is performed using a coordinating organic solvent selected from the group consisting of DMF, NMP, and THF.

[15] Formula: AX
(Where
A is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted alkenyl group; and
X is a halogen, a mesylate group, a tosylate group, a triflate group, or a carboxylic acid halide group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group, or an unsubstituted or substituted alkynyl group;
Y is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR ¹ ) ₂ , ZnX ¹ , AlR ² ₂ , SnR ³ ₃ , MgX ² , or SiR ⁴ _3, wherein, ^{X 1} and ^{X 2} is halogen and ^{R 1,} R 2, ^{R 3} and ^{R 4} are each independently hydrogen or alkyl)
In the presence of a catalyst containing ultrafine transition metal particles containing at least one transition metal selected from the group consisting of Group 8 to Group 11 transition metals and a coordinating organic solvent. According to the formula: AB
(In the formula, A and B are as described above.)
A cross-coupling reaction comprising obtaining a product represented by

[16] The cross-coupling reaction according to [15], which is appropriately performed in the presence of a base.

[17] The cross-coupling reaction according to any one of [15] or [16], wherein the reaction solvent is a coordination organic solvent alone or a mixture with water.

[18] The cross coupling according to any one of [15] to [17], wherein the amount of the catalyst used is 10 ⁻¹ to 10 ⁻⁷ mol% based on the amount of the compound represented by AX. reaction.

  The transition metal ultrafine particles of the present invention can efficiently and maximize the use of the metal surface on the catalyst, and can dramatically improve the catalytic activity as compared with the conventional cross-coupling reaction system.

It is a figure which shows each TEM image of a palladium ultrafine particle (A) and a platinum ultrafine particle (B).

The present invention is described in further detail below.
(Definition)
The definitions of terms used in the present specification and claims are shown below. Unless otherwise indicated, the first definition given for a group or term herein applies to the group or term herein individually or as part of another group.

  The term “at least one transition metal selected from the group consisting of Group 8 to Group 11 transition metals” refers to Group 8 transition metals (eg, iron (Fe), ruthenium (Ru), osmium (Os)), Group 9 transition metals (eg, cobalt (Co), rhodium (Rh), iridium (Ir)), Group 10 transition metals (eg, nickel (Ni), palladium (Pd), platinum (Pt)), and It means at least one transition metal selected from the group consisting of group 11 transition metals (for example, copper (Cu), silver (Ag), gold (Au)). Group 10 transition metals are preferred, platinum and palladium are more preferred, and palladium is particularly preferred.

  The term “coordinating organic solvent” means an organic solvent capable of coordinating with a transition metal, such as an amide solvent, an amine solvent, an alcohol solvent, an ether solvent, a ketone solvent, and an ester. A system solvent, a nitrile solvent, a nitro solvent, or a sulfoxide solvent, or a mixed solvent of two or more thereof. Specifically, for example, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMA), 1,3-dimethyl-2-imidazolidinone (DMI), N-methyl-2-pyrrolidone (NMP) ) Amide solvents including carboxylic acid amides such as hexamethylphosphoric triamide (HMPA); amine solvents such as triethylamine, pyridine and ethanolamine; alcohol solvents such as isopropanol and propylene glycol Ether solvents such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran (THF); ketone solvents such as acetone and 2-butanone; ester solvents such as ethyl acetate and methyl acetate; nitrile solvents such as acetonitrile; nitromethane and the like Nitro solvents of dimethyl It includes a sulfoxide-based solvents such as sulfoxide. Amide solvents selected from the group consisting of DMF, N-methylformamide, DMA, N-methylacetamide, DMI, NMP, and HMPA are preferred, and DMF is particularly preferred.

  The term “transition metal ultrafine particles” is a solvent-protected product containing at least one transition metal selected from the group consisting of the above Group 8 to Group 11 transition metals and a coordinating organic solvent, and its average particle A particle having a diameter of nano size is meant. Here, the solvent-protected product means a compound protected with these coordinating solvents. In the present specification, “ultrafine particles” are also referred to as “nanoparticles” or “NCs”.

The average particle size is about 0.5 to 4 nm, preferably 2 nm or less, and more preferably about 1.5 nm. The particle diameter is confirmed by analyzing a transmission electron microscope (TEM) image. For example, TEM images of palladium ultrafine particles and platinum ultrafine particles are shown (FIG. 1). From FIG. 1, the palladium ultrafine particles and the platinum ultrafine particles each have an average particle diameter of about 1.5 nm. In addition, as described in Japanese Patent Application No. 2009-154932, since transition metal ultrafine particles other than palladium and platinum also exhibit fluorescence characteristics, the average particle diameter is 2 nm or less. Also, the correlation between such fluorescence properties and an average particle size of 2 nm or less is described in a number of documents:
1. S. Empedocles, M. Baewndi, Acc. Chem. Res, 1999, 32, 389-396.
2. MA El-Sayed, Acc. Chem. Res, 2001, 34, 257-264.
3. S. Link, MA El-Sayed, Int. Rev. Phys. Chem. 200, 19, 409-453.
4. S. Link, A. Beeby, S. FitzGerald, MA El-Sayed, TG Schaaff, RL
Whetten, J. Phys. Chem. B, 2002, 106, 3410-3415,
5. S. Chen, RS Ingram, MJ Hostetler, JJ Pietron, RW Murrey, TG Schaaff, JT Khoury, MM Alvarez, RL Whetten, Science, 1998, 280, 2098-2101.

で示される反応を意味する。具体的には、有機ハロゲン化物等と末端アルケン等との反応（溝呂木・ヘック反応）、有機ハロゲン化物等と有機亜鉛化合物との反応（根岸カップリング反応）、有機ハロゲン化物等と有機スズ化合物との反応（右田・小杉・スティルカップリング）、有機ハロゲン化物等と末端アルキン等との反応（薗頭カップリング）、有機ハロゲン化物等と有機ホウ素化合物との反応（鈴木・宮浦カップリング）、有機ハロゲン化物と有機アミン化合物との反応（ブッフバルト・ハートウィッグ反応）、有機ハロゲン化物等と有機マグネシウム化合物との反応（熊田・玉尾・コリューカップリング）、有機ハロゲン化物と有機ケイ素化合物との反応（檜山カップリング）等を意図する。特に、溝呂木・ヘック反応および鈴木・宮浦カップリングを意図する。 The term “cross-coupling reaction” means a reaction that selectively binds between two different compounds. In particular, the cross-coupling reaction contemplated by the present invention refers to the following formula where the transition metal compound acts catalytically:

Means the reaction indicated by Specifically, reactions between organic halides and terminal alkenes (Mizorogi / Heck reaction), reactions between organic halides and organic zinc compounds (Negishi coupling reaction), organic halides and organic tin compounds, etc. Reaction (Migita, Kosugi, Stille coupling), reaction of organic halides with terminal alkynes (Soto coupling), reaction of organic halides with organic boron compounds (Suzuki / Miyaura coupling), organic Reactions between halides and organic amine compounds (Buchwald / Hartwig reaction), reactions between organic halides and organic magnesium compounds (Kumada / Tamao / Colleu coupling), reactions between organic halides and organosilicon compounds Intended for (Eizan coupling). In particular, the Mizorogi-Heck reaction and the Suzuki-Miyaura coupling are intended.

  The term “compound represented by the formula: AX” means one of the reaction substrates that acts as an electrophile in the cross-coupling reaction. Here, the group A is a group having at least one carbon-carbon unsaturated bond, specifically, an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, and an unsubstituted or substituted group. Contains an alkenyl group. An unsubstituted or substituted aryl group or an unsubstituted or substituted heteroaryl group is preferred. The X group means a group known as a leaving group in the field of organic chemistry. Specifically, halogen (for example, chloro, bromo, iodo), mesylate group (OMs), tosylate group (OTs), or carboxylic acid halide group (for example, carboxylic acid bromide (C (= O) Br, carboxylic acid) Iodide (C (= O) I)), halogen is preferred, bromo or iodo is more preferred, and iodo is particularly preferred.

The term “compound represented by the formula: BY” means one of the reaction substrates that acts as a nucleophile in the cross-coupling reaction. Here, the group B is a group having at least one carbon-carbon unsaturated bond, specifically, an unsubstituted or substituted aryl, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group. And unsubstituted or substituted alkynyl groups. An unsubstituted or substituted alkenyl group or an unsubstituted or substituted aryl group is preferred. Y group is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR ¹ ) ₂ , ZnX ¹ , AlR ² ₂ , SnR ³ ₃ , MgX ^2. Or SiR ⁴ ₃ where X ¹ and X ² are halogens (chloro, bromo, iodo are preferred, bromo, iodo are more preferred) and R ¹ , R ² , R ³ and R ⁴ are Each is independently hydrogen or alkyl (C1-C6 alkyl is preferable, and methyl, ethyl, and t-butyl are more preferable). An alkoxycarbonyl group (eg ethoxycarbonyl) or B (OR ¹ ) ₂ (R ¹ is hydrogen) is preferred.

  The term “unsubstituted or substituted aryl group” means an aromatic carbocyclic group having 1 to 5 substituents as appropriate. Also included in this definition are polycyclic groups (eg, bicyclic groups) linked in a fused ring fashion. Specific examples include monocyclic aryl groups such as phenyl group, 1-naphthyl group and 2-naphthyl group; bicyclic aryl groups such as phenanthridinyl group, 6-chromanyl group and 5-isoindolyl group. It is done. A phenyl group, a 1-naphthyl group, and a 2-naphthyl group are preferable.

  Here, the substituent may be any group that does not hinder the progress of the cross-coupling reaction, and is known as an electron donating group (for example, amino group, alkyl group, alkoxy group) or electron withdrawing property known in the field of organic chemistry. Any of groups (for example, nitro group, formyl group, oxo group, cyano group, alkoxycarbonyl group) may be used, but an electron donating group is preferable. For example, an alkyl group (for example, an alkyl group having 1 to 6 carbon atoms (for example, a methyl group, an ethyl group)), a halogenated alkyl group (for example, a trifluoromethyl group), a nitro group, a formyl group, an oxo group, Acyl group (eg, acetyl group, propionyl group, butyryl group), amino group (eg, N-methylamino group, N-ethylamino group, N, N-dimethylamino group, N, N-diphenylamino group), hydroxy Group, alkoxy group (for example, methoxy group, ethoxy group), carboxy group, and cyano group. Alkyl groups, halogenated alkyl groups, and alkoxy groups are preferred.

  The term “unsubstituted or substituted heteroaryl group” refers to at least one heteroatom selected from a nitrogen atom, an oxygen atom, or a sulfur atom in at least one ring having 1 to 5 substituents as appropriate. Means an aromatic cyclic group. Also included in this definition are polycyclic groups (eg, bicyclic groups) linked in a fused ring fashion. Specific examples include pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, pyridyl, furyl, thienyl, oxadiazolyl, 2-oxaazepinyl, azepinyl, pyrazinyl Group, pyrimidinyl group, pyridazinyl group, triazinyl group, triazolyl group and the like monocyclic heteroaryl group; and benzothiazolyl group, benzoxazolyl group, benzothienyl group, benzofuryl group, quinolinyl group, quinolinyl-N-oxide group, isoquinolinyl group, Benzoimidazolyl group, benzopyranyl group, indolizinyl group, cinnolinyl group, quinoxalinyl group, indazolyl group, pyrrolopyridyl group, furopyridinyl group (for example, furo [2,3-c] pyridinyl group, furo [ 3,1-b] pyridinyl group or furo [2,3-b] pyridinyl group), benzisothiazolyl group, benzisoxazolyl group, benzodiazinyl group, benzothiopyranyl group, benzotriazolyl group, And bicyclic aryl groups such as bicyclic heteroaryl groups such as benzopyrazolyl group, naphthyridinyl group, phthalazinyl group, purinyl group, pyridopyridyl group, quinazolinyl group, thienofuryl group, thienopyridyl group, and thienothienyl group. A pyridyl group is preferred. As defined in the above “unsubstituted or substituted aryl group”, the substituent may be any group that does not hinder the progress of the cross-coupling reaction, and specific examples are as described above.

  The term “unsubstituted or substituted alkenyl group” means a straight, branched or cyclic group having 2 to 12 carbon atoms and at least one double bond, optionally having 1 to 5 substituents. A hydrocarbon group is meant. Specific examples include ethenyl group (vinyl group), 1-propenyl group, 1-butenyl group, 1-pentenyl group, 1,3-dipentenyl group, cyclohexenyl group and the like. An ethenyl group is preferred. As defined in the above “unsubstituted or substituted aryl group”, the substituent may be any group that does not hinder the progress of the cross-coupling reaction, and specific examples are as described above.

  The term “unsubstituted or substituted alkynyl group” refers to a linear or branched hydrocarbon group having 2 to 6 carbon atoms and one triple bond, optionally having 1 to 3 substituents. means. A terminal alkynyl group in which hydrogen on carbon at one end of acetylene is substituted with a group other than hydrogen is preferable. Specific examples include 1-propynyl, 1-butynyl, 3,3-dimethyl-1-butynyl and the like. 1-propynyl is preferred. As defined in the above “unsubstituted or substituted aryl group”, the substituent may be any group that does not hinder the progress of the cross-coupling reaction, and specific examples are as described above.

  The term “alkoxycarbonyl group” means an alkoxycarbonyl group containing an alkyl group having 1 to 12 carbon atoms, preferably 1 to 8 carbon atoms, more preferably 1 to 6 carbon atoms. Specific examples include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, butoxycarbonyl (n-butoxycarbonyl, iso-butoxycarbonyl, t-butoxycarbonyl), pentyloxycarbonyl, hexyloxycarbonyl and the like. Methoxycarbonyl, ethoxycarbonyl and t-butoxycarbonyl are preferred.

The reaction of the present invention is described in detail below.

(Preparation of catalyst)
The catalyst for cross-coupling reaction of the present invention is prepared as shown in the above reaction formula 1. Specifically, first, as described in Japanese Patent Application No. 2009-154932, the raw materials of Group 8 to Group 11 transition metal compounds are reacted by heating and refluxing in a coordinating organic solvent to obtain a reaction solution. . It is preferable to heat and reflux while irradiating with microwaves. This reaction can be carried out in an air atmosphere. Moreover, reaction temperature is performed near the boiling point of the coordinating organic solvent used normally. Furthermore, the reaction time may vary depending on the reaction conditions such as the solvent used and the reaction temperature, but it is completed in several hours to several days, usually about 4 hours to about 1 day, and preferably about 6 hours. .

The raw material of the Group 8 to Group 11 transition metal compound may be an inorganic compound of each transition metal (for example, chloride, sulfate, or nitrate). Specifically, in the case of Pd, PdCl ₂ , [Pd (NH ₃ ) ₄ ] Cl _2, etc .; in the case of Pt, H ₂ PtCl ₆ , [Pt (NH ₃ ) ₄ ] Cl _2, etc .; in the case of Fe, FeCl ₃ , Fe ₂ (SO ₄ ) ₃ In the case of Au, HAuCl ₄ , Na [Au (CN) ₄ ] etc .; in the case of Cu, CuCl ₂ , CuSO ₄ etc .; in the case of Ag, AgNO ₃ , [Ag (NH ₃ ) ₂ ] NO ₃ etc. are mentioned. Chloride is preferred. These are commercially available, or can be produced by a method known in the field of the organometallic chemistry or a method analogous thereto.

  Next, the obtained reaction solution can be diluted with a coordinating organic solvent and adjusted to a desired concentration to obtain a transition metal ultrafine particle catalyst. Here, when the reaction solvent and the diluting solvent are different, the reaction solvent is distilled off, followed by dilution. For example, a 1 mM reaction solution can be obtained and diluted to a concentration of 10 μM, 100 nM, 10 nM, 1 nM.

(Cross coupling reaction)
The cross coupling reaction is generally performed according to a procedure known as a catalytic cross coupling reaction as shown in the above reaction formula 2. Specifically, the compound (1) represented by the formula: AX and the compound (2) represented by the formula: BY are reacted in the presence of the transition metal ultrafine particle catalyst obtained above. . Here, depending on the type of the cross-coupling reaction, the reaction is performed in the presence of a base. Bases include organic bases (eg triethylamine, pyridine) or inorganic bases (eg hydroxides (eg sodium hydroxide)), carbonates (eg potassium carbonate), bicarbonates (eg sodium bicarbonate) ).

  A compound (1) represented by the formula: AX and a compound (2) represented by the formula: BY, which are reaction substrates, are either commercially available or a method known in the field of organic chemistry, Or it can manufacture by the method according to these.

  As a reaction solvent for the cross-coupling reaction, a coordinating organic solvent alone or a mixture with water can be used. When a mixture with water is used, the ratio of the coordinating organic solvent in the total amount of the reaction solvent is 5% by volume or more, 20% by volume or more, preferably 50% by volume or more. As the coordinating reaction solvent, DMF, NMP and THF are preferable. Particularly, in the case of Mizorogi-Heck reaction, DMF is preferable, and in the case of Suzuki-Miyaura coupling, NMP is preferable.

  The compounding ratio of the compound (1) and the compound (2) as the reaction substrate is such that the amount of the compound (2) is equal or excessive based on the compounding amount of the compound (1). For example, the compound (2) is used in an amount of 1.0 to 3.0 equivalents, 1.0 to 2.0 equivalents, preferably 1.2 to 1.5 equivalents.

The transition metal ultrafine particle catalyst of the present invention is used in an amount of 10 ⁻¹ to 10 ⁻⁷ mol%, 10 ⁻² to 10 ⁻⁷ mol%, preferably 10 ^{− based on the} amount of compound (1) as the reaction substrate. it can be used in ^three to ^10-7 mol%. In particular, it can be used at 10 ⁻⁵ to 10 ⁻⁷ mol% in the case of Mizorogi-Heck reaction, and at 10 ⁻³ mol% in the case of Suzuki-Miyaura coupling.

Catalytic activity can be expressed using the catalyst rotational speed (TON) often used in the field of catalytic chemistry. The catalyst of the present invention exhibits a TON of the order of 10 ⁴ to 10 ⁸ . For example, in the case of the Suzuki-Miyaura coupling, an order of 10 ⁴ , that is, a maximum of 10,000 units of TON, and in the case of the Mizorogi-Heck reaction, an order of 10 ⁴ to 10 ⁸ , that is, a maximum of 100 million units of TON. Can show.

  The coupling reaction of the present invention can be performed at a low temperature (for example, −70 ° C. or lower) to a high temperature (for example, 100 ° C. or higher), and is usually from room temperature to the boiling point of the reaction solvent used, preferably 80 to 140, 100 degreeC-140 degreeC is more preferable.

  The reaction of the present invention is preferably performed in an atmosphere of an inert gas, specifically, in an atmosphere of nitrogen, argon, or helium.

  The reaction of the present invention can be carried out under normal pressure from a normal pressure in a pressure vessel (for example, a commercially available stainless steel pressure vessel such as a pressure tube), and is usually carried out at normal pressure.

  The reaction time of the present invention may vary depending on the reaction conditions such as the solvent used and the reaction temperature, but it is completed in several hours to several days, usually 3 hours to 2 days, and 5 hours to 15 hours. preferable.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples. The transition metal ultrafine particles and the product of the cross-coupling reaction were confirmed by analysis of various spectroscopic analyses. Specifically, one- and two-dimensional proton and carbon 13 nuclear magnetic resonance spectra ( ¹ H NMR, ¹³ C NMR, mass spectrum (MS), infrared absorption spectrum (IR), fluorescence spectrum, transmission electron microscope (TEM) In the nuclear magnetic resonance spectrum, tetramethylsilane was used as an internal standard, and the reaction yield was quantified using silica gel gas chromatography (GC).

The following abbreviations used in the examples will be described.
Me represents a methyl group, Et represents an ethyl group, t-Bu represents a t-butyl group, and Cy represents a cyclohexyl group.

[Reference example]
[Synthesis of transition metal ultrafine particles]
1. Preparation of palladium ultrafine particles The transition metal ultrafine particles used in the present invention were prepared in the same manner as described in Japanese Patent Application No. 2009-154932. Specifically, a rotator was placed in a three-necked flask, washed with DMF, DMF (15 mL) was added, and the three-necked flask was preheated at 140 ° C. for 6 minutes in an air atmosphere. Thereafter, 150 μL of 0.1 M palladium chloride aqueous solution was added, and the mixture was heated to reflux at 140 ° C. for 6 hours for synthesis. The palladium ultrafine particle solution is obtained as a 1 mM solution (1 mM Pd ultrafine particles (nanoparticles) (NCs) / DMF) and analyzed using an ultraviolet-visible absorption spectrum, fluorescence spectrum, and TEM. Was confirmed (FIG. 1A).

2. Preparation of platinum ultrafine particles Prepared in the same manner as the above-mentioned palladium ultrafine particles. Specifically, a rotator was placed in a three-necked flask, washed with DMF, DMF (15 mL) was added, and the three-necked flask was preheated at 140 ° C. for 6 minutes in an air atmosphere. Thereafter, 75 μL of 0.1 M chloroplatinic acid aqueous solution was added, and synthesis was carried out by refluxing at 140 ° C. for 6 hours. The platinum ultrafine particle solution was obtained as a 1 mM solution (1 mM Pt NCs / DMF) and analyzed using an ultraviolet-visible absorption spectrum, a fluorescence spectrum, and TEM to confirm the generation of particles of about 1.5 nm (FIG. 1). (B)).

[Example]
[Preparation of catalyst]
A 1 mM solution of the produced palladium ultrafine particle solution (Pd NCs / DMF) was diluted 100 times with DMF to prepare a 10 μM Pd NCs / DMF solution. Further, a 10 μM Pd NCs / DMF solution was diluted 100 times with DMF to prepare a 100 nM solution. In the same manner, 10 nM and 1 nM Pd NCs / DMF solutions were prepared and used for the reaction.

  Similarly, DMF (15 mL) of a 1 mM Pd NCs / DMF solution was distilled off using an evaporator, and then NMP (15 mL) was added and redispersed. The obtained 1 mM Pd NCs / NMP solution was diluted 100 times with NMP to prepare a 10 μM Pd NCs / NMP solution. In the same manner, 1 μM, 100 nM, 10 nM, and 1 nM Pd NCs / NMP solutions were prepared.

  Further, DMF (15 mL) of 1 mM Pd NCs / DMF solution was distilled off with an evaporator, and then THF (15 mL) was added to redisperse. The obtained 1 mM Pd NCs / THF solution was diluted 100 times with THF to prepare a 10 μM Pd NCs / THF solution. In the same manner, 1 μM, 100 nM, 10 nM, and 1 nM Pd NCs / THF solutions were prepared.

[Cross coupling reaction]
(Mizorogi / Heck reaction)

プレッシャーチューブに回転子を入れ、アルゴン雰囲気のもと、上記［触媒の調製］で合成した1 mMのPd NCs／DMF (1 mL)を加えた。その後、ヨードベンゼン (1 mmol, 204 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；定量的、触媒回転数；>1,000回。

A rotor was placed in the pressure tube, and 1 mM Pd NCs / DMF (1 mL) synthesized in the above [Preparation of catalyst] was added under an argon atmosphere. Then, iodobenzene (1 mmol, 204 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg) and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. It was. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck product yield; quantitative, catalyst rotation;> 1,000 times.

まず、生成したパラジウムナノ粒子溶液(Pd NCs／DMF)の1 mM溶液を100 μL取り、DMF 10 mL中に加えて100倍に希釈し、10 μM Pd NCs／DMFの溶液を調製した。その10μM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、ヨードベンゼン (1 mmol, 204 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；定量的、触媒回転数；>100,000回。

First, 100 μL of a 1 mM solution of the produced palladium nanoparticle solution (Pd NCs / DMF) was taken, added to 10 mL of DMF, and diluted 100-fold to prepare a 10 μM Pd NCs / DMF solution. 1 mL of the 10 μM Pd NCs / DMF solution was added to a pressure tube containing a rotor under an argon atmosphere. Then, iodobenzene (1 mmol, 204 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg) and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. It was. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; quantitative, catalyst turnover;> 100,000 times.

まず、上記［実施例２］で調製したパラジウムナノ粒子溶液(Pd NCs／DMF)の10 μM溶液を100 μL取り、DMF 10 mL中に加えて100倍に希釈し、100 nM Pd NCs／DMFの溶液を調製した。その100 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、ヨードベンゼン (1 mmol, 204 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；>99% 、触媒回転数；>10,000,000回。

First, 100 μL of a 10 μM solution of the palladium nanoparticle solution (Pd NCs / DMF) prepared in [Example 2] above is taken, added to 10 mL of DMF, diluted 100 times, and 100 nM Pd NCs / DMF A solution was prepared. 1 mL of the 100 nM Pd NCs / DMF solution was added to a pressure tube containing a rotor under an argon atmosphere. Then, iodobenzene (1 mmol, 204 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg) and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. It was. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield;> 99%, catalyst rotation;> 10,000,000 times.

1 mMのPd NCs／DMF溶液のDMF (15 mL)をエバポレーターにより留去したのち、NMP (15 mL)を加え、再分散させた。得られた1 mM Pd NCs／NMP溶液を100 μL取り、NMP 10 mLで100倍に希釈し、10 μMのPd NCs／NMP溶液を調製した。同様の操作で、10 μM Pd NCs／NMP溶液を100 μL取り、NMP 10 mLで100倍に希釈し、100 nMのPd NCs／NMP溶液を調製した。その100 nM Pd NCs／NMPの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、ヨードベンゼン (1 mmol, 204 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてNMP (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；30% 、触媒回転数；3,040,000回。

After distilling off DMF (15 mL) of 1 mM Pd NCs / DMF solution with an evaporator, NMP (15 mL) was added and redispersed. 100 μL of the obtained 1 mM Pd NCs / NMP solution was taken and diluted 100-fold with 10 mL of NMP to prepare a 10 μM Pd NCs / NMP solution. In the same manner, 100 μL of 10 μM Pd NCs / NMP solution was taken and diluted 100-fold with 10 mL of NMP to prepare a 100 nM Pd NCs / NMP solution. 1 mL of the 100 nM Pd NCs / NMP solution was added to a pressure tube containing a rotor under an argon atmosphere. Then, iodobenzene (1 mmol, 204 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg), and NMP (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. It was. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield: 30%, catalyst rotation speed: 3,040,000 times.

まず、［実施例３］で調製したパラジウムナノ粒子溶液(Pd NCs／DMF)の100 nM溶液を100 μL取り、DMF 10 mL中に加えて100倍に希釈し、1 nM Pd NCs／DMFの溶液を調製した。その1 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、ヨードベンゼン (1 mmol, 204 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；60% 、触媒回転数；598,000,000回。

First, 100 μL of a 100 nM palladium nanoparticle solution (Pd NCs / DMF) prepared in [Example 3] is taken, added to 10 mL of DMF, diluted 100-fold, and then a 1 nM Pd NCs / DMF solution. Was prepared. 1 mL of the 1 nM Pd NCs / DMF solution was added to a pressure tube containing a rotor under an argon atmosphere. Then, iodobenzene (1 mmol, 204 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg) and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. It was. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; 60%, catalyst rotation speed: 598,000,000 times.

プレッシャーチューブに回転子を入れ、アルゴン雰囲気のもと[触媒の調製]で合成した1 mMのPd NCs／DMF (1 mL)を加えた。その後、ブロモベンゼン (1 mmol, 157 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；23%、触媒回転数；231回。

A rotor was placed in the pressure tube, and 1 mM Pd NCs / DMF (1 mL) synthesized in [Preparation of catalyst] was added under an argon atmosphere. Then, bromobenzene (1 mmol, 157 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg), and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. It was. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; 23%, catalyst rotation speed: 231 times.

［実施例３］で調製した100 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、4-ヨードトルエン (1 mmol, 218 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；47% 、触媒回転数；4,740,000回。

1 mL of a solution of 100 nM Pd NCs / DMF prepared in [Example 3] was added to a pressure tube containing a rotor under an argon atmosphere. Then, 4-iodotoluene (1 mmol, 218 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg), and DMF (1 mL) as a solvent were added, and the reaction was carried out at 140 ° C for 15 hours. Went. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; 47%, catalyst rotation speed: 4,740,000 times.

［実施例３］で調製した100 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、4-ヨードベンゾトリフルオリド (1 mmol, 272 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；41% 、触媒回転数；4,090,000回。

1 mL of a solution of 100 nM Pd NCs / DMF prepared in [Example 3] was added to a pressure tube containing a rotor under an argon atmosphere. Then, 4-iodobenzotrifluoride (1 mmol, 272 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg), DMF (1 mL) as a solvent was added, 140 ° C, 15 Time reaction was performed. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield: 41%, catalyst rotation speed: 4,090,000 times.

［実施例３］で調製した100 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、4-ヨードアニソール (1 mmol, 234 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；20% 、触媒回転数；2,010,000回。

1 mL of a solution of 100 nM Pd NCs / DMF prepared in [Example 3] was added to a pressure tube containing a rotor under an argon atmosphere. Then, 4-iodoanisole (1 mmol, 234 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg), and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. Went. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; 20%, catalyst rotation speed: 2,010,000 times.

［実施例３］で調製した100 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、1-ヨードナフタレン (1 mmol, 254 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；68% 、触媒回転数；6,760,000回。

1 mL of a solution of 100 nM Pd NCs / DMF prepared in [Example 3] was added to a pressure tube containing a rotor under an argon atmosphere. Then, 1-iodonaphthalene (1 mmol, 254 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg), DMF (1 mL) as a solvent was added, and the reaction was carried out at 140 ° C for 15 hours. Went. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; 68%, catalyst rotation speed: 6,760,000 times.

［実施例２］で調製した10 μM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、5-ヨード-2-フルアルデヒド (1 mmol, 222 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；14% 、触媒回転数；14,200回。

1 mL of the 10 μM Pd NCs / DMF solution prepared in [Example 2] was added to a pressure tube containing a rotor under an argon atmosphere. Then, 5-iodo-2-furaldehyde (1 mmol, 222 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg), and DMF (1 mL) as a solvent were added, 140 ° C The reaction was performed for 15 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; 14%, catalyst rotation speed: 14,200 times.

［実施例３］で調製した100 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、2-ヨードチオフェン (1 mmol, 210 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；11% 、触媒回転数；1,090,000回。

1 mL of a solution of 100 nM Pd NCs / DMF prepared in [Example 3] was added to a pressure tube containing a rotor under an argon atmosphere. Then, 2-iodothiophene (1 mmol, 210 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg), and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. Went. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; 11%, catalyst rotation speed: 1,090,000 times.

［実施例３］で調製した100 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、ヨードベンゼン (1 mmol, 204 mg)、アクリル酸シクロヘキシル (1.2 mmol, 185 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；27% 、触媒回転数；2,740,000回。

1 mL of a solution of 100 nM Pd NCs / DMF prepared in [Example 3] was added to a pressure tube containing a rotor under an argon atmosphere. Then, iodobenzene (1 mmol, 204 mg), cyclohexyl acrylate (1.2 mmol, 185 mg), triethylamine (1 mmol, 101 mg), and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. It was. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; 27%, catalyst rotation speed: 2,740,000 times.

［実施例３］で調製した100 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、ヨードベンゼン (1 mmol, 204 mg)、アクリル酸-t-ブチル (1.2 mmol, 154 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；5% 、触媒回転数；530,000回。

1 mL of a solution of 100 nM Pd NCs / DMF prepared in [Example 3] was added to a pressure tube containing a rotor under an argon atmosphere. Then, iodobenzene (1 mmol, 204 mg), acrylic acid-t-butyl (1.2 mmol, 154 mg), triethylamine (1 mmol, 101 mg), and DMF (1 mL) as a solvent were added, 140 ° C, 15 hours Reaction was performed. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield: 5%, catalyst rotation speed: 530,000 times.

［実施例３］で調製した100 nM Pd NCs／DMFの溶液 1 mLをアルゴン雰囲気のもと回転子を入れたプレッシャーチューブに加えた。その後、ヨードベンゼン (1 mmol, 204 mg)、メチルビニルケトン (1.2 mmol, 84 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；12% 、触媒回転数；1,240,000回。

1 mL of a solution of 100 nM Pd NCs / DMF prepared in [Example 3] was added to a pressure tube containing a rotor under an argon atmosphere. Then, iodobenzene (1 mmol, 204 mg), methyl vinyl ketone (1.2 mmol, 84 mg), triethylamine (1 mmol, 101 mg), and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. It was. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck-type product yield; 12%, catalyst rotation speed: 1,240,000 times.

(Suzuki-Miyaura cross-coupling reaction)

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ヨードトルエン (0.5 mmol,109 mg)、フェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、上記[触媒の調製]で調製した1 mMのPd NCs／DMF (1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 86%, 触媒回転数 (TON): 430回。

After adding a rotor to a branched Schlenk and adding 4-iodotoluene (0.5 mmol, 109 mg), phenylboronic acid (0.75 mmol, 91 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere 1 mM Pd NCs / DMF (1 mL) and H ₂ O (1 mL) prepared in the above [Preparation of catalyst] were added, and the reaction was performed at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 86%, catalyst rotation speed (TON): 430 times.

まず、生成したパラジウムナノ粒子溶液(Pd NCs／DMF)の1 mM溶液を100 μL取り、DMF 10 mL中に加えて100倍に希釈し、10 μM Pd NCs／DMFの溶液を調製した。次に、枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ヨードトルエン (0.5 mmol,109 mg)、フェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、10 μM Pd NCs／DMFの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 41%, 触媒回転数 (TON): 20,400回。

First, 100 μL of a 1 mM solution of the produced palladium nanoparticle solution (Pd NCs / DMF) was taken, added to 10 mL of DMF, and diluted 100-fold to prepare a 10 μM Pd NCs / DMF solution. Next, put a rotator in the branched Schlenk and put 4-iodotoluene (0.5 mmol, 109 mg), phenylboronic acid (0.75 mmol, 91 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. After the addition, a 10 μM Pd NCs / DMF solution (1 mL) and H ₂ O (1 mL) were added, and the reaction was performed at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 41%, catalyst rotation speed (TON): 20,400 times.

まず、1 mMのPd NCs／DMF溶液のDMF (15 mL)をエバポレーターにより留去したのち、NMP (15 mL)を加え、再分散させた。得られた1 mM Pd NCs／NMP溶液を100 μL取り、NMP 10 mLで100倍に希釈し、10 μMのPd NCs／NMP溶液を調製した。次に、枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ヨードトルエン (0.5 mmol, 109 mg)、フェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、10 μM Pd NCs／NMPの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 82%, 触媒回転数 (TON): 40,600回。

First, DMF (15 mL) of a 1 mM Pd NCs / DMF solution was distilled off using an evaporator, and then NMP (15 mL) was added and redispersed. 100 μL of the obtained 1 mM Pd NCs / NMP solution was taken and diluted 100-fold with 10 mL of NMP to prepare a 10 μM Pd NCs / NMP solution. Next, put a rotator in the branched Schlenk and put 4-iodotoluene (0.5 mmol, 109 mg), phenylboronic acid (0.75 mmol, 91 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. After the addition, a 10 μM Pd NCs / NMP solution (1 mL) and H ₂ O (1 mL) were added, and the reaction was performed at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 82%, catalyst rotation speed (TON): 40,600 times.

まず、1 mMのPd NCs／DMF溶液のDMF (15 mL)をエバポレーターにより留去したのち、THF (15 mL)を加え、再分散させた。得られた1 mM Pd NCs／THF溶液を100 μL取り、THF 10 mLで100倍に希釈し、10 μMのPd NCs／THF溶液を調製した。溶けなかった粒子は、フィルターによりろ過した。次に、枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ヨードトルエン (0.5 mmol, 109 mg)、フェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、10 μM Pd NCs／THFの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 56%, 触媒回転数 (TON): 28,100回。

First, DMF (15 mL) of a 1 mM Pd NCs / DMF solution was distilled off using an evaporator, and then THF (15 mL) was added and redispersed. 100 μL of the obtained 1 mM Pd NCs / THF solution was taken and diluted 100 times with 10 mL of THF to prepare a 10 μM Pd NCs / THF solution. Undissolved particles were filtered through a filter. Next, put a rotator in the branched Schlenk and put 4-iodotoluene (0.5 mmol, 109 mg), phenylboronic acid (0.75 mmol, 91 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. After the addition, a 10 μM Pd NCs / THF solution (1 mL) and H ₂ O (1 mL) were added, and the reaction was carried out at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 56%, catalyst rotation (TON): 28,100 times.

まず、生成したパラジウムナノ粒子溶液(Pd NCs／DMF)の1 mM溶液を10 μL取り、DMF 10 mL中に加えて100倍に希釈し、1 μM Pd NCs／DMFの溶液を調製した。次に、枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ヨードトルエン (0.5 mmol, 109 mg)、フェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、1 μM Pd NCs／DMFの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 11%, 触媒回転数 (TON): 53,500回。

First, 10 μL of a 1 mM solution of the produced palladium nanoparticle solution (Pd NCs / DMF) was taken and added to 10 mL of DMF and diluted 100 times to prepare a 1 μM Pd NCs / DMF solution. Next, put a rotator in the branched Schlenk and put 4-iodotoluene (0.5 mmol, 109 mg), phenylboronic acid (0.75 mmol, 91 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. After the addition, a solution of 1 μM Pd NCs / DMF (1 mL) and H ₂ O (1 mL) were added, and the reaction was performed at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 11%, catalyst rotation speed (TON): 53,500 times.

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ブロモトルエン (0.5 mmol, 86 mg)、フェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、［実施例１８］で調製した10 μM Pd NCs／NMPの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 43%, 触媒回転数 (TON): 24,000回。

After adding a rotor to a branched Schlenk and adding 4-bromotoluene (0.5 mmol, 86 mg), phenylboronic acid (0.75 mmol, 91 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere A 10 μM Pd NCs / NMP solution (1 mL) and H ₂ O (1 mL) prepared in [Example 18] were added, and the reaction was carried out at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 43%, catalyst rotation speed (TON): 24,000 times.

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ヨードアニソール (0.5 mmol, 117 mg)、フェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、［実施例１８］で調製した10 μM Pd NCs／NMPの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 98%, 触媒回転数 (TON): 49,200回。

After adding a rotor to a Schlenk with branches and adding 4-iodoanisole (0.5 mmol, 117 mg), phenylboronic acid (0.75 mmol, 91 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere A 10 μM Pd NCs / NMP solution (1 mL) and H ₂ O (1 mL) prepared in [Example 18] were added, and the reaction was carried out at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 98%, catalyst rotation speed (TON): 49,200 times.

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもとフェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、［実施例１８］で調製した10 μM Pd NCs／NMPの溶液(1 mL)、4-ヨードベンゾトリフルオリド (0.5 mmol, 136 mg)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 61%, 触媒回転数 (TON): 33,700回。

10 μM Pd prepared in [Example 18] after putting a rotator in a branched Schlenk and adding phenylboronic acid (0.75 mmol, 91 mg) and potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. NCs / NMP solution (1 mL), 4-iodobenzotrifluoride (0.5 mmol, 136 mg), and H ₂ O (1 mL) were added, and the reaction was carried out at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 61%, catalyst rotation speed (TON): 33,700 times.

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもとフェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、［実施例１８］で調製した10 μM Pd NCs／NMPの溶液(1 mL)、4-ヨードナフタレン (0.5 mmol, 127 mg)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 98%, 触媒回転数 (TON): 50,400回。

10 μM Pd prepared in [Example 18] after putting a rotator in a branched Schlenk and adding phenylboronic acid (0.75 mmol, 91 mg) and potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. NCs / NMP solution (1 mL), 4-iodonaphthalene (0.5 mmol, 127 mg), and H ₂ O (1 mL) were added, and the reaction was carried out at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 98%, catalyst rotation speed (TON): 50,400 times.

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもとフェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、［実施例１８］で調製した10 μM Pd NCs／NMPの溶液(1 mL)、2-ヨードチオフェン (0.5 mmol, 105 mg)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 63%, 触媒回転数 (TON): 33,700回。

10 μM Pd prepared in [Example 18] after putting a rotator in a branched Schlenk and adding phenylboronic acid (0.75 mmol, 91 mg) and potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. NCs / NMP solution (1 mL), 2-iodothiophene (0.5 mmol, 105 mg), and H ₂ O (1 mL) were added, and the reaction was carried out at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 63%, catalyst rotation speed (TON): 33,700 times.

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと5-ヨード-2-フルアルデヒド (0.5 mmol, 111 mg)、フェニルボロン酸 (0.75 mmol, 91 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、［実施例１８］で調製した10 μM Pd NCs／NMPの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 54%, 触媒回転数 (TON):27,100回。

Put a rotator in a branched Schlenk, and under an argon atmosphere, 5-iodo-2-furaldehyde (0.5 mmol, 111 mg), phenylboronic acid (0.75 mmol, 91 mg), potassium carbonate (0.5 mmol, 69 mg) Then, 10 μM Pd NCs / NMP solution (1 mL) and H ₂ O (1 mL) prepared in [Example 18] were added and reacted at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 54%, catalyst rotation speed (TON): 27,100 times.

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ヨードトルエン (0.5 mmol,109 mg)、4-クロロフェニルボロン酸 (0.75 mmol, 117 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、［実施例１８］で調製した10 μM Pd NCs／NMPの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 37%, 触媒回転数 (TON): 18,700回。

Put a rotator in a branch Schlenk and add 4-iodotoluene (0.5 mmol, 109 mg), 4-chlorophenylboronic acid (0.75 mmol, 117 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. Thereafter, a solution (1 mL) of 10 μM Pd NCs / NMP prepared in [Example 18] and H ₂ O (1 mL) were added, and the reaction was performed at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 37%, catalyst rotation speed (TON): 18,700 times.

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ヨードトルエン (0.5 mmol,109 mg)、m-ニトロフェニルボロン酸 (0.75 mmol, 125 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、［実施例１８］で調製した10 μM Pd NCs／NMPの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 27%, 触媒回転数 (TON): 13,200回。

Put a rotator in a branched Schlenk and put 4-iodotoluene (0.5 mmol, 109 mg), m-nitrophenylboronic acid (0.75 mmol, 125 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. After the addition, a 10 μM Pd NCs / NMP solution (1 mL) and H ₂ O (1 mL) prepared in [Example 18] were added, and the reaction was performed at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 27%, catalyst rotation speed (TON): 13,200 times.

枝付きシュレンクに回転子を入れ、アルゴン雰囲気のもと4-ヨードトルエン (0.5 mmol,109 mg)、p-メトキシフェニルボロン酸 (0.75 mmol, 114 mg)、炭酸カリウム (0.5 mmol, 69 mg)を加えた後に、［実施例１８］で調製した10 μM Pd NCs／NMPの溶液(1 mL)、H₂O (1 mL)を加え、100 ℃、5時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。カップリング生成物の収率: 56%, 触媒回転数 (TON): 27,900回。

Put a rotator in a branched Schlenk and put 4-iodotoluene (0.5 mmol, 109 mg), p-methoxyphenylboronic acid (0.75 mmol, 114 mg), potassium carbonate (0.5 mmol, 69 mg) under an argon atmosphere. After the addition, a 10 μM Pd NCs / NMP solution (1 mL) and H ₂ O (1 mL) prepared in [Example 18] were added, and the reaction was performed at 100 ° C. for 5 hours. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Yield of coupling product: 56%, catalyst rotation speed (TON): 27,900 times.

  The ultrafine transition metal particles of the present invention have a very high catalytic activity in the catalytic cross-coupling reaction, so that a very efficient utilization of rare metal resources can be realized, and the product of the cross-coupling reaction is It is also useful as a synthetic intermediate for pharmaceuticals and has high industrial utility value.

Claims (10)

A group 8 to a group 8 obtained by heating a halide, sulfate or nitrate of at least one transition metal selected from the group consisting of a group 8 to group 10 transition metal in a coordinating organic solvent . contains at least one transition metal and coordinating organic solvent selected from the group consisting of group 10 transition metal, ligands, not containing components including protective agent or polymer, average particle diameter is 2nm or less Catalyst for cross-coupling reaction containing ultrafine transition metal particles. Formula: AX
(Where
A is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted alkenyl group; and
X is a halogen, a mesylate group, a tosylate group, a triflate group, or a carboxylic acid halide group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group, or an unsubstituted or substituted alkynyl group;
Y is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR ¹ ) ₂ , ZnX ¹ , AlR ² ₂ , SnR ³ ₃ , MgX ² , or SiR ⁴ _3, wherein, ^{X 1} and ^{X 2} is halogen and ^{R 1,} R 2, ^{R 3} and ^{R 4} are each independently hydrogen or alkyl)
By reacting with a compound represented by
Formula: AB
(In the formula, A and B are as described above.)
The catalyst for cross coupling reaction of Claim 1 which is an object for cross coupling reactions which obtains the product shown by these. The catalyst for cross-coupling reaction according to claim 1 or 2 , wherein the transition metal is palladium. The coordinating organic solvent is N, N-dimethylformamide (DMF), N-methylformamide, N, N-dimethylacetamide (DMA), N-methylacetamide, 1,3-dimethyl-2-imidazolidinone (DMI). ), N-methyl-2-pyrrolidone (NMP), and hexamethylphosphoric triamide (HMPA), an amide solvent selected from the group consisting of any one of claims 1 to 3 Catalyst for reaction. Prepared by heating at least one chloride of a transition metal in coordinating organic solvent selected from the group consisting of Group 10 transition metal from Group 8, of any one of claims 1 to 4 A method for producing a catalyst for a cross-coupling reaction. The manufacturing method according to claim 5 , wherein the heating is performed while irradiating microwaves. Formula: AX
(Where
A is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group, or an unsubstituted or substituted alkynyl group; and
X is a halogen, a mesylate group, a tosylate group, a triflate group, or a carboxylic acid halide group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted alkenyl group;
Y is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR ¹ ) ₂ , ZnX ¹ , AlR ² ₂ , SnR ³ ₃ , MgX ² , or SiR ⁴ _3, wherein, ^{X 1} and ^{X 2} is halogen and ^{R 1,} R 2, ^{R 3} and ^{R 4} are each independently hydrogen or alkyl)
Is reacted with the compound represented by formula (A-B) in the presence of the catalyst for cross-coupling reaction according to claim 1.
(In the formula, A and B are as described above.)
A cross-coupling reaction comprising obtaining a product represented by The cross-coupling reaction according to claim 7 , which is appropriately performed in the presence of a base. The cross-coupling reaction according to claim 7 or 8 , wherein the reaction solvent is a coordinating organic solvent alone or a mixture with water. The cross-coupling reaction according to any one of claims 7 to 9 , wherein the catalyst is used in an amount of 10 ^-1 to 10 ^-7 mol% based on the amount of the compound represented by AX.

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