Reaction method for obtaining biaryl compound through Suzuki-Miyaura coupling realized based on C-S bond activation

Abstract

The invention relates to the technical field of organic synthesis chemistry and catalytic chemistry, and discloses a reaction method for obtaining a biaryl compound through Suzuki-Miyaura coupling based on C-S bond activation, aryl sulfide is used as an electrophilic reagent, aryl boric acid ester is used as a nucleophilic reagent, in the presence of a nickel catalyst, a bidentate ligand, alkali and copper salt, a reaction is performed in an organic solvent, and the biaryl compound is obtained. Thus, the corresponding biaryl compound is obtained. According to the method, traditional C-S bonds difficult to break can be efficiently activated under uniform conditions, electron-rich and electron-deficient aryl thioethers and various aryl borates are compatible, and the application range of a substrate is wide; meanwhile, the aryl sulfide does not need to be pre-oxidized or pre-functionalized, the steps are simple, the atom economy is high, and the method is suitable for large-scale production. The obtained biaryl compound can be widely applied to the fields of drug molecule synthesis, organic semiconductor materials and the like.

Description

Technical Field

[0001] This invention relates to the fields of organic synthetic chemistry and catalytic chemistry, specifically to a coupling reaction method for activating carbon-sulfur bonds using transition metal catalysis. More specifically, this invention provides a method for achieving the Suzuki-Miyaura coupling reaction of aryl sulfides and aryl borate esters using a nickel catalytic system. Background Technology

[0002] The Suzuki–Miyaura coupling reaction, as an important method for constructing carbon-carbon bonds, is widely used in the synthesis of drug molecules, functional materials, and natural products. Due to its advantages such as ease of operation, mild conditions, and wide availability of substrates, this reaction holds a significant position in organic synthetic chemistry.

[0003] Existing Suzuki–Miyaura coupling reactions primarily utilize aryl halides as electrophiles. However, halides suffer from drawbacks such as high cost, limited resources, and complex pretreatment procedures. Furthermore, some halogenated aromatic hydrocarbons are prone to side reactions during coupling, restricting their application scope.

[0004] Aryl sulfides are a class of inexpensive and abundant compounds, widely found in petrochemicals and fine chemicals. Due to the high bond energy of the carbon-sulfur bond, their activation is far more difficult than that of the carbon-halogen bond, thus limiting the application of aryl sulfides in the Suzuki–Miyaura coupling reaction. Existing studies mostly rely on palladium or rhodium catalytic systems, and are often only applicable to electron-deficient aryl sulfides, with poor applicability to electron-rich aryl sulfides. This limitation significantly reduces the practical value of this type of reaction in the synthesis of complex molecules.

[0005] Therefore, there is an urgent need to develop a new catalytic system that can directly activate carbon-sulfur bonds and be compatible with both electron-rich and electron-deficient aryl sulfides under uniform conditions, thereby achieving a wider range of substrate applicability and promoting the further application of the Suzuki–Miyaura coupling reaction in fields such as drug synthesis and materials science. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a Suzuki–Miyaura coupling reaction method achieved through C–S bond activation. This method uses aryl thioethers as electrophiles and aryl borate esters as nucleophiles, and the reaction is carried out under the combined action of a nickel catalyst, bidentate phosphine ligands, a base, and a copper salt, thereby efficiently synthesizing a variety of biaryl compounds.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] This invention discloses a reaction method for obtaining biaryl compounds via Suzuki-Miyaura coupling based on C–S bond activation. The method uses aryl thioethers as electrophiles and aryl borate esters as nucleophiles, and the reaction is carried out in an organic solvent in the presence of a nickel catalyst, a bidentate ligand, a base, and a copper salt to yield the corresponding biaryl compounds. The general reaction formula is as follows:

[0009]

[0010] The core of this method lies in the direct oxidative addition of nickel catalysts to the C–S bonds of aryl sulfides, while the metallization process is facilitated by copper salts, and the hydrolysis and activation of borate esters are promoted by introducing a small amount of water. This system is compatible with both electron-rich and electron-deficient aryl sulfides under uniform reaction conditions, significantly expanding the substrate scope of the Suzuki–Miyaura coupling reaction.

[0011] Furthermore, the arylboronic ester is any one of the following compounds:

[0012]

[0013] Wherein, X is a fluorine atom, chlorine atom, bromine atom, or iodine atom; R is an independent hydrogen or straight-chain alkyl group having 1–16 carbon atoms, including: methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecanyl, and n-hexadecyl.

[0014] Furthermore, the aryl sulfide can be any of the following compounds:

[0015]

[0016] Wherein, X is a fluorine atom, chlorine atom, bromine atom, or iodine atom; R is an independent hydrogen or straight-chain alkyl group having 1–16 carbon atoms, including: methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecanyl, and n-hexadecyl.

[0017] Furthermore, the nickel catalyst is bis(1,5-cyclooctadiene)nickel [Ni(COD)2].

[0018] Further, the bidentate ligand is a bidentate phosphine ligand or a bidentate nitrogen ligand, wherein the bidentate phosphine ligand is selected from one of dcype, dppe, dppp, and dppf, and the bidentate nitrogen ligand is selected from one of 2,2′-bipyridine or 1,10-phenanthroline; preferably 1,2-bis(dicyclohexylphosphine)ethane (dcype).

[0019] Furthermore, the copper salt is a cuprous halide, which is selected from CuCl, CuBr, or CuI; preferably CuI.

[0020] Furthermore, the alkali is cesium carbonate.

[0021] Furthermore, water is added to the reaction system as an auxiliary agent to promote the hydrolysis and transmetallization of borate esters.

[0022] Furthermore, the organic solvent is one or more of toluene, o-xylene, p-xylene, and mesitylene.

[0023] Furthermore, the reaction temperature is 80–140°C, preferably 120°C; the reaction time is 0.5–16 hours.

[0024] Furthermore, the method is applicable to gram-scale reaction scale-up.

[0025] More preferably, the specific reaction steps are as follows:

[0026] (1) Under nitrogen protection, arylboronic acid ester, bis(1,5-cyclooctadiene)nickel, 1,2-bis(dicyclohexylphosphine)ethane, cesium carbonate and cuprous iodide were sequentially added to a Schlenk reaction tube that had been flame-dried.

[0027] (2) Then add aryl sulfide. For liquid substrates, the reaction mixture will immediately turn dark after addition.

[0028] (3) Next, anhydrous toluene was added, and water was added dropwise slowly. The resulting reaction mixture was heated and stirred at 120°C for 12 hours.

[0029] (4) After the reaction was complete, the system was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtain the target compound for further analysis. The eluent for silica gel column chromatography was petroleum ether and dichloromethane.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] 1. Broad substrate range: Under the same conditions, it is applicable to both electron-rich and electron-deficient aryl sulfides, avoiding the strict limitations on the electronic effects of substrates imposed by traditional Pd or Rh catalytic systems.

[0032] 2. No pretreatment required: Aryl sulfides can be used directly as electrophilic reagents without converting them into thioesters, sulfoxides or sulfones, thus eliminating pretreatment steps and improving step economy and atom economy.

[0033] 3. Mild conditions: The reaction can be completed in conventional organic solvents and at moderate temperatures, without relying on high pressure or strong oxidation conditions.

[0034] 4. Unique catalyst system: The nickel catalyst directly activates the C–S bond, while the copper salt acts only as a promoter for metallization, rather than as a partial activator of the traditional C–S activating oxidant.

[0035] 5. Suitable for large-scale production: This method has good scalability and can be carried out efficiently at the gram scale, providing a new process route for the synthesis of drug molecules, functional materials and organic semiconductors.

[0036] 6. The method of this invention can efficiently activate traditionally difficult-to-break C–S bonds under suitable conditions, expanding the applicable substrate range of the Suzuki–Miyaura coupling reaction, especially applicable to both electron-rich and electron-deficient aryl sulfides. The resulting biaryl compounds have broad application prospects in drug molecule synthesis, organic light-emitting materials, functional polymers, and semiconductor materials. Detailed Implementation

[0037] The present invention will be further described in detail below through specific embodiments. The following examples are merely descriptive and not limiting, and should not be used to limit the scope of protection of the present invention.

[0038] Example 1

[0039]

[0040] Under nitrogen protection, 2-(methylthio)thiophene (65.0 mg, 0.5 mmol) and 2-(benzo[ b Thiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (195.0 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixture of 10.0 mL of ultradry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 86.6 mg of the target compound as a white solid, with a yield of 80%.

[0041] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1H NMR (500 MHz, CDCl3) δ 7.78 (d, J =7.9 Hz, 1H), 7.73 (dd, J =7.8, 1.4 Hz, 1H), 7.40 (s, 1H), 7.36 – 7.27 (m, 4H), 7.06 (dd, J =4.9, 3.8 Hz, 1H).

[0042] Example 2

[0043]

[0044] Under nitrogen protection, 3-(methylthio)thiophene (65.0 mg, 0.5 mmol) and 2-(benzo[ b Thiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboroncyclopentane (195.0 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixture of 10.0 mL of ultradry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 78.7 mg of the target compound as a white solid, with a yield of 73%.

[0045] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1 H NMR (500 MHz, CDCl3) δ 7.80 (d, J = 7.8 Hz, 1H), 7.75 (dd, J = 7.7, 1.4 Hz, 1H), 7.51 (dd, J = 2.9, 1.4 Hz, 1H), 7.45 – 7.37(m, 3H), 7.32 (dtd, J = 21.3, 7.2, 1.3 Hz, 2H).

[0046] Example 3

[0047]

[0048] Under nitrogen protection, 2-methoxy-5-(methylthio)thiophene (80.0 mg, 0.5 mmol) and 2-(benzo[ bThiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (195.0 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixture of 10.0 mL of ultradry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 39.6 mg of the target compound as a white solid, with a yield of 32%.

[0049] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1 H NMR (500 MHz, CDCl3) δ 7.73 (dt, J = 7.8, 0.9 Hz, 1H), 7.67 (dd, J = 7.6, 1.3 Hz, 1H), 7.31 (ddd, J = 7.9, 7.1, 1.2 Hz,1H), 7.25 (ddd, J = 8.3, 7.3, 1.3 Hz, 1H), 7.19 (s, 1H), 6.93 (d, J = 4.0 Hz, 1H), 6.15 (d, J = 4.0 Hz (1H), 3.92 (s, 3H).

[0050] Example 4

[0051]

[0052] Under nitrogen protection, 5-(methylthio)thiophene-2-carboxaldehyde (79.0 mg, 0.5 mmol) and 2-(benzo[ bThiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (195.0 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixture of 10.0 mL of ultradry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 27.0 mg of the target compound as a yellow solid, with a yield of 22%.

[0053] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1 H NMR (500 MHz, CDCl3) δ 9.90 (s, 1H), 7.84– 7.76 (m, 2H), 7.71 (d, J = 3.9 Hz, 1H), 7.60 (s, 1H), 7.37 (qd, J = 6.7, 6.0, 3.4 Hz, 3H).

[0054] Example 5

[0055]

[0056] Under nitrogen protection, 2-(methylthio)-5-phenylthiophene (103.0 mg, 0.5 mmol) and 2-(benzo[ b Thiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboroncyclopentane (195.0 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixture of 10.0 mL of ultradry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 112.5 mg of the target compound as a white solid, with a yield of 77%.

[0057] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1H NMR (500 MHz, CDCl3) δ 7.78 (d, J = 7.9 Hz, 1H), 7.73 (d, J = 7.7 Hz, 1H), 7.63 (dd, J = 7.6, 1.6 Hz, 2H), 7.43 – 7.37 (m,3H), 7.37 – 7.28 (m, 3H), 7.27 (s, 2H).

[0058] Example 6

[0059]

[0060] Under nitrogen protection, 2-(methylthio)benzo[ b Thiophene (90.0 mg, 0.5 mmol), 2-(benzo[ b Thiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (195.0 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixture of 10.0 mL of ultradry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 119.6 mg of the target compound in flaky crystals, with a yield of 90%.

[0061] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1 H NMR (500 MHz, CDCl3) δ 7.81 (dd, J = 7.4,1.7, 0.7 Hz, 2H), 7.77 (dd, 2H), 7.52 (s, 2H), 7.39 – 7.31 (m, 4H).

[0062] Example 7

[0063]

[0064] Under nitrogen protection, 2-(methylthio)benzofuran (82.0 mg, 0.5 mmol) and 2-(benzo[ bThiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (195.0 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixture of 10.0 mL of ultradry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 97.7 mg of the target compound as a white solid, with a yield of 78%.

[0065] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1 H NMR (500 MHz, CDCl3) δ 7.87 – 7.79 (m,2H), 7.73 (s, 1H), 7.58 (dd, J = 7.6, 1.3 Hz, 1H), 7.53 – 7.50 (m, 1H), 7.40 –7.28 (m, 3H), 7.25 (td, J = 7.5, 1.0 Hz, 1H), 7.00 (s, 1H).

[0066] Example 8

[0067]

[0068] Under nitrogen protection, 2-(methylthio)benzo[ d Thiazole (90.5 mg, 0.5 mmol), 2-(benzo[ b Thiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (195.0 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixture of 10.0 mL of ultradry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 110.2 mg of the target compound as a yellow solid, with a yield of 83%.

[0069] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1 H NMR (500 MHz, CDCl3) δ 8.09 (d, J = 8.2, 0.8Hz, 1H), 7.92 (s, 1H), 7.90 – 7.83 (m, 3H), 7.54 – 7.47 (m, 1H), 7.45 – 7.37(m, 3H).

[0070] Example 9

[0071]

[0072] Under nitrogen protection, 2-(methylthio)thiophene (65.0 mg, 0.5 mmol), 2-(5-hexylthiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronacyclopentane (220.6 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixed solvent of ultra-dry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 70.2 mg of the target compound as a colorless oily liquid, with a yield of 56%.

[0073] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1 H NMR (500 MHz, CDCl3) δ 7.15 (dd, J = 5.1,1.2 Hz, 1H), 7.11 – 7.07 (m, 1H), 6.98 (dd, J = 5.2, 3.5 Hz, 2H), 6.69 – 6.65(m, 1H), 2.78 (t, J = 7.6 Hz, 2H), 1.68 (q, J = 7.4 Hz, 2H), 1.45 – 1.22 (m, 6H), 0.89 (td, J = 7.0, 5.8, 3.3 Hz, 3H).

[0074] Example 10

[0075]

[0076] Under nitrogen protection, 2-(methylthio)benzo[ d Oxazole (82.5 mg, 0.5 mmol), 2-(benzo[ b Thiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (195.0 mg, 0.75 mmol), bis(1,5-cyclooctadiene)nickel (27.5 mg, 0.1 mmol), 1,2-bis(dicyclohexylphosphine)ethane (42 mg, 0.1 mmol), cuprous iodide (142.5 mg, 0.75 mmol), and cesium carbonate (570 mg, 1.75 mmol) were placed in a reaction flask. A mixture of 10.0 mL of ultradry toluene and 25 mg of water was added via syringe. The mixture was stirred at 120 °C for 16 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give 87.5 mg of the target compound as a white solid, with a yield of 70%.

[0077] The structure of the product was confirmed by proton nuclear magnetic resonance spectroscopy: 1 H NMR (500 MHz, CDCl3) δ 8.16 (d, J = 0.7 Hz,1H), 7.95 – 7.87 (m, 2H), 7.78 (ddd, J = 6.7, 3.3, 2.1 Hz, 1H), 7.63 – 7.55 (m,1H), 7.49 – 7.41 (m, 2H), 7.41 – 7.34 (m, 2H).

[0078] Example 11

[0079]

[0080] Preparation of an asymmetric terthiophene compound, said compound being used in the fabrication of organic field-effect transistor (OFET) devices. (i) Under nitrogen protection, thiophene[3,2- b Thiophene (1 equivalent) was dissolved in ultra-dry tetrahydrofuran and cooled to -78°C. A solution of n-butyllithium tetrahydrofuran (1.6 mol / L, 1.05 equivalent) was slowly added dropwise. After stirring for 30 minutes, dimethyl disulfide (1.2 equivalent) was added dropwise. Stirring continued at -78°C for 1 hour, followed by natural warming to room temperature and stirring for 3 hours. After the reaction was complete, a saturated ammonium chloride aqueous solution was slowly added to quench the reaction. The mixture was extracted with ethyl acetate, and the organic phase was washed successively with water and saturated sodium chloride solution. After drying with anhydrous sodium sulfate, the mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 2-(methylthio)thiophene[3,2- bThiophene is a pale yellow solid. (ii) Under nitrogen protection, 2-(methylthio)thiophene[3,2- b Thiophene (1 equivalent) was dissolved in anhydrous dichloromethane and cooled to 0°C in an ice-water bath. N-bromosuccinimide (1.05 equivalent) was added in portions, and the mixture was stirred for 1–2 hours. After the starting material was almost completely dissolved, a small amount of saturated sodium bisulfite aqueous solution was added to quench the excess bromine source. The aqueous phase was extracted with dichloromethane after separation. The organic phases were combined and washed successively with water and saturated sodium chloride solution. After drying with anhydrous sodium sulfate, the mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 2-(methylthio)-5-bromothiophene[3,2- b Thiophene is a pale yellow solid. (iii) Under nitrogen protection, 2-(methylthio)-5-bromothiophene[3,2- b Thiophene (1 equivalent), 4,4,5,5-tetramethyl-2-(thien-2-yl)-1,3,2-dioxoborane (1.5 equivalent), tetra(triphenylphosphine)palladium (0.03 equivalent), and potassium carbonate (2 equivalent) were placed in a reaction flask, and 1,4-dioxane / water (volume ratio 4:1) was added to form a mixed solvent. The reaction mixture was stirred at 90°C for 12–16 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted with water, and extracted with dichloromethane. The organic phase was washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 2-(methylthio)-5-(2-thienyl)thiopheno[3,2- b Thiophene is a yellow solid. (iv) Under nitrogen protection, 2-(methylthio)-5-(2-thienyl)thiophene[3,2- b Thiophene (1 equivalent), 2-(5-hexylthiophene-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronacyclopentane (1.5 equivalent), bis(1,5-cyclooctadiene)nickel (0.2 equivalent), 1,2-bis(dicyclohexylphosphine)ethane (0.2 equivalent), cuprous iodide (1.5 equivalent), and cesium carbonate (3.5 equivalent) were added sequentially to a reaction flask. A mixed solvent of ultra-dry toluene and a small amount of water (volume ratio 400:1) was added via syringe. The reaction mixture was stirred in an oil bath at 120°C for approximately 16 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, filtered to remove inorganic salts and catalyst residues, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtain a pale yellow solid, T-TT-HT.

[0081] The above embodiments are merely specific examples to fully illustrate the present invention. The scope of protection of the present invention is determined by the claims and is not limited to the specific embodiments described above. All content disclosed in the specification, including the abstract, and all disclosed methods and steps, can be combined arbitrarily unless these features and / or steps are mutually exclusive combinations. Each technical feature disclosed in the specification, including the abstract, can be replaced by a technical feature that achieves the same, equivalent, or similar purpose, unless otherwise stated. Therefore, unless otherwise stated, each technical feature disclosed in the present invention is merely an example of an equivalent or similar technical feature in a general series. Equivalent substitutions or modifications made by those skilled in the art based on the present invention without departing from the essence of the invention are also within the scope of protection of the present invention.

[0082] Although embodiments of the invention have been disclosed for illustrative purposes, those skilled in the art will understand that various substitutions, variations, and modifications are possible without departing from the spirit and scope of the invention and the appended claims. Therefore, the scope of the invention is not limited to the contents disclosed in the embodiments.

Claims

1. A reaction method for obtaining biaryl compounds based on Suzuki-Miyaura coupling achieved by activation of C-S bonds, characterized by, The reaction is carried out in an organic solvent in the presence of a nickel catalyst, a bidentate ligand, a base and a copper salt, using an aryl sulfide as an electrophilic reagent and an aryl borate as a nucleophilic reagent, thereby obtaining a corresponding biaryl compound, and the reaction formula is as follows: wherein Ar represents a (hetero)aryl system.

2. The method of claim 1, wherein: The aryl borate is any one of the following compounds: ; X is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom; and R is independently hydrogen or a linear alkyl group with a carbon atom number of 1-16.

3. The method of claim 1, wherein: The aryl sulfide can be any one of the following compounds: ; X is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom; and R is independently hydrogen or a linear alkyl group with a carbon atom number of 1-16.

4. The method of claim 1, wherein: The nickel catalyst is bis(1,5-cyclooctadiene)nickel (Ni(COD)2).

5. The method of claim 1, wherein: The bidentate ligand is a bidentate phosphine ligand or a bidentate nitrogen ligand.

6. The method of claim 1, wherein: The copper salt is cuprous halide.

7. The method of claim 1, wherein: The base is cesium carbonate.

8. The method of claim 1, wherein: Water is also added as an auxiliary agent in the reaction system to promote the hydrolysis and transmetalation process of the borate.

9. The method of claim 1, wherein: The organic solvent is one or more of toluene, o-xylene, p-xylene and mesitylene.

10. The method of claim 1, wherein: The reaction temperature is 80-140°C, and the reaction time is 0.5-16 hours.

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