An amphiphilic phosphine ligand, its modified palladium nanocatalyst, preparation method and application in aqueous phase suzuki coupling reaction

Abstract

The present application relates to a kind of amphiphilic phosphine ligand modified palladium nanocatalyst, its preparation method and its application in water-phase suzuki coupling reaction, belong to organic synthesis and metal catalysis technical field.The amphiphilic phosphine ligand is selected from one of and.The palladium nanocatalyst is prepared by the following method: amphiphilic phosphine ligand is dissolved in water to prepare amphiphilic phosphine ligand aqueous solution, add palladium salt precursor and reducing agent, stir under heating condition, in-situ generate amphiphilic phosphine ligand modified palladium nanocatalyst.The catalyst is used for water-phase suzuki coupling reaction, under basic condition and inert gas atmosphere, make aryl bromide or heteroaryl bromide and aryl boronic acid occur coupling reaction, generate biaryl compound.The method uses water as reaction medium, need not add organic cosolvent, palladium is used in low amount, substrate is widely used.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and metal catalysis technology, specifically relating to an amphiphilic phosphine ligand, its modified palladium nanocatalyst, its preparation method, and its application in aqueous Suzuki coupling reactions. Background Technology

[0002] The Suzuki coupling reaction, also known as the Suzuki-Miyaura coupling reaction, is one of the most classic and efficient methods for constructing carbon-carbon bonds, and is widely used in the synthesis of drug molecules, natural products, and organic functional materials. Traditional Suzuki coupling reactions often use organic solvents and typically require a high loading of palladium catalysts. For example, in 2015, Das's group reported a silica-supported palladium nanoparticle catalyst (PdNP@PPh2-SiO2) and its efficient application in the Suzuki coupling reaction, using water and isopropanol as co-solvents to synthesize 22 substrates (RSC Adv., 2015, 5, 3512-3520). In 2023, Ge's group reported a synthetic strategy using a glycosyl surfactant (C8NG) to construct a "nanoreactor" to catalyze the Suzuki coupling reaction, with a palladium to aryl halide molar ratio of 0.2:1 (ACS Appl. Nano Mater. 2023, 6, 1592). (1602). However, this reaction system not only presents environmental and safety issues due to volatile organic solvents, but also easily leads to the waste of precious metal resources and high levels of metal residue in the products. In addition, homogeneous catalysts are sometimes used in traditional Suzuki coupling reactions. These catalysts are usually for single use only because they are difficult to separate from the reaction products and recycle. (Environ. Chem. Lett. 2019, 17, 1585–1602).

[0003] Water, as a safe, inexpensive, non-toxic, and environmentally friendly reaction medium, has significant advantages in green organic synthesis. However, due to the poor solubility of most organic substrates in water and the insufficient stability of traditional phosphine ligands and palladium species in the aqueous phase, aqueous Suzuki coupling systems still face problems such as low reaction efficiency, limited substrate applicability, and easy catalyst deactivation. On the other hand, although palladium nanoparticles are considered important active species in Suzuki reactions, they are prone to aggregation in the aqueous phase, leading to a decrease in catalytic activity. How to construct controlled-formation and stably dispersed palladium nanoparticle active centers in an aqueous environment is a key technical problem for achieving efficient aqueous Suzuki coupling reactions. In existing technologies, to improve the efficiency of aqueous Suzuki coupling reactions, water-soluble phosphine ligands, surfactants, polymer stabilizers, or micellar catalytic systems are typically used to improve the catalyst's dispersibility in water and substrate mass transfer performance. However, while surfactants alone can create hydrophobic microenvironments and increase the reaction opportunities of substrates in the aqueous phase, they are difficult to effectively control the formation and stability of palladium nanoparticles; and traditional phosphine ligands cannot simultaneously achieve aqueous phase compatibility, palladium species stability, and substrate local enrichment capabilities. Therefore, developing a catalytic system that can both form an effective reaction microenvironment in water and regulate the in-situ generation and stable dispersion of palladium nanoparticles is of great technical significance for achieving efficient aqueous Suzuki coupling reactions under conditions of low palladium dosage and no organic cosolvent. Summary of the Invention

[0004] The purpose of this invention is to provide an amphiphilic phosphine ligand, a palladium nanocatalyst modified with it, a preparation method, and its application in an aqueous Suzuki coupling reaction, so as to solve the problems of insufficient aqueous phase adaptability of traditional phosphine ligands, poor stability of palladium species, easy aggregation and deactivation of palladium nanoparticles, and limited reaction efficiency in existing aqueous Suzuki coupling systems.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: This invention first provides an amphiphilic phosphine ligand, wherein the amphiphilic phosphine ligand is... , or The The structural formula is as follows: The structural formula is as follows: The structural formula is as follows: Where n is an integer from 1 to 5.

[0006] The present invention further provides a palladium nanocatalyst modified with an amphiphilic phosphine ligand, the catalyst comprising palladium nanoparticles and the aforementioned amphiphilic phosphine ligand supported on the surface of the palladium nanoparticles.

[0007] Furthermore, the palladium nanoparticles have a diameter of 2~10 nm.

[0008] Furthermore, the palladium nanoparticles are generated by in-situ reduction of a palladium salt precursor in an aqueous phase. The palladium salt precursor is selected from one or more of palladium chloride, palladium acetate, palladium nitrate, or sodium tetrachloropalladate. By combining the interaction between the ligand and the palladium species with the in-situ generation process in the aqueous system, the controlled formation and stable dispersion of palladium nanoparticles can be achieved.

[0009] This invention also provides a method for preparing the above-mentioned amphiphilic phosphine ligand-modified palladium nanocatalyst, comprising the following steps: (1) Dissolve the amphiphilic phosphine ligand in water to prepare an aqueous solution of the amphiphilic phosphine ligand; (2) Add palladium salt precursor and reducing agent to the aqueous solution of the amphiphilic phosphine ligand; (3) Under heating conditions, the reaction is stirred to generate palladium nanocatalysts modified with amphiphilic phosphine ligands in situ.

[0010] Furthermore, the amphiphilic phosphine ligand aqueous solution is a 2 wt% aqueous solution; the reducing agent is ethylene glycol; the heating conditions are 50~70℃; and the stirring reaction time is 6~10h.

[0011] The present invention also provides a Suzuki coupling reaction method, in which aryl bromides or heteroaryl bromides undergo a coupling reaction with arylboronic acid in an aqueous phase using the amphiphilic phosphine ligand-modified palladium nanocatalyst as a catalyst under alkaline conditions and an inert gas atmosphere.

[0012] Further, the molar ratio of palladium to aryl bromide or heteroaryl bromide in the catalyst is 0.00005-0.001:1; the base is selected from one or more of cesium carbonate, potassium carbonate, sodium carbonate, and potassium phosphate; the reaction temperature is 80 ℃~100 ℃, and the reaction time is 2 h~6 h; the molar ratio of aryl bromide or heteroaryl bromide to arylboronic acid is 1:1.0~1:1.5.

[0013] Compared with the prior art, the present invention has the following beneficial effects: (1) The present invention uses amphiphilic phosphine ligands to regulate the in-situ generation and stable dispersion of palladium nanoparticles in the aqueous phase, avoiding the problems of difficult catalyst separation and recovery and insufficient aqueous phase stability in the traditional homogeneous palladium catalytic system.

[0014] (2) The catalytic system provided by the present invention can realize the Suzuki coupling reaction with a lower palladium content, which reduces the amount of precious metal palladium used and improves environmental friendliness.

[0015] (3) The method described in this invention uses water as the reaction medium and the reaction conditions are relatively mild. It is applicable to a variety of aryl bromides, heteroaryl bromides and arylboronic acid substrates and has good substrate applicability. Attached Figure Description

[0016] Figure 1 It is compound 1 prepared in Example 1. NMR spectrum.

[0017] Figure 2 It is compound 1 prepared in Example 1. NMR spectrum.

[0018] Figure 3 It is compound 2 prepared in Example 2. NMR spectrum.

[0019] Figure 4 It is compound 2 prepared in Example 2. NMR spectrum.

[0020] Figure 5 It is compound 3 prepared in Example 3. NMR spectrum.

[0021] Figure 6 It is compound 3 prepared in Example 3. NMR spectrum.

[0022] Figure 7 It is compound 4 prepared in Example 4. NMR spectrum.

[0023] Figure 8 It is compound 4 prepared in Example 4. NMR spectrum.

[0024] Figure 9 It is compound 5 prepared in Example 5. NMR spectrum.

[0025] Figure 10 It is compound 5 prepared in Example 5. NMR spectrum.

[0026] Figure 11 It is compound 6 prepared in Example 6. NMR spectrum.

[0027] Figure 12 It is compound 6 prepared in Example 6. NMR spectrum.

[0028] Figure 13 It is compound 7 prepared in Example 7. NMR spectrum.

[0029] Figure 14 It is compound 7 prepared in Example 7. NMR spectrum.

[0030] Figure 15 It is compound 8 prepared in Example 8. NMR spectrum.

[0031] Figure 16 It is compound 8 prepared in Example 8. NMR spectrum.

[0032] Figure 17 It is compound 9 prepared in Example 9. NMR spectrum.

[0033] Figure 18 It is compound 9 prepared in Example 9. NMR spectrum.

[0034] Figure 19 It is compound 10 prepared in Example 10. NMR spectrum.

[0035] Figure 20 It is compound 10 prepared in Example 10. NMR spectrum. Detailed Implementation

[0036] The present invention will be further described below with reference to embodiments, but the scope of protection of the present invention is not limited to the following embodiments. Any equivalent substitutions or conventional modifications made by those skilled in the art based on the disclosure of the present invention without departing from the spirit and substance of the invention should fall within the scope of protection of the present invention.

[0037] Unless otherwise stated, the raw materials, reagents, and solvents used in the embodiments of this invention are all commercially available or prepared using conventional methods in the art. The reaction temperatures described in the embodiments are all externally measured temperatures; the reaction process can be monitored using conventional methods such as thin-layer chromatography, nuclear magnetic resonance, or mass spectrometry; the products can be separated and purified by column chromatography and characterized by proton NMR, carbon NMR, and high-resolution mass spectrometry.

[0038] Example 1 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 50 °C for 10 h. Then, 0.2 mmol of p-bromoacetophenone, 0.3 mmol of phenylboronic acid, and 0.3 mmol of potassium carbonate were added, nitrogen gas was introduced, and the mixture was heated to 80 °C for 2 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain target product 1. The target product 1... NMR spectra as follows Figure 1 As shown, NMR spectra as follows Figure 2 As shown, the NMR data are as follows: White solid(36.5 mg, 93% yield), NMR (400 MHz, Chloroform-d) δ 8.07-8.01 (m, 2H), 7.72-7.67 (m, 2H), 7.63 (d,J = 7.6 Hz, 2H), 7.52-7.45 (m, 2H),7.44-7.38 (m, 1H), 2.64 (s, 3H). NMR (100 MHz, ) δ 197.92, 145.93,140.02, 135.98, 129.10, 129.06, 128.38, 127.42, 127.37, 26.82. Example 2 Preparation method of biaryl compounds with the following structural formula: Add 0.045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [the desired product]. 2 mL of aqueous solution was added and stirred at 60 °C for 9 h. Then, 0.2 mmol of p-bromoanisole, 0.3 mmol of phenylboronic acid, and 0.3 mmol of potassium phosphate were added, nitrogen gas was introduced, and the mixture was heated to 100 °C for 2 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain target product 2. The target product 2... NMR spectra as follows Figure 3 As shown, NMR spectra as follows Figure 4 As shown, the NMR data are as follows: White solid(33.5 mg, 91% yield), NMR (400 MHz, Chloroform-d) δ 7.61-7.53 (m, 4H), 7.47-7.40 (m, 2H), 7.35-7.30 (m, 1H), 7.04-6.97 (m, 2H), 3.87(s, 3H). NMR (100 MHz, ) δ 159.27, 140.96, 133.90, 128.86, 128.29,126.87, 126.79, 114.33, 55.47. Example 3 Preparation method of biaryl compounds with the following structural formula: Add 0.0035 mg of palladium chloride to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 70 °C for 7 h. Then, p-chlorobromobenzene (0.2 mmol), phenylboronic acid (0.3 mmol), and potassium carbonate (0.3 mmol) were added, nitrogen gas was introduced, and the mixture was heated to 80 °C for 4 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain target product 3. The target product 3... NMR spectra as follows Figure 5 As shown, NMR spectra as follows Figure 6 As shown, the NMR data are as follows: White solid(33.5 mg, 89% yield), NMR (400 MHz, Chloroform-d) δ 7.61-7.56 (m, 2H), 7.56-7.52 (m, 2H), 7.50-7.37 (m, 5H). NMR (100 MHz, ) δ140.10, 139.77, 133.49, 129.03, 129.01, 128.51, 127.71, 127.11. Example 4 Preparation method of biaryl compounds with the following structural formula: Add 0.035 mg of palladium chloride to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 60 °C for 8 h. Then, 0.2 mmol of 2-bromonaphthalene, 0.3 mmol of phenylboronic acid, and 0.3 mmol of potassium carbonate were added, nitrogen gas was introduced, and the mixture was heated to 100 °C for 6 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain target product 4. The target product 4... NMR spectra as follows Figure 7 As shown, NMR spectra as follows Figure 8 As shown, the NMR data are as follows: White solid(34.3 mg, 84% yield), NMR (400 MHz, Chloroform-d) δ 7.94(s, 1H), 7.84-7.74 (m, 3H), 7.69-7.60 (m, 3H), 7.45-7.34 (m, 4H), 7.32-7.25(m, 1H). NMR (100 MHz, ) δ 141.25, 138.68, 133.81, 132.75, 128.98,128.55, 128.33, 127.77, 127.56, 127.48, 126.41, 126.05, 125.93, 125.72. Example 5 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 70 °C for 7 h. Then, 0.2 mmol of p-bromotoluene, 0.3 mmol of phenylboronic acid, and 0.3 mmol of sodium carbonate were added, nitrogen gas was introduced, and the mixture was heated to 90 °C for 2 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain target product 5. The target product 5... NMR spectra as follows Figure 9 As shown, NMR spectra as follows Figure 10As shown, the NMR data are as follows: White solid(29.2 mg, 87% yield), NMR (400 MHz, Chloroform-d) δ 7.62(d,J = 7.9 Hz, 2H), 7.54 (d,J = 8.1 Hz, 2H), 7.48 (d,J = 7.5 Hz, 2H), 7.39-7.34 (m, 1H), 7.29 (d,J = 7.8 Hz, 2H), 2.44 (s, 3H). NMR (100 MHz, ) δ141.29, 138.49, 137.15, 129.62, 128.85, 127.13, 127.11, 21.24. Example 6 Preparation method of biaryl compounds with the following structural formula: Add 0.045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [the desired product]. 2 mL of aqueous solution was added and stirred at 70 °C for 8 h. Then, p-bromobenzonitrile (0.2 mmol), phenylboronic acid (0.3 mmol), and potassium phosphate (0.3 mmol) were added, nitrogen gas was introduced, and the mixture was heated to 80 °C for 4 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain target product 6. The target product 6... NMR spectra as follows Figure 11 As shown, NMR spectra as follows Figure 12 As shown, the NMR data are as follows: White solid(33.7 mg, 90% yield), NMR (400 MHz, Chloroform-d) δ 7.76-7.67 (m, 4H), 7.62-7.57 (m, 2H), 7.49 (tt,J = 6.4, 1.1 Hz, 2H), 7.46-7.40 (m,1H). NMR (100 MHz, ) δ 145.75, 139.25, 132.68, 129.21, 128.76, 127.82,127.32, 119.03, 111.00. Example 7 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 60 °C for 9 h. Then, 0.2 mmol of p-bromobenzyl sulfide, 0.3 mmol of phenylboronic acid, and 0.3 mmol of potassium carbonate were added. Nitrogen gas was introduced, and the mixture was heated to 90 °C for 6 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain target product 7. The target product 7... NMR spectra as follows Figure 13 As shown, NMR spectra as follows Figure 14 As shown, the NMR data are as follows: White solid(36.8 mg, 92% yield), NMR (400 MHz, Chloroform-d) δ 7.65-7.60 (m, 2H), 7.57 (d,J = 8.4 Hz, 2H), 7.49 (d,J = 7.2 Hz, 2H), 7.41-7.34 (m,3H), 2.55 (s, 3H). NMR (100 MHz, ) δ 140.60, 138.09, 137.70, 128.90,127.56, 127.29, 127.03, 126.91, 15.96. Example 8 Preparation method of biaryl compounds with the following structural formula: Add 0.035 mg of palladium chloride to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 70 °C for 6 h. Then, p-nitrobromobenzene (0.2 mmol), phenylboronic acid (0.3 mmol), and potassium carbonate (0.3 mmol) were added, nitrogen gas was introduced, and the mixture was heated to 80 °C for 4 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain target product 8. The target product 8... NMR spectra as follows Figure 15 As shown, NMR spectra as follows Figure 16 As shown, the NMR data are as follows: White solid(37.8mg, 95% yield), NMR (400 MHz, Chloroform-d) δ 8.30(d,J = 8.8 Hz, 2H), 7.74 (d,J = 8.8 Hz, 2H), 7.67-7.60 (m, 2H), 7.49 (dt,J =14.0, 6.9 Hz, 3H). NMR (100 MHz, ) δ 147.72, 147.17, 138.86, 129.27,129.04, 127.90, 127.49, 124.21. Example 9 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 70 °C for 6 h. Then, 0.2 mmol of p-bromobenzaldehyde, 0.3 mmol of phenylboronic acid, and 0.3 mmol of potassium carbonate were added, nitrogen gas was introduced, and the mixture was heated to 80 °C for 2 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 9. The target product 9... NMR spectra as follows Figure 17 As shown, NMR spectra as follows Figure 18 As shown, the NMR data are as follows: White solid(34.6 mg, 95% yield), NMR (400 MHz, Chloroform-d) δ 10.06(s, 1H), 7.98-7.93 (m, 2H), 7.78-7.72 (m, 2H), 7.67-7.62 (m, 2H), 7.52-7.46(m, 2H), 7.46-7.39 (m, 1H). NMR (100 MHz, ) δ 191.98, 147.25, 139.78,135.29, 130.34, 129.10, 128.56, 127.76, 127.45. Example 10 Preparation method of biaryl compounds with the following structural formula: Add 0.045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [the desired product]. 2 mL of aqueous solution was added and stirred at 70 °C for 8 h. Then, p-bromoaniline (0.2 mmol), phenylboronic acid (0.3 mmol), and potassium carbonate (0.3 mmol) were added, nitrogen gas was introduced, and the mixture was heated to 100 °C for 2 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 10. The target product 10... 1 H NMR spectrum as follows Figure 19 As shown, NMR spectra as follows Figure 20 As shown, the NMR data are as follows: White solid(26.0 mg,77% yield), NMR (400 MHz, Chloroform-d) δ 7.63-7.57 (m, 2H), 7.52-7.41 (m, 4H), 7.38-7.29 (m, 1H), 6.83-6.76 (m, 2H), 3.73(s, 2H). NMR (100 MHz, ) δ 145.96, 141.25, 131.60, 128.76, 128.08,126.48, 126.34, 115.47. Example 11 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 60 °C for 9 h. Then, 0.2 mmol of 4-bromotriphenylamine, 0.3 mmol of phenylboronic acid, and 0.3 mmol of potassium carbonate were added, nitrogen gas was introduced, and the mixture was heated to 100 °C for 2 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 11. NMR data are as follows: White solid (59.7 mg, 93% yield), NMR (400 MHz, Chloroform-d) δ7.66-7.61 (m, 2H), 7.57-7.51 (m, 2H), 7.47 (t,J = 7.7 Hz, 2H), 7.40-7.29 (m,5H), 7.23-7.17 (m, 6H), 7.13-7.06 (m, 2H). NMR (100 MHz, ) δ 147.82,147.30, 140.77, 135.26, 129.41, 128.86, 127.90, 126.92, 126.77, 124.54,124.05, 123.04. Example 12 Preparation method of biaryl compounds with the following structural formula: Add 0.035 mg of palladium chloride to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 60 °C for 8 h. Then, 0.2 mmol of 4-bromo-2-methoxyphenol, 0.3 mmol of phenylboronic acid, and 0.3 mmol of potassium carbonate were added. Nitrogen gas was introduced, and the mixture was heated to 90 °C for 2 h. After the reaction was complete, the reaction solution was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 12. NMR data are as follows: White solid(34.8 mg, 87% yield), NMR (400 MHz, Chloroform-d) δ 7.59(dd,J = 8.3, 1.3 Hz, 2H), 7.46 (dd,J = 8.5, 7.0 Hz, 2H), 7.38-7.33 (m, 1H),7.18-7.11 (m, 2H), 7.05 (d,J = 8.1 Hz, 1H), 5.75 (s, 1H), 3.97 (s, 3H). NMR (100 MHz, ) δ 146.83, 145.34, 141.29, 133.85, 128.82, 126.93, 126.85,120.26, 114.82, 109.84, 56.04. Example 13 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 50 °C for 10 h. Then, 0.2 mmol of 4-bromo-1,2-methylenedioxybenzene, 0.3 mmol of phenylboronic acid, and 0.3 mmol of potassium carbonate were added. Nitrogen gas was introduced, and the mixture was heated to 100 °C for 6 h. After the reaction was complete, the reaction solution was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 13. NMR data are as follows: White solid(34.1 mg, 86% yield), NMR (400 MHz, Chloroform-d) δ 7.59-7.52 (m, 2H), 7.44 (t,J = 7.7 Hz, 2H), 7.34 (t,J = 7.3 Hz, 1H), 7.14-7.06 (m,2H), 6.91 (d,J = 7.9 Hz, 1H), 6.02 (s, 2H). NMR (100 MHz, ) δ 148.22,147.17, 141.04, 135.71, 128.85, 127.04, 127.00, 120.74, 108.68, 107.79,101.24. Example 14 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 50 °C for 10 h. Then, o-bromobenzaldehyde (0.2 mmol), phenylboronic acid (0.3 mmol), and potassium carbonate (0.3 mmol) were added, nitrogen gas was introduced, and the mixture was heated to 80 °C for 4 h. After the reaction was complete, the reaction solution was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 14. NMR data are as follows: White solid(34.6 mg, 95% yield), NMR (400 MHz, Chloroform-d) δ 10.00(d,J = 0.9 Hz, 1H), 8.04 (dd,J = 7.8, 1.4 Hz, 1H), 7.64 (td,J = 7.5, 1.5 Hz,1H), 7.53-7.44 (m, 5H), 7.41-7.37 (m, 2H). NMR (100 MHz, ) δ 192.50,146.05, 137.84, 133.81, 133.64, 130.86, 130.19, 128.52, 128.21, 127.86,127.65. Example 15 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 60 °C for 7 h. Then, 0.2 mmol of 3-bromopyridine, 0.3 mmol of phenylboronic acid, and 0.3 mmol of potassium carbonate were added, nitrogen gas was introduced, and the mixture was heated to 100 °C for 6 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 15. NMR data are as follows: White solid(26.3 mg, 85% yield), NMR (400 MHz, Chloroform-d) δ 8.85(d,J = 2.4 Hz, 1H), 8.58 (d,J = 3.2 Hz, 1H), 7.85 (d,J = 8.1 Hz, 1H), 7.57(d,J = 7.1 Hz, 2H), 7.46 (t,J = 7.5 Hz, 2H), 7.42-7.30 (m, 2H). NMR (100MHz, ) δ 148.53, 148.39, 137.87, 136.65, 134.34, 129.11, 128.13, 127.18,123.56. Example 16 Preparation method of biaryl compounds with the following structural formula: Add 0.0035 mg of palladium chloride to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 70 °C for 6 h. Then, 0.2 mmol of p-bromoacetophenone, 0.3 mmol of 2-methoxyphenylboronic acid, and 0.3 mmol of potassium carbonate were added. Nitrogen gas was introduced, and the mixture was heated to 80 °C for 4 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 16. NMR data are as follows: white solid (40.1 mg, 89% yield), (PE / DCM=1:1 as an eluent). NMR(400 MHz, CDCL3) δ 8.01 (d,J = 8.5 Hz, 2H), 7.64 (d,J = 8.4 Hz, 2H), 7.45-7.30 (m, 2H), 7.10-6.98 (m, 2H), 3.83 (s, 3H), 2.64 (s, 3H). NMR (100 MHz, ) δ 198.01, 156.56, 143.70, 135.58, 130.81, 129.83, 129.60, 129.52,128.18, 121.06, 111.43, 55.65, 26.75 Example 17 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 50 °C for 10 h. Then, 0.2 mmol of p-bromoacetophenone, 0.3 mmol of p-cyanobenzoic acid, and 0.3 mmol of potassium carbonate were added. Nitrogen gas was introduced, and the mixture was heated to 90 °C for 4 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 17. NMR data are as follows: White solid(42.0 mg, 95% yield), NMR (400 MHz, Chloroform-d) δ 8.06(d,J = 8.2 Hz, 2H), 7.79-7.65 (m, 6H), 2.64 (s, 3H). NMR (100 MHz, ) δ197.54, 144.39, 143.61, 137.02, 132.84, 129.22, 128.03, 127.55, 118.73,111.99, 26.81. Example 18 Preparation method of biaryl compounds with the following structural formula: Add 0.0035 mg of palladium chloride to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 70 °C for 6 h. Then, 0.2 mmol of p-bromoacetophenone, 0.3 mmol of p-isopropylphenylboronic acid, and 0.3 mmol of potassium carbonate were added. Nitrogen gas was introduced, and the mixture was heated to 80 °C for 2 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 18. NMR data are as follows: White solid(40.0 mg, 84% yield), NMR (400 MHz, Chloroform-d) δ 8.03(d,J = 8.5 Hz, 2H), 7.68 (d,J = 8.4 Hz, 2H), 7.58 (d,J = 8.3 Hz, 2H), 7.35(d,J = 8.2 Hz, 2H), 2.99 (hept,J = 6.9 Hz, 1H), 2.63 (s, 3H), 1.32 (d,J = 7.0Hz, 6H). NMR (100 MHz, ) δ 197.71, 149.23, 145.76, 137.37, 135.67,128.96, 127.26, 127.14, 127.03, 33.92, 26.66, 24.01. Example 19 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 70 °C for 6 h. Then, 0.2 mmol of p-bromoacetophenone, 0.3 mmol of 4-dibenzofuranboronic acid, and 0.3 mmol of potassium carbonate were added. Nitrogen gas was introduced, and the mixture was heated to 90 °C for 2 h. After the reaction was complete, the reaction solution was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 19. NMR data are as follows: White solid(52.6 mg, 92% yield), NMR (400 MHz, Chloroform-d) δ 8.12(d,J = 8.5 Hz, 2H), 8.05-7.94 (m, 4H), 7.65-7.58 (m, 2H), 7.52-7.35 (m, 3H), 2.67 (s, 3H). NMR (100 MHz, ) δ 197.80, 156.22, 153.40, 141.22, 136.21,128.94, 128.78, 127.55, 126.87, 125.25, 124.60, 124.05, 123.40, 123.07,120.83, 120.71, 111.92, 26.76. Example 20 Preparation method of biaryl compounds with the following structural formula: Add 0.0045 mg of palladium acetate to a dry 25 mL Schlenk reaction tube, followed by 2 wt% of [a specific ingredient / component]. 2 mL of aqueous solution was added and stirred at 60 °C for 8 h. Then, 0.2 mmol of p-bromoacetophenone, 0.3 mmol of p-hydroxyphenylboronic acid, and 0.3 mmol of potassium carbonate were added. Nitrogen gas was introduced, and the mixture was heated to 80 °C for 2 h. After the reaction was complete, the reaction mixture was extracted with 3 × 0.5 mL of dichloromethane. The organic layers were combined, and the organic solvent was removed by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain the target product 20. NMR data are as follows: White solid(37.7 mg, 89% yield), NMR (400 MHz, Chloroform-d) δ 8.01(d,J = 8.5 Hz, 2H), 7.91 (d,J = 8.5 Hz, 2H), 7.60 (d,J = 6.9 Hz, 1H), 7.53(d,J = 8.2 Hz, 1H), 7.32 (td,J = 8.4, 7.8, 1.4 Hz, 1H), 7.27-7.22 (m, 1H), 7.13 (s, 1H), 2.61 (s, 3H). NMR (100 MHz, ) δ 197.41, 155.33, 154.65,136.64, 134.68, 129.03, 129.01, 125.27, 124.88, 123.37, 121.44, 111.47,103.77, 26.72. Example 21 Amphiphilic phosphine ligands Preparation method: 1 mmol (346 mg) of o-hydroxymethyltriphenylphosphine was dissolved in 5 mL of anhydrous methanol, and 3.3 mmol (125 mg) of sodium borohydride was slowly added. The mixture was stirred at 25 °C for 30 minutes. After the reaction was completed, 10 mL of distilled water was added to the reaction flask, and the mixture was allowed to stand for 10 minutes. After the product was completely precipitated from the solution, it was filtered, washed, and dried to obtain 334 mg (95% yield) of o-hydroxymethyltriphenylphosphine. 0.1 mmol (35.2 mg) of o-hydroxymethyltriphenylphosphine was dissolved in 2 mL of dry tetrahydrofuran, and 0.33 mmol (70 μL) of sebacyl chloride was added. The mixture was stirred at 30 °C for 12 h. After the reaction was complete, the intermediate product was obtained by extraction with distilled water and dichloromethane. MPEG-750 (0.3 mmol, 225 mg) dissolved in 2 mL of toluene was added to the intermediate product, and the mixture was reacted at 110 °C for 6 h under the catalysis of p-toluenesulfonic acid (0.02 mmol, 3.5 mg). After the reaction was complete, toluene was removed by rotary evaporation, and then 2 mL of saturated sodium bicarbonate aqueous solution and 4 mL of dichloromethane were added. The organic layer was washed with saturated sodium bicarbonate (3 × 2 mL). The extracted organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to obtain 300 mg of a pale yellow waxy solid, denoted as [missing information]. The yield was 90.4%.

[0039] The above descriptions are all partial embodiments of the present invention and are not intended to limit the present invention. Any equivalent changes and modifications made based on the content of this invention are within the protection scope of this invention.

Claims

1. An amphiphilic phosphine ligand, characterized in that, The amphiphilic phosphine ligand is , or The The structural formula is as follows: The structural formula is as follows: The structural formula is as follows: Where n is an integer from 1 to 5.

2. A palladium nanocatalyst modified with an amphiphilic phosphine ligand, characterized in that, The catalyst comprises palladium nanoparticles and the amphiphilic phosphine ligand of claim 1 supported on the surface of the palladium nanoparticles.

3. The palladium nanocatalyst modified with an amphiphilic phosphine ligand according to claim 2, characterized in that, The palladium nanoparticles have a diameter of 2~10 nm.

4. The palladium nanocatalyst modified with an amphiphilic phosphine ligand according to claim 2, characterized in that, The palladium nanoparticles are generated by in-situ reduction of a palladium salt precursor in an aqueous phase. The palladium salt precursor is one or more of palladium chloride, palladium acetate, palladium nitrate, or sodium tetrachloropalladium.

5. A method for preparing palladium nanocatalyst according to any one of claims 2-4, characterized in that, Includes the following steps: (1) Dissolve the amphiphilic phosphine ligand in water to prepare an aqueous solution of the amphiphilic phosphine ligand; (2) Add palladium salt precursor and reducing agent to the aqueous solution of the amphiphilic phosphine ligand; (3) Under heating conditions, the reaction is stirred to generate palladium nanocatalysts modified with amphiphilic phosphine ligands in situ.

6. The preparation method according to claim 5, characterized in that, The aqueous solution of the amphiphilic phosphine ligand in step (1) is a 2 wt% aqueous solution.

7. The preparation method according to claim 5, characterized in that, The reducing agent is ethylene glycol, the palladium salt precursor is one or more of palladium chloride, palladium acetate, palladium nitrate or sodium tetrachloropalladium, the heating condition is 50~70℃, and the stirring reaction time is 6~10h.

8. A Suzuki coupling reaction method, characterized in that, In an aqueous phase, using the palladium nanocatalyst according to any one of claims 2-4 as a catalyst, aryl bromides or heteroaryl bromides undergo a coupling reaction with arylboronic acid under alkaline conditions and an inert gas atmosphere.

9. The method according to claim 8, characterized in that, The molar ratio of palladium to aryl bromide or heteroaryl bromide in the catalyst is 0.00005-0.001:1; the base is selected from one or more of cesium carbonate, potassium carbonate, sodium carbonate, and potassium phosphate; the inert gas is nitrogen; the reaction temperature is 80 ℃~100 ℃, and the reaction time is 2 h~6 h. The molar ratio of aryl bromide or heteroaryl bromide to arylboronic acid is 1:1.0~1:1.5.

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