A method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether

Abstract

The present invention discloses a method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether, belonging to the technical field of organic synthesis. The method includes: selecting a rhodium catalyst, in the presence of a silver salt and an additive, using the aryl halide and the polyfluoroalkyl alcohol as substrates to carry out a coupling reaction, and then obtaining the polyfluoroalkyl aryl ether through purification and separation. Under the system of the present invention described above, the coupling reaction can occur between the raw materials under relatively mild conditions to prepare the polyfluoroalkyl aryl ether in one step. Moreover, the method of the present invention has good generality, high reaction yield, good atom economy, and wide substrate applicability, and can be used to synthesize a series of polyfluoroalkyl aryl ether compounds including those containing hexafluoroisopropoxy aryl ether. The synthesized compounds have potential application values in the fields of pesticides, medicines, etc.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether. Background Art

[0002] Introducing fluorine atoms or fluorine-containing groups into organic compounds can change their physical properties, chemical properties, physiological activities, etc., and can also endow aromatic compounds with unique hydrogen bond effects, electronic effects, liposolubility, chemical and metabolic stability, etc. Polyfluoroalkyl aryl ethers are not easily metabolized in the human body, have good liposolubility, and are easily able to cross the blood-brain barrier. They are a very important structure in drug molecules. For example, riluzole can treat amyotrophic lateral sclerosis, sonidegib can treat basal cell carcinoma, and pretomanid can treat tuberculosis, and such drugs have stronger drug effects and longer action times (G. Landelle, A. Panossian and F. R. Leroux. Trifluoromethyl Ethers and–Thioethers as Tools for Medicinal Chemistry and Drug Discovery, Curr. Top. Med. Chem, 2014, 14, 941–951.). Therefore, it is of great significance to develop an efficient method for synthesizing polyfluoroalkyl aryl ethers.

[0003] In the prior art, fluoroalkyl ethers are usually prepared by reacting fluoroalkanols with fluorinated olefins in the presence of alkali metals or alkali metal hydroxides. However, similar methods cannot be simply applied to the synthesis of polyfluoroalkyl aryl ethers. The use of highly reactive arenediazonium salts (Szele, I.; Zollinger, H. Dediazoniation of arenediazonium ions in homogeneous solution. 10. Solvent effects on the reactions of benzene- and 2,4,6-trimethylbenzenediazonium ion. Evidence for two intermediates, J. Am. Chem. Soc. 1978, 100, 2811–2815.) or diaryliodonium salts (Lindstedt, E.; Stridfeldt, E.; Olofsson, B. Mild Synthesis of Sterically Congested Alkyl Aryl Ethers, Org. Lett. 2016, 18, 4234–4237.) can react with polyfluoroalkanols to form fluoroalkyl ethers. However, arenediazonium salts are prone to explosion during production, and diaryliodonium salts have poor atom economy. In addition, these substrates require multi-step synthesis.

[0004] Aryl halides are widely used chemical raw materials. The aromatic nucleophilic substitution reaction (S N Ar) of aryl halides is one of the most commonly used synthetic methods in medicinal chemistry. Using aryl halides and polyfluoroalkanols to carry out nucleophilic substitution reactions to form polyfluoroalkyl aryl ethers is a very effective strategy. However, when hexafluoroisopropanol is used as the nucleophilic reagent, it is very difficult to carry out S N Ar, and the substrate scope is limited. It can only be compatible with highly electron-deficient aryl fluorides and cannot be compatible with more inexpensive aryl chlorides, etc. Moreover, the yields are generally lower than 30% (Boswell, G. E.; Licause, J. F. A Convenient Large-Scale Synthesis of 4-Fluoro-1-naphthaldehyde and Its Aromatic Nucleophilic Substitution Reactions, J. Org. Chem. 1995, 60, 6592-6594.). Therefore, it is of great value to develop a method with mild conditions that can be compatible with a variety of aryl halides and synthesize polyfluoroalkyl aryl ethers including aryl ethers containing hexafluoroisopropoxy groups in one step. Summary of the Invention

[0005] To solve the problems existing in the above-mentioned prior art, the present invention provides a method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether. This method has rich raw material sources, is easy to implement, can prepare the product through a one-step reaction, has mild reaction conditions, good substrate applicability and high yield.

[0006] Specifically, the following technical solutions are adopted:

[0007] A method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether, comprising: selecting a rhodium catalyst, in the presence of a silver salt and an additive, carrying out a coupling reaction with the aryl halide and the polyfluoroalkyl alcohol as substrates, and then obtaining the polyfluoroalkyl aryl ether through purification and separation;

[0008] The rhodium catalyst is selected from at least one of pentamethylcyclopentadienylrhodium dichloride dimer or its derivatives;

[0009] The structure of the aryl halide is shown in the following formula (I):

[0010] Ar-X (I)

[0011] The structure of the polyfluoroalkyl alcohol is shown in the following formula (II):

[0012] R f -OH (II)

[0013] In formula (I), Ar is a phenyl group or a substituted phenyl group, and X is F, Cl, Br or I; in formula (II), R f is a polyfluoroalkyl group.

[0014] In the reaction system of the present invention, it contains a rhodium catalyst, a silver salt and an additive, as well as the raw material aryl halide and polyfluoroalkyl alcohol. The rhodium catalyst generates a catalytically active species under the action of the silver salt, and then undergoes π coordination with the aryl halide. Under the action of the additive, the polyfluoroalkyl alcohol is deprotonated and then undergoes nucleophilic substitution with the activated aryl halide, and then the obtained polyfluoroalkyl aryl ether dissociates to release the Rh catalyst to participate in the next catalytic cycle.

[0015] Preferably, in formula (I), the substituted phenyl group is an alkyl, alkoxy, aryl, amide, ester or halogen-substituted phenyl group; in formula (II), R f is hexafluoroisopropyl or trifluoroethyl.

[0016] Preferably, in the reaction system, an organic solvent is further included, and the organic solvent is selected from trifluorotoluene, 1,2-dichloroethane or cyclohexane; based on the molar amount of the aryl halide, the dosage of the organic solvent is 0-2 L / mol.

[0017] For considerations of yield and solvent cost, more preferably, the organic solvent is 1,2-dichloroethane or trifluorotoluene, and based on the molar amount of the aryl halide, the solvent dosage is 0 to 1 L / mol.

[0018] The molar ratio of the aryl halide to the polyfluoroalkyl alcohol is 1:1 to 10. Keeping the polyfluoroalkyl alcohol in excess can significantly improve the yield.

[0019] The temperature of the coupling reaction is 40 to 140 °C, and the reaction time is 3 to 24 h. For considerations of yield, the reaction temperature is preferably 80 to 100 °C, and the reaction time is preferably 12 to 24 h.

[0020] The structural formula of the rhodium catalyst includes any one of those shown in the following formulas Cat.1-Cat.14, and the molar ratio of the rhodium catalyst to the aryl halide is 1:5 to 100;

[0021]

[0022] More preferably, the rhodium catalyst is selected from Cat.1, Cat.2, Cat.6, Cat.8 or Cat.9.

[0023] The silver salt is silver trifluoromethanesulfonate, silver bis(trifluoromethanesulfonyl)imide, silver tetrafluoroborate, silver fluoride or silver hexafluorophosphate, and the molar ratio of the silver salt to the aryl halide is 1:1.25 to 25.

[0024] The additive is silver carbonate, potassium phosphate, potassium carbonate, cesium fluoride, cesium carbonate, calcium carbonate, potassium fluoride, sodium carbonate, lithium carbonate, lithium bis(trifluoromethanesulfonyl)imide, silver fluoride or silver oxide, and the molar ratio of the additive to the aryl halide is 0.1 to 10:1. The additive can interact with the halogen atoms of the activated aryl halide, which is beneficial to the progress of the reaction and improves the product yield.

[0025] More preferably, the additive is silver carbonate, silver fluoride or silver oxide, and the molar ratio of the additive to the aryl halide is 0.5 to 2:1.

[0026] Silver fluoride can be used both as a silver salt and as an additive. When silver fluoride is selected as both the silver salt and the additive, the preparation of the polyfluoroalkyl aryl ether can also be successfully achieved.

[0027] After the coupling reaction, the polyfluoroalkyl aryl ether obtained is separated and purified by a silica gel chromatography column.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0029] (1) The method of the present invention can be used to synthesize a series of polyfluoroalkyl aryl ether compounds including hexafluoroisopropoxy aryl ethers, and the synthesized compounds have wide application values in the fields of pesticides, pharmaceuticals, etc.

[0030] (2) The raw materials used in the method of the present invention, aryl halides and polyfluoroalkyl alcohols, are relatively inexpensive, reducing the production cost. Under the action of a rhodium catalyst, a silver salt and an additive, the raw materials can undergo a coupling reaction under relatively mild conditions to prepare polyfluoroalkyl aryl ethers in one step. It can be used for the late modification of complex drug molecules, and the method has good generality, is applicable to various aryl halides with different functional groups and rich sources, the reaction yield is high, up to 95%, the atom economy is good, the steps are simple, and it is easy to implement. Detailed implementation mode

[0031] The present invention will be further clarified below in conjunction with examples. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention.

[0032] The rhodium catalyst used in the examples, Cat.1 (pentamethylcyclopentadienylrhodium dichloride), was purchased from Zhejiang Microtong Catalytic New Materials Co., Ltd., and Cat.2 - Cat.14 were prepared by derivatization reaction using rhodium(III) chloride hydrate as the raw material according to the method of the literature (Mark A.M.; Jeff W.K.; and Melanie S. Improved Synthesis of [Cp R RhCl2]2 Complexes, Organometallics. 2018, 37, 19, 3240–3242).

[0033] Example 1

[0034]

[0035] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 148 mg), Cat.1 ([Cp*RhCl2]2, 0.08 mmol, 49.6 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (AgNTf2, 0.32 mmol, 124.8 mg), additive silver carbonate (0.1 mmol, 27.6 mg), and hexafluoroisopropanol (HFIP, 0.4 mmol, 67.2 mg) were successively added to the reaction flask. Finally, 1,2-dichloroethane (DCE, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, dry loading was performed, and the mixture was passed through a silica gel chromatography column to obtain 159.6 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 79%.

[0036] The NMR detection results of this polyfluoroalkyl aryl ether are as follows:

[0037] 1 1H NMR (600 MHz, CDCl3)) δ 7.82–7.79 (m, 4H), 7.52 (t, J = 7.2 Hz, 2H), 7.47–7.43 (m, 4H), 7.14 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 4.75 (hept, J = 5.4 Hz, 1H), 4.04 (q, J = 6.6 Hz, 2H), 2.73 (t, J = 7.8 Hz, 2H), 2.03 (p, J = 7.2 Hz, 2H).

[0038] 13 13C NMR (150 MHz, CDCl3) δ 155.9, 137.4, 132.0, 131.9, 131.5, 131.4, 131.1, 129.8, 128.5, 128.4, 121.1 (q, J = 282.0 Hz), 117.2, 76.3 (hept, J = 33.0 Hz), 63.9, 63.9, 32.0, 32.0, 31.0.

[0039] 19 19F NMR (565 MHz, CDCl3) δ -73.6.

[0040] Example 2

[0041]

[0042] Under a nitrogen atmosphere, the aryl bromide shown in the above formula (0.4 mmol, 126.6 mg), Cat.2 (0.01 mmol, 67.6 mg), silver salt silver trifluoromethanesulfonate (AgOTf, 0.04 mmol, 15.6 mg), additive silver oxide (0.4 mmol, 92.7 mg), hexafluoroisopropanol (1.2 mmol, 201.6 mg) were successively added to the reaction flask, and finally trifluorotoluene (PhCF3, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method, and passed through a silica gel chromatography column to obtain 109.3 mg of the perfluoroalkyl aryl ether shown in the above formula, and the yield was 68%.

[0043] The NMR detection results of the perfluoroalkyl aryl ether are as follows:

[0044] 1 1H NMR (600 MHz, CDCl3) δ 7.84–7.82 (m, 2H), 7.71–7.70 (m, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 4.81–4.76 (m, 3H).

[0045] 13 13C NMR (150 MHz, CDCl3) δ 167.9, 157.1, 134.1, 132.8, 132.0, 130.5, 123.3, 121.0 (q, J = 280.5 Hz), 117.3, 76.0 (hept, J = 33.0 Hz), 40.8.

[0046] 19 19F NMR (565 MHz, CDCl3) δ -73.6.

[0047] Example 3

[0048]

[0049] Under a nitrogen atmosphere, the aryl iodide shown in the above formula (0.4 mmol, 115.6 mg), Cat.6 (0.01 mmol, 7.4 mg), silver salt silver tetrafluoroborate (0.04 mmol, 15.6 mg), additive silver fluoride (0.2 mmol, 25.4 mg), hexafluoroisopropanol (HFIP, 1.2 mmol, 201.6 mg) were successively added to the reaction flask, and finally n-hexane (Hexane, 0.4 mL) was added. The reaction was stirred at 40 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method, and passed through a silica gel chromatography column to obtain 94.1 mg of the perfluoroalkyl aryl ether shown in the above formula, with a yield of 71%.

[0050] The NMR detection results of the perfluoroalkyl aryl ether are as follows:

[0051] 1 1H NMR (600 MHz, CDCl3) δ 7.16 (d, J = 7.8 Hz, 2H), 7.01 (d, J = 7.8 Hz, 2H), 5.69 (br, 1H), 4.78 (hept, J = 5.4 Hz, 1H), 3.46 (q, J = 6.6 Hz, 2H), 2.78 (t, J = 6.6 Hz, 1H), 1.93 (s, 1H).

[0052] 13 13C NMR (150 MHz, CDCl3) δ 170.1, 156.2, 135.3, 130.2, 121.1 (q, J = 287.8 Hz), 117.4, 76.2 (hept, J = 32.9 Hz), 40.6, 34.8, 23.1.

[0053] 19 19F NMR (565 MHz, CDCl3) δ -73.6.

[0054] Example 4

[0055]

[0056] Under a nitrogen atmosphere, the aryl fluoride shown in the above formula (0.4 mmol, 61.6 mg), Cat.8 (0.01 mmol, 9.4 mg), silver salt silver fluoride (0.04 mmol, 5.0 mg), additive silver carbonate (0.2 mmol, 46.3 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (4 mmol, 0.42 mL) was added. The reaction was stirred at 140 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 86.5 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 72%.

[0057] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0058] 1 H NMR(600MHz,CDCl3)δ7.21(d,J=8.4Hz,2H),7.01(d,J=8.4Hz,2H),4.76(hept,J=6Hz,1H),3.59(t,J=6.6Hz,2H),3.36(s,3H),2.86(t,J=6.6Hz,2H).

[0059] 13 C NMR(150MHz,CDCl3)δ156.2,135.6,130.3,121.1(q,J=282.4Hz),117.2,76.4(hept,J=33.1Hz),73.3,58.6,35.3.

[0060] 19 F NMR(565MHz,CDCl3)δ-73.7.

[0061] Example 5

[0062]

[0063] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 62.4 mg), Cat.9 (0.01 mmol, 7.2 mg), silver salt silver hexafluorophosphate (AgPF6, 0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 50.6 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 24 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 77.9 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 68%.

[0064] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0065] 1 H NMR(600MHz,CDCl3)δ7.22(d,J=7.8Hz,2H),7.03(d,J=7.8Hz,2H),4.77(hept,J=5.4Hz,1H),3.83(t,J=6.6Hz,2H),2.84(t,J=6.6Hz,2H),1.61(br,1H).

[0066] 13 C NMR(150MHz,CDCl3)δ156.3,135.1,130.5,121.1(q,J=285.1Hz),117.4,76.4(hept,J=32.9Hz),63.5,38.2.

[0067] 19 F NMR(565MHz,CDCl3)δ-73.7.

[0068] Example 6

[0069]

[0070] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 141.0 mg), Cat.1 ([Cp*RhCl2]2, 0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonimide) (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to a reaction flask, and finally hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 3 h. After cooling to room temperature, the sample was loaded onto a silica gel column by dry loading, and the polyfluoroalkyl aryl ether shown in the above formula, 159.2 mg, was obtained with a yield of 82%.

[0071] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0072] 1 H NMR(600MHz,CDCl3)δ7.12(d,J=8.4Hz,2H),6.99(d,J=8.4Hz,2H),4.73(hept,J=6.0Hz,1H),3.73(s,1H),2.33–2.24(m,4H),2.09–2.02(m,1H),1.88–1.81(m,1H),1.09–0.95(m,21H).

[0073] 1313C NMR (150 MHz, CDCl3) δ 155.7, 145.5, 127.9, 121.2 (q, J = 282.4 Hz), 116.5, 76.6 (hept, J = 32.7 Hz), 71.2, 47.7, 29.4, 17.8, 15.8, 11.9.

[0074] 19 19F NMR (565 MHz, CDCl3) δ -73.7.

[0075] Example 7

[0076]

[0077] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 96.0 mg), Cat.1 ([Cp*RhCl2]2, 0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg), hexafluoroisopropanol (1.2 mmol, 201.6 mg) were successively added to the reaction flask. Finally, 1,2-dichloroethane (DCE, 2.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 132.8 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 89%.

[0078] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0079] 1 1H NMR (600 MHz, CDCl3) δ 7.16 (d, J = 7.8 Hz, 2H), 6.96 (d, J = 7.8 Hz, 2H), 5.67 (br, 1H), 4.76 (hetp, J = 5.4 Hz, 1H), 3.01 (t, J = 6.0 Hz, 2H), 2.92 (t, J = 7.2 Hz, 2H), 2.43 (t, J = 7.8 Hz, 2H), 1.69–1.63 (m, 1H), 0.80 (d, J = 7.2 Hz, 6H).

[0080] 13 13C NMR (150 MHz, CDCl3) δ 171.7, 156.0, 137.3, 129.8, 121.0 (q, J = 282.1 Hz), 117.2, 76.2 (hept, J = 33.0 Hz), 46.8, 38.3, 30.8, 28.3, 19.8.

[0081] 19 19F NMR (565 MHz, CDCl3) δ -73.7.

[0082] Example 8

[0083]

[0084] Under a nitrogen atmosphere, the aryl bromide shown in the above formula (0.4 mmol, 113.7 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonimide) (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg), hexafluoroisopropanol (1.2 mmol, 201.6 mg) were successively added to the reaction flask. Finally, trifluorotoluene (PhCF3, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 130.3 mg of the polyfluoroalkyl aryl ether shown in the above formula, and the yield was 89%.

[0085] The NMR detection results of the polyfluoroalkyl aryl ether are as follows:

[0086] 1 H NMR(600MHz,CDCl3)δ7.16(d,J=8.4Hz,2H),6.98(d,J=8.4Hz,2H),5.20(br,1H),4.76(hept,J=6.0Hz,1H),2.89(t,J=7.2Hz,2H),2.34(t,J=7.2Hz,2H),1.27(s,9H).

[0087] 13 C NMR(150MHz,CDCl3)δ171.0,156.0,137.5,129.9,121.1(q,J=282.6Hz),117.2,76.3(hept,J=33.0Hz),51.1,39.2,30.8,28.6.

[0088] 19 F NMR(565MHz,CDCl3)δ-73.7.

[0089] Example 9

[0090]

[0091] Under a nitrogen atmosphere, the aryl chloride shown by the above formula (0.4 mmol, 100.1 mg), Cat.1 (0.004 mmol, 2.5 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.016 mmol, 6.2 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to a reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and purified by silica gel column chromatography to obtain 122.7 mg of the polyfluoroalkyl aryl ether shown by the above formula, with a yield of 80%.

[0092] The NMR detection results of the polyfluoroalkyl aryl ether are as follows:

[0093] 1 H NMR(600MHz,CDCl3)δ7.19(d,J=8.4Hz,2H),6.98(d,J=7.8Hz,2H),4.77(hept,J=5.4Hz,1H),3.62–3.47(m,2H),3.37–3.22(m,2H),2.92(t,J=7.8Hz,2H),2.57(t,J=7.8Hz,2H),1.68–1.55(m,2H),1.54–1.40(m,4H).

[0094] 13 C NMR(150MHz,CDCl3)δ170.0,156.0,137.9,129.9,121.1(q,J=285.0Hz),117.2,76.3(hept,J=32.9Hz),46.5,46.5,42.7,34.8,30.6,26.3,25.5,24.4.

[0095] 19 F NMR(565MHz,CDCl3)δ-73.7.

[0096] Example 10

[0097]

[0098] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 68.0 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask, and finally hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 80.1 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 66%.

[0099] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0100] 1 H NMR(600MHz,CDCl3)δ7.48(d,J=7.2Hz,2H),7.45(br,1H),7.03(d,J=7.2Hz,2H),4.75–4.70(m,1H),2.16(s,3H).

[0101] 13 C NMR(150MHz,CDCl3)δ168.4,154.1,134.6,121.7,121.1(q,J=282.0Hz),118.1,76.9(hept,J=33.1Hz),24.4.

[0102] 19 F NMR(565MHz,CDCl3)δ-73.6.

[0103] Example 11

[0104]

[0105] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 78.0 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask, and finally hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 76.2 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 58%.

[0106] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0107] 11H NMR (600 MHz, CDCl3) δ 7.59 (d, J = 9.0 Hz, 2H), 7.08 (d, J = 9.0 Hz, 2H), 4.77 (hept, J = 6.0 Hz, 1H), 3.83 (t, J = 6.6 Hz, 2H), 2.59 (t, J = 8.4 Hz, 2H), 2.16 (p, J = 7.8 Hz, 2H).

[0108] 13 13C NMR (150 MHz, CDCl3) δ 174.1, 154.1, 136.1, 121.5, 121.1 (q, J = 282.3 Hz), 117.7, 76.8 (hept, J = 33.3 Hz), 48.8, 32.4, 17.9.

[0109] 19 19F NMR (565 MHz, CDCl3) δ -73.7.

[0110] Example 12

[0111]

[0112] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 75.0 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 47.3 mg of the perfluoroalkyl aryl ether shown in the above formula, with a yield of 37%.

[0113] The NMR test results of the perfluoroalkyl aryl ether are as follows:

[0114] 1 1H NMR (600 MHz, CDCl3) δ 7.60–7.56 (m, 4H), 7.46 (t, J = 7.8 Hz, 2H), 7.38 (t, J = 7.2 Hz, 1H), 7.17 (d, J = 8.4 Hz, 2H), 4.86 (hept, J = 5.4 Hz, 1H).

[0115] 13 13C NMR (150 MHz, CDCl3) δ 157.05, 139.99, 137.91, 128.86, 128.72, 127.42, 126.97, 121.1 (q, J = 282.0 Hz), 117.53, 76.29 (hept, J = 33.1 Hz).

[0116] 19 F NMR (565 MHz, CDCl3) δ -73.5.

[0117] Example 13

[0118]

[0119] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 122.0 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 134.1 mg of the perfluoroalkyl aryl ether shown in the above formula, with a yield of 77%.

[0120] The NMR detection results of this perfluoroalkyl aryl ether are as follows:

[0121] 1 H NMR (600 MHz, CDCl3) δ 7.43 (d, J = 8.4 Hz, 2H), 7.38 (s, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.16 (d, J = 7.8 Hz, 2H), 4.88 (hept, J = 6.0 Hz, 1H).

[0122] 13 C NMR (150 MHz, CDCl3) δ 157.2, 148.7, 138.1, 134.6, 133.4, 132.1, 131.2, 122.6, 121.1 (q, J = 279.6 Hz), 120.4 (q, J = 255.3 Hz), 119.4, 116.9, 76.1 (hept, J = 33.1 Hz).

[0123] 19 F NMR (565 MHz, CDCl3) δ -57.99, -73.5.

[0124] Example 14

[0125]

[0126] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 68.0 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 101.2 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 84%.

[0127] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0128] 1 H NMR(600MHz,CDCl3)δ7.85(br,1H),7.53(s,1H),7.26(t,J=8.4Hz,1H),7.17(d,J=7.8Hz,1H),6.81(d,J=7.8Hz,1H),4.83(hept,J=5.4Hz,1H),2.17(s,3H).

[0129] 13 C NMR(150MHz,CDCl3)δ168.9,157.8,139.6,130.2,121.0(q,J=285.1Hz),115.6,112.5,108.9,75.8(hept,J=32.9Hz),24.5.

[0130] 19 F NMR(565MHz,CDCl3)δ-73.6.

[0131] Example 15

[0132]

[0133] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 62.4 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 44.1 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 39%.

[0134] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0135] 1 1H NMR (600 MHz, CDCl3) δ 7.33–7.23 (m, 2H), 7.10 (t, J = 7.2 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 4.96 (hept, J = 6.0 Hz, 1H), 3.86 (t, J = 6.6 Hz, 2H), 2.96 (t, J = 6.6 Hz, 2H).

[0136] 13 13C NMR (150 MHz, CDCl3) δ 155.3, 131.9, 128.7, 128.1, 124.1, 121.1 (q, J = 282.3 Hz), 113.2, 75.1 (hept, J = 33.5 Hz), 62.3, 33.4.

[0137] 19 19F NMR (565 MHz, CDCl3) δ -73.5.

[0138] Example 16

[0139]

[0140] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 69.0 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 115.5 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 95%.

[0141] The NMR detection results of the polyfluoroalkyl aryl ether are as follows:

[0142] 1 1H NMR (600 MHz, CDCl3) δ 6.26 (s, 1H), 6.23 (s, 2H), 4.82 (hept, J = 5.4 Hz, 1H), 3.78 (s, 6H).

[0143] 13 13C NMR (150 MHz, CDCl3) δ 161.73, 159.24, 121.1 (q, J = 282.3 Hz), 96.32, 95.73, 75.7 (hept, J = 33.0 Hz), 55.45.

[0144] 1919F NMR (565 MHz, CDCl3) δ -73.6.

[0145] Example 17

[0146]

[0147] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.6 mmol, 69.0 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, trifluoroethanol (5.7 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatographic column to obtain 100.4 mg of the perfluoroalkyl aryl ether shown in the above formula, with a yield of 95%.

[0148] The NMR test results of this perfluoroalkyl aryl ether are as follows:

[0149] 1 1H NMR (600 MHz, CDCl3) δ 7.38 - 7.30 (2H, m), 7.10 - 7.02 (1H, m), 6.99 - 6.93 (2H, m), 4.36 (2H, q, J = 8.0 Hz).

[0150] 13 13C NMR (150 MHz, CDCl3) δ 157.3, 129.7, 122.5, 114.9, 66.1 (q, J = 35.5 Hz).

[0151] 19 19F NMR (565 MHz, CDCl3) δ -74.0.

[0152] Example 18

[0153]

[0154] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 128.7 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatographic column to obtain 108.8 mg of the perfluoroalkyl aryl ether shown in the above formula, with a yield of 60%.

[0155] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0156] 1 H NMR(600MHz,CDCl3)δ7.77(d,J=9.0Hz,1H),7.45(d,J=7.8Hz,2H),7.20(d,J=7.8Hz,2H),6.91(d,J=10.5Hz,1H),6.74(s,1H),4.78(hept,J=5.4Hz,1H),3.83–3.70(m,2H),2.41(t,J=6.6Hz,2H),2.38(s,3H),1.61–1.57(m,2H).

[0157] 13 C NMR(150MHz,CDCl3)δ154.4,143.7,136.4,133.5,132.8,129.6,127.0,126.8,121.0(q,J=279Hz),117.6,115.1,76.2(hept,J=32.9Hz),46.3,26.6,21.1.

[0158] 19 F NMR(565MHz,CDCl3)δ-73.6.

[0159] Example 19

[0160]

[0161] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 97.1 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), and additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to a reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto a silica gel column by dry method, and 98.2 mg of the polyfluoroalkyl aryl ether shown in the above formula was obtained with a yield of 66%.

[0162] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0163] 1 H NMR(600MHz,CDCl3)δ6.96(d,J=8.4Hz,2H),6.84(d,J=9.0Hz,2H),4.67(hept,J=5.4Hz,1H),4.22(q,J=6.6Hz,2H),1.56(s,6H),1.24(t,J=7.2Hz,3H).

[0164] 13 13C NMR (150 MHz, CDCl3) δ 173.9, 152.9, 152.3, 121.1 (q, J = 282.2 Hz), 120.9, 118.4, 77.1 (hept, J = 32.9 Hz), 61.4, 25.2, 13.9.

[0165] 19 19F NMR (565 MHz, CDCl3) δ -73.8.

[0166] Example 20

[0167]

[0168] Under a nitrogen atmosphere, the aryl bromide shown in the above formula (0.4 mmol, 85.2 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 60.0 mg of the perfluoroalkyl aryl ether shown in the above formula, with a yield of 50%.

[0169] The NMR test results of the perfluoroalkyl aryl ether are as follows:

[0170] 1 1H NMR (600 MHz, CDCl3) δ 6.81 (dd, J = 8.8, 2.9 Hz, 1H), 6.78 (d, J = 2.5 Hz, 1H), 6.73 (d, J = 8.9 Hz, 1H), 4.62 (hept, J = 5.8 Hz, 1H), 4.18–4.09 (m, 2H), 2.75 (q, J = 7.0 Hz, 2H), 1.97 (dq, J = 12.0, 6.2 Hz, 2H).

[0171] 13 13C NMR (151 MHz, CDCl3) δ 154.0, 151.9, 132.2, 123.4, 121.2 (q, J = 282.2 Hz), 118.9, 117.7, 77.4 (hept, J = 32.9 Hz), 66.4, 25.0, 22.0.

[0172] 19 19F NMR (565 MHz, CDCl3) δ -73.7.

[0173] Example 21

[0174]

[0175] Under a nitrogen atmosphere, the aryl chloride shown in the above formula (0.4 mmol, 58.4 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 100.0 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 90%.

[0176] The NMR detection results of the polyfluoroalkyl aryl ether are as follows:

[0177] 1 H NMR (600 MHz, CDCl3) δ 7.61 (d, J = 7.5 Hz, 1H), 7.33 (t, J = 7.8 Hz, 1H), 7.04 (t, J = 7.4 Hz, 2H), 4.90 (hept, J = 5.4 Hz, 1H), 1.26 (s, 3H).

[0178] 13 C NMR (150 MHz, CDCl3) δ 153.9, 134.4, 128.9, 125.7, 121.2 (q, J = 282.5 Hz) 116.4, 113.7, 76.2 (hept, J = 32.7 Hz), 29.7.

[0179] 19 F NMR (565 MHz, CDCl3) δ -73.1.

[0180] Example 22

[0181]

[0182] Under a nitrogen atmosphere, the aryl bromide shown in the above formula (0.4 mmol, 85.2 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 82.2 mg of the polyfluoroalkyl aryl ether shown in the above formula, with a yield of 65%.

[0183] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0184] 1 H NMR(600MHz,CDCl3)δ7.85(d,J=7.2Hz,1H),7.74(s,1H),7.44(t,J=7.2Hz,1H),7.28(d,J=7.2Hz,1H),4.91(m,1H),4.40(d,J=6.6Hz,2H),1.40(t,J=6.6Hz,3H).

[0185] 13 C NMR(151MHz,CDCl3)δ165.5,157.3,132.6,130.1,125.7,121.9,121.0(q,J=281.6Hz),117.4,75.8(hept,J=33.2Hz),61.5,14.21.

[0186] 19 F NMR(565MHz,CDCl3)δ-73.6.

[0187] Example 23

[0188]

[0189] Under a nitrogen atmosphere, the aryl bromide shown in the above formula (0.4 mmol, 68.4 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), and additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to a reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto a silica gel column by dry method, and 98.1 mg of the polyfluoroalkyl aryl ether shown in the above formula was obtained with a yield of 95%.

[0190] The NMR test results of the polyfluoroalkyl aryl ether are as follows:

[0191] 1 H NMR(600MHz,CDCl3)δ7.15(d,J=8.4Hz,2H),6.97(d,J=8.4Hz,2H),4.73(hept,J=6.0Hz,1H),2.33(s,3H).

[0192] 1313C NMR (150 MHz, CDCl3) δ 155.7, 134.4, 130.5, 121.2 (q, J = 282.5 Hz), 117.2, 76.6 (hept, J = 32.7 Hz), 20.5.

[0193] 19 19F NMR (565 MHz, CDCl3) δ -73.7.

[0194] Example 24

[0195]

[0196] Under a nitrogen atmosphere, the aryl bromide shown in the above formula (0.4 mmol, 85.2 mg), Cat.1 (0.01 mmol, 6.2 mg), silver salt silver bis(trifluoromethanesulfonyl)imide (0.04 mmol, 15.6 mg), and additive silver carbonate (0.2 mmol, 55.2 mg) were successively added to the reaction flask. Finally, hexafluoroisopropanol (3.8 mmol, 0.4 mL) was added. The reaction was stirred at 80 °C for 12 h. After cooling to room temperature, the sample was loaded onto the column by dry method and passed through a silica gel chromatography column to obtain 114.1 mg of the perfluoroalkyl aryl ether shown in the above formula, with a yield of 95%.

[0197] The NMR detection results of the perfluoroalkyl aryl ether are as follows:

[0198] 1 1H NMR (600 MHz, CDCl3) δ 7.36 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 4.76 (hept, J = 6.0 Hz, 1H), 1.31 (s, 9H).

[0199] 13 13C NMR (150 MHz, CDCl3) δ 155.5, 147.7, 126.9, 121.2 (q, J = 285.2 Hz) 116.8, 76.4 (hept, J = 32.7 Hz), 34.3, 31.4.

[0200] 19 19F NMR (565 MHz, CDCl3) δ -73.7.

[0201] The preparation process parameters of each example are shown in Table 1 below:

[0202] Table 1 Preparation process parameter table of Examples 1 - 24

[0203]

[0204]

[0205]

[0206] The embodiments described above have elaborated on the technical solutions of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not used to limit the present invention. Any modifications, supplements, or substitutions in a similar manner within the scope of the principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether, comprising: A rhodium catalyst is selected, and in the presence of a silver salt and an additive, an aryl halide and a polyfluoroalkyl alcohol are used as substrates for a coupling reaction, and then the polyfluoroalkyl aryl ether is obtained through purification and separation. The rhodium catalyst is selected from at least one of pentamethylcyclopentadienylrhodium dichloride dimer or its derivatives. The structure of the aryl halide is shown by the following formula (I): （I） The structure of the polyfluoroalkyl alcohol is shown by the following formula (II): (II) In formula (I), Ar is phenyl or substituted phenyl, and X is F, Cl, Br or I; in formula (II), R f is hexafluoroisopropyl or trifluoroethyl; The additive is silver carbonate, silver fluoride or silver oxide. The structural formula of the rhodium catalyst includes any one shown by the following formulas Cat.1-Cat.

14. ； The silver salt is silver trifluoromethanesulfonate, silver bis(trifluoromethanesulfonyl)imide, silver tetrafluoroborate, silver fluoride or silver hexafluorophosphate.

2. The method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether according to claim 1, characterized in that, In formula (I), the substituted phenyl is phenyl substituted by alkyl, alkoxy, aryl, amido, ester or halogen.

3. The method for directly coupling an aryl halide with a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether according to claim 1, characterized in that, In the reaction system, an organic solvent is further included, and the organic solvent is selected from trifluorotoluene, 1,2-dichloroethane or cyclohexane; based on the molar amount of the aryl halide, the dosage of the organic solvent is 0-2 L / mol.

4. The method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether according to claim 1, wherein The molar ratio of the aryl halide to the polyfluoroalkyl alcohol is 1:1-10.

5. The method for directly coupling an aryl halide with a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether according to claim 1, wherein, The temperature of the coupling reaction is 40-140 °C, and the reaction time is 3-24 h.

6. The method for directly coupling an aryl halide with a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether according to claim 1, characterized in that, The molar ratio of the rhodium catalyst to the aryl halide is 1:5-100.

7. The method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether according to claim 1, characterized in that, The molar ratio of the silver salt to the aryl halide is 1:1.25-25.

8. The method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether according to claim 1, characterized in that, The molar ratio of the additive to the aryl halide is 0.1-10:

1.

9. The method for directly coupling an aryl halide with a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether according to claim 1, characterized in that, The molar ratio of the additive to the aryl halide is 0.5-2:

1.

10. The method for directly coupling an aryl halide and a polyfluoroalkyl alcohol to synthesize a polyfluoroalkyl aryl ether according to claim 1, characterized in that, After the coupling reaction, the polyfluoroalkyl aryl ether obtained is separated and purified by a silica gel chromatography column.

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