CN115010600B - Method for synthesizing polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon bond carboxylation reaction - Google Patents

Method for synthesizing polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon bond carboxylation reaction Download PDF

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CN115010600B
CN115010600B CN202210620427.6A CN202210620427A CN115010600B CN 115010600 B CN115010600 B CN 115010600B CN 202210620427 A CN202210620427 A CN 202210620427A CN 115010600 B CN115010600 B CN 115010600B
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carboxylic acid
polyfluoroaryl
aryl
acid compound
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CN115010600A (en
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余达刚
伯知豫
颜思顺
高田宇
宋磊
冉川昆
何轶
章炜
曹光梅
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Sichuan University
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Abstract

The invention discloses a method for synthesizing a polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon bond carboxylation reaction, which belongs to the technical field of organic synthesis and specifically comprises the following steps: adding a reaction substrate, a photocatalyst, a hydrogen atom transfer reagent, a reducing agent and a base into a reaction vessel, and then adding the mixture into CO 2 The solvent is added under the atmosphere, and the reaction is stirred at room temperature under the condition of light irradiation. And (3) separating and purifying the reaction product to obtain the polyfluoroaryl carboxylic acid compound. The scheme of the invention has the characteristics of mild reaction conditions, wide range of reaction substrates, good yield and regioselectivity, low-cost and easily available raw materials and the like, can efficiently realize the cleavage of aryl fluorocarbon bonds and carboxylation reaction thereof, and synthesizes important polyfluoroaryl carboxylic acid compounds, thereby having good application prospects.

Description

Method for synthesizing polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon bond carboxylation reaction
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing a polyfluoroaryl carboxylic acid compound based on an aryl fluorocarbon bond carboxylation reaction.
Background
Fluorine is the element with the largest electronegativity in nature, and the physical and chemical properties and the physiological activity of the molecule can be changed by introducing fluorine atoms into functional molecules. The polyfluoroaryl carboxylic acid is an important polyfluoro building block, has special properties, and has wide application in the fields of medicines, pesticides, organic photoelectric materials and the like. The cheap and easily available polyfluoro compound is used as a substrate, and the partially fluorinated compound with important application value can be constructed through the selective functional group reaction of the C-F bond. The strategy step is economical and is one of the most effective means for constructing partially fluorinated compounds. However, since the bond dissociation energy of the c—f bond is high, the hydrophilicity of the fluorine atom is strong, and selective cleavage of the c—f bond and functionalization reaction thereof present a great challenge.
On the other hand, carbon dioxide (CO 2 ) The carbon-C1 synthesizer has the advantages of low cost, easy availability, no toxicity, no harm, recycling, and the like, is an excellent carbon-C1 synthesizer in synthetic chemistry, and can be used for synthesizing various bulk chemicals and fine chemicals. Carbon dioxide is used as a carboxyl source, easily obtained polyfluoroaromatic hydrocarbon is used as a substrate, and an important polyfluoroaryl carboxylic acid compound can be constructed through the selective carboxylation reaction of polyfluoroaromatic hydrocarbon C-F bonds. However, the prior art has few reports, is mainly realized by means of electroreduction or transition metal catalysis, has the defects of needing to use a sacrificial anode and an equivalent metal reducing agent, additionally introducing a guiding group, having harsh reaction conditions and the like, and has a large development space. The selective carboxylation of aryl C-F bonds with inexpensive reducing agents under mild conditions is highly desirable.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a method for synthesizing a polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon bond carboxylation reaction, which can effectively solve the problems that a sacrificial anode or equivalent metal reducing agent is required to be used for aryl C-F bond selective carboxylation reaction, a guide group is additionally introduced, the reaction condition is harsh and the like in the prior art, and can synthesize the polyfluoroaryl carboxylic acid compound by taking green and cheap formate as the reducing agent at room temperature, and has the characteristics of mild reaction condition, wide reaction substrate range, good yield and regioselectivity, low cost and easy obtainment of raw materials.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: provided is a method for synthesizing a polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon bond carboxylation reaction, which comprises the following steps:
adding a reaction substrate, a photocatalyst, a hydrogen atom transfer reagent, a reducing agent and a base into a reaction vessel, and then adding the mixture into CO 2 Adding a solvent under the atmosphere,stirring at room temperature under the illumination condition for reacting for 0.1-72 h, and then separating and purifying to obtain the polyfluoroaryl carboxylic acid compound;
the structural general formula of the reaction substrate is shown as formula (I) or formula (II):
wherein R is 1 、R 2 、R 4 And R is 5 Each independently is a hydrogen atom or a fluorine atom; r is R 3 Substituted phenyl, naphthyl, fluorenyl, heteroaryl, ester, carboxyl, amido, alkyl, alkenyl, alkynyl, cyano, boron, silicon, phosphino, amino, thioether, alkoxy, acyloxy, or aryloxy; r is R 7 And R is 8 Each independently is a hydrogen atom or a fluorine atom; r is R 6 And R is 9 Is phenyl, naphthyl, fluorenyl, heteroaryl, ester, carboxyl, amido, alkyl, alkenyl, alkynyl, cyano, boron, silicon, phosphine, amine, thioether, alkoxy, acyloxy or aryloxy.
On the basis of the technical scheme, the invention can be improved as follows.
Further, the mol ratio of the reducing agent, the reaction substrate, the photocatalyst, the hydrogen atom transfer reagent and the alkali is 1-5:1:0.001-0.2:0.01-2:1-10.
Further, the reaction substrate is a pentafluoroarene compound, a tetrafluoroarene compound or a trifluoroarene compound; wherein,
the pentafluoroaromatic hydrocarbon compound is one of the following compounds:
the tetrafluoro aromatic hydrocarbon compound is one of the following compounds:
the trifluoro aromatic hydrocarbon compound is one of the following compounds:
further, the photocatalyst is a D-A type photocatalyst or an organometallic photocatalyst.
Further, the reducing agent is formate, oxalate, organic amine, hans ester or nitrogen-containing heterocycle.
Further, the hydrogen atom transfer reagent is N, N-dimethylethanolamine, arylthiol, heteroaryl thiol, alkylthiol, nitrogen-containing heterocycle, benzoate, alkoxy base, or siloxy base.
Further, the aryl thiophenol is 2,4, 6-triisopropylthiophenol, 2,4, 6-tri-tert-butylthiophenol, 4-tert-butylthiophenol or 2-methoxycarbonyl thiophenol; the alkyl mercaptan is cyclohexyl mercaptan, ethyl thioglycolate or ethyl 2-mercaptopropionate.
Further, the solvent was MeCN, DMF, DMAc, DMSO, NMP.
Further, the base is a carbonate, bicarbonate, fluoride salt, alkoxy base, phosphate, hydrogen phosphate, carboxylate, or organic base.
Further, the pressure of the carbon dioxide in the reaction vessel is 0.1 to 30 times of the atmospheric pressure; the distance between the light source and the reaction vessel is 0.1-10 cm, the wavelength of light is 300-560 nm, and the power of the light source is 1-100W.
The beneficial effects of the invention are as follows:
1. the invention provides a method for synthesizing a polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon bond carboxylation reaction. Under the catalysis of visible light, using pentafluoroaromatic hydrocarbon compounds, tetrafluoro aromatic hydrocarbon compounds or trifluoro aromatic hydrocarbon compounds as reaction substrates, using carbon dioxide as a carboxylic acid source, and simultaneously adding a photocatalyst, a hydrogen atom transfer reagent, a reducing agent and alkali to prepare polyfluoroaryl carboxylic acid compounds; the method has the characteristics of mild reaction conditions, wide reaction of reaction substrates, good yield and regioselectivity, and cheap and easily obtained raw materials;
2. the synthesis method provided by the invention has good reactivity for pentafluoroaromatic hydrocarbon compounds, tetrafluoroaromatic hydrocarbon compounds and trifluoroaromatic hydrocarbon compounds, and has the characteristics of wide range of reaction substrates, good yield and good regioselectivity;
3. the invention realizes the selective carboxylation reaction of the polyfluoroaromatic hydrocarbon fluorocarbon bond promoted by the visible light for the first time. The reaction efficiently realizes the selective cleavage of aryl C-F bond and introduces important carboxyl functional groups under mild conditions, and the important polyfluoroaryl carboxylic acid compound is prepared, so that the method has wide application prospect.
Drawings
FIG. 1 is a schematic diagram of the synthesis mechanism of the present invention.
Detailed Description
The following describes the present invention in detail with reference to examples.
Example 1
A method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl fluorocarbon bond carboxylation reaction, wherein the synthesis reaction formula is shown in formula (1-1).
The synthesis method comprises the following steps:
after drying a 25ml Schlenk reaction tube equipped with a stirrer under vacuum by heating, the reaction substrate pentafluoroarene (0.2 mmol,1.0equiv, if the substrate is solid) and the photocatalyst Ir (ppy) are added 2 (dtbbpy)PF 6 (4.6 mg,0.025mmol,2.5 mol%). Subsequently, the reaction tube is moved into a glove box, and the reducing agent HCO is added in sequence 2 K (33.6 mg,0.4mmol,2 equiv), hydrogen atom transfer reagent N, N-dimethylethanolamine (DABCO, 13.4mg,0.12mmol,60 mol%), base CsF (76 mg,0.5mmol,2.5 equiv), base Cs 2 CO 3 (78.2 mg,0.24mmol,1.2 equiv). Then sealing the reaction tube by using a corresponding cock of the reaction tube, removing the reaction tube from the glove box, and pumping and replacing the reaction tube with CO by using double-row tubes 2 The atmosphere was repeated 3 times. Subsequently at CO 2 The reaction substrate pentafluoroarene compound (if the substrate is a liquid) and super dry DMF (2 mL) are sequentially injected into the reaction tube using a syringe under an atmosphere. The reaction tube was sealed immediately after the completion of the addition. The reaction tube was fixed in a water bath, the rotational speed of the stirrer used for the reaction was adjusted to 650r/min, a 30W blue LED lamp (wavelength of 450nm or so) was used to irradiate at a distance of 0.5cm, and a fan was used to radiate heat, so that the reaction temperature was maintained at 25-30 ℃. After stirring for 30-34 hours, 5mL of ethyl acetate was added to the reaction mixture to dilute the mixture, 2mL of 2N hydrochloric acid and 5mL of water were added to quench the reaction, and stirring was performed for 1 minute. Subsequently, the reaction solution was extracted 3 times with 3mL of ethyl acetate, and the organic phases were combined and the residual solvent was thoroughly removed using rotary evaporation. The crude product obtained was transferred to a 25mL eggplant-shaped bottle with 2mL of methanol and 2mL of diethyl ether, and trimethylsilyl diazomethane (0.3 mL,3equiv,0.6mmol,2M in n-hexane) was added dropwise at 0℃and reacted at room temperature for 1 hour. Thereafter, trimethylsilyl diazomethane (0.3 mL,3equiv,0.6mmol,2M n-hexane solution) was continuously added dropwise at 0deg.C, and the reaction was continued at room temperature for 1 hour. After the esterification, the mixture was separated and purified by column chromatography. The purification conditions are as follows: washing with petroleum ether and dichloromethane=7:1-3:1 (v: v) mixed solvent to obtain the target product. The specific reaction results are shown in Table 1.
TABLE 1 yield of corresponding products with pentafluoroaromatic compounds as substrates
Note that:the standard reaction conditions in table 1 were the same as described above, the regioselectivity was determined by crude GC, and the yield was isolated yield; a is reaction for 42h; b is the use of 2.5 equivalents of HCO 2 K, performing K; c is the use of 2.5 equivalents CsF and 1.5 equivalents Cs 2 CO 3 As a base, reacting for 30 hours; d is a reaction time of 48 hours; e is the use of 2.5 equivalents Cs 2 CO 3 As a base, 2mL of DMF and 300. Mu.L of DMSO were used as a mixed solvent.
The experimental results show that the tetrafluoro aromatic hydrocarbon compounds can be obtained with high yield and good regioselectivity. A variety of functional groups such as tertiary butyl, methylthio, methoxy, cyclopropyl, trifluoromethoxy, fluorine atoms, benzyl C-H bonds, and the like are compatible with the reaction system. Heterocycles such as fluorenyl, naphthyl, dibenzofuran, thiophene, furan, and the like are also compatible with the reaction system. The target reaction can also be smoothly carried out by the non-biphenyl type pentafluoroaromatic hydrocarbon.
Example 2
A method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl fluorocarbon bond carboxylation reaction, wherein the synthetic reaction formula is shown in the formula (1-2).
The synthesis method comprises the following steps:
after heating and drying a 25ml Schlenk reaction tube equipped with a stirrer under vacuum, the reaction substrate tetrafluoroaromatic compound (0.2 mmol,1.0equiv, if the substrate is solid) and the photocatalyst Ir (ppy) were added 2 (dtbbpy)PF 6 (4.6 mg,0.025mmol,2.5 mol%). Subsequently, the reaction tube is moved into a glove box, and the reducing agent HCO is added in sequence 2 K (33.6 mg,0.4mmol,2 equiv), hydrogen atom transfer reagent DABCO (13.4 mg,0.12mmol,60 mol%), base CsF (76 mg,0.5mmol,2.5 equiv), base Cs 2 CO 3 (78.2 mg,0.24mmol,1.2 equiv). Then sealing the reaction tube by using a corresponding cock of the reaction tube, removing the reaction tube from the glove box, and pumping and replacing the reaction tube with CO by using double-row tubes 2 The atmosphere was repeated 3 times. Subsequently at CO 2 Use of injections in an atmosphereThe reactor sequentially injects the reaction substrate trifluoroaromatic compounds (if the substrate is liquid) and ultra-dry DMF (2 mL) into the reaction tube. The reaction tube was sealed immediately after the completion of the addition. The reaction tube was fixed in a water bath, the rotational speed of the stirrer used for the reaction was adjusted to 650r/min, a 30W blue LED lamp (wavelength of 450nm or so) was used to irradiate at a distance of 0.5cm, and a fan was used to radiate heat, so that the reaction temperature was maintained at 25-30 ℃. After stirring for 12-72 hours, 5mL of ethyl acetate was added to the reaction mixture to dilute, 2mL of 2N hydrochloric acid and 5mL of water were added to quench the reaction, and stirring was performed for 1 minute. Subsequently, the reaction solution was extracted 3 times with 3mL of ethyl acetate, and the organic phases were combined and the residual solvent was thoroughly removed using rotary evaporation. The crude product obtained was transferred to a 25mL eggplant-shaped bottle with 2mL of methanol and 2mL of diethyl ether, and trimethylsilyl diazomethane (0.2 mL,2equiv,0.4mmol,2M in n-hexane) was added dropwise at 0℃and reacted at room temperature for 1 hour. Thereafter, trimethylsilyl diazomethane (0.2 mL,2equiv,0.4mmol,2M n-hexane solution) was continuously added dropwise at 0deg.C, and the reaction was continued at room temperature for 1 hour. After the esterification, the mixture was separated and purified by column chromatography. The purification conditions are as follows: washing with petroleum ether and dichloromethane=7:1-2:1 (v: v) mixed solvent to obtain the target product. The specific reaction results are shown in Table 2.
TABLE 2 yields of corresponding products with tetrafluoro aromatic compounds as substrates
Note that: the standard reaction conditions in table 2 were the same as described above, with regioselectivity determined by crude GC; a is the use of 3 equivalents of potassium formate.
The experimental data show that the neutral and electron-donating substituted tetrafluoroaromatic hydrocarbon can also smoothly carry out carboxylation reaction of fluorocarbon bonds, and the trifluoro aryl carboxylic acid product which is difficult to synthesize by other methods can be obtained with moderate yield and regioselectivity.
Example 3
A method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl fluorocarbon bond carboxylation reaction, wherein the synthetic reaction formula is shown in the formula (1-3).
The synthesis method comprises the following steps:
after heating and drying a 25ml Schlenk reaction tube equipped with a stirrer under vacuum, the reaction substrate trifluoroaromatics (0.2 mmol,1.0equiv, if the substrate is solid) and the photocatalyst Ir (ppy) are added 2 (dtbbpy)PF 6 (4.6 mg,0.025mmol,2.5 mol%). Subsequently, the reaction tube is moved into a glove box, and the reducing agent HCO is added in sequence 2 K (42.0 mg,0.5mmol,2.5 equiv.), hydrogen atom transfer reagent DABCO (13.4 mg,0.12mmol,60 mol%), base Cs 2 CO 3 (162.9 mg,0.5mmol,2.5 equiv). Then sealing the reaction tube by using a corresponding cock of the reaction tube, removing the reaction tube from the glove box, and pumping and replacing the reaction tube with CO by using double-row tubes 2 The atmosphere was repeated 3 times. Subsequently at CO 2 The reaction substrate trifluoroaromatic compound (if the substrate is a liquid), super-dry DMF (2 mL), super-dry DMSO (300 μL) were sequentially injected into the reaction tube using a syringe under an atmosphere. The reaction tube was sealed immediately after the completion of the addition. The reaction tube was fixed in a water bath, the rotational speed of the stirrer used for the reaction was adjusted to 650r/min, a 30W blue LED lamp (wavelength of 450nm or so) was used to irradiate at a distance of 0.5cm, and a fan was used to radiate heat, so that the reaction temperature was maintained at 25-30 ℃. After stirring the reaction for 24-38 hours, 5mL of ethyl acetate was added to the reaction mixture to dilute it, and 2mL of 2N hydrochloric acid and 5mL of water were added to quench the reaction, followed by stirring for 1 minute. Subsequently, the reaction solution was extracted 3 times with 3mL of ethyl acetate, and the organic phases were combined and the residual solvent was thoroughly removed using rotary evaporation. The crude product obtained was transferred to a 25mL eggplant-shaped bottle with 2mL of methanol and 2mL of diethyl ether, and trimethylsilyl diazomethane (0.2 mL,2equiv,0.4mmol,2M in n-hexane) was added dropwise at 0℃and reacted at room temperature for 1 hour. Thereafter, trimethylsilyl diazomethane (0.2 mL,2equiv,0.4mmol,2M n-hexane solution) was continuously added dropwise at 0deg.C, and the reaction was continued at room temperature for 1 hour. After the esterification, the mixture was separated and purified by column chromatography. The purification conditions are as follows: petroleum ether is used, dichloromethane=5:1-2:1 (v: v) or petroleum ether is used, ethyl acetate=50:1Washing with mixed solvent of 5:1 (v: v) to obtain the target product. The specific reaction results are shown in Table 3.
TABLE 3 yields of corresponding products with trifluoroaromatics as substrates
Note that: the standard reaction conditions in table 3 were the same as above, the product was in a single configuration, and the yield was isolated; a is reaction for 32h; b is the use of 3 equivalents of HCO 2 K, performing K; c using DMSO as a solvent, and reacting for 24 hours; d is using 2mol% Ir (ppy) 2 (dtbbpy)PF 6 50mol% DABCO,2 equivalent HCO 2 K, reacting for 32h; e is the use of 3.5 equivalents of HCO 2 K。
The experimental result shows that the trifluoroarene substrate can smoothly undergo fluorocarbon bond carboxylation reaction, and the target product is obtained in a single configuration. Various electron-withdrawing groups such as ester groups, cyano groups, sulfonamide groups, fluorine atoms, pyridine and the like, and various electron-donating groups such as methoxy groups, thiophene, long-chain alkyl groups and the like can be compatible with the reaction system. Some natural product derivatives, as well as commercially available liquid crystal material molecules, can also undergo fluorocarbon-bond carboxylation reactions smoothly, yielding difluoroaryl carboxylic acid products that are difficult to synthesize by other methods.
Experimental example 1
This experimental example 1 uses 4'- (tert-butyl) -2,3,4,5, 6-pentafluoro-1, 1' -biphenyl as a reaction substrate, and the influence on the reaction yield was examined by changing the reaction conditions: 1a substrate (0.2 mmol,1 equiv), ir (ppy) 2 (dtbbpy)PF 6 (0.05mmol，2.5mol％，4.6mg)，HCO 2 K(2equiv，33.6mg)，DABCO(0.12mmol，60mol％，13.4mg)，CsF(0.5mmol，2.0equiv，76mg)，Cs 2 CO 3 (0.24 mmol,1.2equiv,78.2 mg) of ultra-dry solvent DMF (2 ml), the experimental results are shown in Table 4.
The reaction equation is shown below:
TABLE 4 yields of products under different reaction conditions with 4'- (tert-butyl) -2,3,4,5, 6-pentafluoro-1, 1' -biphenyl as substrate
Note that: the isolation yields are shown in Table 4. The bracket is the nuclear magnetic yield of the nuclear magnetic hydrogen spectrum internal standard with dibromomethane; a is the use of 50 mole% DABCO,2.5 equivalents Cs 2 CO 3 As a single base, reacting for 24 hours; b is using 2mol% Ir (ppy) 2 (dtbbpy)PF 6 10mol%2,4, 6-triisopropylthiophenol, 2.5 equivalents Cs 2 CO 3 As a single base, the reaction was carried out for 32h.
As can be seen from the data in Table 4 above, the yields are as high as 78% under the reaction conditions of the present invention. A series of control experiments show that the light, the photocatalyst and the CO 2 The reducing agent plays an indispensable role in the reaction, and the target product cannot be obtained or can be obtained only in trace amount when any one of the reducing agents is absent. The hydrogen atom transfer reagent and the base have a remarkable promoting effect on the reaction. When other photosensitizers or hydrogen atom transfer reagents are used, the yield is greatly reduced, mainly by increasing the raw material surplus or by-products of defluorination and hydrogenation. Replacement of CsF/Cs 2 CO 3 The yield is obviously reduced when the alkali is a single component alkali, and the raw material residue is increased or the defluorination and hydrogenation byproducts are increased. When the solvent is replaced by MeCN, the reaction cannot occur; when the solvent is replaced by DMSO, the yield is reduced, and the byproducts of defluorination and hydrogenation are obviously increased.
In addition, based on the results of the prior experimental study, the inventors propose a reaction mechanism as shown in fig. 1. Firstly, a Single Electron Transfer (SET) process is carried out on DABCO and an excited state photosensitizer to obtain a reduced state photosensitizer and DABCO free radical cation. Subsequent DABCO radical cation and HCO 2 K undergoes a Hydrogen Atom Transfer (HAT) process to give a massThe protonated DABCO and the carbon dioxide radical anion. The carbon dioxide radical anion then reduces the polyfluoroaromatic hydrocarbon substrate to a polyfluoroaryl radical by a Single Electron Transfer (SET) process. The aryl radical and the reduced photosensitizer are reduced into polyfluoroaryl carbanion through a Single Electron Transfer (SET) process, and finally nucleophilic attack carbon dioxide is carried out to generate polyfluoroaryl carboxylate, and the polyfluoroaryl carboxylate is acidified and esterified to obtain the target product.
The products prepared by the invention are subjected to nuclear magnetic resonance and mass spectrometry characterization analysis. The results of the nuclear magnetic resonance and mass spectrometry characterization data are consistent with the obtained product. The specific characterization data are as follows:
4'- (tert-butyl) -2,3,5, 6-tetrafluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
16.4Hz),123.33,110.78(t,J＝15.8Hz),53.21,15.38,9.85； 19 F NMR(376MHz,Chloroform-d)δ-139.06--141.87(m),-141.39--144.60(m)；HRMS(ESI+):calculated for C 18 H 16 F 4 NaO 2 + [M+Na] + 363.0979,found 363.0979.
2,3,5, 6-tetrafluoro-4 '- (methylthio) - [1,1' -biphenyl ] -4-carboxylic acid methyl ester
(t,J＝15.9Hz),53.25,15.09； 19 F NMR(376MHz,Chloroform-d)δ-139.24--139.92(m),-142.53--142.94(m)；HRMS(ESI+):calculated for C 15 H 11 F 4 O 2 S + [M+H] + 331.0410,found 331.0413.
2,3,5, 6-tetrafluoro-4 '-methoxy- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
MHz,Chloroform-d)δ-139.79--139.95(m),-143.01--143.18(m)；HRMS(ESI+):calculated for C 15 H 11 F 4 NO 3 + [M+H] + 315.0639,found 315.0635.
4 '-cyclopropyl-2, 3,5, 6-tetrafluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
Hz),125.69,123.80(t,J＝16.5Hz),123.59,110.88(t,J＝15.8Hz),53.18,34.79,31.12； 19 F NMR(376MHz,Chloroform-d)δ-139.60--140.10(m),-142.51--143.09(m)；HRMS(ESI+):calculated for C 17 H 13 F 4 O 2 + [M+H] + 325.0846,found 325.0841.
2,3,5, 6-tetrafluoro-4 '- (trifluoromethoxy) - [1,1' -biphenyl ] -4-carboxylic acid methyl ester
131.73(t,J＝2.3Hz),125.07(t,J＝2.5Hz),122.30(t,J＝16.3Hz),121.02,120.39(q,J＝258.2Hz),111.83(t,J＝16.0Hz),53.27； 19 F NMR(376MHz,Chloroform-d)δ-57.88,-138.11--141.04(m),-141.73--145.64(m)；HRMS(ESI+):calculated for C 15 H 8 F 7 O 3 + [M+H] + 369.0356,found 369.0362.
2,3,4',5, 6-pentafluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
122.72(t,J＝16.5Hz),122.40(d,J＝2.8Hz),116.00(d,J＝21.9Hz),111.36(t,J＝15.8Hz),53.32； 19 F NMR(376MHz,Chloroform-d)δ-110.46,-138.79--139.71(m),-142.23--142.87(m)；HRMS(ESI+):calculated for C 14 H 8 F 5 O 2 + [M+H] + 303.0439,found303.0436.
2,3,5, 6-tetrafluoro-3 ',4' -dimethyl- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
NMR(376MHz,Chloroform-d)δ-139.71--140.08(m),-142.34--142.81(m)；HRMS(ESI+):calculated for C 12 H 13 F 4 O 2 + [M+H] + 313.0846,found 313.0842.
2,3,5, 6-tetrafluoro-3 ',4' -dimethoxy- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
Traits: white solid
1 H NMR(400MHz,Chloroform-d)δ7.08(dq,J＝8.3,1.6Hz,1H),7.03-6.96(m,2H),4.00(s,-142.19--143.63(m)；HRMS(ESI+):calculated for C 16 H 13 F 4 O 4 + [M+H] + 345.0744,found 345.0738.
4- (1, 2-Dimethoxybenzene-5) -2,3,5, 6-tetrafluorobenzoic acid methyl ester
110.83(t,J＝15.8Hz),110.21(t,J＝2.3Hz),108.64,101.60,53.25； 19 F NMR(376MHz,Chloroform-d)δ-138.67--140.56(m),-141.93--143.30(m)；HRMS(ESI+):calculated for C 15 H 9 F 4 O 4 + [M+H] + 329.0431,found 329.0428.
2,3,5, 6-tetrafluoro-4 ' -methoxy-3 ' - (trifluoromethyl) - [1,1' -biphenyl ] -4-carboxylic acid methyl ester
(m),123.09(q,J＝108.4Hz),122.13(t,J＝60.2Hz),119.28(q,J＝31.3Hz),118.21,112.26,111.40(t,J＝16.1Hz),56.10,53.29； 19 F NMR(376MHz,Chloroform-d)δ-62.89,-137.57--140.78(m),-140.78--144.34(m)；HRMS(ESI+):calculated for C 16 H 10 F 7 O 3 + [M+H] + 383.0513,found 383.0511.
2,3,5, 6-tetrafluoro-3 ',5' -dimethyl- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
NMR(376MHz,Chloroform-d)δ-139.35--140.56(m),-141.81--143.10(m)；HRMS(ESI+):calculated for C 16 H 13 F 4 O 2 + [M+H] + 313.0846,found 313.0848.
2,3,5, 6-tetrafluoro-4 '-methoxy-3', 5 '-dimethyl- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
calculated for C 17 H 15 F 4 O 3 + [M+H] + 343.0952,found 343.0957.
2,3,5, 6-tetrafluoro-2 '-phenoxy- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
120.55(t,J＝18.5Hz),119.54,117.91,117.83-117.30(m),111.68(t,J＝15.9Hz),53.26； 19 F NMR(376MHz,Chloroform-d)δ-139.20--139.34(m),-140.07--140.21(m)；HRMS(ESI+):calculated for C 20 H 13 F 4 O 3 + [M+H] + 377.0795,found 377.0797.
2,3,5, 6-tetrafluoro-2 ',4' -dimethyl- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
19.5Hz),123.08(t,J＝1.9Hz),111.51(t,J＝15.8Hz),53.31,21.26,19.58； 19 F NMR(376MHz,Chloroform-d)δ-139.65--139.79(m),-139.79--139.94(m)；HRMS(ESI+):calculated for C 16 H 13 F 4 O 2 + [M+H] + 313.0846,found 313.0843.
4- (9, 9-dimethylfluorene-2) -2,3,5, 6-tetrafluoro-benzoic acid methyl ester
(t,J＝2.1Hz),128.11,127.19,125.02,124.46(t,J＝2.4Hz),124.33(t,J＝16.0Hz),122.73,120.51,120.18,110.88(t,J＝15.7Hz),53.28,47.07,26.97； 19 F NMR(376MHz,Chloroform-d)δ-139.46--139.96(m),-142.24--142.65(m)；HRMS(ESI+):calculated for C 23 H 17 F 4 O 2 + [M+H] + 401.1159,found401.1157.
2,3,5, 6-tetrafluoro-4- (naphthalene-2) -benzoic acid methyl ester
127.43,126.79,126.71(t,J＝1.9Hz),123.94,123.88(t,J＝16.5Hz),111.37(t,J＝15.9Hz),53.32； 19 F NMR(376MHz,Chloroform-d)δ-138.22--140.07(m),-141.84--142.90(m)；HRMS(ESI+):calculated for C 18 H 11 F 4 O 2 + [M+H] + 335.0690,found 335.0686.
2,3,5, 6-tetrafluoro-4- (6-methoxynaphthalene-2) -benzoic acid methyl ester
134.83,129.95,129.90(t,J＝2.3Hz),128.38,127.22(t,J＝2.1Hz),127.14,123.98(t,J＝16.5Hz),121.48,119.68,110.90(t,J＝15.8Hz),105.55,55.37,53.27； 19 F NMR(376MHz,Chloroform-d)δ-139.51--139.75(m),-142.46--142.73(m)；HRMS(ESI+):calculated for C 19 H 13 F 4 O 3 + [M+H] + 365.0795,found 365.0790.
4- (dibenzofuran-2) -2,3,5, 6-tetrafluorobenzoic acid methyl ester
J＝248.9,14.2,4.4Hz),128.11,125.58,124.93,124.62(t,J＝2.3Hz),123.66(t,J＝16.4Hz),123.46,123.14,121.04,120.81,113.50(t,J＝2.3Hz),111.87,111.43(t,J＝15.9Hz),53.34； 19 F NMR(376MHz,Chloroform-d)δ-139.04--139.52(m),-142.01--142.57(m)；HRMS(ESI+):calculated for C 20 H 11 F 4 O 3 + [M+H] + 375.0639,found 375.0637.
2,3,5, 6-tetrafluoro-4- (thiophene-2) -benzoic acid methyl ester
127.51,127.16-126.79(m),117.52(t,J＝14.5Hz),109.82(t,J＝15.5Hz),53.24； 19 F NMR(376MHz,Chloroform-d)δ-139.05--139.34(m),-139.41--139.68(m)；HRMS(ESI+):calculated for C 12 H 7 F 4 O 2 S + [M+H] + 291.0097,found 291.0095.
2,3,5, 6-tetrafluoro-4- (furan-2) -benzoic acid methyl ester
Traits: white solid
109.88(t,J＝15.6Hz),53.21； 19 F NMR(376MHz,Chloroform-d)δ-139.43--140.00(m),-140.44--140.98(m)；HRMS(ESI+):calculated for C 12 H 7 F 4 O 3 + [M+H] + 275.0326,found275.0323.
2,3,5, 6-tetrafluoro-4- (5-methylfuran-2) -benzoic acid methyl ester
7.3Hz),114.04(t,J＝13.5Hz),108.87(t,J＝15.5Hz),108.44,53.12,13.78； 19 F NMR(376MHz,Chloroform-d)δ-139.88--140.10(m),-141.15--141.43(m)；HRMS(ESI+):calculated for C 13 H 9 F 4 O 3 + [M+H] + 289.0482,found 289.0478.
4- (Diphenylamino) -2,3,5, 6-tetrafluorobenzoic acid methyl ester
122.12,53.18； 19 F NMR(376MHz,Chloroform-d)δ-134.99--141.41(m),-141.41--146.57(m)；HRMS(ESI+):calculated for C 20 H 14 F 4 NO 2 + [M+H] + 376.0955,found 376.0954.
2,3,5, 6-tetrafluoro-4 '- (pentyloxy) - [1,1' -biphenyl ] -4-carboxylic acid methyl ester
160.17,146.21-143.40(m),145.44-142.18(m),131.38(t,J＝2.5Hz),123.71(t,J＝16.1Hz),118.29,114.66,110.43(t,J＝15.7Hz),68.07,53.20,28.84,28.15,22.42,13.99； 19 F NMR(376MHz,Chloroform-d)δ-138.20--142.39(m),-141.76--146.57(m)；HRMS(ESI+):calculated for C 19 H 19 F 4 O 3 + [M+H] + 371.1265,found 371.1262.
2,3,5, 6-tetrafluoro-4 '- (heptyloxy) - [1,1' -biphenyl ] -4-carboxylic acid methyl ester
160.18,146.48-143.61(m),145.20-142.41(m),131.38(t,J＝2.4Hz),123.71(t,J＝16.4Hz),118.28,114.66,110.43(t,J＝15.7Hz),68.09,53.19,31.76,29.14,29.03,25.96,22.59,14.06； 19 FNMR(376MHz,Chloroform-d)δ-139.06--140.24(m),-142.96--143.81(m)；HRMS(ESI+):calculated for C 21 H 23 F 4 O 3 + [M+H] + 399.1578,found 399.1574.
3, 5-difluoro- [1,1 '-biphenyl ] -4,4' -dicarboxylic acid methyl ester
141.86(t,J＝2.2Hz),130.61,130.33,126.96,110.99-110.43(m),109.83(t,J＝18.1Hz),52.78,52.27； 19 F NMR(376MHz,Chloroform-d)δ-109.04；HRMS(ESI+):C 16 H 13 F 2 O 4 + [M+H] + 307.0776,found 307.0772.
4 '-cyano-3, 5-difluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
112.90,111.41-110.56(m),110.46,52.91； 19 F NMR(376MHz,Chloroform-d)δ-108.46；HRMS(ESI+):calculated for C 15 H 10 F 2 NO 2 + [M+H] + 274.0674,found 274.0673.
4'- (N, N-diethylsulfonamide) -3, 5-difluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
127.76,127.65,111.53-110.55(m),110.09(t,J＝17.9Hz),52.88,42.09,14.17； 19 F NMR(376MHz,Chloroform-d)δ-108.72；HRMS(ESI+):calculated for C 18 H 19 F 2 NNaO 4 S + [M+Na] + 406.0895,found406.0890.
3,4', 5-trifluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
＝21.7Hz),110.63-110.11(m),109.09(t,J＝17.8Hz),52.89； 19 FNMR(376MHz,Chloroform-d)δ-109.31,-112.27；HRMS(ESI+):calculated for C 14 H 10 F 3 O 2 + [M+H] + 267.0627,found 267.0623.
3 '-cyano-3, 5-difluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
J＝18.0Hz),52.92； 19 F NMR(376MHz,Chloroform-d)δ-108.40；HRMS(ESI+):C 15 H 10 F 2 NO 2 + [M+H] + 274.0674,found 274.0674.
3,3', 5' -tetrafluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
25.3Hz),52.89； 19 F NMR(376MHz,Chloroform-d)δ-108.22(t,J＝7.9Hz),-108.68(d,J＝9.1Hz)；HRMS(ESI+):calculated for C 14 H 9 F 4 O 2 + [M+H] + 285.0533,found 285.0533.
3, 5-difluoro-3 ' -methoxy- [1,1' -biphenyl ] -4,4' -dicarboxylic acid methyl ester
Hz),142.86(t,J＝2.2Hz),132.48,120.45,118.80,111.03-110.60(m),110.57,109.90(t,J＝17.8Hz),56.16,52.81,52.16； 19 F NMR(376MHz,Chloroform-d)δ-109.04(d,J＝9.2Hz)；HRMS(ESI+):calculated for C 17 H 14 F 2 NaO 5 + [M+Na] + 359.0702,found 359.0696.
3',5' -difluoro-2-methyl- [1,1 '-biphenyl ] -4,4' -dicarboxylic acid methyl ester
Hz),141.20,140.92(t,J＝2.5Hz),131.49,130.22,130.05,124.24,111.12-110.24(m),109.73(t,J＝17.9Hz),52.81,52.01,21.88； 19 F NMR(376MHz,Chloroform-d)δ-109.17；HRMS(ESI+):calculated for C 17 H 15 F 2 O 5 + [M+H] + 321.0933,found 321.0931./>
3, 5-difluoro-4 '-methoxy- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
55.42,52.66； 19 F NMR(376MHz,Chloroform-d)δ-109.70；HRMS(ESI+):C 15 H 13 F 2 O 3 + [M+H] + 279.0827,found 279.0825.
2, 6-difluoro-4- (thiophene-2) -benzoic acid methyl ester
109.22-108.79(m),108.58(t,J＝17.6Hz),52.72； 19 F NMR(376MHz,Chloroform-d)δ-109.18(d,J＝9.6Hz)；HRMS(ESI+):calculated for C 12 H 9 F 2 O 2 S + [M+H] + 255.0286,found 255.0286.
2, 6-difluoro-4- (pyridine-2) -benzoic acid methyl ester
137.58,123.95,121.13,110.44(t,J＝18.9Hz),110.03-109.64(m),51.91； 19 F NMR(376MHz,Methanol-d 4 )δ-111.98；HRMS(ESI+):calculated for C 13 H 10 F 2 NO 2 + [M+H] + 250.0674,found250.0671.
4-Hexaoxycarbonyl-2, 6-difluorobenzoic acid methyl ester
Hz),161.34,160.25(dd,J＝257.4,6.2Hz),135.02(t,J＝9.5Hz),114.66(t,J＝18.9Hz),113.55-112.62(m),66.30,53.07,31.39,28.50,25.60,22.51,13.97； 19 F NMR(376MHz,Chloroform-d)δ-109.08；HRMS(ESI+):calculated for C 15 H 19 F 2 O 4 + [M+H] + 301.1246,found 301.1247.
4' - (1S, 3S, 4R) -3-isopropyl-4-methylcyclohexyl) -4-methyl-3, 5-difluoro- [1,1' -biphenyl ] -4,4' -dicarboxylic acid dimethyl ester
1.54(m,2H),1.24-1.08(m,2H),1.00-0.92(m,7H),0.83(d,J＝6.9Hz,3H)； 13 C NMR(101MHz,Chloroform-d)δ162.07(t,J＝1.6Hz),161.10(dd,J＝256.3,7.1Hz),149.30,146.58(t,J＝10.3Hz),135.15(d,J＝2.3Hz),127.64,126.84,110.75-109.56(m),108.58(t,J＝17.7Hz),52.67,44.33,37.32,37.24,34.20,33.47,32.19,26.63,22.71,14.11； 19 F NMR(376MHz,Chloroform-d)δ-109.05；HRMS(ESI+):calculated for C 25 H 29 F 2 O 4 + [M+H] + 431.2028,found431.2028.
4' - (hexyl-3-en-1-yl) oxycarbonyl-3, 5-difluoro- [1,1' -biphenyl ] -4,4' -dicarboxylic acid dimethyl ester
Traits: viscous colorless liquid
(t,J＝1.5Hz),160.78(dd,J＝255.0,7.0Hz),161.65,145.20(t,J＝10.1Hz),141.65,134.93,134.15,130.67,130.63,129.84,126.86,124.06,123.62,110.92-109.98(m),109.63(t,J＝17.7Hz),64.50,64.42,51.90,31.73,26.39,25.29,20.16,13.25,12.82； 19 F NMR(376MHz,Methanol-d 4 )δ-111.48,-111.54；HRMS(ESI+):C 21 H 20 F 2 NaO 4 + [M+Na] + 397.1222,found397.1217.
3, 5-difluoro-4 '- ((1 s,4 r) -4-propylcyclohexyl) - [1,1' -biphenyl ] -4-carboxylic acid methyl ester
(m,4H),1.46(qd,J＝12.6,3.3Hz,2H),1.38-1.28(m,3H),1.26-1.16(m,2H),1.05(qd,J＝13.1,12.4,3.7Hz,2H),0.89(t,J＝7.2Hz,3H)； 13 C NMR(101MHz,Chloroform-d)δ162.09(t,J＝1.6Hz),161.10(dd,J＝256.2,7.0Hz),149.30,146.59(t,J＝10.3Hz),135.16(d,J＝2.3Hz),127.64,126.84,110.54-109.81(m),108.48(t,J＝17.7Hz),52.69,44.33,39.64,36.94,34.19,33.43,20.00,14.39； 19 F NMR(376MHz,Chloroform-d)δ-109.78(d,J＝10.0Hz)；HRMS(ESI+):calculated for C 23 H 26 F 2 NaO 2 + [M+Na] + 395.1793,found 395.1790.
3, 5-difluoro-4 '- ((1 s,4 r) -4-pentylcyclohexyl) - [1,1' -biphenyl ] -4-carboxylic acid methyl ester
1.37-1.18(m,9H),1.06(tdd,J＝14.2,11.3,3.7Hz,2H),0.90(t,J＝6.9Hz,3H)； 13 C NMR(101MHz,Chloroform-d)δ162.07(t,J＝1.6Hz),161.10(dd,J＝256.3,7.1Hz),149.30,146.58(t,J＝10.3Hz),135.16(t,J＝2.3Hz),127.64,126.84,110.50-109.88(m),108.58(t,J＝17.7Hz),52.67,44.33,37.32,37.24,34.20,33.47,32.19,26.63,22.71,14.11； 19 F NMR(376MHz,Chloroform-d)δ-109.74；HRMS(ESI+):calculated for C 25 H 30 F 2 NaO 2 + [M+Na] + 423.2106,found 423.2102./>
2,3, 5-trifluoro-4 '-methyl- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
Traits: white solid
9.8,1.5Hz),129.95(dt,J＝3.2,1.8Hz),129.56,128.62(d,J＝3.4Hz),111.80(ddd,J＝24.7,3.8,2.1Hz),110.09(dd,J＝19.3,14.3Hz),52.95,21.27； 19 F NMR(376MHz,Chloroform-d)δ-115.70(dd,J＝15.1,10.2Hz),-132.89(d,J＝20.6Hz),-146.45(ddd,J＝20.6,14.8,5.4Hz)；HRMS(ESI+):calculated for C 15 H 12 F 3 O 2 + [M+H] + 281.0784,found 281.0787.
2,3, 5-trifluoro-4 '-methoxy- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
(ddd,J＝247.0,13.5,4.1Hz),133.77(t,J＝10.1Hz),130.09(d,J＝3.6Hz),125.08(dt,J＝3.0,1.8Hz),114.28,111.50(ddd,J＝24.8,3.7,2.2Hz),109.67(dd,J＝19.3,14.4Hz),55.35,52.92； 19 F NMR(376MHz,Chloroform-d)δ-115.69(d,J＝15.0Hz),-132.92(d,J＝20.3Hz),-146.71(dd,J＝20.4,15.0Hz)；HRMS(ESI+):calculated for C 15 H 12 F 3 O 3 + [M+H] + 297.0733,found 297.0733.
While specific embodiments of the invention have been described in detail in connection with the examples, it should not be construed as limiting the scope of protection of the patent. Various modifications and variations which may be made by those skilled in the art without the creative effort are within the scope of the patent described in the claims.

Claims (3)

1. A method for synthesizing a polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon bond carboxylation reaction, which is characterized by comprising the following steps:
adding a reaction substrate, a photocatalyst, a hydrogen atom transfer reagent, a reducing agent and a base into a reaction vessel, and then adding the mixture into CO 2 Adding a solvent under the atmosphere, stirring at room temperature for reaction for 0.1-72 h under the illumination condition, and then separating and purifying to obtain a polyfluoroaryl carboxylic acid compound;
the structural general formula of the reaction substrate is shown in the formulas (I) - (III):
，
wherein R is 1 Is one of the following substituents:
，
R 4 is that t Bu、SMe、cyclopropyl、OCF 3 Or F;
R 2 is one of the following substituents:
，
R 3 is one of the following substituents:
；
the photocatalyst is Ir (ppy) 2 (dtbbpy)PF 6 ；
The reducing agent is potassium formate;
the hydrogen atom transfer reagent is N, N-dimethylethanolamine;
the solvent is DMF;
the alkali is CsF and Cs 2 CO 3 Is a mixture of (a) and (b).
2. The method for synthesizing a polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon linkage carboxylation according to claim 1, wherein the method comprises the following steps: the molar ratio of the reducing agent to the reaction substrate to the photocatalyst to the hydrogen atom transfer reagent to the alkali is 1-5:1:0.001-0.2:0.01-2:1-10.
3. The method for synthesizing a polyfluoroaryl carboxylic acid compound based on aryl fluorocarbon linkage carboxylation according to claim 1, wherein the method comprises the following steps: the pressure of the carbon dioxide in the reaction container is 0.1-30 times of the atmospheric pressure; the distance between the light source and the reaction vessel is 0.1-10 cm, the wavelength of light is 300-560 nm, and the power of the light source is 1-100W.
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