CN115010600A - Method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl fluorocarbon bond carboxylation reaction - Google Patents

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

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CN115010600A
CN115010600A CN202210620427.6A CN202210620427A CN115010600A CN 115010600 A CN115010600 A CN 115010600A CN 202210620427 A CN202210620427 A CN 202210620427A CN 115010600 A CN115010600 A CN 115010600A
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polyfluoroaryl
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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 polyfluoroaryl carboxylic acid compounds based on aryl carbon fluorine 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 agent, a reducing agent and a base into a reaction vessel, and then adding into CO 2 Adding solvent under atmosphere, and stirring at room temperature under the condition of light irradiation. And 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, cheap and easily-obtained raw materials and the like, can efficiently realize the breakage of aryl carbon fluorine bonds and the carboxylation reaction thereof, synthesizes important polyfluoroaryl carboxylic acid compounds, and has good application prospect.

Description

Method for synthesizing polyfluoroaryl carboxylic acid compounds 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 polyfluoroaryl carboxylic acid compounds based on aryl carbon-fluorine bond carboxylation.
Background
Fluorine is the element with the largest electronegativity in nature, and fluorine atoms are introduced into functional molecules to change the physical and chemical properties and physiological activities of the molecules. The polyfluoro aryl carboxylic acid has special properties as an important polyfluoro building block, and has wide application in the fields of medicines, pesticides, organic photoelectric materials and the like. The method takes a polyfluoro compound which is cheap and easy to obtain as a substrate, and can construct a part of fluoro compound with important application value through the selective functional group reaction of a C-F bond. The strategy has high economical steps and is one of the most effective means for constructing partial fluoro compounds. However, due to the high bond dissociation energy of the C-F bond, the strong affinity of fluorine atoms, the selective cleavage of the C-F bond and the functionalization thereof present major challenges.
Carbon dioxide (CO) on the other hand 2 ) The method has the advantages of low price, easy obtaining, no toxicity, no harm, recycling, and the like, is an excellent carbon-carbon (C1) synthon 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 polyfluorinated aromatic hydrocarbon is used as a substrate, and an important polyfluorinated aryl carboxylic acid compound can be constructed through the selective carboxylation reaction of a polyfluorinated aromatic hydrocarbon C-F bond. However, the reports in the field are few so far, the method is mainly realized by means of electro-reduction or transition metal catalysis, and the defects that a sacrificial anode, an equivalent metal reducing agent are required to be used, a guide group is additionally introduced, reaction conditions are harsh and the like exist, and the method has a large development space. The selective carboxylation reaction of aryl C-F bond with cheap reducing agent under mild condition is in need of development.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl carbon-fluorine bond carboxylation reaction, which can effectively solve the problems that a sacrificial anode or equivalent metal reducing agent is required 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, can synthesize the polyfluoroaryl carboxylic acid compounds by taking green and cheap formate as a reducing agent at room temperature, and has the characteristics of mild reaction condition, wide range of reaction substrates, good yield and regioselectivity, and cheap and easily-obtained raw materials.
In order to achieve the purpose, the invention adopts the technical scheme that: the method for synthesizing the polyfluoroaryl carboxylic acid compounds based on aryl carbon-fluorine bond carboxylation reaction comprises the following steps:
adding a reaction substrate, a photocatalyst, a hydrogen atom transfer agent, a reducing agent and a base into a reaction vessel, and then adding the mixture in CO 2 Adding a solvent in the atmosphere, stirring and reacting for 0.1-72 h at room temperature under the illumination condition, and then separating and purifying to obtain a poly-fluorine aryl carboxylic acid compound;
the structural general formula of the reaction substrate is shown as formula (I) or formula (II):
Figure BDA0003676402990000021
wherein R is 1 、R 2 、R 4 And R 5 Each independently is a hydrogen atom or a fluorine atom; r 3 Is substituted phenyl, naphthyl, fluorenyl, heteroaryl, ester group, carboxyl, amido, alkyl, alkenyl, alkynyl, cyano, boron, silicon, phosphino, amine, thioether, alkoxy, acyloxy or aryloxy; r 7 And R 8 Each independently is a hydrogen atom or a fluorine atom; r 6 And R 9 Is phenyl, naphthyl, fluorenyl, heteroaryl, ester group, carboxyl, amide group, alkyl, alkenyl, alkynyl, cyano, boron group, silicon group, phosphine group, amine group, thioether group, alkoxy, acyloxy or aryloxy.
On the basis of the technical scheme, the invention can be further improved as follows.
Further, 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.
Further, the reaction substrate is a pentafluoroaromatic compound, a tetrafluoroaromatic compound or a trifluoroaromatic compound; wherein the content of the first and second substances,
the pentafluoroarene compound is one of the following compounds:
Figure BDA0003676402990000022
Figure BDA0003676402990000031
the tetrafluoro arene compound is one of the following compounds:
Figure BDA0003676402990000032
the trifluoroarene compound is one of the following compounds:
Figure BDA0003676402990000033
Figure BDA0003676402990000041
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 agent is N, N-dimethylethanolamine, arylthiophenol, heteroaryl thiol, alkylthiol, nitrogen-containing heterocycle, benzoate, alkoxy base or siloxy base.
Further, the aryl thiophenol is 2,4, 6-triisopropyl thiophenol, 2,4, 6-tri-tert-butyl thiophenol, 4-tert-butyl thiophenol or 2-methoxycarbonyl thiophenol; the alkyl mercaptan is cyclohexyl mercaptan, ethyl thioglycolate or ethyl 2-mercaptopropionate.
Further, the solvent is MeCN, DMF, DMAc, DMSO, NMP.
Further, the base is a carbonate, bicarbonate, fluoride, alkoxy base, phosphate, hydrogen phosphate, carboxylate, or organic base.
Further, the pressure of carbon dioxide in the reaction container is 0.1-30 times of 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 invention has the beneficial effects that:
1. the invention provides a method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl carbon-fluorine bond carboxylation reaction. Under the catalysis of visible light, a pentafluoro aryl hydrocarbon compound, a tetrafluoro aryl hydrocarbon compound or a trifluoro aryl hydrocarbon compound is used as a reaction substrate, carbon dioxide is used as a carboxylic acid source, and a photocatalyst, a hydrogen atom transfer reagent, a reducing agent and alkali are added simultaneously to prepare a polyfluoro aryl carboxylic acid compound; 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 compounds, tetrafluoroaromatic compounds and trifluoroaromatic compounds, and has the characteristics of wide range of reaction substrates, and good yield and regioselectivity;
3. the invention realizes the selective carboxylation reaction of the carbon-fluorine bond of the polyfluorinated aromatic hydrocarbon promoted by visible light for the first time. The reaction efficiently realizes the selective breakage of aryl C-F bonds under mild conditions and introduces important carboxyl functional groups to prepare important polyfluoroaryl carboxylic acid compounds, and has wide application prospect.
Drawings
FIG. 1 is a schematic diagram of the synthetic mechanism of the present invention.
Detailed Description
The following examples are provided to illustrate specific embodiments of the present invention.
Example 1
A method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl fluorocarbon bond carboxylation reaction is disclosed, wherein the synthetic reaction formula is shown as a formula (1-1).
Figure BDA0003676402990000051
The synthesis method comprises the following steps:
a25 ml Schlenk reaction tube equipped with a stirrerAfter drying by heating under vacuum, the reaction substrate pentafluoroaromatic compound (0.2mmol, 1.0equiv if the substrate is solid) and photocatalyst Ir (ppy) 2 (dtbbpy)PF 6 (4.6mg, 0.025mmol, 2.5 mol%). Then the reaction tube is moved into a glove box, and reducing agent HCO is added in sequence 2 K (33.6mg, 0.4mmol, 2equiv), hydrogen atom transfer reagent N, N-dimethylethanolamine (DABCO, 13.4mg, 0.12mmol, 60 mol%), base CsF (76mg, 0.5mmol, 2.5equiv), base Cs 2 CO 3 (78.2mg, 0.24mmol, 1.2 equiv). Then the reaction tube is sealed by using the corresponding cock of the reaction tube, the glove box is removed, and the reaction tube is pumped and replaced by CO by using a double-row tube 2 Atmosphere, repeat 3 times. Then in CO 2 The reaction substrate, a pentafluoroarene compound (if the substrate is liquid) and ultra-dry DMF (2mL) were injected into the reaction tube sequentially using a syringe under an atmosphere. The reaction tube was sealed immediately after the addition. Fixing the reaction tube in a water bath kettle, adjusting the rotation speed of a stirrer used for reaction to 650r/min, irradiating at a distance of 0.5cm by using a 30W blue LED lamp (the wavelength is about 450 nm), and radiating by using a fan to maintain the reaction temperature at 25-30 ℃. After stirring and reacting for 30-34 hours, adding 5mL of ethyl acetate into the reaction mixture for dilution, adding 2mL of 2N hydrochloric acid and 5mL of water for quenching reaction, and 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 completely removed using rotary evaporation. The crude product thus obtained was transferred to a 25mL eggplant-shaped bottle using 2mL of methanol and 2mL of diethyl ether, and trimethylsilyl diazomethane (0.3mL, 3equiv, 0.6mmol, 2M n-hexane solution) was added dropwise at 0 ℃ and reacted at room temperature for 1 hour. Thereafter, trimethylsilyl diazomethane (0.3mL, 3equiv, 0.6mmol, 2M n-hexane solution) was further added dropwise at 0 ℃ and reacted at room temperature for 1 hour. After the esterification, the mixture was separated and purified by column chromatography. The purification conditions were: washing with a mixed solvent of petroleum ether and dichloromethane, namely 7: 1-3: 1(v: v), so as to obtain the target product. The specific reaction results are shown in Table 1.
TABLE 1 yield of pentafluoroaromatic compounds as substrate and corresponding products
Figure BDA0003676402990000052
Figure BDA0003676402990000061
Note: the standard reaction conditions in table 1 are the same as described above, regioselectivity is determined by crude GC, yield is isolated yield; a is reaction for 42 h; b is 2.5 equivalents of HCO 2 K; c is 2.5 equivalents CsF and 1.5 equivalents Cs 2 CO 3 As a base, reacting for 30 h; d is reaction for 48 hours; e is 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 fluoroaryl hydrocarbon compounds can obtain the tetrafluoroaryl carboxylic acid compounds with higher yield and good regioselectivity. Various functional groups such as t-butyl, methylthio, methoxy, cyclopropyl, trifluoromethoxy, fluorine atom, and benzyl C-H bond, etc. are compatible with the reaction system. Fluorene groups, naphthyl groups, and heterocycles such as dibenzofuran, thiophene, and furan can also be compatible with the reaction system. The target reaction can also be smoothly carried out by using the non-biphenyl type pentafluoro aromatic hydrocarbon.
Example 2
A method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl carbon fluorine bond carboxylation reaction is disclosed, wherein the synthetic reaction formula is shown as a formula (1-2).
Figure BDA0003676402990000062
The synthesis method comprises the following steps:
after a 25ml Schlenk reaction tube equipped with a stirrer was dried by heating under vacuum, the reaction substrate tetrafluoroarene compound (0.2mmol, 1.0equiv if the substrate is solid) and photocatalyst Ir (ppy) were added 2 (dtbbpy)PF 6 (4.6mg, 0.025mmol, 2.5 mol%). Then the reaction tube is moved into a glove box, and reducing agents HCO are added in sequence 2 K (33.6mg, 0.4mmol, 2equiv), hydrogen atom transfer reagent DABCO (13.4mg, 0.12mmol, 60 mol%), baseCsF (76mg, 0.5mmol, 2.5equiv), alkali Cs 2 CO 3 (78.2mg, 0.24mmol, 1.2 equiv). Then the reaction tube is sealed by a corresponding cock of the reaction tube, the glove box is moved out, and the reaction tube is pumped and replaced by CO by a double-row tube 2 Atmosphere, repeat 3 times. Then in CO 2 Under the atmosphere, a reaction substrate, namely a trifluoroarene compound (if the substrate is liquid), and ultra-dry DMF (2mL) are injected into a reaction tube in sequence by using a syringe. The reaction tube was sealed immediately after the addition. Fixing the reaction tube in a water bath kettle, adjusting the rotation speed of a stirrer used for reaction to 650r/min, irradiating at a distance of 0.5cm by using a 30W blue LED lamp (the wavelength is about 450 nm), and radiating by using a fan to maintain the reaction temperature at 25-30 ℃. Stirring for reaction for 12-72 h, adding 5mL of ethyl acetate to the reaction mixture for dilution, adding 2mL of 2N hydrochloric acid and 5mL of water for quenching reaction, and stirring for 1 min. Subsequently, the reaction solution was extracted 3 times with 3mL of ethyl acetate, and the organic phases were combined and the residual solvent was completely removed using rotary evaporation. The crude product thus obtained was transferred to a 25mL eggplant-shaped bottle using 2mL of methanol and 2mL of diethyl ether, and trimethylsilyl diazomethane (0.2mL, 2equiv, 0.4mmol, 2M in n-hexane) was added dropwise at 0 ℃ and reacted at room temperature for 1 hour. Thereafter, trimethylsilyl diazomethane (0.2mL, 2equiv, 0.4mmol, 2M n-hexane solution) was further added dropwise at 0 ℃ and reacted at room temperature for 1 hour. After the esterification, the mixture was separated and purified by column chromatography. The purification conditions were: washing with a mixed solvent of petroleum ether and dichloromethane, namely 7: 1-2: 1(v: v), so as to obtain the target product. The specific reaction results are shown in Table 2.
TABLE 2 yield of tetrafluoroarene compounds as substrates and corresponding products
Figure BDA0003676402990000071
Note: the standard reaction conditions in table 2 are the same as described above, and the regioselectivity is determined by crude GC; a is 3 equivalents of potassium formate used.
The above experimental data show that the electron neutral and electron donating group substituted tetrafluoroarene can also smoothly perform the carboxylation reaction of the carbon-fluorine bond, and obtain the trifluoroaryl carboxylic acid product which is difficult to synthesize by other methods with moderate yield and regioselectivity.
Example 3
A method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl fluorocarbon bond carboxylation reaction has a synthetic reaction formula shown as a formula (1-3).
Figure BDA0003676402990000072
The synthesis method comprises the following steps:
after a 25ml Schlenk reaction tube equipped with a stirrer was dried by heating under vacuum, a reaction substrate of a trifluoroaromatic hydrocarbon compound (0.2mmol, 1.0equiv, if the substrate is a solid) and a photocatalyst Ir (ppy) were added 2 (dtbbpy)PF 6 (4.6mg, 0.025mmol, 2.5 mol%). Then the reaction tube is moved into a glove box, and reducing agent HCO is added in sequence 2 K (42.0mg, 0.5mmol, 2.5equiv), hydrogen atom transfer reagent DABCO (13.4mg, 0.12mmol, 60 mol%), base Cs 2 CO 3 (162.9mg, 0.5mmol, 2.5 equiv). Then the reaction tube is sealed by using the corresponding cock of the reaction tube, the glove box is removed, and the reaction tube is pumped and replaced by CO by using a double-row tube 2 Atmosphere, repeat 3 times. Then in CO 2 The reaction substrate, a trifluoroarene compound (if the substrate is a liquid), ultra-dry DMF (2mL) and ultra-dry DMSO (300 μ L) are sequentially injected into the reaction tube by using a syringe under an atmosphere. The reaction tube was sealed immediately after the addition. Fixing the reaction tube in a water bath kettle, adjusting the rotation speed of a stirrer used for reaction to 650r/min, irradiating at a distance of 0.5cm by using a 30W blue LED lamp (the wavelength is about 450 nm), and radiating by using a fan to maintain the reaction temperature at 25-30 ℃. After stirring the reaction mixture for 24 to 38 hours, the reaction mixture was diluted with 5mL of ethyl acetate, quenched with 2mL of 2N hydrochloric acid and 5mL of water, and stirred 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 completely removed using rotary evaporation. The crude product thus obtained was transferred to a 25mL eggplant-shaped bottle using 2mL of methanol and 2mL of diethyl ether, and trimethylsilyl diazomethane (0.2mL, 2equiv, 0.4mmol, 2M n-hexane solution) was added dropwise at 0 ℃ to react at room temperature for 1 hour. Thereafter, trimethylsilyl diazomethane (0.2mL, 2equiv, 0.4mmol, 2M n-hexane solution) was further added dropwise at 0 ℃ and reacted at room temperature for 1 hour. After the esterification, the mixture was separated and purified by column chromatography. The purification conditions were: washing with a mixed solvent of petroleum ether and dichloromethane, namely 5: 1-2: 1(v: v), or petroleum ether and ethyl acetate, namely 50: 1-5: 1(v: v) to obtain the target product. The specific reaction results are shown in Table 3.
TABLE 3 yield of trifluoroarene compounds as substrate and corresponding products
Figure BDA0003676402990000081
Note: the standard reaction conditions in table 3 are the same as above, the product is of a single configuration, and the yield is the isolated yield; a is reaction for 32 h; b is the use of 3 equivalents of HCO 2 K; c, using DMSO as a solvent, and reacting for 24 hours; d is the use of 2 mol% Ir (ppy) 2 (dtbbpy)PF 6 50 mol% DABCO, 2 equivalents HCO 2 K, reacting for 32 hours; e is the use of 3.5 equivalents of HCO 2 K。
The experimental results show that the trifluoroarene substrate can also smoothly generate the carbon-fluorine bond carboxylation reaction, and a target product is obtained in a single configuration. Various electron-withdrawing groups such as an ester group, a cyano group, a sulfonamide group, a fluorine atom, and pyridine, and various electron-donating groups such as a methoxy group, thiophene, and a long-chain alkyl group are compatible with the reaction system. Some natural product derivatives and commercially available liquid crystal material molecules can also undergo a carbon-fluorine bond carboxylation reaction smoothly, and difluoroaryl carboxylic acid products which are difficult to synthesize by other methods are generated.
Experimental example 1
In this experimental example 1, 4'- (tert-butyl) -2,3,4,5, 6-pentafluoro-1, 1' -biphenyl was used as a reaction substrate, and the influence on the reaction yield was examined by changing the reaction conditions: 1a substrate (0.2mmol, 1equiv), 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 (0.24mmol，1.2equiv,78.2mg)，Ultra dry solvent DMF (2ml) and the results are shown in Table 4.
The reaction equation is as follows:
Figure BDA0003676402990000091
TABLE 4 product yields under different reaction conditions with 4'- (tert-butyl) -2,3,4,5, 6-pentafluoro-1, 1' -biphenyl as substrate
Figure BDA0003676402990000092
Figure BDA0003676402990000101
Note: the isolation yield is shown in table 4. The nuclear magnetic yield with dibromomethane as an internal nuclear magnetic hydrogen spectrum standard is shown in brackets; a is 50 mol% DABCO, 2.5 equivalents Cs 2 CO 3 As a single base, reacting for 24 h; b is the use of 2 mol% Ir (ppy) 2 (dtbbpy)PF 6 10 mol% 2,4, 6-triisopropylthiophenol, 2.5 equivalents Cs 2 CO 3 As single base, react for 32 h.
As can be seen from the data in Table 4 above, the yield was 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 are irradiated 2 The reducing agent plays an indispensable role in the reaction, and any item which is not available or only can obtain trace target products is lacked. The hydrogen atom transfer reagent and the base significantly promote the reaction. When other photosensitizers or hydrogen atom transfer agents are used, the yield is greatly reduced, mainly the raw material residue or the defluorination hydrogenation by-products are increased. Replacement of CsF/Cs 2 CO 3 The yield is obviously reduced when the alkali is a single component, and the raw material residue or the defluorination hydrogenation by-products are increased. The reaction cannot occur when the solvent is replaced by MeCN; when the solvent is replaced by DMSO, the yield is reduced, and the byproducts of defluorination and hydrogenation are increased obviously.
In addition, the results of the prior experimental studiesBased on the above, the inventors propose a reaction mechanism as shown in fig. 1. Firstly, the DABCO and the excited photosensitizer generate a Single Electron Transfer (SET) process to obtain a reduced photosensitizer and DABCO radical cations. Subsequent formation of DABCO radical cation with HCO 2 K undergoes a Hydrogen Atom Transfer (HAT) process to yield protonated DABCO and carbon dioxide radical anions. The carbon dioxide radical anion then reduces the polyfluoroarene substrate to a polyfluoroaryl radical by a Single Electron Transfer (SET) process. The aryl free radical and a reduction-state photosensitizer are reduced into polyfluoroaryl carbanions through a Single Electron Transfer (SET) process, finally, nucleophilic attack carbon dioxide is carried out to generate polyfluoroaryl carboxylate, and a target product is obtained after acidification and esterification treatment.
The product prepared by the invention is subjected to nuclear magnetic resonance and mass spectrum characterization analysis. The results of nuclear magnetic and mass spectrum 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
Figure BDA0003676402990000102
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
Figure BDA0003676402990000103
(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
Figure BDA0003676402990000111
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
Figure BDA0003676402990000112
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
Figure BDA0003676402990000113
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
Figure BDA0003676402990000114
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
Figure BDA0003676402990000121
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
The characteristics are as follows: 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,
Figure BDA0003676402990000122
-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-Dimethoxyphenylene-5) -2,3,5, 6-tetrafluorobenzoic acid methyl ester
Figure BDA0003676402990000123
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
Figure BDA0003676402990000124
(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
Figure BDA0003676402990000131
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
Figure BDA0003676402990000132
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
Figure BDA0003676402990000133
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
Figure BDA0003676402990000134
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
Figure BDA0003676402990000141
(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
Figure BDA0003676402990000142
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
Figure BDA0003676402990000143
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
Figure BDA0003676402990000144
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
Figure BDA0003676402990000151
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
The characteristics are as follows: white solid
Figure BDA0003676402990000152
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
Figure BDA0003676402990000153
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
Figure BDA0003676402990000154
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
Figure BDA0003676402990000161
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
Figure BDA0003676402990000162
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
Figure BDA0003676402990000163
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
Figure BDA0003676402990000164
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-diethylsulfonamido) -3, 5-difluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
Figure BDA0003676402990000171
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
Figure BDA0003676402990000172
＝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
Figure BDA0003676402990000173
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',5,5' -tetrafluoro- [1,1' -biphenyl ] -4-carboxylic acid methyl ester
Figure BDA0003676402990000174
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
Figure BDA0003676402990000181
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
Figure BDA0003676402990000182
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
Figure BDA0003676402990000183
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
Figure BDA0003676402990000184
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
Figure BDA0003676402990000185
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-Hexycarbonyl-2, 6-difluorobenzoic acid methyl ester
Figure BDA0003676402990000191
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' -Diformic acid dimethyl ester
Figure BDA0003676402990000192
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
The characteristics are as follows: viscous colorless liquid
Figure BDA0003676402990000193
(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 '- ((1s,4r) -4-propylcyclohexyl) - [1,1' -biphenyl ] -4-carboxylic acid methyl ester
Figure BDA0003676402990000194
(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 '- ((1s,4r) -4-pentylcyclohexyl) - [1,1' -biphenyl ] -4-carboxylic acid methyl ester
Figure BDA0003676402990000201
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
The characteristics are as follows: white solid
Figure BDA0003676402990000202
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
Figure BDA0003676402990000203
(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 the present invention has been described in detail with reference to the embodiments, it should not be construed as limited to the scope of the patent. Various modifications and changes may be made by those skilled in the art without inventive step within the scope of the appended claims.

Claims (9)

1. A method for synthesizing polyfluoroaryl carboxylic acid compounds based on aryl fluorocarbon bond carboxylation reaction is characterized by comprising the following steps:
adding a reaction substrate, a photocatalyst, a hydrogen atom transfer agent, a reducing agent and a base into a reaction vessel, and then adding the mixture in CO 2 Adding a solvent in the atmosphere, stirring and reacting for 0.1-72 h at room temperature under the illumination condition, and then separating and purifying to obtain a poly-fluorine aryl carboxylic acid compound;
the structural general formula of the reaction substrate is shown as formula (I) or formula (II):
Figure FDA0003676402980000011
wherein R is 1 、R 2 、R 4 And R 5 Each independently is a hydrogen atom or a fluorine atom; r 3 Is substituted benzeneA group, naphthyl, fluorenyl, heteroaryl, ester, carboxyl, amide, alkyl, alkenyl, alkynyl, cyano, boron, silicon, phosphine, amine, thioether, alkoxy, acyloxy, or aryloxy; r 7 And R 8 Each independently is a hydrogen atom or a fluorine atom; r 6 And R 9 Is phenyl, naphthyl, fluorenyl, heteroaryl, ester group, carboxyl, amide group, alkyl, alkenyl, alkynyl, cyano, boron group, silicon group, phosphine group, amine group, thioether group, alkoxy, acyloxy or aryloxy.
2. The method for synthesizing polyfluoroaryl carboxylic acids based on aryl fluorocarbon bonding carboxylation reaction according to claim 1, wherein: 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 polyfluoroaryl carboxylic acids based on aryl fluorocarbon linkage carboxylation reaction according to claim 1 or 2, wherein: the photocatalyst is a D-A type photocatalyst or an organic metal photocatalyst.
4. The method for synthesizing polyfluoroaryl carboxylic acids based on aryl fluorocarbon bond carboxylation reaction as claimed in claim 1 or 2, wherein: the reducing agent is formate, oxalate, organic amine, hans ester or nitrogen-containing heterocycle.
5. The method for synthesizing polyfluoroaryl carboxylic acids based on aryl fluorocarbon bond carboxylation reaction as claimed in claim 1 or 2, wherein: the hydrogen atom transfer reagent is N, N-dimethylethanolamine, aryl thiophenol, heteroaryl thiol, alkyl thiol, nitrogen-containing heterocycle, benzoate, alkoxy base or siloxy base.
6. The method for synthesizing polyfluoroaryl carboxylic acids based on aryl C-F bond carboxylation reaction of claim 5, wherein: the aryl thiophenol is 2,4, 6-triisopropyl thiophenol, 2,4, 6-tri-tert-butyl thiophenol, 4-tert-butyl thiophenol or 2-methoxycarbonyl thiophenol; the alkyl mercaptan is cyclohexyl mercaptan, ethyl thioglycolate or ethyl 2-mercaptopropionate.
7. The method for synthesizing polyfluoroaryl carboxylic acids based on aryl fluorocarbon bonding carboxylation reaction according to claim 1, wherein: the solvent is MeCN, DMF, DMAc, DMSO or NMP.
8. The method for synthesizing polyfluoroaryl carboxylic acids based on aryl fluorocarbon bonding carboxylation reaction according to claim 1, wherein: the base is a carbonate, bicarbonate, fluoride, alkoxy base, phosphate, hydrogen phosphate, carboxylate, or an organic base.
9. The method for synthesizing polyfluoroaryl carboxylic acids based on aryl fluorocarbon bonding carboxylation reaction according to claim 1, wherein: the pressure of the carbon dioxide in the reaction container is 0.1-30 times of 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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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11889833B2 (en) 2022-01-14 2024-02-06 Enko Chem, Inc. Protoporphyrinogen oxidase inhibitors

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108752232A (en) * 2018-05-14 2018-11-06 四川大学 A kind of synthetic method of α-quaternary carbon amino acid
US20190372010A1 (en) * 2018-05-30 2019-12-05 Universal Display Corporation Host materials for electroluminescent devices
CN113444005A (en) * 2021-07-26 2021-09-28 四川大学 Method for synthesizing novel glutaric acid compound from diaryl substituted non-activated olefin
CN115073250A (en) * 2021-03-16 2022-09-20 四川大学 Based on sp 3 Method for synthesizing alpha-aryl acetic acid or alpha-fluorocarboxylic acid compound by virtue of carbon-fluorine bond carboxylation reaction

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108752232A (en) * 2018-05-14 2018-11-06 四川大学 A kind of synthetic method of α-quaternary carbon amino acid
US20190372010A1 (en) * 2018-05-30 2019-12-05 Universal Display Corporation Host materials for electroluminescent devices
CN115073250A (en) * 2021-03-16 2022-09-20 四川大学 Based on sp 3 Method for synthesizing alpha-aryl acetic acid or alpha-fluorocarboxylic acid compound by virtue of carbon-fluorine bond carboxylation reaction
CN113444005A (en) * 2021-07-26 2021-09-28 四川大学 Method for synthesizing novel glutaric acid compound from diaryl substituted non-activated olefin

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BO, ZHI-YU，等: "Visible-light photoredox-catalyzed selective carboxylation of C(sp2)-F bonds in polyfluoroarenes with CO2", 《CHINESE JOURNAL OF CATALYSIS 》, vol. 43, no. 9, pages 2388 - 2394, XP087135865, DOI: 10.1016/S1872-2067(22)64140-8 *
CHUAN ZHU，等: "Selective C–F bond carboxylation of gemdifluoroalkenes with CO2 by photoredox/palladium dual catalysis", 《CHEMICAL SCIENCE》, no. 10, pages 6721 *
SHIGENO, MASANORI，等: "Direct C-H carboxylation forming polyfunctionalized aromatic carboxylic acids by combined Bronsted bases", 《ORGANIC LETTERS》, vol. 24, no. 3, pages 809 - 814 *
ZHEN ZHANG，等: "Visible Light-Driven Catalytic Reductive Carboxylation with CO2", 《ACS CATAL.》, pages 10871 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11889833B2 (en) 2022-01-14 2024-02-06 Enko Chem, Inc. Protoporphyrinogen oxidase inhibitors

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