阅读说明：本技术 一种氟代烯基酮类化合物的制备方法 (Preparation method of fluoro alkenyl ketone compound ) 是由 史大永 张众 李祥乾 于 2021-01-13 设计创作，主要内容包括：本发明公开了一种氟代烯基酮类化合物的制备方法,该制备方法包括：氩气保护下将炔烃、溴二氟烷基类化合物、水、碳酸锂、苯基吡啶和三苯基吡啶铱溶于溶剂中,在光照条件下,室温搅拌反应12h,旋除溶剂后经硅胶柱分离得到氟代烯基酮类化合物。本发明制备方法操作简单,反应原料简单易得,可以立体专一的得到氟代烯基酮类化合物,所得到的化合物是一类非常有用的有机中间体并且具有潜在的药用价值,具有多种生物活性。(The invention discloses a preparation method of fluoro alkenyl ketone compounds, which comprises the following steps: under the protection of argon, dissolving alkyne, bromine difluoro alkyl compound, water, lithium carbonate, phenylpyridine and triphenyl pyridine iridium in a solvent, stirring and reacting for 12 hours at room temperature under the condition of illumination, and separating by a silica gel column after removing the solvent to obtain the fluoro alkenyl ketone compound. The preparation method is simple to operate, the reaction raw materials are simple and easy to obtain, the fluoro alkenyl ketone compound can be obtained stereospecifically, and the obtained compound is a very useful organic intermediate and has potential medicinal value and multiple biological activities.)

1. A method for preparing a fluoroalkenyl ketone compound, comprising:

dissolving alkyne and bromine difluoroalkyl compounds in a solvent, adding a photocatalyst, alkali and an additive, reacting for 12 hours at room temperature under the irradiation of visible light, removing the solvent by spinning, and separating by a silica gel column to obtain fluoro alkenyl ketone compounds;

the mol ratio of the alkyne to the bromine difluoroalkyl compound to the water is 1: 1.2: 30, of a nitrogen-containing gas;

the structural formula of the alkyne compound is shown in formula 3, the structural formula of the bromine difluoroalkyl compound is shown in formula 2,β-the structural formula of the fluoro alkenyl ketone compound is formula 1;

wherein: r¹、R²Is an alkyl group or an aryl group having 1 to 15 carbon atoms, wherein the aryl group is an aryl group having an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkoxy group, an aryl group, an aralkyl group, an aryloxy group, fluorine, chlorine, bromine, a cyano group and a nitro group at the ortho-para position; or an aryl-fused-ring aryl group; r¹And R²Are the same or different; r³Is a polyfluoroalkyl group having 1 to 15 carbon atoms, or an amide group, a phosphoramide group, or an ester group.

2. The process for preparing fluoroalkenyl ketones according to claim 1 wherein the solvent is acetonitrile, dimethyl sulfoxide, N-dimethylformamide, acetone, tetrahydrofuran, 1, 4-dioxane or a mixture thereof.

3. The process for preparing fluoroalkenyl ketones according to claim 1, wherein the visible light conditions are blue light and sunlight.

4. The process for producing fluoroalkenyl ketones according to claim 1, wherein the base is sodium carbonate, potassium carbonate, cesium carbonate or lithium carbonate.

5. The process for preparing fluoroalkenyl ketones according to claim 1, wherein the catalyst is iridium triphenylpyridinate or iridium tris (2, 4-difluorophenyl) pyridinate.

6. The method for producing fluoroalkenyl ketones according to claim 1, wherein the alkyl group is a linear or branched alkyl group having 1 to 12 carbon atoms.

7. The method of preparing fluoroalkenyl ketones according to claim 1, wherein the cycloalkylalkyl group is a cyclic alkyl group having 3 to 15 carbon atoms.

8. The method for producing fluoroalkenyl ketones according to claim 1, wherein the aryloxy group is an aryloxy group having 7 to 15 carbon atoms.

9. The process for preparing fluoroalkenyl ketones according to claim 1, wherein the additive added is phenylpyridine.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of fluoro alkenyl ketone compounds.

Background

The fluorine-containing compound is a very important organic intermediate and has wide application in the fields of pharmaceutical chemistry and synthetic chemistry. When fluorine atoms are introduced into the structure of a molecule, the properties of the drug molecule, such as lipid solubility, metabolic stability, molecular conformation, and the ability to hydrogen bond, can be significantly altered. Fluoroolefins currently exhibit a number of biological activities in pharmaceutical chemistry, such as anti-cancer (s. Osada, s. Sano, m. Ueyama, y. Chuman, h. Kodama and k. Sakaguchi,Bioorg. Med. Chem., 2010, 18, 605； J. Kanazawa, T. Takahashi , S. Akinaga , T. Tamaoki and M. Okabe , Anti-Cancer Drugs1998, 9, 653), sterilization (r. J.Sciotti, M. Pliushchev, P. E. Wiedeman, D. Balli, R. Flamm, A. M. Nilius, K. Marsh, D. Stolarik, R. Jolly, R. Ulrich and S. W. Djuric, Bioorg. Med. Chem. Lett., 2002, 12, 2121； Y. Asahina , K. Iwase , F. Iinuma , M. Hosaka and T. Ishizaki , J. Med. Chem.2005, 48, 3194), anti-HIV (S. Oishi, H. Kamitani, Y. Kodera, K. Watanabe, K. Kobayashi, T. Narumi, K. Tomita, H. Ohno, T. Naito, E. Kodama, M. Matsuoka and N. Fujii,Org. Biomol. Chem.2009, 7, 2872), treatment of diabetes (s.d. Edmondson, l. Wei, j. Xu, j. Shang, s. Xu, j. Pang, a. Chaudhary, d.c. Dean, h. He, b. Leiting, k.a. Lyons, r.a. Patel, s.b. Patel, g. Scapin, j.k. Wu, m.g. Beconi, n.a. Thornberry and a.e. Weber,Bioorg. Med. Chem. Lett.2008, 18, 2409), and so on.

In view of the importance of fluoroalkenyl ketones, a number of preparative processes have been developed in succession. Control of stereoselectivity of fluoroalkenyl ketones, particularly tetrasubstituted fluoroalkenyl ketones, has been a difficult point in the synthesis of fluoroalkenyl ketones.

In the synthesis method using olefin as raw material, tri-substituted fluoroketene can be prepared by using olefin and trimethylsilyldifluoroalkyl compound under the action of excess silver fluoride and using oxygen as oxidant. The solvent required by the method is a solvent with high boiling point and is not easy to process, and equivalent silver fluoride is required to be used in the reaction, so the method is expensive. (Wu, Y. -b.; Lu, G. -p.; Yuan, T.; Xu, Z. -b.; Wan, L.; Cai, C.).Chem. Commun. 2016,52(94), 13668-13670..). The method is characterized in that vinyl enol silicon ether is used as a raw material, ethyl difluorobromoacetate is used as a fluorination reagent, pentamethyldiethylenetriamine is used as alkali, and the synthesis of fluoroketene can be realized under the action of cuprous iodide and triethylchlorosilane, however, a vinyl enol silicon ether substrate is usually required to be prepared at present, and trisubstituted fluoroketene is mainly synthesized. (Li, Y.; Liu, J.; ZHao, S.; Du, X.; Guo, M.; ZHao, W.; Tang, X.; Wang, G.,Org. Lett. 2018,20(4), 917-920.). Ketone is used as raw material, ethyl difluorobromoacetate is used as fluorinating agent, and the fluorinating agent can be used under the condition of transition metal nickel or illuminationThe synthesis of fluoroketene can be realized, and the reaction needs to use strong alkali which is sensitive to water and has harsh conditions. (a) Li, C, Cao, Y-X, Jin, R-X, Bian, K-J, Qin, Z-Y, Lan, Q, Wang, X-S,Chem. Sci. 2019,10(40), 9285-9291；b）Li, K.; Chen, J.; Yang, C.; Zhang, K.; Pan, C.; Fan, B. Org. Lett. 2020,22(11) 4261-4265.) the preparation of Z-type fluoroketene can be realized under the condition of illumination by taking enol ester as a raw material, the raw material for reaction needs to be synthesized from ketone, and the reaction can not obtain E-type fluoroketene. (Li, W. -p.; Zhu, Y. -c.; Zhou, Y. -j.; Yang, H. -w.; Zhu, C. -j.),Tetrahedron 2019,75 (12), 1647-1651.）。

as described above, no report has been made on the production of fluoroalkenyl ketone compounds from alkynes. The main problem of the synthesis of fluoroalkenyl ketones via other substrates, including alkenes, ketones, enolsilyl ethers and enol esters, is the limited synthesis of the substrates, in particular the stereoselective synthesis of tetra-substituted fluoroalkenyl ketones. Meanwhile, the reaction conditions are harsh, sensitive to water and strong alkali is needed.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a preparation method of a fluoro-alkenylketone compound, which has the advantages of simple and easily obtained raw materials, no need of complicated operation and suitability for large-scale preparation.

The invention provides a preparation method of fluoro alkenyl ketone compounds, which adopts simple and easily obtained alkyne compounds, bromine difluoroalkyl compounds and water as raw materials to effectively synthesize the fluoro alkenyl ketone compounds by blue light irradiation under the condition of normal temperature in the presence of photosensitizer triphenylpyridine iridium and alkali.

The invention provides a preparation method of fluoro alkenyl ketone compounds, which comprises the following specific technical scheme:

dissolving alkyne, bromine difluoro alkyl compound, water, lithium carbonate, phenylpyridine and triphenyl pyridine iridium in a solvent under the protection of argon, stirring and reacting for 12 hours at room temperature under the condition of illumination, and separating by a silica gel column after removing the solvent to obtain fluoro alkenyl ketone compound;

the mol ratio of the alkyne to the bromine difluoroalkyl compound to the water is 1: 2: 30, of a nitrogen-containing gas;

the structural formula of the alkyne compound is shown in formula 2, the structural formula of the bromine difluoroalkyl compound is shown in formula 3, and the structural formula of the fluoro alkenyl ketone compound is shown in formula 1;

in the above reaction formula:

R¹, R²represents an alkyl group or an aryl group having 1 to 15 carbon atoms, wherein the aryl group is an aryl group having an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkoxy group, an aryl group, an aralkyl group, an aryloxy group, fluorine, chlorine, bromine, a cyano group and a nitro group at the ortho-or meta-para-position; aryl groups may be fused; r¹、R²Are the same or different. R³Is a polyfluoroalkyl group having 1 to 15 carbon atoms, or an amide group, a phosphoramide group, or an ester group.

Wherein the alkyl refers to a straight chain or branched chain alkyl group having 1 to 15 carbon atoms, such as: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, nonyl, decyl, undecyl, dodecyl and the like. The linear or branched alkyl group having 1 to 12 carbon atoms is preferable, the linear or branched alkyl group having 1 to 10 carbon atoms is particularly preferable, and the linear or branched alkyl group having 1 to 8 carbon atoms is most preferable.

The cycloalkyl group means a cyclic alkyl group having 3 to 15 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc., preferably cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl.

The cycloalkylalkyl group means a cyclic alkyl group having 4 to 15 carbon atoms, such as cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cycloheptylmethyl group, cyclooctylmethyl group, cyclopropylethyl group, cyclobutylethyl group, cyclopentylethyl group, cyclohexylethyl group, cycloheptylethyl group, cyclooctylethyl group, cyclopropylpropyl group, cyclobutylpropyl group, cyclopentylpropyl group, cyclohexylpropyl group, cycloheptylpropyl group, cyclooctylpropyl group and the like, and preferably cyclopropylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cycloheptylmethyl group, cyclopropylethyl group, cyclopentylethyl group, cyclohexylethyl group, cycloheptylethyl group, cyclopropylpropyl group, cyclopentylpropyl group, cyclohexylpropyl group, cycloheptylpropyl group.

The aryl group is an aryl group having 6 to 15 carbon atoms. Preferably phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-hydroxyphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-cyanophenyl, m-cyanophenyl, p-cyanophenyl, biphenyl, 1-naphthyl, 2-naphthyl, substituted naphthyl and polyalkyl-substituted phenyl, polyhalo-substituted phenyl and phenyl which is polysubstituted with random combinations of alkyl, halogen, hydroxy, alkoxy, etc.

The aralkyl group refers to an aralkyl group having 7 to 15 carbon atoms. Preferably benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, biphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, substituted naphthylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl, etc.

The aryloxy group is an aryloxy group having 7 to 15 carbon atoms. Preferably phenoxy, o-methylphenoxy, m-methylphenoxy, p-methylphenoxy, o-methoxyphenoxy, m-methoxyphenoxy, p-methoxyphenoxy, o-fluorophenoxy, m-fluorophenoxy, p-fluorophenoxy, o-chlorophenoxy, m-chlorophenoxy, p-chlorophenoxy, o-nitrophenoxy, m-nitrophenoxy, p-nitrophenoxy, o-cyanophenoxy, m-cyanophenoxy, p-cyanophenoxy, diphenoxy, 1-naphthoxy, 2-naphthoxy, substituted naphthoxy, benzyloxy, phenethyloxy, phenylpropyloxy, phenylbutoxy, phenylpentoxy and the like.

Preferred R¹Represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, nonyl, decyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, p-tolyl, p-chlorophenyl, p-fluorophenyl, p-nitrophenyl, p-methoxyphenyl, benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, o-n-nitrobenzyl, p-chlorobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-, Biphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl, more preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, o-nitrobenzyl, p-nitrobenzyl, o-cyanobenzylPhenylmethyl, p-cyanobenzyl, diphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, phenylethyl, phenylpropyl, phenylbutyl, most preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenylmethyl, phenylethyl, phenylpropyl.

Preferred R²Represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, nonyl, decyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, p-tolyl, p-chlorophenyl, p-fluorophenyl, p-nitrophenyl, p-methoxyphenyl, benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, o-n-nitrobenzyl, p-chlorobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-, Biphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl, more preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenyl, benzyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl, p-methoxybenzyl, o-fluorobenzyl, m-fluorobenzyl, p-fluorobenzyl, o-chlorobenzyl, m-chlorobenzyl, p-chlorobenzyl, o-nitrobenzyl, m-nitrobenzyl, p-nitrobenzyl, o-cyanobenzyl, m-cyanobenzyl, p-cyanobenzyl, o-n-nitrobenzyl, p-nitrobenz, Biphenylmethyl, 1-naphthylmethyl,2-naphthylmethyl, phenylethyl, phenylpropyl, phenylbutyl, most preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, phenylmethyl, phenylethyl, phenylpropyl.

Prepared fluoroalkenyl ketones, e.g.

1aa：R¹ =Ph R² = Me; R³ = CO₂Et

1bb：R¹ =Ph R² = Hex R³ = CO₂Et;

1cc：R¹ =Ph R² = -(CH₂)₄OMe R³ = CO₂Et;

1dd：R¹ = 4-MePh R² = n-Pr R³ = CO₂Et;

1ee：R¹ = (3-Me, 4-F)Ph R² = n-Pr R³ = CO₂Et;

The preparation method of the fluoro alkenyl ketone compound has the advantages and positive effects that:

the preparation method provided by the invention takes the alkyne, the bromine difluoroalkyl compound and the water which are easy to obtain as raw materials, and the preparation method can be purchased through open commercial market channels. The method is simple to operate, is insensitive to water, has a short synthetic route, can be used for synthesizing the fluoro alkenyl ketone compound with structural diversity, has good stereoselectivity, and has very important significance for the synthesis and application of the compound containing the fluoro alkenyl ketone skeleton.

The fluoro alkenyl ketone compound prepared by the preparation method is a very important organic compound, has wide application in the fields of pharmaceutical chemistry and synthetic chemistry, and shows various biological activities, such as being used as anti-cancer, sterilization, anti-HIV and anti-diabetes drugs and the like.

Drawings

FIG. 1 is a reaction equation of the process for producing fluoroalkenyl ketones according to the present invention.

Detailed Description

The invention is further illustrated by the following examples, which are not to be construed as limiting the invention thereto.

The preparation method of the fluoro alkenyl ketone compound comprises the steps of dissolving alkyne, bromine difluoro alkyl compound, water, lithium carbonate, phenylpyridine and triphenyl pyridine iridium in a solvent under the protection of argon, stirring and reacting for 12 hours at room temperature under the condition of illumination, removing the solvent by spinning, and separating by a silica gel column to obtain the fluoro alkenyl ketone compound, wherein the reaction structural formula is shown in figure 1; wherein, the raw materials of alkyne and bromine difluoroalkyl compounds can be directly purchased.

Example one

（E) -2-fluoro-3-methyl-4-oxo-4-phenyl-2-enoic acid ethyl ester 1aa

1-phenyl-1-propyne (0.2 mmol, 23.2 mg), ethyl bromodifluoroacetate (0.4 mmol, 81.2 mg), water (0.12 mL), lithium carbonate (0.3 mmol, 22.2 mg), phenylpyridine (0.04 mmol, 6.2 mg) and iridium triphenylpyridine (0.04 mmol, 2.6 mg) were dissolved in acetonitrile (2 mL) under an argon atmosphere, and the reaction was stirred at room temperature for 12 hours under illumination, and 32.3 mg of a colorless oily liquid was obtained by separation on a silica gel column after removal of the solvent by rotation, with a yield of 68%.¹H NMR (600 MHz, CDCl₃) δ 7.93 – 7.89 (m, 2H), 7.64 – 7.58 (m, 1H), 7.49 (t, J = 7.8 Hz, 2H), 4.07 (q, J = 7.1 Hz, 2H), 2.11 (d, J = 3.6 Hz, 3H), 1.02 (t, J = 7.1 Hz, 3H). ¹³C NMR (151 MHz, CDCl₃) δ 193.5 (d, J = 6.0 Hz), 159.5 (d, J = 35.6 Hz), 144.7 (d, J= 263.9 Hz), 135.0 (d, J = 3.4 Hz), 133.8, 129.2 (d, J = 11.8 Hz), 128.9, 128.8, 62.0, 14.5 (d, J = 5.7 Hz), 13.5. ¹⁹F NMR (565 MHz, CDCl₃) δ -127.21. HRMS (ESI) calcd for C₁₃H₁₂FO₃ ⁺ [M-H]⁺ m/z: 235.0776, found: 235.0768。

Example two

（E) -3-benzoyl-2-fluoroketone-2-enoic acid ethyl ester 1bb

1-phenyl-1-octyne (0.2 mmol, 37.2 mg), ethyl bromodifluoroacetate (0.4 mmol, 81.2 mg), water (0.12 mL), lithium carbonate (0.3 mmol, 22.2 mg), phenylpyridine (0.04 mmol, 6.2 mg) and iridium triphenylpyridine (0.04 mmol, 2.6 mg) were dissolved in acetonitrile (2 mL) under an argon atmosphere, and the reaction was stirred at room temperature for 12 hours under illumination, and 47.5 mg of a colorless oily liquid was obtained by separation on a silica gel column after removal of the solvent by rotation, with a yield of 78%.¹H NMR (600 MHz, CDCl₃) δ 7.91 (d, J = 7.3 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 4.05 (q, J = 7.1 Hz, 2H), 2.53 – 2.47 (m, 2H), 1.48 (sext, J = 7.6 Hz, 2H), 1.34 (sext, J = 7.4 Hz, 2H), 1.29 – 1.22 (m, 4H), 1.01 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 6.9 Hz, 3H). ¹³C NMR (151 MHz, CDCl₃) δ 193.1 (d, J = 6.4 Hz), 159.7 (d, J = 36.0 Hz), 144.8 (d, J = 263.4 Hz), 135.8 (d, J = 3.3 Hz), 133.6, 133.2 (d, J = 11.0 Hz), 128.8, 128.8, 62.0, 31.3, 29.0, 28.8 (d, J = 4.1 Hz), 27.0 (d, J = 1.8 Hz), 22.4, 14.0, 13.5. ¹⁹F NMR (565 MHz, CDCl₃) δ -127.41。

EXAMPLE III

（E) -3-benzoyl-2-fluoro-7-methoxyhept-2-enoic acid ethyl ester 1cc

1-phenyl-6-methoxy-1-hexyne (0.2 mmol, 37.6 mg), ethyl bromodifluoroacetate (0.4 mml, 81.2 mg), water (0.12 mL), lithium carbonate (0.3 mmol, 22.2 mg), phenylpyridine (0.04 mmol, 6.2 mg) and iridium triphenylpyridine (0.04 mmol, 2.6 mg) were dissolved in acetonitrile (2 mL) under argon, the reaction was stirred at room temperature for 12h under light, and after removal of the solvent by spinning, 37.2 mg of a colorless oily liquid was isolated by silica gel column separation, yield 60%.¹H NMR (600 MHz, CDCl₃) δ 7.92 – 7.85 (m, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.8 Hz, 2H), 4.04 (q, J = 7.1 Hz, 2H), 3.33 (t, J = 6.2 Hz, 2H), 3.27 (s, 3H), 2.51 (td, J = 7.9, 2.7 Hz, 2H), 1.64 – 1.59 (m, 2H), 1.58 – 1.52 (m, 2H), 0.99 (t, J = 7.1 Hz, 3H). ¹³C NMR (151 MHz, CDCl₃) δ 194.0 (d, J = 6.3 Hz), 159.6 (d, J = 36.0 Hz), 144.9 (d, J = 264.2 Hz), 135.6 (d, J = 3.4 Hz), 133.7, 132.7 (d, J = 11.0 Hz), 128.8, 128.8, 72.0, 62.0, 58.5, 29.2, 28.5 (d, J = 4.0 Hz), 23.8 (d, J = 2.1 Hz), 13.5. ¹⁹F NMR (565 MHz, CDCl₃) δ -126.94。

Example four

（E) -2-fluoro-3- (4-methylbenzoyl) hex-2-enoic acid ethyl ester 1dd

1-p-methylphenyl-1-pentyne (0.2 mmol, 31.6 mg), ethyl bromodifluoroacetate (0.4 mmol, 81.2 mg), water (0.12 mL), lithium carbonate (0.3 mmol, 22.2 mg), phenylpyridine (0.04 mmol, 6.2 mg) and iridium triphenylpyridine (0.04 mmol, 2.6 mg) were dissolved in acetonitrile (2 mL) under an argon atmosphere, and the reaction was stirred at room temperature for 12 hours under light irradiation, and separated by a silica gel column after removal of the solvent to give 41.8 mg of a colorless oily liquid with a yield of 75%.¹H NMR (600 MHz, CDCl₃) δ 7.80 (d, J = 8.1 Hz, 1H), 7.27 (d, J = 7.9 Hz, 1H), 4.06 (q, J = 7.1 Hz, 1H), 1.51 (sext, J = 7.6 Hz, 2H), 2.42 (s, 1H), 1.57 – 1.47 (m, 1H), 1.03 (t, J = 7.1 Hz, 2H), 0.95 (t, J = 7.3 Hz, 2H). ¹³C NMR (151 MHz, CDCl₃) δ 192.8 (d, J = 6.4 Hz), 159.7 (d, J = 36.1 Hz), 144.7 (d, J = 263.5 Hz), 144.6, 133.3 (d, J = 3.7 Hz), 133.1 (d, J = 10.9 Hz), 129.4, 128.9, 61.9, 30.7 (d, J = 3.6 Hz), 21.7, 20.5, 13.9, 13.5. ¹⁹F NMR (565 MHz, CDCl₃) δ -127.78。

EXAMPLE five

(E) -2-fluoro-3- (4-fluoro-3-methylbenzoyl) hexyl-2-enoic acid ethyl ester 1ee

Under the protection of argon, 1- (3-methyl-4-fluorophenyl) -1-pentyne (0.2 mmol, 35.2 mg) and bromine are addedEthyl fluoroacetate (0.4 mmol, 81.2 mg), water (0.12 mL), lithium carbonate (0.3 mmol, 22.2 mg), phenylpyridine (0.04 mmol, 6.2 mg) and iridium triphenylpyridine (0.04 mmol, 2.6 mg) were dissolved in acetonitrile (2 mL), and the reaction was stirred at room temperature under light irradiation for 12 hours, and after removing the solvent by rotation, was separated by means of a silica gel column to give 42.4 mg of a colorless oily liquid in a yield of 72%.¹H NMR (600 MHz, CDCl₃) δ 7.80 (d, J = 6.3 Hz, 1H), 7.75 – 7.69 (m, 1H), 7.08 (t, J= 8.8 Hz, 1H), 4.10 (q, J = 7.1 Hz, 2H), 2.50 – 2.44 (m, 2H), 2.33 (s, 3H), 1.51 (sext, J = 7.6 Hz, 2H), 1.08 (t, J = 7.1 Hz, 3H), 0.96 (t, J = 7.3 Hz, 3H). ¹³C NMR (151 MHz, CDCl₃) δ 191.8 (d, J = 6.5 Hz), 164.7 (d, J = 254.9 Hz), 159.7 (d, J = 35.9 Hz), 144.7 (d, J = 265.1 Hz), 133.0 (d, J = 11.6 Hz), 132.4 (d, J = 6.8 Hz), 131.9 (t, J = 3.4 Hz), 128.9 (d, J = 9.2 Hz), 125.8 (d, J = 18.4 Hz), 115.5 (d, J = 23.2 Hz), 62.0, 30.7 (d, J = 3.5 Hz), 20.5 (d, J = 1.7 Hz), 13.8, 13.6. ¹⁹F NMR (565 MHz, CDCl₃) δ -108.04, -127.47。