阅读说明：本技术 一种可见光促进的烯烃的芳基氟烷基化产物及其制备方法 (Visible light promoted aryl fluoralkylation product of olefin and preparation method thereof ) 是由 刘乐 贺重隆 汪民 王淡宁 张珂瑗 于 2021-08-31 设计创作，主要内容包括：一种可见光促进的烯烃的芳基氟烷基化产物及其制备方法,其结构为β-芳基γ-氟烷基脂肪醇,如下式所示,其中R～(1)官能团包括但不限于氢、烷基、环烷基,R～(2)官能团包括但不限于氢、烷基、环烷基,Ar官能团包括但不限于苯环、取代苯环、芳基杂环,R-(f)官能团包括但不限于CF-(2)H,CF-(3),C-(4)F-(9),C-(6)F-(13),CF-(2)CO-(2)Me,CF-(2)CO-(2)R～(1),CF-(2)CO-(2)NHR～(1),CF-(2)CO-(2)NHAr；本发明在可见光驱动下,通过氟烷基自由基对烯烃的加成、芳基迁移来快速制备芳基氟烷基化产物,该反应过程无需高温高压、操作过程简单、后处理简单、对环境污染小、催化剂廉价易得；此外,该反应可以通过连续流动过程,扩大的反应物的用量,缩短了反应时间,为后续工业化生产提供支持。(A visible light promoted aryl fluoroalkyl product of olefin and its preparation method, its structure is beta-aryl gamma-fluoroalkyl fatty alcohol, as shown in the following formula, wherein R is 1 Functional groups include, but are not limited to, hydrogen, alkyl, cycloalkyl, R 2 Functional groups include, but are not limited to, hydrogen, alkyl, cycloalkyl, ArFunctional groups include, but are not limited to, benzene rings, substituted benzene rings, aryl heterocycles, R f Functional groups include, but are not limited to CF 2 H,CF 3 ,C 4 F 9 ,C 6 F 13 ,CF 2 CO 2 Me,CF 2 CO 2 R 1 ,CF 2 CO 2 NHR 1 ,CF 2 CO 2 NHAr; the method is driven by visible light, the aryl fluoralkylated product is rapidly prepared by the addition of fluoralkyl free radicals to olefin and the migration of aryl, and the reaction process does not need high temperature and high pressure, is simple in operation process, simple in post-treatment, small in environmental pollution and cheap and easily available in catalyst; in addition, the reaction can be carried out through a continuous flow process, the dosage of reactants is enlarged, the reaction time is shortened, and the support is provided for the subsequent industrial production.)

1. A visible light promoted aryl fluoroalkyl alkylation product of olefin, which is characterized in that the structure of the product is beta-aryl gamma-fluoroalkyl fatty alcohol, as shown in the following formula,

wherein R is¹Functional groups include, but are not limited to, hydrogen, alkyl, cycloalkyl, R²Functional groups include, but are not limited to, hydrogen, alkyl, cycloalkyl, Ar functional groups include, but are not limited to, benzene rings, substituted benzene rings, arylheterazolesRing, R_fFunctional groups include, but are not limited to CF₂H,CF₃,C₄F₉,C₆F₁₃,CF₂CO₂Me,CF₂CO₂R¹,CF₂CO₂NHR¹,CF₂CO₂NHAr。

2. The process of claim 1, comprising the steps of:

1) in a nitrogen atmosphere, sequentially adding an olefin compound A mmol, a fluoroalkyl halide B mmol, a photosensitizer C mol% and a reaction solvent D mL into a Schlenk tube provided with magnetons, and then respectively adding alkali E mol and acid F mol; a, B, E, F and 1: (1.0-3.0): (1% -10%): (1.0-3.0): (1.0-3.0), wherein the reaction concentration of the olefin compound A mmol in the reaction solvent D mL is 0.01-0.5 mol/L;

2) carrying out reaction under the irradiation of visible light, and monitoring the reaction by a TLC plate until the reaction is complete;

3) quenching the reaction with saturated ammonium chloride water solution, extracting with ethyl acetate, distilling the mixed solution under reduced pressure, evaporating to remove the solvent, and performing column chromatography on the crude product to obtain the aryl fluoroalkyl product of the olefin, namely the beta-aryl gamma-fluoroalkyl fatty alcohol.

3. The process of claim 1, wherein the continuous flow process comprises the steps of:

1) sequentially adding an olefin compound A mmol, a fluoroalkyl halide B mmol, photosensitizer C mol% and a reaction solvent D mL into a reaction liquid storage bottle in a nitrogen atmosphere, and respectively adding alkali E mol and acid F mol to prepare homogeneous reaction liquid; a, B, E, F and 1: (1.0-3.0): (1% -10%): (1.0-3.0): (1.0-3.0), wherein the reaction concentration of the olefin compound A mmol in the reaction solvent D mL is 0.01-0.5 mol/L;

2) introducing the reaction solution into a colorless transparent tube through a continuous flow chemical reactor, circularly flowing the reaction solution in the transparent tube for reaction under the irradiation of visible light, wherein the flow rate is 2-15mL/min, and monitoring the reaction process through a TLC plate;

3) after the reaction is completed, quenching the reaction by using a saturated ammonium chloride aqueous solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, carrying out pressure distillation, distilling to remove a solvent to obtain a crude product, and separating and purifying by using column chromatography to obtain the aryl fluoroalkyl product of the olefin.

4. The process for the preparation of the visible light promoted arylfluoroalkylation product of an alkene as claimed in claim 2 or 3 wherein the photosensitizer comprises one or more of an iridium complex photosensitizer, a ruthenium complex photosensitizer, and an organic small molecule photosensitizer; the iridium complex photosensitizer comprises: [ Ir (dF (CF)₃)ppy)₂(dtbbpy)]PF₆、[Ir(ppy)₂(dtbbpy)]PF₆、[Ir(dF(CF₃)ppy)₂(5,5’-dCF₃bpy)]PF₆(ii) a The ruthenium complex photosensitizer comprises: ru (bpz)₃(PF₆)₂、Ru(bpm)₃(PF₆)₂、Ru(dtbppy)₃(PF₆)₂、Ru(phen)₃Cl₂(ii) a The organic small molecule photosensitizer comprises: mesiridinium salt, fluorescein, triphenylpyranium salt, eosin, 4CzIPN, methyl red, methylene blue, rhodoleic acid, tetraphenylporphyrin, rhodamine and vitamin B2.

5. The method of claim 2 or 3, wherein the base is an organic base selected from one or more of triethylamine, diisopropylethylamine, N-dimethylaniline, triethylenediamine, tetrabutyl amine, and urotropin.

6. The method as claimed in claim 2 or 3, wherein the irradiation with visible light comprises 460-470nm blue light.

7. The process of claim 2 or 3, wherein the acid is an organic acid selected from the group consisting of formic acid, acetic acid, propionic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, and p-toluenesulfonic acid.

8. The process of claim 2 or 3, wherein the fluoroalkyl halide comprises one or more of alkyl difluorohaloacetate, difluorohaloacetamide, and perfluoroalkyl halide; the difluorohaloacetic acid alkyl ester comprises difluorohaloacetic acid ethyl ester, difluorohaloacetic acid benzyl ester, difluorohaloacetic acid hexyl ester and difluorohaloacetic acid allyl alcohol ester; the difluorohaloacetamides include difluorohaloacetanilide, difluorohaloacetylcyclopropylamine, difluorohaloacetylcyclopentylamine, difluorohaloacetylcyclohexylamine, difluorohaloacetanilide, difluorohaloacetoacetic aliphatic amines and difluorohaloacetoacetic aromatic amines; perfluoroalkyl halides include perfluoroiodobutane, perfluoroiodohexane, perfluoroiodoheptane, togni's reagent.

9. The process of claim 2 or 3, wherein the solvent comprises ethyl acetate, dichloromethane, 1, 2-dichloroethane, acetonitrile, tetrahydrofuran, toluene, trifluorotoluene, N-dimethylformamide.

10. The method as claimed in claim 2 or 3, wherein the crude product obtained by the reaction is purified by column chromatography using 200-300 mesh silica gel prepared by ethyl acetate: petroleum ether is eluent with the ratio of 10:1, and then the aryl fluoralkylated product of the olefin is obtained.

Technical Field

The invention belongs to the technical field of chemical synthesis, and particularly relates to a visible light-promoted aryl fluoroalkyl product of olefin and a preparation method thereof.

Background

Fluoride-containing compounds are widely present in the fields of medical intermediates, material science, and the like, and introduction of fluorine atoms into molecules generally has a positive effect on permeability, lipophilicity, and metabolic stability of the molecules (curr. Therefore, the synthesis of various classes of fluorine-containing compounds has attracted extensive attention in academia. The realization of the construction of fluorine-containing compounds through the addition of fluorine-containing fragments to unsaturated double bonds of olefins has become a research hotspot in the field of organic synthesis. However, the simultaneous introduction of fluoroalkyl and aryl groups into olefins still presents challenges to achieving the bifunctional of olefins. Currently, there are few methods for obtaining aryl fluoroalkylation products of olefins, and it is generally required to obtain aryl by catalytic capture of radicals by transition metals (copper, palladium, etc.) after addition of fluoroalkyl radicals to olefins, followed by reductive elimination (j.org.chem.2018, 83,3013; j.am.chem.soc.2015,137, 14578). However, the use of the transition metal catalyst not only increases the reaction cost, but also causes the problem of heavy metal residue, and in the reported reactions, the reactions are often multi-component reactions, the number of byproducts is large, the reaction temperature is generally high, and the difficulty of industrial production is increased.

Visible light has become a hot topic of research by chemists in recent years as a clean, inexpensive and inexhaustible energy source on the surface of the earth. The discovery of the photocatalyst pushes the development of photocatalysis in the field of organic synthesis to the climax, and provides a new way for synthesizing new compounds. The application of visible light to chemical reactions often has the following advantages: 1) the reaction conditions are mild, and the tolerance of the functional group is better. 2) The energy consumption in the reaction processes of heating or cooling and the like is reduced, the operation is safer, and the environment is more protected. 3) Can combine with the continuous flow chemical strategy, and is easy to realize large-scale production and low-cost synthesis. Therefore, the search for the aryl fluoralkylated derivatives of the visible light promoted olefin derivatives without the participation of the transition metal is undoubtedly a new green synthetic strategy and has very important research value.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention aims to provide a visible light-promoted aryl fluoroalkyl product of olefin and a preparation method thereof, wherein the aryl fluoroalkyl product is quickly prepared by addition and aryl migration of fluoroalkyl free radicals to the olefin under the drive of visible light.

In order to achieve the purpose, the invention adopts the following technical scheme.

A visible light promoted aryl fluoroalkyl alkylate product of olefin has a structure of beta-aryl gamma-fluoroalkyl fatty alcohol, which is shown as the following formula,

wherein R is¹Functional groups include, but are not limited to, hydrogen, alkyl, cycloalkyl, R²Functional groups include, but are not limited to, hydrogen, alkyl, cycloalkyl, Ar functional groups include, but are not limited to, benzene rings, substituted benzene rings, aryl heterocycles, R_fFunctional groups include, but are not limited to CF₂H,CF₃,C₄F₉,C₆F₁₃,CF₂CO₂Me, CF₂CO₂R¹,CF₂CO₂NHR¹,CF₂CO₂NHAr。

The preparation method of the visible light promoted alkene-based aryl fluoralkylation product comprises the following steps:

1) in a nitrogen atmosphere, sequentially adding an olefin compound A mmol, a fluoroalkyl halide B mmol, a photosensitizer C mol% and a reaction solvent D mL into a Schlenk tube provided with magnetons, and then respectively adding alkali E mol and acid F mol; a, B, E, F and 1: (1.0-3.0): (1% -10%): (1.0-3.0): (1.0-3.0), wherein the reaction concentration of the olefin compound A mmol in the reaction solvent D mL is 0.01-0.5 mol/L;

2) carrying out reaction under the irradiation of visible light, and monitoring the reaction by a TLC plate until the reaction is complete;

3) quenching the reaction with saturated ammonium chloride water solution, extracting with ethyl acetate, distilling the mixed solution under reduced pressure, evaporating to remove the solvent, and performing column chromatography on the crude product to obtain the aryl fluoroalkyl product of the olefin, namely the beta-aryl gamma-fluoroalkyl fatty alcohol.

The preparation method of the visible light promoted alkene aryl fluoro alkylation product adopts continuous flow preparation and comprises the following steps:

1) sequentially adding an olefin compound A mmol, a fluoroalkyl halide B mmol, photosensitizer C mol% and a reaction solvent D mL into a reaction liquid storage bottle in a nitrogen atmosphere, and respectively adding alkali E mol and acid F mol to prepare homogeneous reaction liquid; a, B, E, F and 1: (1.0-3.0): (1% -10%): (1.0-3.0): (1.0-3.0), wherein the reaction concentration of the olefin compound A mmol in the reaction solvent D mL is 0.01-0.5 mol/L;

2) introducing the reaction solution into a colorless transparent tube through a continuous flow chemical reactor, circularly flowing the reaction solution in the transparent tube for reaction under the irradiation of visible light, wherein the flow rate is 2-15mL/min, and monitoring the reaction process through a TLC plate;

3) after the reaction is completed, quenching the reaction by using a saturated ammonium chloride aqueous solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, carrying out pressure distillation, distilling to remove a solvent to obtain a crude product, and separating and purifying by using column chromatography to obtain the aryl fluoroalkyl product of the olefin.

The photosensitizer comprises one or more of an iridium complex photosensitizer, a ruthenium complex photosensitizer and an organic micromolecular photosensitizer; the iridium complex photosensitizer comprises: [ Ir (dF (CF)₃)ppy)₂(dtbbpy)]PF₆、[Ir(ppy)₂(dtbbpy)]PF₆、 [Ir(dF(CF₃)ppy)₂(5,5’-dCF₃bpy)]PF₆(ii) a The ruthenium complex photosensitizer comprises: ru (bpz)₃(PF₆)₂、Ru(bpm)₃(PF₆)₂、Ru(dtbppy)₃(PF₆)₂、Ru(phen)₃Cl₂(ii) a The organic small molecule photosensitizer comprises: mesiridinium salt, fluorescein, triphenylpyranium salt, eosin, 4CzIPN, methyl red, methylene blue, rhodoleic acid, tetraphenylporphyrin, rhodamine and vitamin B2.

The alkali is organic alkali, and comprises one or more of triethylamine, diisopropylethylamine, N-dimethylaniline, triethylene diamine, tetrabutyl amine and urotropine.

The visible light irradiation comprises 460-470nm blue light.

The acid is organic acid, and comprises one or more of formic acid, acetic acid, propionic acid, trifluoroacetic acid, trifluoromethanesulfonic acid and p-toluenesulfonic acid.

The fluoroalkyl halide comprises one or more of difluorohaloacetic acid alkyl ester, difluorohaloacetamide and perfluoroalkyl halide; the difluorohaloacetic acid alkyl ester comprises difluorohaloacetic acid ethyl ester, difluorohaloacetic acid benzyl ester, difluorohaloacetic acid hexyl ester and difluorohaloacetic acid allyl alcohol ester; the difluorohaloacetamides include difluorohaloacetanilide, difluorohaloacetylcyclopropylamine, difluorohaloacetylcyclopentylamine, difluorohaloacetylcyclohexylamine, difluorohaloacetanilide, difluorohaloacetoacetic aliphatic amines and difluorohaloacetoacetic aromatic amines; perfluoroalkyl halides include perfluoroiodobutane, perfluoroiodohexane, perfluoroiodoheptane, togni's reagent.

The solvent comprises ethyl acetate, dichloromethane, 1, 2-dichloroethane, acetonitrile, tetrahydrofuran, toluene, trifluorotoluene and N, N-dimethylformamide.

When the crude product prepared by the reaction is purified by column chromatography, silica gel with 200-mesh and 300-mesh is adopted, and the reaction is carried out by ethyl acetate: petroleum ether is eluent with the ratio of 10:1, and then the aryl fluoralkylated product of the olefin is obtained.

Compared with the prior art, the invention has the beneficial effects that:

the present invention provides a new simple and mild process for the synthesis of aryl fluoroalkylation products of olefins. Under the drive of visible light, the aryl fluoralkylated product is rapidly prepared through the addition of fluoralkyl free radical to olefin and the migration of aryl. The reaction process does not need high temperature and high pressure, the operation process is simple, the post-treatment is simple, the environmental pollution is small, and the catalyst is cheap and easy to obtain. In addition, the reaction can be carried out through a continuous flow process, the dosage of reactants is enlarged, the reaction time is shortened, and the support is provided for the subsequent industrial production.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of aryl fluoroalkylation product 3aa of an olefin.

FIG. 2 is a nuclear magnetic fluorine spectrum of aryl fluoroalkylation product 3aa of an olefin.

FIG. 3 is a nuclear magnetic carbon spectrum of aryl fluoroalkylation product 3aa of an olefin.

FIG. 4 is a nuclear magnetic hydrogen spectrum of aryl fluoroalkylation product 3ab of olefin.

FIG. 5 is a nuclear magnetic fluorine spectrum of aryl fluoroalkylation product 3ab of olefin.

FIG. 6 is a nuclear magnetic carbon spectrum of aryl fluoroalkylation product 3ab of olefin.

FIG. 7 is a nuclear magnetic hydrogen spectrum of aryl fluoroalkylation product 3ac of an olefin.

FIG. 8 is a nuclear magnetic fluorine spectrum of aryl fluoroalkylation product 3ac of an olefin.

FIG. 9 is a nuclear magnetic carbon spectrum of aryl fluoroalkylation product 3ac of an olefin.

FIG. 10 is a nuclear magnetic hydrogen spectrum of aryl fluoroalkylation product 3ad of an olefin.

FIG. 11 is a nuclear magnetic fluorine spectrum of aryl fluoroalkylation product 3ad of an olefin.

FIG. 12 is a nuclear magnetic carbon spectrum of aryl fluoroalkylation product 3ad of an olefin.

FIG. 13 is a nuclear magnetic hydrogen spectrum of the aryl fluoroalkylation product 3ae of an olefin.

FIG. 14 is a nuclear magnetic fluorine spectrum of the aryl fluoroalkylation product 3ae of an olefin.

FIG. 15 is a nuclear magnetic carbon spectrum of the aryl fluoroalkylation product 3ae of an olefin.

FIG. 16 is a nuclear magnetic hydrogen spectrum of aryl fluoroalkylation product 3af of an olefin.

FIG. 17 is a nuclear magnetic fluorine spectrum of the aryl fluoroalkylation product 3af of an olefin.

FIG. 18 is a nuclear magnetic carbon spectrum of the aryl fluoroalkylation product 3af of an olefin.

FIG. 19 is a nuclear magnetic hydrogen spectrum of aryl fluoroalkylation product 3ag of olefin.

FIG. 20 is a nuclear magnetic fluorine spectrum of aryl fluoroalkylation product 3ag of olefin.

FIG. 21 is a nuclear magnetic carbon spectrum of aryl fluoroalkylation product 3ag of olefin.

FIG. 22 is a nuclear magnetic hydrogen spectrum of aryl fluoroalkylation product 3ah of olefin.

FIG. 23 is a nuclear magnetic fluorine spectrum of aryl fluoroalkylation product 3ah of olefin.

FIG. 24 is a nuclear magnetic carbon spectrum of aryl fluoroalkylation product 3ah of olefin.

FIG. 25 is a nuclear magnetic hydrogen spectrum of aryl fluoroalkylation product 3ai of olefin.

FIG. 26 is a nuclear magnetic fluorine spectrum of aryl fluoroalkylation product 3ai of olefin.

FIG. 27 is a nuclear magnetic carbon spectrum of aryl fluoroalkylation product 3ai of an olefin.

Detailed description of the preferred embodiments

The present invention will be described in detail with reference to the accompanying drawings.

Example 1

The reaction scheme for implementing the invention is shown in the following chart:

the product prepared in this example had the structure:

the preparation method of the embodiment comprises the following steps: under the nitrogen atmosphere, fillingTo a 250mL Schlenk tube with magnetons were added sequentially triphenylpyrane tetrafluoroborate (198mg,5 mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8g,10mmol) and acetonitrile (100 mL). Ethyl difluorobromoacetate (2.56mL,20mmol), tri-n-butylamine (4.76mL,20mmol), and formic acid (0.78mL,20mmol) were added to the reaction, respectively. After sealing the reaction tube, the reaction tube was transferred to a visible light (460-. After completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain a crude product of the reaction, which was separated by column chromatography to obtain 3aa (2.92g, 86%) of a yellow liquid, which is an arylfluoroalkylated product of olefin.¹H NMR(400MHz,CDCl₃)δ7.14-7.08(m,4H),3.91-3.85 (m,2H),3.37-3.32(m,1H),3.25-3.23(m,1H),2.85-2.70 (m,1H),2.57-2.45(m,1H),2.31(s,3H),1.95-1.91(m,1H), 1.75-1.57(m,4H),1.49-1.44(m,1H),1.31-1.21(m,2H), 1.17(t,J＝7.2Hz,3H),1.12-1.06(m,1H),1.02-0.93(m, 1H).¹⁹F NMR(376MHz,CDCl₃)δ-101.3(dt,J＝255.7,15.0Hz, 1F),-105.6(ddd,J＝255.7,22.6,15.0Hz,1F).¹³C NMR(100 MHz,CDCl₃)δ164.3(t,J_C-F＝32.5Hz),138.0,135.9,128.8, 128.6,116.4(t,J_C-F＝248.1Hz),71.3,62.5,51.1,40.2(q, J_C-F＝3.0Hz),36.5(t,J_C-F＝22.5Hz),36.0,26.9,25.3,24.5, 20.9,13.6.HRMS(ESI,m/z):calcd.for C₁₉H₂₆F₂O₃Na⁺363.1742, found 363.1737.

Example 2

The product prepared in this example had the structure:

to a 250mL Schlenk tube containing magnetons, Ru (bpm) was added in this order under a nitrogen atmosphere₃(PF₆)₂(171.91mg,2 mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8g,10mmol) and acetonitrile (100 mL). Further, difluorobromoacetic acid benzyl ester (5.12g,20mmol), diisopropylethylamine (3.31mL,20mmol) and formic acid (0.78mL,20mmol) were added to the reaction. After sealing the reaction tube, the reaction tube was transferred to a visible light (460-. After completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain a crude product of the reaction, which was separated by column chromatography to obtain an arylfluoroalkylated product of olefin, yellow liquid 3ab (2.54g, 63%).¹H NMR(400MHz,CDCl₃)δ7.37–7.32(m,3H),7.25–7.23(m, 2H),7.11–7.05(m,4H),4.87–4.77(m,1H),3.32–3.26 (m,1H),3.20–3.17(m,1H),2.85–2.71(m,1H),2.58– 2.46(m,1H),2.30(s,3H),1.89–1.86(m,1H),1.63–1.54 (m,4H),1.46–1.40(m,1H),1.26–1.02(m,3H),0.94– 0.88(m,1H).¹⁹F NMR(376MHz,CDCl₃)δ-101.2(dt,J＝255.9, 15.2Hz,1F),-104.9(ddd,J＝255.9,21.1,14.4Hz,1F).¹³C NMR(100MHz,CDCl₃)δ164.1(t,J_C–F＝32.9Hz),137.9,135.9, 134.2,128.9,128.7,128.6,128.2,116.5(t,J_C–F＝249.6Hz), 71.3,67.9,51.0,40.4(dd,J_C–F＝5.4,3.2Hz),36.7(t,J_C–F＝22.3Hz),36.0,27.0,25.3,24.5,20.9.HRMS(ESI,m/z):calcd. for C₂₂H₂₆F₂O₃Na⁺425.1899,found 425.1907.

Example 3

The product prepared in this example had the structure:

to a 250mL Schlenk tube containing magnetons, 4-CzIPN (473mg,3 mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8g,10mmol), and toluene (100mL) were added in that order under a nitrogen atmosphere. Difluorobromoacetanilide (5.00g,20 mmol), tri-n-butylamine (4.76mL,20mmol) and formic acid (0.78mL,20mmol) were then added to the reaction, respectively. After sealing the reaction tube, the reaction tube was transferred to a visible light (460-. After completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate. Distilling under reduced pressure to remove solvent to obtain crude reaction product, and separating by column chromatographyThis gave an arylfluoroalkylation product of olefin, 3ac (3.14g, 81%) as a yellow liquid.¹H NMR(400MHz,CDCl₃)δ 7.80(s,1H),7.40(d,J＝8.4Hz,2H),7.32(t,J＝7.6Hz, 2H),7.18–7.13(m,3H),7.06(d,J＝7.7Hz,2H),3.48– 3.42(m,1H),3.35–3.31(m,1H),2.87–2.60(m,1H),2.25 (s,3H),2.15(s,1H),1.98–1.95(m,1H),1.69–1.58(m, 3H),1.46(t,J＝7.6Hz,1H),1.31–1.14(m,2H),1.08–0.91(m,2H).¹⁹F NMR(376MHz,CDCl₃)δ-100.3(dt,J＝255.0, 13.8Hz,1F),-103.2(ddd,J＝255.0,24.0,13.7Hz,1F).¹³C NMR(100MHz,CDCl₃)δ162.4(t,J_C–F＝28.4Hz),138.4,136.0, 135.8,129.0,128.8,127.6,125.5,120.2,118.7(t,J_C–F＝253.5 Hz),71.3,51.5,39.7(dd,J_C–F＝4.3,2.5Hz),35.7,33.9(t, J_C–F＝22.1Hz),26.1,25.4,24.7,20.9.HRMS(ESI,m/z):calcd. for C₂₃H₂₇F₂NO₂Na⁺410.1902,found 410.1909.

Example 4

The product prepared in this example had the structure:

to a 250mL Schlenk tube containing magnetons, Ir (ppy) was added in order under a nitrogen atmosphere₃(131mg,1 mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8g,10mmol) and dichloroethane (100 mL). Perfluoroiodobutane (5.00g,20 mmol), triethylamine (2.78mL,20mmol) and formic acid (0.78mL,20mmol) were then added to the reaction, respectively. After sealing the reaction tube, transferring the reaction tube to a visible light (460-. After completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain a crude product of the reaction, which was separated by column chromatography to obtain an arylfluoroalkylated product of olefin, 3ad (1.46g, 35%) as a yellow liquid.¹H NMR(400MHz,CDCl₃) δ7.18–7.12(m,4H),3.39–3.27(m,2H),2.82–2.56(m, 2H),2.34(s,3H),1.93–1.89(m,1H),1.71–1.47(m,5H), 1.32–1.24(m,1H),1.14–1.09(m,2H),1.00–0.93(m, 1H).¹⁹F NMR(376MHz,CDCl₃)δ-81.0–-81.1(m,3F),-112.2 –-124.6(m,2F),-124.4–-124.5(m,2F),-125.8–-125.9 (m,2F).¹³C NMR(101MHz,CDCl₃)δ138.3,136.1,128.8,128.5, 71.6,50.6,40.0,36.5,33.1(t,J_C–F＝20.5Hz),28.1,25.4, 24.5,21.0.HRMS(ESI,m/z):calcd.for C₁₉H₂₁F₉ONa⁺459.1341, found 459.1345.

Example 5

The product prepared in this example had the structure:

to a 250mL Schlenk tube containing magnetons, Fluorescein (389.4mg,5 mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8g,10mmol), and acetonitrile (100mL) were added in this order under a nitrogen atmosphere. 1- (trifluoromethyl) -1, 2-phenyliodosyl-3 (1H) -one (6.32g,20mmol), tri-n-butylamine (4.76mL,20mmol) and trifluoroacetic acid (1.48mL,20mmol) were then added to the reaction, respectively. After sealing the reaction tube, the reaction tube was transferred to a visible light (460-. After completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to obtain a crude product of the reaction, which was separated by column chromatography to obtain an arylfluoroalkylated product of olefin, yellow liquid 3ae (2.14g, 75%).¹H NMR(400MHz,CDCl₃)δ7.17–7.11(m,4H),3.34– 3.31(m,1H),3.29–3.23(m,1H),2.77–2.62(m,2H),2.34 (s,3H),1.93–1.90(m,1H),1.70–1.59(m,3H),1.57– 1.50(m,1H),1.43(s,1H),1.32–1.23(m,1H),1.15–1.09 (m,2H),0.99–0.89(m,1H).¹⁹F NMR(376MHz,CDCl₃)δ-63.8 (t,J＝10.5Hz,3F).¹³C NMR(100MHz,CDCl₃)δ138.0,136.1, 128.8,127.3(q,J_C–F＝552.4,276.1Hz),71.6,50.2,41.5,36.6 (q,J_C–F＝25.6Hz),36.5,27.9,25.4,24.5,21.0.HRMS(ESI, m/z):calcd.for C₁₆H₂₁F₃OH⁺287.1617,found 287.1632.

Example 6

In this example, a continuous flow reactor was used to perform the reaction, and the structure of the product prepared was:

the preparation method of the embodiment comprises the following steps: triphenylpyranyl tetrafluoroborate (594mg,5 mol%), 2-vinylcyclohexyl p-toluenesulfonate (8.4g,30mmol) and acetonitrile (200mL) were sequentially added to a 250mL stock reaction flask under a nitrogen atmosphere, and ethyl difluorobromoacetate (7.68mL,60mmol), tri-n-butylamine (14.28mL,60mmol) and formic acid (2.34mL,60mmol) were added to the reaction flask, respectively, to prepare a homogeneous reaction solution. The reaction solution was introduced into a colorless transparent tube by connecting to a continuous flow reactor with a sealed tube. Under the irradiation of visible light, the reaction solution was circulated in a transparent tube to carry out the reaction at a flow rate of 5mL/min, and the progress of the reaction was checked by TLC plate. After 8h of reaction, the reaction was completed, quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate. The crude reaction product is obtained after the solvent is evaporated under reduced pressure, and the crude reaction product is separated by column chromatography to obtain the aryl fluoralkylated product of the olefin, namely 3aa (9.16g, 90%) of yellow liquid.¹H NMR(400MHz,CDCl₃)δ 7.14-7.08(m,4H),3.91-3.85(m,2H),3.37-3.32(m,1H), 3.25-3.23(m,1H),2.85-2.70(m,1H),2.57-2.45(m,1H), 2.31(s,3H),1.95-1.91(m,1H),1.75-1.57(m,4H),1.49 -1.44(m,1H),1.31-1.21(m,2H),1.17(t,J＝7.2Hz,3H), 1.12-1.06(m,1H),1.02-0.93(m,1H).¹⁹F NMR(376MHz,CDCl₃) δ-101.3(dt,J＝255.7,15.0Hz,1F),-105.6(ddd,J＝255.7, 22.6,15.0Hz,1F).¹³C NMR(100MHz,CDCl₃)δ164.3(t,J_C-F＝ 32.5Hz),138.0,135.9,128.8,128.6,116.4(t,J_C-F＝248.1Hz), 71.3,62.5,51.1,40.2(q,J_C-F＝3.0Hz),36.5(t,J_C-F＝22.5 Hz),36.0,26.9,25.3,24.5,20.9,13.6.HRMS(ESI,m/z):calcd. for C₁₉H₂₆F₂O₃Na⁺363.1742,found 363.1737.

Compared with the reaction in the embodiment 1, the continuous flow synthesis method can simply realize the amplification of the reaction scale, is simple and convenient to operate, obviously shortens the reaction time, improves the reaction efficiency and improves the product yield.

Referring to the above preparation method, the details of the examples of the photosensitizer, the acid-base additive and the solvent are summarized as follows:

TABLE 1 summary of the invention for the example cases of photosensitizer, acid-base additive and solvent

The examples of the variations of the reaction substrates with reference to the above preparation methods are summarized as follows:

TABLE 2 summary of the invention for the example cases of the reaction raw materials