CN113735710B - Visible light promoted aryl fluoralkylation product of olefin and preparation method thereof - Google Patents

Visible light promoted aryl fluoralkylation product of olefin and preparation method thereof Download PDF

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CN113735710B
CN113735710B CN202111016869.1A CN202111016869A CN113735710B CN 113735710 B CN113735710 B CN 113735710B CN 202111016869 A CN202111016869 A CN 202111016869A CN 113735710 B CN113735710 B CN 113735710B
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CN113735710A (en
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刘乐
贺重隆
汪民
王淡宁
张珂瑗
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Xian Jiaotong University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C07C235/38—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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Abstract

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,
Figure DDA0003240153120000011
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, ar functional 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, and can quickly prepare the aryl fluoroalkyl product through the addition of the fluoroalkyl free radical to the olefin and the aryl migration, 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.

Description

Visible light promoted aryl fluoralkylation product of olefin and preparation method thereof
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 used in the fields of pharmaceutical intermediates, material science, etc., 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 arylation 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 condition is 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,
Figure BDA0003240153100000021
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, ar functional 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 preparation method of the visible light promoted alkene-based aryl fluoralkylation product comprises the following steps:
1) In the 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 filled with magnetons, and then respectively adding an alkali E mol and an acid F mol; a: B: C: E: F =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 0.01-0.5mol/L;
2) Carrying out the 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, a photosensitizer C mol% and a reaction solvent D mL into a reaction liquid storage bottle in a nitrogen atmosphere, and then respectively adding an alkali E mol and an acid F mol to prepare homogeneous reaction liquid; a: B: C: E: F =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 0.01-0.5mol/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 iridium complex photosensitizer, ruthenium complex photosensitizer and organic micromolecular photosensitizer; the iridium complex photosensitizer comprises: [ Ir (dF (CF) 3 )ppy) 2 (dtbbpy)]PF 6 、[Ir(ppy) 2 (dtbbpy)]PF 6 、 [Ir(dF(CF 3 )ppy) 2 (5,5’-dCF 3 bpy)]PF 6 (ii) a The ruthenium complex photosensitizer comprises: ru (bpz) 3 (PF 6 ) 2 、Ru(bpm) 3 (PF 6 ) 2 、Ru(dtbppy) 3 (PF 6 ) 2 、Ru(phen) 3 Cl 2 (ii) a The organic small molecule photosensitizer comprises: mesiridinium salt, fluorescein, triphenylpyrane 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 esters include difluorohaloacetic acid ethyl ester, difluorohaloacetic acid benzyl ester, difluorohaloacetic acid hexyl ester, difluorohaloacetic acid allyl ester; the difluorohaloacetamides include difluorohaloacetanilides, difluorohaloacetylcyclopropylamines, difluorohaloacetylcyclopentylamines, difluorohaloacetylcyclohexylamines, difluorohaloacetanilides, difluorohaloacetoacetamidofatty amines, difluorohaloacetoacetarylamines; perfluoroalkyl halides include perfluoroiodobutane, perfluoroiodohexane, perfluoroiodoheptane, togni's reagent.
The solvent comprises ethyl acetate, dichloromethane, 1,2-dichloroethane, acetonitrile, tetrahydrofuran, toluene, benzotrifluoride and N, N-dimethylformamide.
When the crude product prepared by the reaction is purified by column chromatography, 200-300 meshes of silica gel is adopted, and the reaction is carried out by the following steps of: petroleum ether =10, 1, to give the arylfluoroalkylation product of the olefin.
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 3aa, an aryl fluoroalkylation product 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 an aryl fluoroalkylation product 3ab of an 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 the aryl fluoroalkylation product 3ad of an olefin.
FIG. 13 is a nuclear magnetic hydrogen spectrum of the aryl fluoroalkylation product 3ae of 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 an aryl fluoroalkylation product 3ag of an 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:
Figure BDA0003240153100000071
the product prepared in this example had the structure:
Figure BDA0003240153100000072
the preparation method of the embodiment comprises the following steps: to a 250mL Schlenk tube containing magnetons, triphenylpyrane tetrafluoroborate (198mg, 5 mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8g, 10mmol), and acetonitrile (100 mL) were added in this order under a nitrogen atmosphere. Ethyl difluorobromoacetate (2.56mL, 20mmol), tri-n-butylamine (4.76mL, 20 mmol) and formic acid (0.78mL, 20mmol) were further added to the reaction, respectively. The reaction tube was sealed and transferred to visible light (460-470nm, 7W) under stirring, reacted for 24 hours, and the progress of the reaction was checked by TLC plate. 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 (2.92 g, 86%) of a yellow liquid, which is an arylfluoroalkylated product of olefin. 1 H NMR(400MHz,CDCl 3 )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). 19 F NMR(376MHz,CDCl 3 )δ-101.3(dt,J＝255.7,15.0Hz, 1F),-105.6(ddd,J＝255.7,22.6,15.0Hz,1F). 13 C NMR(100 MHz,CDCl 3 )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 C 19 H 26 F 2 O 3 Na + 363.1742, found 363.1737.
Example 2
The product prepared in this example had the structure:
Figure BDA0003240153100000081
to a 250mL Schlenk tube containing magnetons, ru (bpm) was added in this order under a nitrogen atmosphere 3 (PF 6 ) 2 (171.91mg, 2mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8g, 10mmol) and acetonitrile (100 mL). Further, difluorobromobenzoic acid benzyl ester (5.12g, 20mmol), diisopropylethylamine (3.31mL, 20mmol) and formic acid (0.78mL, 20mmol) were added to the reaction, respectively. The reaction tube was sealed and transferred to visible light (460-470nm, 7W) under stirring, reacted for 24 hours, and the progress of the reaction was checked by TLC plate. 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 distilled off 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%). 1 H NMR(400MHz,CDCl 3 )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). 19 F NMR(376MHz,CDCl 3 )δ-101.2(dt,J＝255.9, 15.2Hz,1F),-104.9(ddd,J＝255.9,21.1,14.4Hz,1F). 13 C NMR(100MHz,CDCl 3 )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 C 22 H 26 F 2 O 3 Na + 425.1899,found 425.1907.
Example 3
The product prepared in this example has the structure:
Figure BDA0003240153100000091
to a 250mL Schlenk tube containing magnetons, 4-CzIPN (473mg, 3mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8g, 10 mmol), and toluene (100 mL) were added in this 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. The reaction tube was sealed, and the reaction tube was transferred to a visible light (460-470nm, 7W) and stirred, reacted for 24 hours, and the progress of the reaction was checked by TLC plate. 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. And (3) distilling under reduced pressure to remove the solvent to obtain a reaction crude product, and separating by column chromatography to obtain an aryl fluoralkylated product of olefin, namely 3ac (3.14g, 81%) as a yellow liquid. 1 H NMR(400MHz,CDCl 3 )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). 19 F NMR(376MHz,CDCl 3 )δ-100.3(dt,J＝255.0, 13.8Hz,1F),-103.2(ddd,J＝255.0,24.0,13.7Hz,1F). 13 C NMR(100MHz,CDCl 3 )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 C 23 H 27 F 2 NO 2 Na + 410.1902,found 410.1909.
Example 4
The product prepared in this example had the structure:
Figure BDA0003240153100000101
to a 250mL Schlenk tube containing magnetons, ir (ppy) was added in order under a nitrogen atmosphere 3 (131mg, 1mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8 g,10 mmol) and dichloroethane (100 mL). Further, perfluoroiodobutane (5.00 g,20 mmol), triethylamine (2.78mL, 20mmol) and formic acid (0.78mL, 20mmol) were added to the reaction, respectively. The reaction tube was sealed and then transferred to a visible light (460-470nm, 7W) and stirred for reaction for 24 hours, and the progress of the reaction was checked by TLC plate. 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 is evaporated under reduced pressure to obtain a reaction crude product, and the reaction crude product is separated by column chromatography to obtain an aryl fluoralkylated product of olefin, namely 3ad (1.46g, 35%) as a yellow liquid. 1 H NMR(400MHz,CDCl 3 ) 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). 19 F NMR(376MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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 C 19 H 21 F 9 ONa + 459.1341, found 459.1345.
Example 5
The product prepared in this example had the structure:
Figure BDA0003240153100000111
to a 250mL Schlenk tube charged with magnetons, fluorescein (389.4 mg,5 mol%), 2-vinylcyclohexyl p-toluenesulfonate (2.8g, 10mmol), and acetonitrile (100 mL) were added in this order under a nitrogen atmosphere. 1- (trifluoromethyl) -1,2-phenyliodoacyl-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. Sealing the reaction tube and transferring to visible light (460-470nm, 7W), reacting for 24h, and detecting the reaction progress by a TLC plate. 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 (2.14 g, 75%). 1 H NMR(400MHz,CDCl 3 )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). 19 F NMR(376MHz,CDCl 3 )δ-63.8 (t,J＝10.5Hz,3F). 13 C NMR(100MHz,CDCl 3 )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 C 16 H 21 F 3 OH + 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:
Figure BDA0003240153100000121
the preparation method of the embodiment comprises the following steps: triphenylpyrane tetrafluoroborate (594 mg,5 mol%), 2-vinylcyclohexyl p-toluenesulfonate (8.4 g, 30mmol) and acetonitrile (200 mL) 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 circularly flows in a transparent tube to carry out reaction, the flow rate is 5mL/min, and the reaction progress is detected by a 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. Reduced pressureThe crude reaction product is obtained after the solvent is removed by evaporation, and the aryl fluoralkylated product of the olefin is obtained by column chromatography separation, namely 3aa (9.16g, 90%) of yellow liquid. 1 H NMR(400MHz,CDCl 3 )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). 19 F NMR(376MHz,CDCl 3 ) δ-101.3(dt,J＝255.7,15.0Hz,1F),-105.6(ddd,J＝255.7, 22.6,15.0Hz,1F). 13 C NMR(100MHz,CDCl 3 )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 C 19 H 26 F 2 O 3 Na + 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 examples of photosensitizers, acid-base additives and solvents
Figure BDA0003240153100000131
Figure BDA0003240153100000141
Figure BDA0003240153100000151
The examples of the variations of the reaction substrates, referred to the above preparation, are summarized below:
TABLE 2 summary of the invention for the example cases of the reaction raw materials
Figure BDA0003240153100000152

Claims (4)

1. A process for preparing a visible light-promoted arylfluoroalkylation product of an olefin 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 DmL into a Schlenk tube provided with magnetons, and then respectively adding alkali E mol and acid F mol; a: B: C: E: F =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 0.01-0.5mol/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 aqueous 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 an aryl fluoroalkyl product of olefin, namely beta-aryl gamma-fluoroalkyl fatty alcohol; the specific raw materials and products are as follows:
Figure FDA0003800791470000011
Figure FDA0003800791470000021
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)]PF 6 、[Ir(ppy) 2 (dtbbpy)]PF 6 、[Ir(dF(CF 3 )ppy) 2 (5,5’-dCF 3 bpy)]PF 6 (ii) a The ruthenium complex photosensitizer comprises: ru (bpz) 3 (PF 6 ) 2 、Ru(bpm) 3 (PF 6 ) 2 、Ru(dtbppy) 3 (PF 6 ) 2 、Ru(phen) 3 Cl 2 (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 adopts one or more of triethylamine, diisopropylethylamine, N-dimethylaniline, triethylene diamine, tetrabutyl amine and urotropine;
the acid is organic acid, and is one or more of formic acid, acetic acid, propionic acid, trifluoroacetic acid, trifluoromethanesulfonic acid and p-toluenesulfonic acid;
the solvent is selected from ethyl acetate, dichloromethane, 1,2-dichloroethane, acetonitrile, tetrahydrofuran, toluene, trifluorotoluene and N, N-dimethylformamide.
2. A process for preparing a visible light promoted arylfluoroalkylation product of an olefin, characterized by a continuous flow preparation comprising 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, C, E, F =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 0.01-0.5mol/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 anhydrous sodium sulfate, carrying out pressure distillation, distilling to remove a solvent to obtain a crude product, and separating and purifying by column chromatography to obtain an aryl fluoroalkyl product of olefin;
the specific raw materials and products are as follows:
Figure FDA0003800791470000031
Figure FDA0003800791470000041
Figure FDA0003800791470000051
the photosensitizer comprises one or more of iridium complex photosensitizer, ruthenium complex photosensitizer and organic micromolecular photosensitizer; the iridium complex photosensitizer comprises: [ Ir (dF (CF) 3 )ppy) 2 (dtbbpy)]PF 6 、[Ir(ppy) 2 (dtbbpy)]PF 6 、[Ir(dF(CF 3 )ppy) 2 (5,5’-dCF 3 bpy)]PF 6 (ii) a The ruthenium complex photosensitizer comprises: ru (bpz) 3 (PF 6 ) 2 、Ru(bpm) 3 (PF 6 ) 2 、Ru(dtbppy) 3 (PF 6 ) 2 、Ru(phen) 3 Cl 2 (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 is one or more of triethylamine, diisopropylethylamine, N-dimethylaniline, triethylene diamine, tetrabutyl amine and urotropine;
the acid is organic acid and is one or more of formic acid, acetic acid, propionic acid, trifluoroacetic acid, trifluoromethanesulfonic acid and p-toluenesulfonic acid;
the solvent is selected from ethyl acetate, dichloromethane, 1,2-dichloroethane, acetonitrile, tetrahydrofuran, toluene, trifluorotoluene and N, N-dimethylformamide.
3. The process of claim 1 or 2, wherein the visible light irradiation is selected from the group consisting of 460 nm to 470nm blue light.
4. The method of claim 1 or 2, wherein the crude product of the reaction is purified by column chromatography using 200-300 mesh silica gel prepared by ethyl acetate: petroleum ether =10, 1, to give the arylfluoroalkylation product of the olefin.
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