CN111072605B - Preparation method of fluoroalkyl-substituted benzofuran derivative or indole derivative - Google Patents
Preparation method of fluoroalkyl-substituted benzofuran derivative or indole derivative Download PDFInfo
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
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- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
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Abstract
The invention belongs to the technical field of pharmaceutical chemical synthesis, and discloses a preparation method of a fluoroalkyl-substituted benzofuran derivative or indole derivative, which comprises the following steps: taking a 2-allyl phenol compound or a 2-allyl-aniline compound as a raw material, adding alkali, a fluoroalkyl reagent, a solvent and a photocatalyst, stirring the obtained solution under the atmosphere of illumination and nitrogen for reaction, extracting the reaction solution after the reaction is finished, removing the solvent under reduced pressure to obtain a crude product, and purifying to obtain the fluoroalkyl-substituted benzofuran derivative or indole derivative. The method for synthesizing fluoroalkyl-substituted benzofuran derivatives and indole derivatives efficiently through photocatalysis has the advantages of simplicity, easiness, mild reaction conditions, wide adaptability to substrates, high product yield and good industrial application prospect.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical chemical synthesis, and particularly relates to a synthesis method of visible light catalytic fluoroalkyl-substituted benzofuran derivatives and indole derivatives.
Background
The fluoroalkyl group not only has the characteristic of common fluorine-containing atoms, but also has unique chemical properties and medicinal value, for example, the metabolic stability of the molecule in a living body can be improved, the molecule is not easy to hydrolyze, and the bioactivity of the molecule can be greatly improved. Meanwhile, the heterocyclic structure is also a ubiquitous structural framework in natural products, materials and bioactive compounds. According to market survey data, displaying: of the first 200 marketed drugs, about 70% are heterocyclic compounds. Therefore, the fluorine-containing alkyl heterocyclic compound is a very important skeleton structure and is widely applied to scientific fields of medicines, pesticides, materials and the like.
Introduction of fluoroalkyl groups into heterocyclic compounds is one of the most straightforward synthetic methods for constructing fluoroalkyl heterocyclic compounds. However, heterocycles generally require presynthesis or pre-functionalization ((a) v. bacauan, s. cardinal, m.yamauchi, m.kondo, d.f.fernandez, r.remy, d.w.c.macmillan, angelw.chem., int.ed.,2018,57, 12543), (b) p.dai, x.yu, p.teng, w.h.zhang, c.den, org.lett, 2018,20,6901, (c) j.rong, l.den, p.tan, c.ni, y.gu, j.hu, angelw.chem., int.ed.,2016,55,2743, (d) r.kamoto, h.kakawari, k.shuwa, mare.7, orge.chem., 20119, rog.e.7, right.7, right, right.7, right, left, right, substrate, right, substrate, right, substrate, right. Among the syntheses of fluoroalkyl heterocyclic compounds, bifunctional cyclization of olefins is one of the most efficient and practical methods. Relatively few reports have been made of the cyclization of the direct fluoroalkyl difunctional groups of olefins relative to the direct fluoroalkylation of heterocycles. For example, Jr topic group uses fluoroalkyl sulfonyl chloride as a fluorine reagent, and realizes fluoroalkyl carbon cyclization reaction of olefin by visible light photocatalysis (x.j.tang, c.s.thomson, w.r.dolbier Jr., org.lett.,2014,16, 4594). Furthermore, we have carried out an oxo/amino fluoroalkyl cyclization of olefins in 2017 by palladium catalysis (j.liao, l.fan, w.guo, z.zhang, j.li, c.zhu, y.ren, w.wu, h.jiang.org.lett.,2017,14, 1008).
In recent years, the visible light redox reaction has been rapidly developed in organic synthesis due to the advantages of high reaction efficiency, recyclable catalyst, mild reaction conditions, environmental friendliness and the like. Therefore, the development of environmentally friendly, one-step, efficient and visible light catalyzed synthesis methods of fluoroalkyl-substituted benzofuran derivatives and indole derivatives has been receiving extensive attention from the scientific and industrial fields.
Disclosure of Invention
In order to solve the defects and shortcomings of the prior art, the invention aims to provide a high-efficiency green synthesis method of visible light catalysis fluoroalkyl-substituted benzofuran derivatives and indole derivatives.
The purpose of the invention is realized by the following technical scheme:
a method for preparing fluoroalkyl-substituted benzofuran derivatives or indole derivatives, which comprises the following steps:
taking an allyl compound as a raw material, adding alkali, a fluoroalkyl reagent, a solvent and a photocatalyst, stirring the obtained solution under the illumination and nitrogen atmosphere for reaction, extracting the reaction solution after the reaction is finished, removing the solvent under reduced pressure to obtain a crude product, and purifying to obtain a fluoroalkyl-substituted benzofuran derivative or indole derivative;
the allyl compound is a 2-allyl phenol compound or a 2-allyl-aniline compound;
the photocatalyst is any one or two of the following:
the reaction is shown as the following formula (I):
preferably, the fluoroalkyl reagent is one or more of ethyl difluoroiodoacetate, perfluoroiodopropane, perfluoroiodobutane, perfluorohexyliodoalkane, perfluorooctyliodoalkane, and 1-iodoperfluorodecane.
Preferably, the alkali is one or more of potassium acetate, potassium carbonate, potassium phosphate, triethylamine, cesium carbonate, 1, 8-diazabicyclo [5.4.0] undec-7-ene, triethylenediamine and 4-dimethylaminopyridine.
Preferably, the solvent is acetonitrile, dichloromethane, tetrahydrofuran, 1, 4-dioxane, toluene, isopropanol, ethanol, acetone, N-dimethylformamide or an aqueous solution.
Preferably, the reaction time is 8-24 hours, and the reaction temperature is 20 +/-10 ℃.
Preferably, the wavelength of the reaction light source is 380-500 nm.
Preferably, the molar ratio of the allyl compound to the fluoroalkyl reagent is 1 (0.5-5); the molar ratio of the catalyst to the allyl compound is (0.005-0.1) to 1; the molar ratio of the allyl compound to the base is 1 (1-5).
Preferably, the molar ratio of the allyl compound to the fluoroalkyl reagent is 1 (1-2); the molar ratio of the catalyst to the allyl compound is (0.01-0.02): 1; the molar ratio of the allyl compound to the alkali is 1 (1.5-2.5).
Preferably, the allylic compound has a structural formula:
wherein Het is a heterocyclic structure, Ar is an aryl structure, and X is an oxygen atom or a p-toluenesulfonyl-substituted nitrogen atom.
Preferably, the heterocyclic structure is a phenyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-acetylphenyl group, a 2-formylphenyl group, a 3-methylphenyl group, a 2-methyl-4-formylphenyl group, a 3, 5-dimethyl-4-formylphenyl group, a 1, 2-methylenedioxyphenyl group, a 3-benzofuranonyl group, or a coumarin group.
The allylic compound may be 2-allylphenol, 2-allyl-4-methylphenol, 2-allyl-4-carboxaldehyde-6-methylphenol, 6-allyl-7-hydroxy-coumarin, 3-allyl-2-hydroxybenzaldehyde, N- (2-allyl-4-methoxyphenyl) -4-methylbenzenesulfonamide, N- (2-allyl-4-chlorophenyl) -4-methylbenzenesulfonamide, N- (2-allylphenyl) -4-methylbenzenesulfonamide, or the like.
Preferably, the solvent of the extraction is ethyl acetate; the purification adopts column chromatography, the eluent is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is (50-1): 1.
Compared with the prior art, the preparation method has the following advantages and beneficial effects:
(1) the method takes the 2-allyl phenol compound or the 2-allyl-aniline compound and the fluoroalkyl reagent as raw materials, generates oxygen/fluoroalkyl bifunctional cyclization reaction of olefin under the promotion of a photocatalyst, and efficiently synthesizes fluoroalkyl-substituted benzofuran derivatives and indole derivatives in one step.
(2) The synthesis reaction of the invention adopts a conventional test tube container, does not need a high-temperature and high-pressure resistant reaction kettle, and has simple and safe operation and mild reaction conditions.
(3) The synthesis method disclosed by the invention has the advantages of good adaptability to functional groups, wide adaptability to substrates, high product yield, good regioselectivity and good industrial application prospect.
Drawings
FIGS. 1,2 and 3 are respectively a hydrogen spectrum, a fluorine spectrum and a carbon spectrum of the product obtained in example 1.
FIGS. 4, 5 and 6 are the hydrogen spectrum, fluorine spectrum and carbon spectrum of the product obtained in example 2, respectively.
FIGS. 7, 8 and 9 are the hydrogen spectrum, fluorine spectrum and carbon spectrum of the product obtained in example 3, respectively.
FIGS. 10, 11 and 12 are the hydrogen spectrum, fluorine spectrum and carbon spectrum of the product obtained in example 4, respectively.
FIGS. 13, 14 and 15 are the hydrogen spectrum, fluorine spectrum and carbon spectrum of the product obtained in example 5, respectively.
FIGS. 16, 17 and 18 are the hydrogen spectrum, fluorine spectrum and carbon spectrum of the product obtained in example 6, respectively.
FIGS. 19, 20 and 21 are a hydrogen spectrum, a fluorine spectrum and a carbon spectrum of the product obtained in example 7, respectively.
FIGS. 22, 23 and 24 are a hydrogen spectrum, a fluorine spectrum and a carbon spectrum of the product obtained in example 8, respectively.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the present invention is not limited thereto.
Example 1
In a 25 ml Schlenk tube reaction flask, 0.2 mmol of 2-allylphenol, 0.002 mmol of photocatalyst (1), 0.4 mmol of ethyl difluoroiodoacetate, 0.4 mmol of triethylenediamine and 2 ml of acetonitrile were added, and the reaction was stirred at 25 ℃ for 12 hours under nitrogen atmosphere under 5W of blue LED illumination with a wavelength of 450 nm. After the reaction is finished, extracting the reaction solution by ethyl acetate, removing the solvent by reduced pressure rotary evaporation, and then separating and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 50:1, and the yield is 90%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,CDCl3)δ7.19-7.10(m,2H),6.90-6.83(m,1H),6.73(d,J＝8.0Hz,1H),5.07-4.99(m,1H),4.41-4.33(m,2H),3.42(dd,J＝9.1Hz,J＝15.6Hz,1H),2.95(dd,J＝7.0Hz,J＝15.6Hz,1H),2.75-2.66(m,1H),2.41(ddd,J＝4.7Hz,J＝14.8Hz,J＝27.4Hz,1H),1.37(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ163.9(t,J＝30.0Hz),158.7,128.3,125.8,125.1,121.0,114.9(t,J＝249.1Hz),109.7,76.5(dd,J＝3.2Hz,J＝7.3Hz),63.1,41.0(t,J＝20.0Hz),35.9,14.0；19F NMR(376MHz,CDCl3)δ-102.11(dt,J＝12.6Hz,J＝263.6Hz,1F),-107.92(ddd,J＝14.8Hz,J＝22.1Hz,J＝263.6Hz,1F).
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 2
In a 25 ml Schlenk tube reaction flask, 0.2 mmol of 2-allyl-4-methylphenol, 0.002 mmol of photocatalyst (1), 0.4 mmol of ethyl difluoroiodoacetate, 0.4 mmol of potassium acetate and 2 ml of toluene were added, and the reaction system was stirred at 30 ℃ for 20 hours under nitrogen atmosphere under 5W of blue LED light with a wavelength of 400 nm. After the reaction is finished, extracting the reaction solution by ethyl acetate, removing the solvent by rotary evaporation under reduced pressure, and then separating and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1, and the yield is 80%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,CDCl3)δ6.99(s,1H),6.91(d,J＝8.1Hz,1H),6.61(d,J＝8.1Hz,1H),5.03-4.96(m,1H),4.40-4.32(m,2H),3.37(dd,J＝9.0Hz,J＝15.6Hz,1H),2.90(dd,J＝7.0Hz,J＝15.6Hz,1H),2.78-2.64(m,1H),2.44-2.32(m,1H),2.28(s,3H),1.36(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3)δ163.8(t,J＝30.0Hz),156.5,130.2,128.6,125.8,125.6,114.8(t,J＝249.5Hz),109.1,76.6(dd,J＝3.2Hz,J＝7.0Hz),63.0,40.9(t,J＝20.0Hz),35.9,20.8,13.9；19F NMR(376MHz,CDCl3)δ-101.85(dt,J＝12.4Hz,J＝263.2Hz,1F),-107.67(ddd,J＝14.8Hz,J＝22.1Hz,J＝263.6Hz,1F)。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 3
In a 25 ml Schlenk tube reaction flask, 0.2 mmol of 2-allyl-4-carboxaldehyde-6-methylphenol, 0.002 mmol of photocatalyst (1), 0.4 mmol of ethyl difluoroiodoacetate, 0.4 mmol of 1, 8-diazabicyclo [5.4.0] undec-7-ene and 2 ml of acetonitrile were added, and the reaction system was stirred under nitrogen atmosphere at 20 ℃ for 10 hours under illumination of a 5W blue LED with a wavelength of 420 nm. After the reaction is finished, extracting the reaction solution by ethyl acetate, removing the solvent by rotary evaporation under reduced pressure, and then separating and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1, and the yield is 90%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,CDCl3)δ9.80(s,1H),7.54(d,J＝21.6Hz,2H),5.19-5.12(m,1H),4.38(q,J＝6.7Hz,2H),3.48(dd,J＝9.2Hz,J＝15.8Hz,1H),3.02(dd,J＝7.4Hz,J＝15.8Hz,1H),2.84-2.69(m,1H),2.48(ddd,J＝4.8Hz,J＝15.7Hz,J＝19.5Hz,1H),2.22(s,3H),1.38(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)δ190.8,163.7(t,J＝32.1Hz),162.7,133.5,130.9,126.5,124.0,120.4,114.6(t,J＝247.9Hz),78.0(dd,J＝2.6Hz,J＝6.4Hz),63.1,40.9(t,J＝23.1Hz),35.4,35.3,15.0,14.0；19F NMR(376MHz,CDCl3)δ-101.74(dt,J＝13.0Hz,J＝265.2Hz,1F),-107.23(ddd,J＝15.6Hz,J＝20.5Hz,J＝265.3Hz,1F).。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 4
0.2 mmol of 6-allyl-7-hydroxy-coumarin, 0.002 mmol of the photocatalyst (1), 0.4 mmol of ethyl difluoroiodoacetate, 0.4 mmol of potassium phosphate and 2 ml of dichloromethane are added into a 25 ml Schlenk tube reactor, and the reaction system is stirred and reacted for 18 hours at 25 ℃ under nitrogen atmosphere under the illumination of a 5W blue LED with the wavelength of 450 nm. After the reaction is finished, extracting the reaction solution by ethyl acetate, removing the solvent by reduced pressure rotary evaporation, and then carrying out column chromatography separation and purification to obtain the target product, wherein the used column chromatography eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 25:1, and the yield is 80%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,CDCl3)7.65(d,1H,J＝9.5Hz),7.30(d,1H,J＝9.2Hz),6.70(d,1H,J＝8.3Hz),6.23(d,1H,J＝9.5Hz),5.24(ddd,1H,J＝4.6Hz,J＝8.9Hz,J＝15.9Hz),4.41-4.35(m,1H),3.60(dd,1H,J＝9.3Hz,J＝16.1Hz),3.11(dd,1H,J＝7.1Hz,J＝16.1Hz),2.84-2.69(m,1H),2.50(ddt,1H,J＝4.5Hz,J＝12.6Hz,J＝15.1Hz),1.38(t,1H,J＝7.2Hz)；13C NMR(100MHz,CDCl3)δ162.7,160.9,151.4,144.0,129.1,114.4(t,J＝251.0Hz),113.4,112.8,112.6,107.0,100.0,78.83(dd,J＝3.3Hz,J＝6.9Hz),63.2,40.8(t,J＝23.3Hz),32.6,13.9；19F NMR(376MHz,C3D6O)δ-104.70(ddd,J＝8.5Hz,J＝24.8Hz,J＝263.4Hz,1F),-106.96(ddd,J＝14.6Hz,J＝23.2Hz,J＝263.4Hz,1F)。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 5
In a 25 ml Schlenk tube reaction flask, 0.2 mmol of 3-allyl-2-hydroxybenzaldehyde, 0.002 mmol of photocatalyst (2), 0.4 mmol of perfluorohexyliodoalkane, 0.4 mmol of potassium acetate and 2 ml of acetone were added, and the reaction system was stirred under nitrogen atmosphere at 25 ℃ for 15 hours under illumination of a 460nm blue LED. After the reaction is finished, extracting the reaction solution by ethyl acetate, removing the solvent by reduced pressure rotary evaporation, and then carrying out column chromatography separation and purification to obtain the target product, wherein the used column chromatography eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1, and the yield is 78%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,C3D6O)δ10.06(s,1H),7.38(dd,J＝7.6Hz,J＝16.1Hz,2H),6.83(t,J＝7.5Hz,1H),5.33-5.25(m,1H),3.46(dd,J＝9.2Hz,J＝16.0Hz,1H),3.03(dd,J＝7.5Hz,J＝16.2Hz,1H),2.86-2.70(m,2H)；13C NMR(100MHz,C3D6O)δ188.2,162.6,132.2,130.3,126.7,122.2,120.9,79.2,37.5(t,J＝20.6Hz),35.8；19F NMR(376MHz,C3D6O)δ-80.79(t,J＝10.3Hz,3F),-110.66(ddd,J＝13.4Hz,J＝27.1Hz,J＝273.5Hz,1F),-112.87(ddd,J＝12.6Hz,J＝25.3Hz,J＝36.8Hz,1F),-121.31(d,J＝10.7Hz,2F),-122.42(s,2F),-123.01(s,2F),-125.81(dd,J＝10.4Hz,J＝18.9Hz,2F)。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 6
In a 25 ml Schlenk tube reaction flask, 0.2 mmol of N- (2-allyl-4-methoxyphenyl) -4-methylbenzenesulfonamide, 0.0025 mmol of photocatalyst (1), 0.4 mmol of ethyl difluoroiodoacetate, 0.4 mmol of triethylenediamine and 2 ml of acetonitrile were added, and the reaction was stirred at 25 ℃ for 12 hours under nitrogen atmosphere under 5W of a 410nm blue LED illumination. After the reaction is finished, extracting the reaction solution by ethyl acetate, removing the solvent by rotary evaporation under reduced pressure, and then separating and purifying by column chromatography to obtain the target product, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1, and the yield is 80%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,C3D6O)δ7.37(dd,J＝8.4Hz,J＝15.8Hz,3H),7.15(d,J＝8.0Hz,2H),6.69(dd,J＝2.1Hz,J＝8.7Hz,1H),6.57(s,1H),4.49-4.43(m,1H),4.31-4.21(m,2H),3.60(s,3H),2.65(dd,J＝8.7Hz,J＝16.6Hz,1H),2.60-2.50(m,2H),2.44-2.31(m,1H),2.21(s,3H),1.22(t,J＝7.0Hz,3H)；13C NMR(100MHz,C3D6O)δ164.0(t,J＝3.4Hz),158.8,145.1,135.2,147.7(d,J＝3.4Hz),130.4,128.1,119.4,116.1(t,J＝249.5Hz),113.9,111.5,63.8,58.3(t,J＝50.1Hz),55.7,41.3(t,J＝22.1Hz),35.5,21.3,14.0；19F NMR(376MHz,C3D6O)δ-102.99(ddd,J＝13.9Hz,J＝16.5Hz,J＝264.7Hz,1F),-106.53(dt,J＝18.2Hz,J＝264.9Hz,1F)。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 7
In a 25 ml Schlenk tube reaction flask, 0.2 mmol of N- (2-allyl-4-chlorophenyl) -4-methylbenzenesulfonamide, 0.003 mmol of photocatalyst (1), 0.4 mmol of ethyl difluoroiodoacetate, 0.4 mmol of 1, 8-diazabicyclo [5.4.0] undec-7-ene and 2 ml of toluene were added, and the reaction was stirred under illumination by a 5W blue LED with a wavelength of 420nm at 25 ℃ under a nitrogen atmosphere for 12 hours. After the reaction is finished, extracting the reaction solution by ethyl acetate, removing the solvent by reduced pressure rotary evaporation, and then carrying out column chromatography separation and purification to obtain the target product, wherein the used column chromatography eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1, and the yield is 75%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,C3D6O)δ7.44(d,J＝8.2Hz,2H),7.40(d,J＝8.5Hz,1H),7.18(d,J＝8.1Hz,2H),7.12(dd,J＝1.7Hz,J＝8.6Hz,1H),7.01(d,J＝1.1Hz,1H),4.49(ddd,J＝3.7Hz,J＝8.7Hz,J＝13.0Hz,1H),4.23(q,J＝7.1Hz,2H),2.85-2.80(m,1H),2.69-2.59(m,2H),2.56-2.43(m,1H),2.21(s,2H),1.20(t,J＝7.0Hz,3H)；13C NMR(100MHz,C3D6O)δ163.7(t,J＝32.2Hz),145.3,140.4,134.8,134.7,130.4,128.2,127.8,126.0,118.8,115.8(t,J＝250.2Hz),63.6,58.1,41.2(t,J＝21.8Hz),34.9,21.0,13.7；19F NMR(376MHz,C3D6O)δ-103.37(ddd,J＝13.6Hz,J＝18.0Hz,J＝264.6Hz,1F),-106.27(dt,J＝17.9Hz,J＝264.7Hz,1F)。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 8
In a 25 ml Schlenk tube reaction flask, 0.2 mmol of N- (2-allylphenyl) -4-methylbenzenesulfonamide, 0.003 mmol of photocatalyst (1), 0.4 mmol of perfluoroiodobutane, 0.4 mmol of 1, 8-diazabicyclo [5.4.0] undec-7-ene and 2 ml of acetonitrile were added, and the reaction was stirred under 5W of 410nm blue LED illumination at 25 ℃ under nitrogen atmosphere for 12 hours. After the reaction is finished, extracting the reaction solution by ethyl acetate, removing the solvent by reduced pressure rotary evaporation, and then carrying out column chromatography separation and purification to obtain the target product, wherein the used column chromatography eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1, and the yield is 71%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,C3D6O)δ7.57(dd,J＝2.4Hz,J＝8.5Hz,3H),7.19(dd,J＝7.9Hz,J＝17.4Hz,3H),7.06(d,J＝7.4Hz,1H),6.98(t,J＝7.4Hz,1H),4.72-4.65(m,1H),3.05(dd,J＝9.6Hz,J＝16.7Hz,1H),2.96-2.80(m,2H),2.75-2.59(m,1H),2.26(s,3H)；13C NMR(100MHz,C3D6O)δ145.5,141.5,135.1,132.0,130.6,128.6,128.0,126.2,125.7,117.5,57.0,38.1(t,J＝19.1Hz),35.5(d,J＝2.1Hz),21.3；19F NMR(376MHz,C3D6O)δ-80.74(m,3F),-111.15(m,1F),-112.86(m,1F),-123.84(m,2F),-125.32(m,2F)。
the structure of the resulting product is deduced from the above data as shown in the following formula:
the above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (6)
1. A method for preparing fluoroalkyl-substituted benzofuran derivatives or indole derivatives, which is characterized by comprising the following steps:
taking an allyl compound as a raw material, adding alkali, a fluoroalkyl reagent, a solvent and a photocatalyst, stirring the obtained solution under the illumination and nitrogen atmosphere for reaction, extracting the reaction solution after the reaction is finished, removing the solvent under reduced pressure to obtain a crude product, and purifying to obtain a fluoroalkyl-substituted benzofuran derivative or indole derivative;
the allyl compounds are 2-allylphenol, 2-allyl-4-methylphenol, 2-allyl-4-formaldehyde-6-methylphenol, 6-allyl-7-hydroxy-coumarin, N- (2-allyl-4-methoxyphenyl) -4-methylbenzenesulfonamide, N- (2-allyl-4-chlorphenyl) -4-methylbenzenesulfonamide and N- (2-allyl-phenyl) -4-methylbenzenesulfonamide;
the photocatalyst is as follows:
the fluoroalkyl-substituted benzofuran derivative or indole derivative is
The fluoroalkyl reagent is ethyl difluoroiodoacetate;
the alkali is any one or two of potassium acetate, potassium phosphate, 1, 8-diazabicyclo [5.4.0] undec-7-ene and triethylene diamine; the solvent is acetonitrile, toluene and dichloromethane.
2. The method according to claim 1, wherein the reaction time is 8 to 24 hours and the reaction temperature is 20 ± 10 ℃.
3. The method according to claim 2, wherein the wavelength of the reaction light source is 380 to 500 nm.
4. The method according to any one of claims 1 to 3, wherein the molar ratio of the allylic compound to the fluoroalkyl reagent is 1 (0.5 to 5); the molar ratio of the catalyst to the allyl compound is (0.005-0.1) to 1; the molar ratio of the allyl compound to the base is 1 (1-5).
5. The method according to claim 4, wherein the molar ratio of the allylic compound to the fluoroalkyl reagent is 1 (1-2); the molar ratio of the catalyst to the allyl compound is (0.01-0.02): 1; the molar ratio of the allyl compound to the alkali is 1 (1.5-2.5).
6. The method according to any one of claims 1 to 3, wherein the solvent for extraction is ethyl acetate; the purification adopts column chromatography, the eluent is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is (50-1): 1.
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