3-arylated / 3-alkenylated coumarin compound, preparation method and application of 3-arylated / 3-alkenylated coumarin compound

Abstract

The invention discloses a 3-arylated / 3-alkenylated coumarin compound as well as a preparation method and application thereof.According to the method, bifunctionalization of an alkyne ester compound and organic halide is catalyzed by gold to obtain 3-arylated / alkenylated coumarin, and the 3-arylated / 3-alkenylated coumarin compound is prepared through the following steps: in an inert gas atmosphere, performing a reaction to obtain 3-arylated / alkenylated coumarin; the method comprises the following steps: dissolving a gold catalyst, a halogen transfer reagent, alkali, iodobenzene / iodo-alkenyl benzene and an alkyne ester compound in a dry solvent, and then continuously reacting at 80-100 DEG C until a reaction substrate is completely consumed to obtain a target product. According to the invention, no external oxidant is added, the reaction can be smoothly carried out under mild conditions, the gold catalyst, the halogen transfer reagent, the alkali, the solvent, the alkyne ester compound and the iodobenzene (or iodo-alkenyl benzene) compound are mixed by using a one-pot method, and a series of 3-arylated (or alkenylated) coumarin compounds can be prepared at excellent yield. The conversion has a wide substrate application range and good functional group tolerance, and is worthy of popularization and application.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a 3-aryl / alkenyl coumarin compound, a preparation method and application thereof. Background Art

[0002] Coumarin and its derivatives, such as warfarin (coumarin oral anticoagulant), osthole (anti-inflammatory, analgesic, antibacterial, antipruritic, antioxidant and neuroprotective), isopsoralen (anti-diabetic, anti-cancer, antiviral), elusive (anti-tumor), etc., have important application value in drug synthesis, biomedicine and pesticide fields due to their unique biological activity. Therefore, the green and efficient synthesis of coumarin compounds has become a research hotspot in recent years.

[0003] Coumarin compounds are usually synthesized by the reaction of salicylaldehyde and acetic anhydride, which requires the addition of stoichiometric metal catalysts or high temperature requirements; such as the traditional Perkin synthesis method, which mainly uses weak base sodium acetate as a catalyst, salicylaldehyde and acetic anhydride as raw materials, and prepares the coumarin parent nucleus through condensation cyclization. This method is also the main method for industrial preparation of coumarin, but the reaction time required for this method is long, the temperature requirement is high, there are many side reactions, and the yield is not high. The Pechmann condensation method is an improved method for synthesizing coumarin, and its main feature is that substituted phenols are used instead of salicylaldehyde as raw materials. Since substituted phenols are more likely to undergo substitution reactions than salicylaldehyde, the Pechmann condensation method is conducive to expanding the types of coumarin derivatives. In addition, the reaction uses Lewis acid as a catalyst, and substituted phenols and substituted ethyl acetoacetate are condensed and cyclized to form coumarin. The reaction operation is simple and the yield is high. However, the Pechmann condensation method also has some disadvantages, such as easy generation of waste and environmental pollution, which need to be optimized and improved in practical applications.

[0004] Therefore, it is particularly important to develop a strategy for preparing 3-arylated (or olefinated) coumarins under efficient and mild reaction conditions. Summary of the invention

[0005] The object of the present invention is to overcome the above-mentioned shortcomings and provide a method for preparing 3-arylated (or olefinated) coumarin compounds from acetylene ester compounds.

[0006] The object of the present invention is achieved in that:

[0007] A method for preparing 3-aryl / alkenyl coumarin compounds, wherein the method uses gold to catalyze the bifunctionalization of acetylene ester compounds and organic halides to obtain 3-aryl / alkenyl coumarin, comprising dissolving a gold catalyst, a halogen transfer reagent, a base, iodine (or iodoalkenylbenzene) and an acetylene ester compound in a dry solvent under an inert gas atmosphere, and continuously reacting at 80° C. to 100° C. until the reaction substrate is completely consumed to obtain a target product, wherein the general reaction formula is as follows:

[0008]

[0009] The specific operation steps of the present invention are as follows:

[0010] (1) In an inert gas atmosphere, a gold catalyst, a halogen transfer reagent, a base, a solvent, an acetylene ester compound, and an iodobenzene (or iodoalkenylbenzene) compound are added to a reaction tube in a one-pot method;

[0011] (2) reacting at 80-100° C. for 6-12 hours, monitoring complete consumption of the reaction substrate by TLC, and purifying the residue to obtain the target product.

[0012] Furthermore, the gold catalyst is any one of Ph3PAuCl, IPrAuCl, JohnphosAu(MeCN)SbF6, Me2SAuCl, and MeDalPhosAuCl.

[0013] Furthermore, the halogen transfer reagent is any one of silver bis(trifluoromethanesulfonyl)imide, silver trifluoromethanesulfonate, silver hexafluoroantimonate, and silver tetrafluoroborate.

[0014] Furthermore, the base is any one of sodium carbonate, potassium carbonate, disodium hydrogen phosphate, dipotassium hydrogen phosphate and potassium benzoate.

[0015] Furthermore, the solvent is any one of dry dichloromethane, dry acetonitrile, dry 1,2-dichloroethane, dry methanol and dry 1,4-dioxane, preferably 1,2-dichloroethane.

[0016] Further, the molar ratio of the alkynyl ester compound to the iodobenzene (or iodoalkenylbenzene) compound is 1:(2-4); the molar ratio of the alkynyl ester compound to the gold catalyst is 1:(0.05-0.10); the molar ratio of the alkynyl ester compound to the halogen transfer reagent is 1:(2-4); the molar ratio of the alkynyl ester compound to the base is 1:(2-4). Preferably, the molar ratio of the alkynyl ester compound to the iodobenzene (or iodoalkenylbenzene) compound is 1:2; the molar ratio of the alkynyl ester compound to the gold catalyst is 1:0.10; the molar ratio of the alkynyl ester compound to the halogen transfer reagent is 1:2; the molar ratio of the alkynyl ester compound to the base is 1:2.5.

[0017] Furthermore, the inert gas atmosphere is provided by at least one of a nitrogen environment and an argon environment, preferably an argon environment.

[0018] The 3-aryl / alkenyl coumarin compounds prepared by the preparation method of the present invention can be widely used in the fields of drug synthesis, biomedicine, etc.

[0019] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0020] The present invention does not require the addition of an external oxidant, and the reaction can be smoothly carried out under mild conditions. A gold catalyst, a halogen transfer reagent, a base, a solvent, an alkynyl ester compound and an iodobenzene (or iodoalkenylbenzene) compound are mixed by a one-pot method to prepare a series of 3-arylated (or alkenylated) coumarin compounds with excellent yields. This transformation has a wide substrate range and good functional group tolerance. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a schematic diagram of the reaction formula of the present invention;

[0022] Figure 2 and Figure 3 are respectively the H and C nuclear magnetic resonance spectra of Example 1;

[0023] Figures 4 to 6 They are respectively the H NMR spectrum, C spectrum and F spectrum of Example 2;

[0024] Figure 7 and Figure 8 are respectively the H and C nuclear magnetic resonance spectra of Example 3;

[0025] Fig. 9 and Fig.10 are respectively the H and C nuclear magnetic resonance spectra of Example 4;

[0026] Fig.11 and Fig.12are respectively the H and C nuclear magnetic resonance spectra of Example 5;

[0027] Fig.13 and Fig.14 are respectively the H NMR spectrum and C NMR spectrum of Example 6;

[0028] Fig.15 and Fig.16 are respectively the H NMR spectrum and C NMR spectrum of Example 7;

[0029] Fig.17 and Fig.18 are respectively the H NMR spectrum and C NMR spectrum of Example 8;

[0030] Fig.19 and Fig. 20 are respectively the H NMR spectrum and C NMR spectrum of Example 9;

[0031] Figures 21 to 23 They are respectively the H NMR spectrum, C spectrum and F spectrum of Example 10. DETAILED DESCRIPTION

[0032] The present invention is further described below in conjunction with the embodiments and drawings, but the present invention is not limited in any way. Any changes or substitutions made based on the teachings of the present invention belong to the protection scope of the present invention.

[0033] In the present invention, the NMR spectrum is measured by a Bruker AV400 superconducting nuclear magnetic resonance instrument, wherein the deuterated reagent is deuterated chloroform (CDC13), the hydrogen spectrum uses tetramethylsilane as the internal standard, and the carbon spectrum uses CDC13 (δ=77.0) as the internal standard.

[0034] The 200-300 mesh silica gel column for column chromatography was purchased from Beijing Inokai Technology Co., Ltd.; the 0.2 mm thin layer chromatography silica gel plate for TLC was purchased from Yantai Chemical Industry Research Institute. Unless otherwise specified, the reagents and solvents used in the present invention were purified by standard methods (refer to the "Reagent Purification Manual") before use.

[0035] The method of the present invention for obtaining 3-arylated (or olefinated) coumarin by gold-catalyzed bifunctionalization of alkynyl ester compounds and organic halides is to dissolve a gold catalyst, a halogen transfer reagent, a base, iodobenzene (or iodoalkenylbenzene) and alkynyl ester compounds in a dry solvent under an inert gas atmosphere, and then react at 80° C. to 100° C. for 6 to 12 hours to obtain the target product. The general reaction formula is as follows:

[0036]

[0037] Wherein: R1 is selected from any one of alkyl, halogen and heterocycle; R2 is selected from any one of alkyl and aryl; R3 is selected from any one of aryl and alkyl; R4 is selected from any one of alkyl and aryl.

[0038] The structural formulas of the acetylenic esters and iodobenzene (or iodoalkenylbenzene) compounds of the present invention are shown in the following formulas I, II and III.

[0039]

[0040]

[0041] The present invention is further described below with specific implementation cases:

[0042] Example 1

[0043]

[0044] Under argon atmosphere, phenylpropiolate (44.4 mg, 0.2 mmol), 4-methoxyiodobenzene (93.6 mg, 0.4 mmol), Ph3PAuCl (9.9 mg, 0.02 mmol), silver hexafluoroantimonate (137.5 mg, 0.4 mmol), potassium carbonate (55.2 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 1,2-dichloroethane (2.0 mL) was added. The mixture was reacted at 80° C. for 9 hours and monitored by TLC until phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product 3-(4-methoxyphenyl)-4-phenyl-2H-chromen-2-one (59.1 mg, 90% yield).

[0045] See also Figure 2 and Figure 3 , Mp = 178-181°C; 1 H NMR (400MHz, CDCl3) δ7.54-7.49(m,1H),7.41(d,J=8.0Hz,1H),7.35-7.30(m,3H),7.2 3-7.16(m,2H),7.15-7.11(m,2H),7.09-7.04(m,2H),6.74-6.70(m,2H),3.73(s,3H); 13C NMR (101MHz, CDCl3) δ161.51,158.79,153.01,151.00,134.65,131.80,131.18,129.34,128. 29,128.20,127.62,126.50,125.96,124.02,120.55,116.64,113.20,55.06.HRMS(ESI)calcd for C 22 H 16 O3(M+H) + 328.1099, found 328.1173.

[0046] Example 2

[0047]

[0048] Under argon atmosphere, phenylpropiolate (44.4 mg, 0.2 mmol), 4-fluoroiodobenzene (88.8 mg, 0.4 mmol), Ph3PAuCl (9.9 mg, 0.02 mmol), tetrafluoroborate (77.8 mg, 0.4 mmol), sodium carbonate (42.4 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and dichloromethane (2.0 mL) was added. The mixture was reacted at 90° C. for 7 hours and monitored by TLC until phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product 3-(4-fluorophenyl)-4-phenyl-2H-chromen-2-one (53.78 mg, 85% yield).

[0049] See also Figures 4 to 6 , Mp = 167-170 ° C; 1 H NMR (400MHz, CDCl3) δ7.54 (td, J=8.2, 1.8Hz, 1H), 7.43 (d, J=8.2Hz, 1H), 7.3 5-7.31(m,3H),7.24-7.17(m,2H),7.14-7.08(m,4H),6.87(t,J=8.7Hz,2H); 13 C NMR (101MHz, CDCl3) δ163.19,161.19,160.73,153.13,151.85,134.27,132.40,132.31,131.58,1 29.74,129.71,129.25,128.46,128.39,127.78,125.88,124.19,120.33,116.74,114.93,114.72; 19F NMR(376MHz, CDCl3)δ-113.73; HRMS(ESI)calcd for C 21 H 13 FO2(M+H) + 317.0900, found 317.0977.

[0050] Example 3

[0051]

[0052] Under argon atmosphere, phenylpropiolate (44.4 mg, 0.2 mmol), 3-iodothiophene (84.01 mg, 0.4 mmol), IPrAuCl (12.4 mg, 0.02 mmol), silver hexafluoroantimonate (137.5 mg, 0.4 mmol), dipotassium hydrogen phosphate (69.7 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 1,2-dichloroethane (2.0 mL) was added, and the mixture was reacted at 85° C. for 12 hours, and monitored by TLC until phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product 4-phenyl 3-thiophene 2H-chromen 2-one (48.6 mg, 80% yield).

[0053] See also Figure 7 and Figure 8 , Mp = 188-191°C; 1 H NMR (400MHz, CDCl3) δ7.52(ddd,J=8.6,6.6,2.2Hz,1H),7.43-7.38(m,4H),7.22-7.15(m,5H),7.09(dd,J=5.1,3.0Hz,1H),6.85(dd,J=5.0,1.3Hz,1H); 13 C NMR (101MHz, CDCl3) δ160.86,152.82,150.79,134.96,133.27,131.32,129.35,129.08,1 28.59,128.56,127.67,127.23,124.12,123.82,121.82,120.48,116.62.HRMS(ESI)calcd for C 19 H 12 O2S(M+H) + 305.0558, found 305.0637.

[0054] Example 4

[0055]

[0056] Under argon atmosphere, phenylpent-2-ynoate (34.8 mg, 0.2 mmol), 4-methoxyiodobenzene (93.6 mg, 0.4 mmol), IPrAuCl (12.4 mg, 0.02 mmol), silver hexafluoroantimonate (137.5 mg, 0.4 mmol), potassium carbonate (55.2 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 1,2-dichloroethane (2.0 mL) was added. The mixture was reacted at 100° C. for 9 hours and monitored by TLC until phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product 4-ethyl-3-(4-methoxyphenyl)-2H-chromen-2-one (45.97 mg, 82% yield).

[0057] See also Fig. 9 and Fig.10 , Mp = 170-173 ° C; 1 H NMR (400MHz, CDCl3) δ7.68(t,J=9.1Hz,1H),7.52(q,J=8.2Hz,1H),7.29(dt,J=62.2,9.4Hz,4H) ,6.99(t,J=8.6Hz,2H),3.84(d,J=9.6Hz,3H),2.76-2.63(m,2H),1.19(dt,J=10.5,7.4Hz,3H); 13 C NMR (101MHz, CDCl3) δ161.52,159.32,153.26,153.12,131.06,131.04,130.67,130.64,126.58,126.48,126.46,125 .08,125.06,124.17,124.15,119.20,117.12,117.09,114.01,113.98,55.23,22.79,14.16,14.14.HRMS(ESI)calcd for C 18 H 16 O3(M+H) + 281.1099, found 281.1172.

[0058] Example 5

[0059]

[0060] Under argon atmosphere, phenylpropiolate (44.4 mg, 0.2 mmol), 4-methyliodobenzene (87.2 mg, 0.4 mmol), JohnphosAu(MeCN)SbF6 (15.4 mg, 0.02 mmol), silver bis(trifluoromethanesulfonyl)imide (155.2 mg, 0.4 mmol), disodium hydrogen phosphate (56.8 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 1,2-dichloroethane (2.0 mL) was added. The mixture was reacted at 90° C. for 8 hours and monitored by TLC until phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product 4-phenyl-3-(4-methylphenyl)-2H-chromen-2-one (56.2 mg, 90% yield).

[0061] See also Fig.11 and Fig.12 , Mp = 170-173 ° C; 1 H NMR (400MHz, CDCl3) δ7.56-7.50(m,1H),7.43(d,J=8.2Hz,1H),7.35-7.30(m,3H),7.23-7.13(m,4H),7.05-6.99(m,4H),2.26(s,3H); 13 CNMR (101MHz, CDCl3) δ161.39,153.07,151.15,137.32,134.56,131.24,130.74,130.31,129. 30,128.44,128.22,128.20,127.66,126.90,124.02,120.53,116.65,21.19.HRMS(ESI)calcd for C 22 H 16 O2(M+H) + 313.1150, found 313.1223.

[0062] Example 6

[0063]

[0064] Under argon atmosphere, p-tolyl-3-phenylacrylate (47.2 mg, 0.2 mmol), 4-methoxyiodobenzene (93.6 mg, 0.4 mmol), JohnphosAu(MeCN)SbF6 (15.4 mg, 0.02 mmol), silver trifluoromethanesulfonate (102.7 mg, 0.4 mmol), potassium carbonate (55.2 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, 1,2-dichloroethane (2.0 mL) was added, and the mixture was reacted at 100°C for 9 hours, monitored by TLC until phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product 3-(4-methoxyphenyl)-6-methyl-4-phenyl-2H-chromen-2-one (54.7 mg, 80% yield).

[0065] See also Fig.13 and Fig.14 , Mp = 206-209 ° C; 1 H NMR (400MHz, CDCl3) δ7.36-7.29 (m, 5H), 7.12 (dd, J = 7.1, 2.4Hz, 2H), 7.07-7.03 ( m,2H),6.97(dt,J=1.7,1.0Hz,1H),6.73-6.69(m,2H),3.73(s,3H),2.29(s,3H); 13 C NMR (101MHz, CDCl3) δ161.70,158.71,151.16,151.02,134.77,133.67,132.21,131.79,129.34, 128.26,128.13,127.29,126.42,126.12,120.20,116.40,113.16,55.05,20.93.HRMS(ESI)calcd for C 23 H 18 O3(M+H) + 343.1256, found 343.1332.

[0066] Example 7

[0067]

[0068] Under argon atmosphere, 1,1'-biphenyl-4-phenylpropiolate (59.6 mg, 0.2 mmol), 4-methoxyiodobenzene (93.6 mg, 0.4 mmol), Me2SAuCl (5.9 mg, 0.02 mmol), silver hexafluoroantimonate (137.5 mg, 0.4 mmol), potassium carbonate (55.2 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, 1,2-dichloroethane (2.0 mL) was added, and the mixture was reacted at 80°C for 8 hours, monitored by TLC until 1,1'-biphenyl-4-phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product 3-(4-methoxyphenyl)-4,6-diphenyl-2H-chromen-2-one (66.3 mg, 82% yield).

[0069] See also Fig.15 and Fig.16 , Mp = 173-176°C; 1 H NMR (400MHz, CDCl3) δ7.75 (dd, J=8.6, 2.2Hz, 1H), 7.50 (d, J=8.5Hz, 1H), 7.46-7.31 (m ,9H),7.19(dd,J=7.5,2.0Hz,2H),7.12-7.07(m,2H),6.77-6.72(m,2H),3.75(s,3H); 13 C NMR (101MHz, CDCl3) δ161.43,158.79,152.44,151.01,139.70,137.32,134.51,131.80,130.12,129.33,128.83 ,128.37,128.31,127.49,126.96,126.80,125.94,125.81,120.72,117.04,113.19,55.04.HRMS(ESI)calcdfor C 28 H 20 O3(M+H) + 405.1412, found 405.1493.

[0070] Example 8

[0071]

[0072] Under argon atmosphere, phenylpropiolate (44.4 mg, 0.2 mmol), (E)-(iododecene) (106.5 mg, 0.4 mmol), Me2SAuCl (5.9 mg, 0.02 mmol), tetrafluoroborate (77.8 mg, 0.4 mmol), potassium carbonate (55.2 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 1,2-dichloroethane (2.0 mL) was added. The mixture was reacted at 90° C. for 9 hours and monitored by TLC until phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product (E)-3-(decene)-4-phenyl-2H-chromen-2-one (57.6 mg, 80% yield).

[0073] See also Fig.17 and Fig.18 , 1 H NMR (400MHz, CDCl3) δ7.56-7.48 (m, 3H), 7.44 (ddd, J = 8.5, 7.1, 1.6Hz, 1H), 7 .35(dd,J=8.3,1.2Hz,1H),7.25(dt,J=7.8,1.7Hz,2H),7.14-7.08(m,1H),7 .00(dd,J=8.0,1.6Hz,1H),6.89(dt,J=15.8,7.1Hz,1H),5.94(d,J=15.8Hz, 1H),2.03(qd,J=7.2,1.5Hz,2H),1.34-1.19(m,12H),0.87(t,J=6.9Hz,3H); 13 C NMR (101MHz, CDCl3) δ160.16,152.01,148.66,140.14,134.86,130.58,128.87,128.75,128.53,127.23,123. 90,122.53,121.74,120.92,116.26,34.27,31.84,29.35,29.21,29.08,28.90,22.64,14.09.HRMS(ESI)calcd for C 25 H 28 O2(M+H) + 361.2089, found 361.2166.

[0074] Example 9

[0075]

[0076] Under argon atmosphere, phenylpropiolate (44.4 mg, 0.2 mmol), (E)-1-(2-iodovinyl)-4-methylbenzene (97.6 mg, 0.4 mmol), MeDalPhosAuCl (13.1 mg, 0.02 mmol), silver hexafluoroantimonate (137.5 mg, 0.4 mmol), potassium benzoate (64.1 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 1,2-dichloroethane (2.0 mL) was added. The mixture was reacted at 100° C. for 6 hours and monitored by TLC until phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product (E)-3-(4-methylphenylvinyl)-4-phenyl-2H-chromen-2-one (57.5 mg, 85% yield).

[0077] See also Fig.19 and Fig. 20 , Mp = 122-123 ° C; 1 H NMR (400MHz, CDCl3) δ7.92(d,J=16.2Hz,1H),7.57(d,J=7.2Hz,3H),7.48(t,J=7.6Hz,1H),7.38(d,J=8.2Hz ,1H),7.35-7.29(m,2H),7.15(t,J=8.9Hz,3H),7.06(d,J=7.8Hz,3H),6.66(d,J=16.2Hz,1H),2.31(s,3H); 13 C NMR (101MHz, CDCl3) δ159.88,152.11,149.78,138.06,135.64,134.88,134.68,130.86,129.24,129. 03,128.85,128.81,127.34,126.73,124.03,121.56,120.89,120.75,116.34,21.22.HRMS(ESI)calcd for C 24 H 18 O2(M+H) + 338.1307, found 338.1381.

[0078] Example 10

[0079]

[0080] Under argon atmosphere, phenylpropiolate (44.4 mg, 0.2 mmol), (E)-1-fluoro-4-(2-iodovinyl)benzene (99.2 mg, 0.4 mmol), MeDalPhosAuCl (13.1 mg, 0.02 mmol), silver hexafluoroantimonate (137.5 mg, 0.4 mmol), potassium benzoate (64.1 mg, 0.4 mmol) were added to a Schlenk tube equipped with a magnetic stirrer, and 1,2-dichloroethane (2.0 mL) was added. The mixture was reacted at 100° C. for 12 hours and monitored by TLC until phenylpropiolate was completely consumed. The residue was purified by silica gel column chromatography to obtain the product (E)-3-(4-fluorostyrene)-4-phenyl-2H-chromen-2-one (56.7 mg, 83% yield).

[0081] See also Figure 21 to Figure 23 , Mp = 138-141°C; 1 H NMR (400MHz, CDCl3) δ7.91 (d, J=16.2Hz, 1H), 7.63-7.54 (m, 3H), 7.48 (ddd, J=8.5, 7.1, 1.6Hz, 1H), 7.38 (dd, J=8.3, 1.2Hz, 1H), 7. 34-7.28(m,2H),7.24-7.18(m,2H),7.18-7.12(m,1H),7.06(dd,J=8.0,1.6Hz,1H),6.94(t,J=8.7Hz,2H),6.60(d,J=16.2Hz,1H); 13 C NMR (101MHz, CDCl3) δ163.78,161.31,159.86,152.15,150.35,134.54,134.38,133.82,133.79,131.09,128.9 9,128.94,128.91,128.38,128.30,127.44,124.13,121.39,121.36,121.23,120.79,116.40,115.61,115.40; 19 F NMR(376MHz,CDCl3)δ-113.30.HRMS(ESI)calcd for C 23 H 15 FO2(M+H) + 343.1056, found 343.1130.

Claims

1. A method for preparing 3-arylated / 3-alkenylated coumarin compounds, characterized in that: The method uses gold to catalyze the bifunctionalization of acetylene ester compounds and organic halides to obtain 3-aryl / alkenyl coumarin, comprising dissolving a gold catalyst, a halogen transfer reagent, a base, iodobenzenes / iodoalkenylbenzenes and acetylene ester compounds in a dry solvent under an inert gas atmosphere, and then continuously reacting at 80° C. to 100° C. until the reaction substrate is completely consumed to obtain the target product; The general reaction formula is as follows: Wherein: R1 is selected from any one of alkyl, halogen and heterocycle; R2 is selected from any one of alkyl and aryl; R3 is selected from any one of aryl and alkyl; R4 is selected from any one of alkyl and aryl.

2. The preparation method according to claim 1, characterized in that: The gold catalyst is any one of Ph3PAuCl, IPrAuCl, JohnphosAu(MeCN)SbF6, Me2SAuCl, and MeDalPhosAuCl.

3. The preparation method according to claim 1, characterized in that: The halogen transfer reagent is one or more of silver bis(trifluoromethanesulfonyl)imide, silver trifluoromethanesulfonate, silver hexafluoroantimonate, and silver tetrafluoroborate.

4. The preparation method according to claim 1, characterized in that: The alkali is one or more of sodium carbonate, potassium carbonate, disodium hydrogen phosphate, dipotassium hydrogen phosphate and potassium benzoate.

5. The preparation method according to claim 1, characterized in that: The solvent is one or more of dry dichloromethane, dry acetonitrile, dry 1,2-dichloroethane, dry methanol and dry 1,4-dioxane, preferably dry 1,2-dichloroethane.

6. The preparation method according to claim 1, characterized in that: The molar ratio of the acetylenic ester compound to the iodobenzene or iodoalkenylbenzene compound is 1:2-4; The molar ratio of the acetylene ester compound to the gold catalyst is 1:0.05-0.10; The molar ratio of the acetylene ester compound to the halogen transfer reagent is 1:2-4; The molar ratio of the acetylene ester compound to the base is 1:2-4.

7. The preparation method according to any one of claims 1 to 6, characterized in that: The reaction lasts for 6 to 12 hours, and the residue is purified by silica gel column chromatography to obtain the target product.

8. The preparation method according to claim 1, characterized in that: The alkynyl ester compound is phenyl propiolate, the iodinated alkenyl benzene compound is (E)-iodinated decene, the halogen transfer reagent is silver tetrafluoroborate, and the target product is (E)-3-(decene)-4-phenyl-2H-chromene-2-one, and the reaction formula is as follows:

9. A 3-alkenylated coumarin compound (E)-3-(decene)-4-phenyl-2H-chromen-2-one prepared according to the preparation method of claim 8.

10. Use of the 3-alkenylated coumarin compound (E)-3-(decene)-4-phenyl-2H-chromen-2-one according to claim 9 in drug synthesis and biomedicine.

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