A method for synthesizing 3-alkenylbenzofurans

Abstract

The application discloses a synthesis method of 3-alkenyl benzofuran compounds. The method uses 2-vinyloxy phenyl acetylene compounds as reaction raw materials, and under the catalysis of a cheap transition metal (Co, Zn) and a mild reaction condition (40 DEG C), a series of 3-alkenyl benzofuran compounds are conveniently prepared. Compared with the prior art, the method has the advantages of easy raw material source, wide substrate adaptation range, economical and cheap catalytic system, high target product yield and the like, and is suitable for industrialized production.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic pharmaceutical synthesis intermediates, and particularly relates to a synthesis method of 3-alkenyl benzofuran compounds. BACKGROUND

[0002] Benzofuran compounds widely exist in natural products and physiological active compounds, and show extensive biological activities, including antibacterial, anti-inflammatory, antitumor, insecticidal, etc. Patent CN102180846B discloses a resveratrol dimer derivative with the following structure which has broad-spectrum tumor inhibitory activity against cancer cells. The patent reports that the method for synthesizing the compound needs to provide a corresponding 3-iodobenzofuran compound as a substrate in advance, and then a Heck reaction is performed with a styrene compound to prepare the resveratrol dimer derivative. The 3-alkenyl benzofuran compound is a commonly used synthetic intermediate in the field of organic and pharmaceutical synthesis, which can be prepared into the aforementioned resveratrol dimer derivative through a Heck reaction with an iodoarene compound. Therefore, it is of great significance to study the synthesis of 3-alkenyl benzofuran compounds.

[0003] However, the existing methods for preparing 3-alkenyl benzofuran compounds have many defects. For example, CN109369584 discloses a class of 2-aryl / alkyl-3-(substituted alkene) naphthofuran derivatives and a synthesis method thereof. The method is prepared in a mild condition catalyzed by iron through tandem of enyne Claisen rearrangement and oxidative coupling. However, the method needs to provide a complex structure of aryl 1,3-substituted enyne methyl ether substrate, which significantly reduces the industrial application value of the synthesis strategy. Ken Tanaka et al. reported that 3-alkenyl benzofuran compounds were prepared from o-vinyl-oxyphenylacetylene substrates in a [Rh(cod)2]BF4 / rac-binap catalytic reaction system (Angew. Chem. Int. Ed. 2012, 51, 5976-5980). On the one hand, the method uses an expensive rhodium / phosphine ligand catalytic system, and on the other hand, the yield of the target product is only 15-16%, which obviously does not have practical production significance. In addition, other methods for preparing 3-alkenyl benzofuran compounds also involve complex reaction substrates and reaction conditions (Org. Lett., 2021, 23, 3064-3069). Therefore, it is of great significance to develop a method for conveniently preparing 3-alkenyl benzofuran compounds under economic and mild conditions. SUMMARY

[0004] The purpose of the present application is to overcome the defects of the prior art and provide a new method for conveniently preparing 3-alkenyl benzofuran compounds under economic and mild conditions.

[0005] A method for synthesizing 3-alkenylbenzofuran compounds according to the present invention includes the following steps:

[0006] A 2-ethyleneoxyphenylacetylene compound (Formula 1), a cobalt salt catalyst, an organophosphorus ligand, zinc powder, and an organic solvent were sequentially added to a reactor. The reactor was then stirred under an inert atmosphere at room temperature to 60°C. After complete reaction, post-treatment yielded a 3-alkenylbenzofuran compound (Formula 2). The reaction formula is as follows:

[0007]

[0008] In the above reaction formula, R1 is a substituted or unsubstituted C. 1-20 Alkyl, substituted or unsubstituted C 6-20 Aryl, C 2-20 heteroaryl, C 3-8 cycloalkyl; wherein the substituents in the substituted or unsubstituted form are selected from halogens, -CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkoxycarbonyl, -N(C) 1-6 Alkyl)2, C 6-14 Aryl, C 6-14 aryloxy group, C 7-15 Araneoxy group.

[0009] m represents an integer of 0, 1, 2, 3, or 4, and R2 may be the same or different, and is independently selected from H, halogen, -CN, and C, respectively. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups.

[0010] Preferably, R1 is substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted phenyl, thiophene, furanyl, cyclohexyl, cyclopentyl; wherein the substituent in the substituted or unsubstituted group is selected from fluorine, chlorine, bromine, -CN, methyl, methoxy, trifluoromethyl, -COOMe, -N(Me)2, phenyl, benzyloxy.

[0011] m represents 0 or 1, and R2 is selected from H, fluorine, chlorine, bromine, -CN, methyl, methoxy, trifluoromethyl, and trifluoromethoxy.

[0012] Most preferably, R1 is phenethyl, 3-chloropropyl, benzyloxyethyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 4-N,N-dimethylaminophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-methoxycarbonylphenyl, thienyl, cyclohexyl.

[0013] m represents 0 or 1, and R2 is selected from H, chloro, -CN, methyl, methoxy.

[0014] According to the aforementioned synthetic method of the present application, preferably, the cobalt salt catalyst is selected from any one or mixture of several of CoBr2, CoCl2, CoI2, Co(OAc)2; most preferably CoBr2.

[0015] According to the aforementioned synthetic method of the present application, preferably, the organic phosphine ligand is selected from one or mixture of several of the following organic phosphine ligands:

[0016]

[0017] Most preferably, the organic phosphine ligand is dppp.

[0018] According to the aforementioned synthetic method of the present application, the molar ratio of the 2-vinyloxyphenylacetylene compound of formula 1, the cobalt salt catalyst, the organic phosphine ligand and the zinc powder is 1: (0.01-0.1): (0.01-0.12): (0.2-0.8); preferably, the molar ratio of the 2-vinyloxyphenylacetylene compound of formula 1, the cobalt salt catalyst, the organic phosphine ligand and the zinc powder is 1:0.05:0.06:0.5.

[0019] According to the aforementioned synthetic method of the present application, the organic solvent is selected from any one or mixture of several of dichloromethane, dichloroethane, acetonitrile, chlorobenzene; preferably, the organic solvent is dichloromethane.

[0020] According to the aforementioned synthetic method of the present application, the inert atmosphere is nitrogen atmosphere or argon atmosphere.

[0021] According to the aforementioned synthetic method of the present application, the reaction temperature for stirring reaction is preferably 40°C; the reaction time is 8-48 hours, preferably 12-24 hours.

[0022] According to the aforementioned synthetic method of the present application, the post-treatment operation is as follows: after the reaction is completed, the reaction solution is filtered, the filtrate is concentrated to dryness under reduced pressure, and the residue is separated by silica gel column chromatography to obtain the 3-alkenylbenzofuran compound of formula 2.

[0023] Compared with the prior art, the method of the present application has the following significant advantages:

[0024] 1) The present application first reports that 2-vinyloxyphenylacetylene compounds are used as reaction raw materials, a series of 3-alkenylbenzofuran compounds are prepared under the catalytic reaction system of cheap transition metal (Co, Zn) and mild reaction conditions (40℃), compared with the prior art, the raw material is easy to obtain, the substrate is wide, the catalytic system is economical and cheap, and the yield of the target product is high, which is suitable for industrial production.

[0025] 2) The 3-alkenylbenzofuran compounds prepared by the present application can be used as a synthon to construct various biologically active compounds such as resveratrol dimer derivatives described in the first paragraph of the specification by classical organic synthesis reactions such as HECK reaction, etc., so the synthesis method of the present application also enriches the synthesis routes of the prior art for preparing these biologically active compounds. DETAILED DESCRIPTION

[0026] The present application will be further described in detail below in combination with specific examples. In the following text, unless otherwise specified, the methods used are conventional methods in the art; each raw material and reagent used is obtained by conventional commercial route and is not further purified, and / or is prepared according to the preparation method of the known compounds in the prior art (such as Angew. Chem. Int. Ed. 2012, 51, 5976-5980, etc.).

[0027] Reaction condition optimization test of examples 1-18

[0028] With o-vinyloxydiphenylacetylene represented by formula 1a as a template substrate, the influence of different catalytic reaction conditions on the yield of 2-phenyl-3-vinylbenzofuran represented by formula 2a was discussed, and the results are shown in Table 1, and the reaction formula is as follows:

[0029]

[0030] Table 1:

[0031]

[0032] Taking example 1 as an example, the typical test operation is as follows:

[0033] Into a Schlenk tube reactor equipped with a stir bar, 2-ethenyloxydiphenylacetylene (0.2 mmol) represented by Formula 1a, CoBr2(5 mol%), dppp (6 mol%), Zn (50 mol%), DCM (1 mL) were added successively, then the atmosphere in the reactor was converted with argon for three times, after the reactor was placed in a 40 °C oil bath with stirring for 16 hours, the reaction was detected by TLC or GC-MS, the raw material was consumed, the reaction was terminated, the reaction liquid was filtered through a short column of silica gel, washed with ethyl acetate, and the filtrate was collected and concentrated under reduced pressure to obtain a residue, which was separated by silica gel column chromatography (elution solvent: n-hexane / ethyl acetate v / v = 5:1~20:1), and concentrated under reduced pressure to obtain 2-phenyl-3-vinylbenzofuran represented by Formula 2a in the form of colorless oil, with a yield of 83%. 1 H NMR (400 MHz, CDCI3) δ: 7.92-7.90 (m, 1H), 7.85 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 7.6 Hz, 1H), 7.55-7.51 (m, 2H), 7.46-7.42 (m, 1H), 7.41-7.33 (m, 2H), 7.10-7.02 (m, 1H), 6.00 (dd, J = 17.8, 1.2 Hz, 1H), 5.57 (dd, J = 11.4, 1.3 Hz, 1H); 13 C{ 1 H} NMR (101 MHz, CDCI3) δ: 154.3, 152.8, 130.7, 128.6, 128.6, 128.0, 127.9, 127.8, 124.6, 123.0, 120.8, 116.7, 114.6, 111.3; HRMS m / z (EI) calcd for C 16 H 12 O: 220.0888; Found: 220.0883.

[0034] Example 2-18, in addition to the reaction variables shown in Table 1, the rest of the parameters and operations are exactly the same as Example 1.

[0035] As can be seen from Table 1, the catalytic reaction conditions of Example 1 are the optimal reaction conditions. In order to investigate the universality of the optimal reaction conditions, the present application further explores the selection of different substituents of the reaction substrate under the optimal reaction conditions (Example 1), and successfully prepares a series of 3-alkenylbenzofuran compounds. The product structure and yield results are as follows:

[0036]

[0037]

[0038] Structural characterization of the product:

[0039] Compound 2b: white solid; 1 H NMR (400 MHz, CDC13) δ: 7.90-7.87 (m, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.56-7.54 (m, 1H), 7.38-7.30 (m, 4H), 7.07-6.99 (m, 1H), 5.96 (dd, J = 17.8, 1.3 Hz, 1H), 5.53 (dd, J = 11.4, 1.3 Hz, 1H), 2.45 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDC13) δ: 154.2, 153.1, 138.8, 129.3, 128.1, 128.0, 127.9, 127.8, 124.4, 123.0, 120.7, 116.3, 114.1, 111.2 21.4.

[0040] Compound 2c: light yellow oily liquid; 1 H NMR (400 MHz, CDC13) δ: 7.89-7.87 (m, 1H), 7.57-7.55 (m, 1H), 7.44-7.30 (m, 5H), 7.08-7.01 (m, 1H), 7.00-6.97 (m, 1H), 1.22 (s, 12H), 1.21 (s, 12H), 0.76 (t, J = 7.5 Hz, 1H); 13 C{ 1 H} NMR (101 MHz, CDC13) δ: 159.7, 154.3, 152.5, 131.9, 129.6, 127.9 (Two signals overlap), 124.7, 123.0, 120.8, 120.4, 116.9, 114.83, 114.6, 113.0, 111.3, 55.3.

[0041] Compound 2e: light yellow oily liquid; 1 H NMR (400 MHz, CDC13) δ: 7.88-7.84 (m, 1H), 7.73-7.70 (m, 2H), 7.55-7.50 (m, 1H), 7.34-7.27 (m, 2H), 7.08-7.01 (m, 1H), 6.84-6.80 (m, 2H), 5.92 (dd, J = 17.8, 1.3 Hz, 1H), 5.48 (dd, J = 11.4, 1.3 Hz, 1H), 3.05 (s, 6H); 13 C{ 1H NMR (101 MHz, CDC13) δ: 154.2, 154.0, 150.5, 129.0, 128.6, 128.3, 123.7, 122.8, 120.3, 118.4, 115.1, 112.2, 111.9, 110.9, 40.2.

[0042] Compound 2i: white solid; 1 H NMR (400 MHz, CDC13) δ: 7.87-7.85 (m, 1H), 7.75-7.72 (m, 2H), 7.54-7.52 (m, 1H), 7.48-7.45 (m, 2H), 7.38-7.29 (m, 2H), 6.97-6.92 (m, 1H), 5.96 (dd, J = 17.8, 1.4 Hz, 1H), 5.56 (dd, J = 11.4, 1.3 Hz, 1H); 13 C{1H} NMR (101 MHz, CDC13) δ: 154.3, 151.4, 134.6, 129.2, 128.9 (Two signals overlap), 127.8, 127.6, 124.9, 123.2, 120.9, 117.5, 115.1, 111.3.

[0043] Compound 2j: white solid; 1 H NMR (400 MHz, CDC13) δ: 7.86-7.84 (m, 1H), 7.69-7.60 (m, 4H), 7.53-7.51 (m, 1H), 7.37-7.28 (m, 2H), 6.98-6.90 (m, 1H), 5.95 (dd, J = 17.8, 1.3 Hz, 1H), 5.55 (dd, J = 11.4, 1.3 Hz, 1H); 13 C{ 1 H} NMR (101 MHz, CDC13) δ: 154.3, 151.41, 131.9, 129.6, 129.2, 127.9, 127.6, 125.0, 123.2, 122.9, 120.9, 117.6, 115.2, 111.3.

[0044] Compound 2l: light yellow oily liquid; 1H NMR (400 MHz, CDC13) δ: 7.91 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.0 Hz, 1H), 7.41-7.31 (m, 2H), 7.02-6.94 (m, 1H), 5.99 (dd, J = 17.8, 1.2 Hz, 1H), 5.61 (dd, J = 11.4, 1.2 Hz, 1H); 13 C{ 1 H} NMR (101 MHz, CDC13) δ: 154.5, 150.6, 134.1, 130.2 (q, J = 32.6 Hz), 128.09, 127.76, 127.71, 127.32, 125.6 (q, J = 3.8 Hz), 125.4, 124.0 (d, J = 271.7 Hz), 123.3, 121.1, 118.3, 116.4, 111.4; 19 F NMR (377 MHz, CDC13) δ: -62.6.

[0045] Compound 2m: white solid; 1 H NMR (400 MHz, CDC13) δ: 7.89 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 7.6 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.0 Hz, 1H), 7.41-7.37 (m, 1H), 7.34-7.30 (m, 1H), 6.98-6.90 (m, 1H), 5.98 (dd, J = 17.8, 1.1 Hz, 1H), 5.64 (dd, J = 11.4, 1.2 Hz, 1H); 13 C{ 1 H} NMR (101 MHz, CDC13) δ: 154.5, 149.6, 134.8, 132.3, 127.7, 127.6, 127.0, 125.7, 123.4, 121.1, 119.1, 118.6, 117.3, 111.5, 111.4.

[0046] Compound 2n: white solid; 1H NMR (400 MHz, CDCI3) δ: 8.14 (d, J = 7.6 Hz, 2H), 7.86 (t, J = 8.0 Hz, 3H), 7.53 (d, J = 8.0 Hz, 1 H), 7.39-7.29 (m, 2H), 7.03-6.96 (m, 1 H), 5.98 (dd, J = 17.8, 1.2 Hz, 1 H), 5.60 (dd, J = 11.4, 1.2 Hz, 1 H), 3.95 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDCI3) δ: 166.6, 154.5, 151.0, 134.8, 129.8, 129.6, 127.8, 127.5, 127.3, 125.3, 123.2, 121.0, 118.1, 116.4, 111.4, 52.2; HRMS m / z (EI) calcd for C 18 H 14 O3: 278.0943; Found: 278.0937.

[0047] Compound 2r: pale yellow oily liquid; 1 H NMR (400 MHz, CDCI3) δ: 7.84-7.82 (m, 1 H), 7.53-7.49 (m, 2H), 7.46-7.44 (m, 1 H), 7.35-7.27 (m, 2H), 7.18-7.15 (m, 1 H), 7.14-7.06 (m, 1 H), 5.97 (dd, J = 17.7, 1.3 Hz, 1 H), 5.55 (dd, J = 11.4, 1.3 Hz, 1 H); 13 C{ 1 H} NMR (101 MHz, CDCI3) δ: 154.2, 148.2, 139.6, 132.5, 127.7, 127.3, 126.9, 126.6, 124.8, 123.2, 120.8, 117.1, 114.2, 111.2.

[0048] Compound 2v: pale yellow oily liquid; 1 H NMR (400 MHz, CDCI3) δ: 7.80-7.78 (m, 1 H), 7.49-7.46 (m, 1 H), 7.33-7.28 (m, 4H), 7.25-7.22 (m, 3H), 6.71-6.63 (m, 1 H), 5.75 (d, J = 17.8 Hz, 1 H), 5.32 (d, J = 11.4 Hz, 1 H), 3.17-3.13 (m, 2H), 3.10-3.06 (m, 1 H); 13 C{ 1H NMR (101 MHz, CDC13) δ: 156.0, 154.2, 140.8, 128.5, 128.3, 127.2, 126.8, 126.2, 123.7, 122.8, 120.3, 114.3, 114.1, 110.9, 34.4, 28.9.

[0049] Compound 2s: pale yellow oily liquid; 1 H NMR (400 MHz, CDC13) δ: 7.81-7.75 (m, 1H), 7.44-7.39 (m, 1H), 7.29-7.23 (m, 2H), 6.82-6.75 (m, 1H), 5.80 (dd, J = 17.8, 1.2 Hz, 1H), 5.37 (dd, J = 11.4, 1.2 Hz, 1H), 3.57 (t, J = 6.4 Hz, 1H), 3.01 (t, J = 7.2 Hz, 1H), 2.45 - 2.07 (m, 1H); 13 C{ 1 H NMR (101 MHz, CDC13) δ: 155.1, 154.2, 127.0, 126.8, 123.9, 122.9, 120.4, 114.7 (Two signals overlap), 110.9, 44.0, 30.8, 23.7.

[0050] Compound 2z: pale yellow oily liquid; 1 H NMR (400 MHz, CDC13) δ: 7.71-7.68 (m, 1H), 7.34-7.32 (m, 1H), 7.24-7.15 (m, 7H), 6.74-6.67 (m, 1H), 5.72 (dd, J = 17.8, 1.2 Hz, 1H), 5.28 (dd, J = 11.4, 1.2 Hz, 1H), 4.45 (s, 2H), 3.74 (t, J = 6.8 Hz, 2H), 3.07 (t, J = 6.8 Hz, 2H); 13 C{ 1 H NMR (101 MHz, CDC13) δ: 154.2, 153.9, 138.1, 128.3, 127.6 (Two signals overlap), 127.1, 127.0, 123.8, 122.8, 120.3, 115.0, 114.6, 111.0, 73.0, 67.9, 27.8.

[0051] Compound 2af: colorless oily liquid; 1H NMR (400 MHz, CDC13) δ: 7.81-7.78 (m, 1H), 7.48-7.44 (m, 1H), 7.30-7.25 (m, 2H), 6.88-6.81 (m, 1H), 5.80 (d, J = 17.8 Hz, 1H), 5.36 (dd, J = 11.4, 1.2 Hz, 1H), 3.01-2.93 (m, 1H), 1.91-1.89 (m, 4H), 1.81-1.72 (m, 3H), 1.48-1.30 (m, 3H); 13 C{ 1 H} NMR (101 MHz, CDC13) δ: 13 C NMR (101 MHz, CDC13) δ 161.1, 154.0, 127.3, 127.1, 123.4, 122.6, 120.3, 113.8, 112.0, 110.9, 36.4, 31.2, 26.3, 25.8.

[0052] Compound 2ai: colorless oily liquid; 1 H NMR (400 MHz, CDC13) δ: 7.84 (d, J = 7.2 Hz, 2H), 7.70 (s, 1H), 7.54-7.51 (m, 2H), 7.47-7.42 (m, 2H), 7.20-7.18 (m, 1H), 7.08-7.01 (m, 1H), 5.99 (dd, J = 17.8, 1.1 Hz, 1H), 5.56 (dd, J = 11.4, 1.3 Hz, 1H), 2.54 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDC13) δ: 152.9, 152.8, 132.4, 130.8, 128.6, 128.5, 128.1, 128.0, 127.8, 125.8, 120.7, 116.5, 114.4, 110.7, 21.5.

[0053] Compound 2ak: white solid; 1 H NMR (400 MHz, CDC13) δ: 7.81-7.77 (m, 3H), 7.52-7.48 (m, 2H), 7.45-7.41 (m, 2H), 7.30-7.28 (m, 1H), 6.99-6.92 (m, 1H), 5.89 (dd, J = 17.9, 1.2 Hz, 1H), 5.54 (dd, J = 11.4, 1.2 Hz, 1H); 13 C{ 1H} NMR (101 MHz, CDC13) δ: 153.9, 152.6, 130.2, 129.3, 129.0, 128.7, 127.8, 127.4, 124.7, 120.4, 117.3, 114.2, 112.1.

[0054] Compound 2am: white solid; 1 H NMR (400 MHz, CDC13) δ: 8.11 (s, 1H), 7.76 (d, J = 7.2 Hz, 2H), 7.58-7.42 (m, 5H), 6.95-6.88 (m, 1H), 5.86 (d, J = 17.9 Hz, 1H), 5.58 (d, J = 11.5 Hz, 1H); 13 C{ 1 H} NMR (101 MHz, CDC13) δ: 155.8, 154.5, 129.5, 129.4, 128.7 (Two signals overlap), 128.1, 127.8, 126.7, 125.6, 119.4, 118.2, 114.1, 112.3, 106.8.

[0055] The above-described embodiments are merely preferred embodiments of the present application, but are not exhaustive of the feasible implementations of the present application. Any obvious modifications made by those skilled in the art without departing from the principles and spirit of the present application should be considered to be within the scope of protection of the claims of the present application.

Claims

1. A method for synthesizing a 3-alkenylbenzofuran compound, characterized by, The method comprises the following steps: The 2-vinyloxyphenylacetylene compound shown in formula 1, a cobalt salt catalyst, an organic phosphine ligand, zinc powder and an organic solvent are sequentially added into a reactor, and then the reactor is stirred and reacted at room temperature to 60 DEG C under an inert atmosphere, and after the reaction is completed, the 3-alkenylbenzofuran compound shown in formula 2 is obtained through post-treatment. ； In the above reaction formula, R1 is a substituted or unsubstituted C. 1-20 Alkyl, substituted or unsubstituted C 6-20 Aryl, C 2-20 heteroaryl, C 3-8 cycloalkyl; wherein the substituents in the substituted or unsubstituted form are selected from halogens, -CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkoxycarbonyl, -N(C) 1-6 Alkyl)2, C 6-14 Aryl, C 6-14 aryloxy group, C 7-15 arylalkoxy; m denotes an integer of 0, 1, 2, 3 or 4, R2are the same or different and are each independently selected from the group consisting of H, halogen, -CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy; The cobalt salt catalyst is selected from any one or mixture of several of CoBr2, CoCl2, CoI2 and Co(OAc)2. The organic phosphine ligand is selected from one or mixture of several of the following organic phosphine ligands: 。 2. The method of synthesis of claim 1, wherein, R1is substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted phenyl, thienyl, furanyl, cyclohexyl, cyclopentyl; wherein the substituents in the substituted or unsubstituted are selected from the group consisting of fluorine, chlorine, bromine, -CN, methyl, methoxy, trifluoromethyl, -COOMe, -N(Me)2, phenyl, benzyloxy; m represents 0 or 1, and R2 is selected from H, fluorine, chlorine, bromine, -CN, methyl, methoxy, trifluoromethyl and trifluoromethoxy.

3. The method of synthesis of claim 2, wherein, R1 is phenethyl, 3-chloropropyl, benzyloxyethyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 4-N,N-dimethylaminophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-methoxycarbonylphenyl, thienyl and cyclohexyl. m represents 0 or 1, and R2 is selected from H, chlorine, -CN, methyl and methoxy.

4. The method of synthesis according to any one of claims 1 to 3, wherein, The cobalt salt catalyst is CoBr2.

5. The method of synthesis of claim 4, wherein, The organic phosphine ligand is dppp.

6. The method of synthesis according to any one of claims 1-3, wherein, The feeding molar ratio of the 2-vinyloxyphenylacetylene compound shown in formula 1, the cobalt salt catalyst, the organic phosphine ligand and the zinc powder is 1: (0.01-0.1): (0.01-0.12): (0.2-0.8).

7. The method of synthesis of claim 6, wherein, The feeding molar ratio of the 2-vinyloxyphenylacetylene compound shown in formula 1, the cobalt salt catalyst, the organic phosphine ligand and the zinc powder is 1: 0.05: 0.06: 0.

5.

8. The method of synthesis according to any one of claims 1-3, wherein, The organic solvent is selected from any one or mixture of several of dichloromethane, dichloroethane, acetonitrile and chlorobenzene.

9. The method of synthesis of claim 8, wherein, The organic solvent is dichloromethane.

10. The method of synthesis according to any one of claims 1-3, wherein, The inert atmosphere is nitrogen atmosphere or argon atmosphere.

11. The method of synthesis according to any one of claims 1-3, wherein, The reaction temperature of the stirring reaction is 40 DEG C, and the reaction time is 8-48 hours.

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