A green synthesis method for a load-free recyclable Heck reaction

Abstract

The present invention discloses a green synthesis method for Heck reaction without load and recyclable. In this method, in water / polyethylene glycol 200 (PEG200), Pd(OAc)2 catalyzes the Heck reaction to obtain excellent co-production yields. Moreover, the reaction system composed of palladium acetate can be directly reused 3 to 5 times without activation and maintain good co-production yields.

Description

Technical Field

[0001] This application belongs to the technical field of organic synthesis methods, and particularly relates to a green synthesis method for a load-free recyclable Heck reaction. Background Art

[0002] The palladium-catalyzed Heck cross-coupling reaction is one of the most effective methods for constructing C-C bonds. However, palladium catalysts are expensive noble metals, which to some extent limits their practical applications. To reduce the reaction cost of the Heck reaction, a large amount of research work has been done on the recycling of palladium catalysts. Currently, most of the research work is to immobilize palladium metal on inert carrier materials to achieve the reuse of the catalyst in the Heck reaction. For example, Debabrata Maiti et al. reported that palladium was immobilized on a composite material of CaO, MgO, SiO2, Fe2O3 and Al2O3, and the palladium catalyst could be reused 5 times (ChemistrySelect 2022, 7, e202200925). Fezzeh Aryanasab et al. reported that palladium was immobilized on a composite material with Fe3O4 as the main body, and the palladium catalyst could be reused 6 times (Appl Organomet Chem. 2021;35:e6198.). And Renan S. Galaverna et al. reported that palladium was immobilized on a polymer material, and the palladium catalyst could be reused 7 times (Eur. J. Org. Chem. 2022, e202200376), etc. These immobilized palladiums have achieved the recycling of the catalyst in the catalytic Heck reaction and shown good catalytic performance, but there are also some defects. For example, immobilizing palladium on inert materials is a multi-step and complex preparation process, which takes a long time and has a high synthesis cost. Moreover, in the cumbersome preparation process, new impurities are likely to be introduced, and these problems will affect the practical application value of such catalytic materials.

[0003] The research group of the inventors has been long-term committed to the study of palladium-catalyzed coupling reactions under ligand-free conditions. It has been found that Suzuki and Heck coupling reactions can occur smoothly in the reaction medium of ionic liquid / water, with palladium chloride as the catalyst and without ligands. Experiments have shown that when iodoarenes and bromoarenes undergo coupling reactions, the ionic liquid / water reaction system still has good catalytic activity after being reused 3-5 times (Organic Chemistry. 2017, 37(11)). However, the current level of development of existing technologies still knows very little about the toxicity data and toxic mechanism of ionic liquids. The Royal Society of Chemistry in the UK has pointed out that the biggest obstacle to the application of ionic liquids is the lack of information on their fundamental physical properties and toxicology. Most of the preparation, regeneration, and disposal processes of ionic liquids involve volatile organic compounds and traditional organic solvents. Coupled with their own environmental toxicity and difficulty in biodegradation, the wide application of ionic liquids is thus restricted.

[0004] Polyethylene glycol (PEG) is stable and non-volatile at high temperatures, and is biodegradable and non-toxic. It is a type of environmentally friendly reaction medium. We reported the study of the cross-coupling reaction between haloarenes and arylboronic acids under ligand-free conditions in PEG-400 / H2O (Journal of Jinggangshan University (Natural Science Edition) (2020, 41(01)). In this study, the inventors conducted a reuse test on the catalyst. The results showed that when the base was added and the reaction raw materials were recharged into the reaction system after extraction and separation, the reaction hardly occurred and did not have the characteristic of catalyst reuse. In the present invention, the inventors experimentally studied and found that in water / polyethylene glycol 200 (PEG200), the Heck reaction catalyzed by Pd(OAc)2 can obtain excellent coupling yields, and the reaction system composed of palladium acetate can be directly reused 3-5 times without activation and maintain good coupling yields. Furthermore, a method for the Heck reaction catalyzed by Pd(OAc)2 with high efficiency, ligand-free, and reusable is provided. Summary of the Invention

[0005] The object of the present invention is to overcome the defects of the existing technology that the preparation process of solid-phase supported palladium catalysts is complex and costly, and that ionic liquids are expensive, toxic, and difficult to biodegrade, and to propose a green synthesis method for the ligand-free recyclable Heck reaction.

[0006] A green synthesis method for the ligand-free recyclable Heck reaction provided by the present invention includes the following steps:

[0007] Add the haloarene compound shown in Formula I, the olefin compound shown in Formula II, Pd(OAc)2, a base, PEG200, and water into a reactor, and then place the reactor in a stirring reaction at 50-100 °C. After the reaction is complete, the target product shown in Formula III is obtained through post-treatment; the reaction formula is as follows:

[0008]

[0009] In the above reaction formula, Ar represents a substituted or unsubstituted C 6-20 aryl group, a substituted or unsubstituted C 2-20 heteroaryl group;

[0010] X is selected from bromine or iodine;

[0011] R1 is selected from hydrogen, C 1-20 alkyl group, C 6-20 aryl group;

[0012] R2 is selected from C 1-20 alkyl group, C 1-20 alkoxycarbonyl group, -COOH, a substituted or unsubstituted C 6-20 aryl group.

[0013] In any part of the present invention, the substituents in the substituted or unsubstituted are selected from halogen, -OH, -SH, -CN, -NO2, C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 acyl group, C 1-6 alkylthio group, C 6-20 aryl group, C 1-6 alkoxycarbonyl group.

[0014] In any part of the present invention, the heteroatoms in the heteroaryl group are O, N or S atoms, and examples of the heteroaryl group include furyl, thienyl, pyridine, indolyl, benzofuryl, benzothienyl, triazinyl, oxazolyl, benzoxazolyl, quinolinyl, etc.

[0015] In any part of the present invention, examples of the aryl group include phenyl, naphthyl, anthryl, phenanthryl, biphenyl, fluorenyl, etc.

[0016] In any part of the present invention, examples of the alkyl group or alkyl moiety include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, n-pentyl, isopentyl, neopentyl, n-hexyl, etc.

[0017] According to the foregoing method of the present invention, preferably, Ar represents a substituted or unsubstituted phenyl or naphthyl group;

[0018] X is selected from iodine;

[0019] R1 is selected from hydrogen;

[0020] R2 is selected from C 1-6 alkoxycarbonyl group, a substituted or unsubstituted phenyl group;

[0021] Wherein the substituents in the substituted or unsubstituted ones are selected from fluorine, chlorine, bromine, methyl, ethyl, tert-butyl, -CN, -NO2, methoxy, ethoxy, tert-butoxy, acetyl, ethoxycarbonyl, tert-butoxycarbonyl, methylthio, phenyl.

[0022] Further preferably, Ar represents phenyl, naphthyl, biphenyl, phenyl substituted with methoxy, phenyl substituted with methyl, fluorophenyl, chlorophenyl, phenyl substituted with acetyl, phenyl substituted with cyano, phenyl substituted with tert-butoxycarbonyl;

[0023] X is selected from iodine;

[0024] R1 is selected from hydrogen;

[0025] R2 is selected from methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, chlorophenyl, phenyl substituted with methyl, phenyl substituted with methoxy, fluorophenyl, phenyl substituted with acetyl, phenyl substituted with cyano, phenyl substituted with tert-butoxycarbonyl.

[0026] According to the foregoing synthesis method of the present invention, wherein the volume ratio of PEG200 to water is 1:1.

[0027] According to the foregoing synthesis method of the present invention, wherein the base is an alkali metal carbonate and / or an alkali metal bicarbonate, including one or a mixture of several of potassium carbonate, sodium carbonate, lithium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, etc., preferably potassium carbonate or cesium carbonate, and most preferably potassium carbonate.

[0028] According to the foregoing synthesis method of the present invention, the molar ratio of the haloaromatic compound shown in formula I, the olefin compound shown in formula II, Pd(OAc)2 and the base is 1:(0.5~1):(0.01~0.1):(1~3); preferably 1:0.75:0.05:1.5.

[0029] According to the foregoing synthesis method of the present invention, wherein the reaction temperature is preferably 60-80 °C, most preferably 60 °C; the time required for the reaction to be complete is 4~24 hours, preferably 6~14 hours, and most preferably 6 hours.

[0030] According to the foregoing synthesis method of the present invention, the post-treatment operation is as follows: after the reaction is complete, the reaction solution is extracted with petroleum ether / ethyl acetate, the petroleum ether / ethyl acetate organic phase is dried with anhydrous MgSO4, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is separated by column chromatography to obtain the target product.

[0031] According to the foregoing synthesis method of the present invention, it further includes the following steps:

[0032] The reaction system after extraction was heated to remove the residual petroleum ether / ethyl acetate, cooled to room temperature, and then the halogenated aromatic compound shown in Formula I, the olefinic compound shown in Formula II, and the base were added continuously. The next Heck coupling reaction was carried out under the aforementioned reaction conditions to achieve the reuse of the catalyst Pd(OAc)₂.

[0033] Compared with the prior art, the present invention has the following advantages:

[0034] 1) The present invention discloses for the first time a green synthesis method for a load-free recyclable Heck reaction, which can achieve an efficient Heck coupling reaction in a PEG200 / water reaction medium. Among them, PEG200 is a human injection, which is non-toxic and harmless, realizing the greening of the reaction medium and having little environmental impact.

[0035] 2) The green synthesis method for the load-free recyclable Heck reaction of the present invention has a wide substrate adaptation range, and the highest yield can reach 98%. The reaction conditions are mild and simple, and it is easy to be popularized and applied industrially.

[0036] 3) The green synthesis method for the load-free recyclable Heck reaction of the present invention realizes the reuse of the catalyst Pd(OAc)₂, effectively reducing the cost and avoiding the defects of the complex preparation process, high cost of the solid-phase supported palladium catalyst in the prior art, and the high price, high toxicity and difficult biodegradation of using ionic liquids. It can be reused more than five times. The reuse of the solvent system also significantly improves the atom economy of the reaction, meeting the requirements of the development of green chemistry. Description of the Drawings

[0037] Figure 1 It is the ¹H NMR spectrum of the product of Example 6.

[0038] Figure 2 It is the ¹³C NMR spectrum of the product of Example 6.

[0039] Figure 3 It is the ¹H NMR spectrum of the product of Example 15.

[0040] Figure 4 It is the ¹³C NMR spectrum of the product of Example 15.

[0041] Figure 5 It is the ¹H NMR spectrum of the product of Example 16.

[0042] Figure 6 It is the ¹³C NMR spectrum of the product of Example 16.

[0043] Figure 7 It is the ¹H NMR spectrum of the product of Example 17.

[0044] Figure 8It is the carbon-13 NMR spectrum of the product of Example 17.

[0045] Figure 9 It is the proton NMR spectrum of the product of Example 18.

[0046] Figure 10 It is the carbon-13 NMR spectrum of the product of Example 18. Detailed implementation manners

[0047] The present invention will be further described in detail below in conjunction with specific embodiments. In the following text, unless otherwise specified, the methods used are all conventional methods in the art, and the various reagents and raw materials involved are obtained through conventional commercial channels and / or prepared by known methods in the art.

[0048] Examples 1-14 Reaction condition optimization tests

[0049] Using iodobenzene and tert-butyl acrylate as template substrates, the effects of different reaction conditions on the yield of the target product were investigated. The reaction formula is as follows:

[0050] .

[0051] Table 1:

[0052]

[0053] Reaction conditions: 0.3 mmol of tert-butyl acrylate, 0.4 mmol of iodobenzene, 0.015 mmol (5 mol%) of palladium acetate, PEG + water = 1.2 mL, air, reaction time 6 hours.

[0054] Taking Example 6 as an example, the typical test operation is as follows:

[0055] Add iodobenzene (0.4 mmol, 81.6 mg), tert-butyl acrylate (0.3 mmol, 38.4 mg), K2CO3 (0.45 mmol, 62.2 mg), Pd(OAc)2 (0.015 mmol, 3.4 mg), PEG200 (0.6 mL) and water (0.6 mL) into a reaction tube, react under an oil bath at 60 °C, monitor the reaction by TLC, after 6 hours the reaction is complete, extract with petroleum ether / ethyl acetate (petroleum ether:ethyl acetate = 10:1, 10 mL × 5), dry the petroleum ether / ethyl acetate organic phase with anhydrous MgSO4, filter, and then evaporate the solvent under reduced pressure to obtain the crude product, and obtain 58.8 mg of the target product by column chromatography separation (eluted with ethyl acetate / petroleum ether). 1 H NMR (400 MHz, CDCl3) δ 7.59 (d, J= 16.0 Hz, 1H), 7.51–7.49 (m, 2H),,7.37–7.35 (m, 3H), 6.37 (d, J = 16.0 Hz, 1H), 1.54 (s,9H). 13 C NMR (100 MHz,CDCl3) δ 166.26, 143.48, 134.62, 129.89, 128.76, 127.89, 120.15, 80.42,28.15。

[0056] Catalyst recycling test

[0057] The reaction system after extraction with petroleum ether / ethyl acetate in Example 6 was heated to remove the residual petroleum ether / ethyl acetate, cooled to room temperature, and iodobenzene (0.4 mmol), tert-butyl acrylate (0.3 mmol) and K2CO3 (0.45 mmol) were added to the reaction tube. The next Heck coupling reaction was carried out at 60 °C. This was repeated four times, and the results are shown in Table 2:

[0058] Table 2:

[0059]

[0060] Example 15

[0061]

[0062] p-Methyl iodobenzene (0.4 mmol, 87.2 mg), tert-butyl acrylate (0.3 mmol, 38.4 mg), K2CO3 (0.45 mmol, 62.2 mg), Pd(OAc)2 (0.015 mmol, 3.4 mg), PEG200 (0.6 mL) and water (0.6 mL) were added to the reaction tube. The reaction was carried out in an oil bath at 60 °C, and the reaction was monitored by TLC. After 9 hours, the reaction was complete. The mixture was extracted with petroleum ether / ethyl acetate (petroleum ether∶ethyl acetate = 10∶1, 10 mL×5). The organic phase of petroleum ether / ethyl acetate was dried over anhydrous MgSO4, filtered, and the solvent was evaporated under reduced pressure to obtain the crude product. The target product was obtained by column chromatography (eluted with ethyl acetate / petroleum ether), and the yield was 95%. 1 H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 16.0 Hz, 1H), 7.40 (d, J =8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.32 (d,J = 16.0 Hz, 1H), 2.36 (s, 3H), 1.53 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 166.51, 143.51, 140.25, 131.86, 129.50, 127.90, 119.03, 80.31, 28.17。

[0063] Catalyst recycling test

[0064] The reaction system after extraction with petroleum ether / ethyl acetate in Example 15 was heated to remove the residual petroleum ether / ethyl acetate, cooled to room temperature, and p-iodotoluene (0.4 mmol), tert-butyl acrylate (0.3 mmol) and K2CO3 (0.45 mmol) were added to the reaction tube, and the next Heck coupling reaction was carried out at 60 °C. This was repeated four times, and the results are shown in Table 3:

[0065] Table 3:

[0066]

[0067] Example 16

[0068]

[0069] p-Acetyl iodobenzene (0.4 mmol, 98.4 mg), tert-butyl acrylate (0.3 mmol, 38.4 mg), K2CO3 (0.45 mmol, 62.2 mg), Pd(OAc)2 (0.015 mmol, 3.4 mg), PEG200 (0.6 mL) and water (0.6 mL) were added to the reaction tube, and the reaction was carried out in an oil bath at 60 °C. The reaction was monitored by TLC. After 8 hours, the reaction was complete. The reaction mixture was extracted with petroleum ether / ethyl acetate (petroleum ether∶ethyl acetate = 10∶1, 10 mL×5). The organic phase of petroleum ether / ethyl acetate was dried over anhydrous MgSO4, filtered, and the solvent was evaporated under reduced pressure to obtain the crude product. The target product was obtained by column chromatography (eluted with ethyl acetate / petroleum ether), and the yield was 98%. 1 H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.3 Hz, 2H), 7.60 (d, J = 16.0 Hz, 1H), 7.59 (d, J = 8.3 Hz, 2H), 6.46 (d, J= 16.0 Hz, 1H), 2.61 (s, 3H), 1.54 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 197.33, 165.73, 141.92, 139.01, 137.72, 128.77, 127.96, 122.71, 80.89, 28.10, 26.63。

[0070] Catalyst recycling test

[0071] The reaction system after extraction with petroleum ether / ethyl acetate in Example 16 was heated to remove the residual petroleum ether / ethyl acetate, cooled to room temperature, and then p-iodoacetophenone (0.4 mmol), tert-butyl acrylate (0.3 mmol) and K2CO3 (0.45 mmol) were added to the reaction tube, and the next Heck coupling reaction was carried out at 60 °C. This was repeated four times, and the results are shown in Table 4:

[0072] Table 4:

[0073]

[0074] Example 17

[0075]

[0076] 1-Iodonaphthalene (0.4 mmol, 101.6 mg), tert-butyl acrylate (0.3 mmol, 38.4 mg), K2CO3 (0.45 mmol, 62.2 mg), Pd(OAc)2 (0.015 mmol, 3.4 mg), PEG200 (0.6 mL) and water (0.6 mL) were added to a reaction tube and reacted in an oil bath at 60 °C. The reaction was monitored by TLC. After 7 hours, the reaction was complete. The reaction mixture was extracted with petroleum ether / ethyl acetate (petroleum ether∶ethyl acetate = 10∶1, 10 mL×5). The organic phase of petroleum ether / ethyl acetate was dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure to obtain a crude product. The target product was obtained by column chromatography (eluted with ethyl acetate / petroleum ether), and the yield was 95%. 1 H NMR (400 MHz, CDCl3) δ 8.43 (d, J = 15.7 Hz, 1H), 8.19 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 8.2 Hz, 2H), 7.72 (d, J= 7.2 Hz, 1H), 7.61 – 7.40(m, 3H), 6.45 (d, J = 15.7 Hz, 1H), 1.57 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ166.22, 140.55, 133.62, 132.00, 131.38, 130.16, 128.64, 126.70, 126.11,125.42, 124.86, 123.44, 122.81, 80.61, 28.22。

[0077] Catalyst recycling test

[0078] The reaction system after extraction with petroleum ether / ethyl acetate in Example 17 was heated to remove the residual petroleum ether / ethyl acetate, cooled to room temperature, and 1-iodonaphthalene (0.4 mmol), tert-butyl acrylate (0.3 mmol) and K2CO3 (0.45 mmol) were added to the reaction tube. The next Heck coupling reaction was carried out at 60 °C. This was repeated four times, and the results are shown in Table 5:

[0079] Table 5:

[0080]

[0081] Example 18

[0082]

[0083] Iodobenzene (0.4 mmol, 81.6 mg), p-chlorostyrene (0.3 mmol, 41.6 mg), K2CO3 (0.45 mmol, 62.2 mg), Pd(OAc)2 (0.015 mmol, 3.4 mg), PEG200 (0.6 mL) and water (0.6 mL) were added to the reaction tube. The reaction was carried out in an oil bath at 60 °C, and the reaction was monitored by TLC. After 10 hours, the reaction was complete. The reaction mixture was extracted with petroleum ether / ethyl acetate (petroleum ether∶ethyl acetate = 10∶1, 10 mL×5). The organic phase of petroleum ether / ethyl acetate was dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure to obtain the crude product. The target product was obtained by column chromatography (eluted with ethyl acetate / petroleum ether), and the yield was 86%. 1 H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 7.4 Hz, 2H), 7.41 (d, J= 8.5 Hz, 2H), 7.37 – 7.22 (m, 5H), 7.07 (d, J = 16.4 Hz, 1H), 7.02 (d, J = 16.4 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 136.93, 135.79, 133.12, 129.26, 128.80, 128.70, 127.83, 127.62, 127.31, 126.52。

[0084] Catalyst recycling test

[0085] The reaction system after extraction with petroleum ether / ethyl acetate in Example 18 was heated to remove the residual petroleum ether / ethyl acetate, cooled to room temperature, and iodobenzene (0.4 mmol), p-chlorostyrene (0.3 mmol) and K2CO3 (0.45 mmol) were further added to the reaction tube, and the next Heck coupling reaction was carried out at 60 °C. This was repeated twice, and the results are shown in Table 6:

[0086] Table 6:

[0087] Number of cycles Reaction time Yield 1 12 79% 2 14 75%

[0088] The above-described embodiments are only the preferred embodiments of the present invention, and not an exhaustive list of the feasible embodiments of the present invention. For those skilled in the art, any obvious modifications made without departing from the principle and spirit of the present invention should be considered to be included within the protection scope of the claims of the present invention.

Claims

1. A green synthesis method for load-free recyclable Heck reaction, characterized in that, It includes the following steps: Add the haloaromatic compound shown in Formula I, the olefin compound shown in Formula II, Pd(OAc)2, a base, PEG200 and water into a reactor. Subsequently, place the reactor at 60 °C and stir for reaction. After the reaction is complete, perform post-treatment to obtain the target product shown in Formula III; the reaction formula is as follows: ； In the above reaction formula, Ar represents a substituted or unsubstituted C 6-20 aryl group, a substituted or unsubstituted C 2-20 heteroaryl group; X is selected from bromine or iodine; R1 is selected from hydrogen, C 1-20 alkyl, C 6-20 aryl; R2 is selected from C 1-20 alkoxycarbonyl, -COOH, substituted or unsubstituted C 6-20 aryl; Among them, the substituents in the substituted or unsubstituted are selected from halogen, -OH, -SH, -CN, -NO2, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 acyl, C 1-6 alkylthio, C 6-20 aryl, C 1-6 alkoxycarbonyl; And among them, the volume ratio of PEG200 to water is 1:1; The base is selected from potassium carbonate or cesium carbonate.

2. The synthesis method according to claim 1, wherein Ar represents a substituted or unsubstituted phenyl or naphthyl; X is selected from iodine; R1 is selected from hydrogen; R2 is selected from C 1-6 alkoxycarbonyl, substituted or unsubstituted phenyl; Among them, the substituents in the substituted or unsubstituted are selected from fluorine, chlorine, bromine, methyl, ethyl, tert-butyl, -CN, -NO2, methoxy, ethoxy, tert-butoxy, acetyl, ethoxycarbonyl, tert-butoxycarbonyl, methylthio, phenyl.

3. The synthesis method according to claim 1 or 2, characterized in that, Ar represents phenyl, naphthyl, biphenyl, methoxy-substituted phenyl, methyl-substituted phenyl, fluorophenyl, chlorophenyl, acetyl-substituted phenyl, cyano-substituted phenyl, tert-butoxycarbonyl-substituted phenyl; X is selected from iodine; R1 is selected from hydrogen; R2 is selected from methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, chlorophenyl, methyl-substituted phenyl, methoxy-substituted phenyl, fluorophenyl, acetyl-substituted phenyl, cyano-substituted phenyl, tert-butoxycarbonyl-substituted phenyl.

4. The synthesis method according to claim 1 or 2, characterized in that, The feeding molar ratio of the haloaromatic compound shown in Formula I, the olefin compound shown in Formula II, Pd(OAc)2 and the base is 1:(0.5~1):(0.01~0.1):(1~3).

5. The synthesis method according to claim 1 or 2, characterized in that The time required for the reaction to be complete is 6~14 hours.

6. The synthesis method according to claim 1 or 2, characterized in that The post-treatment operation is as follows: After the reaction is complete, extract the reaction solution with petroleum ether / ethyl acetate. Dry the petroleum ether / ethyl acetate organic phase with anhydrous MgSO4, filter, and then distill off the solvent under reduced pressure to obtain a crude product, and obtain the target product by column chromatography separation.

7. The synthesis method according to claim 6, wherein The synthesis method further includes the following steps: Heat the reaction system after extraction to remove the residual petroleum ether / ethyl acetate, cool to room temperature, and continue to add the haloaromatic compound shown in Formula I, the olefin compound shown in Formula II and the base to carry out the next Heck coupling reaction to realize the reuse of the catalyst Pd(OAc)2.

8. The synthesis method according to claim 7, characterized in that, The number of reuse times is 3~5 times.

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