A method for synthesizing a 7-position quaternary carbon substituted dibenzopyran compound

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of 7-position quaternary carbon-substituted dibenzopyran compounds. The 7-position quaternary carbon-substituted dibenzopyran compounds are synthesized by mixing 2'-isopropenyl-1,1'-biphenyl-2-phenol compounds, allyl acetate derivatives, a palladium catalyst and an organic solvent to perform Wacker type cross-coupling cascade reaction. The 2'-isopropenyl-1,1'-biphenyl-2-phenol compounds and the allyl acetate derivatives are used as starting materials, and the Wacker type cross-coupling cascade reaction is performed under the action of the palladium catalyst to obtain a series of 7-position quaternary carbon-substituted dibenzopyran compounds. The synthesis method has high yield, and the yield can reach 97%, and is suitable for the synthesis of a series of 7-position quaternary carbon-substituted dibenzopyran compounds containing different substituents, and provides important material basis for the biological activity evaluation of structure-related natural products and lead compounds.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing dibenzopyran compounds with 7-position quaternary carbon substitution. Background Technology

[0002] As an important structural unit, the 7-position quaternary carbon-substituted dibenzopyran fragment is widely present in the structure of natural products, such as the phenolic quinone type diterpenoid natural products cochlearol T and F. Therefore, how to achieve the efficient construction of this fragment has become a problem that organic chemists urgently need to solve.

[0003] Palladium-catalyzed tandem cyclization reactions have shown irreplaceable advantages in constructing complex molecular structures and multi-substituted stereocenters. Among them, palladium-catalyzed Wacker-type cross-coupling tandem reactions have demonstrated significant efficiency in constructing benzopyran structures. In 2016, Tang Wenjun's research group (Angew. Chem. Int. Ed. 2016, 55, 5044-5048) developed a Wacker-type cross-coupling tandem reaction based on 2-butenylphenol, and on this basis, achieved the construction of a series of compounds containing benzopyran structural units. However, the main limitation of this method lies in the fact that the benzene ring and alkene can only be catalyzed by sp... 3 Carbon atoms or heteroatoms are linked together, for those connected via sp 2 No substrates with carbon atom linkages have been reported, yet such substrates are key precursors for the synthesis of natural products containing dibenzopyran fragments with quaternary carbon substitution at the 7-position. Summary of the Invention

[0004] In view of this, the object of the present invention is to provide a method for synthesizing dibenzopyran compounds with 7-position quaternary carbon substitution. The present invention uses 2'-isopropenyl-1,1'-biphenyl-2-phenolic compounds and allyl acetate derivatives as starting materials, and a Wacker-type cross-coupling tandem reaction is carried out under palladium catalysis to obtain a series of dibenzopyran compounds with 7-position quaternary carbon substitution.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] This invention provides a method for synthesizing dibenzopyran compounds with quaternary carbon substitution at the 7-position, comprising the following steps:

[0007] A Wacker-type cross-coupling tandem reaction was carried out with 2'-isopropenyl-1,1'-biphenyl-2-phenolic compounds, allyl acetate derivatives, palladium catalysts and organic solvents to obtain the 7-position quaternary carbon-substituted dibenzopyran compounds.

[0008] The structural formulas of the 2'-isopropenyl-1,1'-biphenyl-2-phenolic compounds are shown in Formula 1-1 or 1-2, the structural formulas of the allyl acetate derivatives are shown in Formula 2, and the structural formulas of the 7-position quaternary carbon-substituted dibenzopyran compounds are shown in Formula 3-1 or 3-2.

[0009]

[0010] In Formulas 1-1 and 3-1, R1 includes one or more of H, F, F3C, Me, OMe and OH, and R2 includes one or more of H, OH, Me, OMe and OTBS.

[0011] Preferably, the molar ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the allyl acetate derivative is 0.12–1.35:0.36–4.05.

[0012] Preferably, the palladium catalyst comprises one or more of palladium(II) hexafluoroacetylacetonate, palladium(II) trifluoroacetate, palladium(II) acetate, palladium(II) dichloride, and palladium(II) acetylacetonate.

[0013] Preferably, the molar ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the palladium catalyst is 0.12–1.35:0.006–0.07.

[0014] Preferably, the molar ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the palladium catalyst is 1:0.025 to 0.05.

[0015] Preferably, the organic solvent includes one or more of toluene, benzene, trifluorotoluene, mesitylene, xylene, monofluorobenzene, hexafluorobenzene, and monochlorobenzene.

[0016] Preferably, the ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the organic solvent is 0.12–1.35 mmol: 2–10 mL.

[0017] Preferably, the Wacker-type cross-coupling series reaction is carried out at a temperature of 50–70°C for 12–24 hours.

[0018] Preferably, the Wacker-type cross-coupled series reaction is carried out at a temperature of 60°C for 12 to 24 hours.

[0019] Preferably, the Wacker-type cross-coupling tandem reaction is followed by silica gel column purification, wherein the eluent for silica gel column purification is petroleum ether and ethyl acetate, and the gradient elution ratio of petroleum ether and ethyl acetate is 30 / 1 to 20 / 1.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] This invention provides a method for synthesizing 7-position quaternary carbon-substituted dibenzopyran compounds, comprising the following steps: mixing 2'-isopropenyl-1,1'-biphenyl-2-phenolic compounds, allyl acetate derivatives, palladium catalysts, and organic solvents to conduct a Wacker-type cross-coupling tandem reaction to obtain the 7-position quaternary carbon-substituted dibenzopyran compounds. This invention uses 2'-isopropenyl-1,1'-biphenyl-2-phenolic compounds and allyl acetate derivatives as starting materials, and successfully obtains a series of 7-position quaternary carbon-substituted dibenzopyran compounds through a Wacker-type cross-coupling tandem reaction under the action of a palladium catalyst. Moreover, the synthesis method of this invention has a high yield, reaching up to 97%.

[0022] The synthesis method of this invention has the advantages of being simple, efficient, easy to operate, and low in cost. It is applicable to the synthesis of a series of 7-position quaternary carbon dibenzopyran compounds containing different substituents, and provides an important material basis for the evaluation of the bioactivity of structure-related natural products and lead compounds. Detailed Implementation

[0023] This invention provides a method for synthesizing dibenzopyran compounds with quaternary carbon substitution at the 7-position, comprising the following steps:

[0024] A Wacker-type cross-coupling tandem reaction was carried out with 2'-isopropenyl-1,1'-biphenyl-2-phenolic compounds, allyl acetate derivatives, palladium catalysts and organic solvents to obtain the 7-position quaternary carbon-substituted dibenzopyran compounds.

[0025] The structural formulas of the 2'-isopropenyl-1,1'-biphenyl-2-phenolic compounds are shown in Formula 1-1 or 1-2, the structural formulas of the allyl acetate derivatives are shown in Formula 2, and the structural formulas of the 7-position quaternary carbon-substituted dibenzopyran compounds are shown in Formula 3-1 or 3-2.

[0026]

[0027] In Formulas 1-1 and 3-1, R1 includes one or more of H, F, F3C, Me, OMe and OH, and R2 includes one or more of H, OH, Me, OMe and OTBS.

[0028] Unless otherwise specified, all materials and equipment used in this invention are commercially available products in the field.

[0029] In this invention, Formula 1-1 preferably includes compounds represented by Formulas 1a-1d and 1f-1l:

[0030]

[0031] In this invention, the molar ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the allyl acetate derivative is preferably 0.12-1.35:0.36-4.05, more preferably 1:3.

[0032] In this invention, the palladium catalyst is preferably a divalent palladium catalyst, which preferably includes one or more of palladium(II) hexafluoroacetylacetonate, palladium(II) trifluoroacetate, palladium(II) acetate, palladium(II) dichloride, and palladium(II) acetylacetonate, and more preferably palladium(II) hexafluoroacetylacetonate.

[0033] In this invention, the molar ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the palladium catalyst is preferably 0.12-1.35:0.006-0.07, more preferably 1:0.025-0.05.

[0034] In this invention, the organic solvent preferably includes one or more of toluene, benzene, trifluorotoluene, mesitylene, xylene, monofluorobenzene, hexafluorobenzene, and monochlorobenzene.

[0035] In this invention, the preferred ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the organic solvent is 0.12-1.35 mmol: 2-10 mL, more preferably 0.12-1.35 mmol: 3 mL.

[0036] In this invention, when the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound, allyl acetate derivative, palladium catalyst and organic solvent are mixed, it is preferable to also add a base, wherein the base preferably includes one or more of sodium bicarbonate, sodium carbonate, potassium fluoride, cesium fluoride, potassium phosphate and sodium acetate.

[0037] In this invention, the molar ratio of the palladium catalyst to the base is preferably 0.025-0.2:0-4.0, more preferably 0.05:3.

[0038] In this invention, the temperature of the Wacker-type cross-coupling tandem reaction is preferably 50–70°C, more preferably 60°C, and the time is preferably 12–24 hours, more preferably 12 hours. During the Wacker-type cross-coupling tandem reaction, the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound (1) and the allyl acetate derivative (2) react to generate a 7-position quaternary carbon-substituted dibenzopyran compound (3), as shown in the following formula:

[0039]

[0040] When the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound has the structural formula of formula 1h or formula 1i, the products obtained are the natural products cochlearol T and F, respectively, with the structural formulas shown in formulas 3h and 3i:

[0041]

[0042] In this invention, the Wacker-type cross-coupling tandem reaction is preferably carried out under oil bath and stirring conditions. This invention does not have special requirements for the stirring speed, and the speed commonly used by those skilled in the art can be used.

[0043] In this invention, the Wacker-type cross-coupling tandem reaction preferably includes cooling and concentrating the resulting reaction solution, and then purifying the concentrated solution by silica gel column chromatography to obtain the 7-position quaternary carbon-substituted dibenzopyran compound.

[0044] In this invention, the concentration is preferably vacuum concentration.

[0045] In this invention, the eluent for silica gel column purification is preferably petroleum ether and ethyl acetate, and the gradient elution ratio of petroleum ether and ethyl acetate is preferably 30 / 1 to 20 / 1.

[0046] This invention provides a method for synthesizing 7-position quaternary carbon-substituted dibenzopyran compounds via palladium-catalyzed Wacker-type cross-coupling tandem reaction. This method can synthesize a series of natural products and lead compounds containing 7-position quaternary carbon-substituted dibenzopyran fragments, providing a sufficient material basis for subsequent screening of biological activities.

[0047] To further illustrate the present invention, the synthesis method of the 7-position quaternary carbon-substituted dibenzopyran compound provided by the present invention will be described in detail below with reference to the accompanying drawings and embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0048] Example 1

[0049]

[0050] Biphenyl compound 1a (100 mg, 0.29 mmol, 1.0 equiv) and 3 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (111 mg, 0.87 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (7.5 mg, 0.0145 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting materials were completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3a (99 mg, 0.24 mmol), with a yield of 83%.

[0051] Raw material structure characterization data: 1 H NMR (600MHz, CDCl3) δ (ppm): 7.25-7.24 (m, 2H), 7.15 (d, J = 6.4Hz, 1H), 6.95-6.93 (m, 2H), 6.86-6 .84(m.1H),6.77-6.75(m,1H),5.01(s,2H),4.90(s,1H),1.70(s,3H),1.00(s,9H),0.23(s,6H);

[0052] 13 C NMR (151MHz, CDCl3) δ (ppm): 155.3, 152.6, 145.5, 136.9, 135.3, 130.7, 130.5, 129.3, 128.2, 122.4, 120.5, 119.9, 116.1, 115.7, 25.8 (three carbons),23.4,18.3,-4.2(two carbons);

[0053] HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 28 O2SiNa 363.1751; Found 363.1749.

[0054] Product structure characterization data: 1H NMR (600MHz, CDCl3) δ (ppm): 7.64 (d, J = 7.8Hz, 1H), 7.23-7.19 (m, 2H), 7.05 (d, J = 8.3Hz, 1H), 7.02-6.99 (m, 1H), 6.96-6.94 (m, 1H), 6.78-6.75 (m, 1H),5.05-5.03(m,1H),2.06-2.03(m,2H),1.95-1.90(m,1H),1.77-1.72 (m,1H),1.65(s,3H),1.63(s,3H),1.51(s,3H),1.03(s,9H),0.25(s,6H);

[0055] 13 C NMR (151MHz, CDCl3) δ (ppm): 155.3, 153.0, 131.8 (two carbons),130.3,129.5,125.2,124.1,122.9,122.4,121.4,119.5,118.1,113.6,79.7,40.2,25.9(threecarbons),25.8(two carbons),23.0,18.4,17.6,-4.2(two carbons).;

[0056] HRMS(ESI)m / z:[M+Na] + Calcd for C 26 H 36 O2SiNa 431.2377; Found 431.2377.

[0057] Example 2

[0058]

[0059] Biphenyl compound 1b (100 mg, 0.28 mmol, 1.0 equiv) and 3 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (107.6 mg, 0.84 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (7.3 mg, 0.014 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3b (97 mg, 0.25 mmol), with a yield of 82%.

[0060] Raw material structure characterization data:1 1H NMR (600 MHz, CDCl3) δ (ppm): 7.23 (d, J = 8.3 Hz, 1H), 7.05 (dd, J = 8.2 Hz and 1.6 Hz, 1H), 6.94 - 6.95 (m, 1H), 6.84 - 6.82 (m, 2H), 6.74 (d, J = 2.5 Hz, 1H), 5.00 (s, 1H), 4.91 (s, 1H), 4.85 (s, 1H), 2.29 (s, 3H), 1.70 (s, 3H), 0.99 (s, 9H), 0.22 (s, 6H);

[0061] 13 13C NMR (151 MHz, CDCl3) δ (ppm): 155.3, 150.4, 145.7, 136.8, 135.7, 130.9, 130.6, 129.8, 129.6, 128.0, 122.5, 119.8, 115.9, 115.5, 25.8 (three carbons), 23.5, 20.7, 18.3, -4.2 (two carbons);

[0062] HRMS (ESI) m / z: [M+Na] + Calcd for C 22 H 30 O2SiNa 377.1903; Found 377.1907.

[0063] Product structure characterization data: 1 1H NMR (600 MHz, CDCl3) δ (ppm): 7.43 (s, 1H), 7.17 (d, J = 2.2 Hz, 1H), 7.05 - 7.01 (m, 2H), 6.85 (d, J = 8.1 Hz, 1H), 6.75 (dd, J = 8.3 Hz and 2.3 Hz, 1H), 5.03 (t, J = 6.8 Hz, 1H), 2.37 (s, 3H), 2.09 - 2.00 (m, 2H), 1.93 - 1.88 (m, 1H), 1.75 - 1.70 (m, 1H), 1.63 (s, 6H), 1.52 (s, 3H), 1.03 (s, 9H), 0.25 (s, 6H);

[0064] 13C NMR (151MHz, CDCl3) δ (ppm): 155.2, 150.8, 132.0, 131.7, 130.5, 130.4, 130.2, 125.2, 124.2, 123.3, 122.1, 119.2, 117.8, 113.6, 79.5, 40.0, 25.9 (three carbons),25.8,25.7,23.0,21.1,18.4,17.7,-4.2(two carbons);

[0065] HRMS(ESI)m / z:[M+Na] + Calcd for C 27 H 38 O2SiNa 445.2533; Found 445.2536.

[0066] Example 3

[0067]

[0068] Biphenyl compound 1c (50 mg, 0.14 mmol, 1.0 equiv) and 2 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (54 mg, 0.42 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (3.6 mg, 0.007 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3c (45 mg, 0.1 mmol), with a yield of 75%.

[0069] Raw material structure characterization data: 1 H NMR (600MHz, CDCl3) δ (ppm): 7.24 (d, J = 8.4Hz, 1H), 6.96-6.93 (m, 1H), 6.89-6.84 (m, 3H), 6.73 (d, J = 2.5Hz, 1H),5.03-5.02(m,1H),4.91-4.90(m,1H),5.01(s,1H),4.88(s,1H),1.72(s,3H),0.99(s,9H),0.22(s,6H);

[0070] 1313C NMR (151 MHz, CDCl3) δ (ppm): 157.6, 156.0, 155.4, 148.7, 145.1, 136.7, 134.4, 130.8, 122.2, 120.3, 116.7 (d, J = 8.2 Hz, 1C), 116.6 (d, J = 6.8 Hz, 1C), 116.4, 115.6 (d, J = 22.7 Hz, 1C), 25.8 (three carbons), 23.5, 18.3, -4.2 (two carbons); 19 19F NMR (376 MHz, CDCl3) δ (ppm): -124.5;

[0071] HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 27 FO2SiNa 381.1657; Found 381.1657.

[0072] Product structure characterization data: 1 1H NMR (600 MHz, CDCl3) δ (ppm): 7.30 (dd, J = 9.5 Hz and 2.8 Hz, 1H), 7.07 (d, J = 2.4 Hz, 1H), 7.04 (d, J = 8.3 Hz, 1H), 6.92 - 6.86 (m, 2H), 6.78 (dd, J = 8.3 Hz and 2.4 Hz, 1H), 5.02 (t, J = 7.1 Hz, 1H), 2.04 - 2.00 (m, 2H), 1.91 - 1.86 (m, 1H), 1.73 - 1.67 (m, 1H), 1.62 (s, 6H), 1.50 (s, 3H), 1.01 (s, 9H), 0.24 (s, 6H);

[0073] 13 13C NMR (151 MHz, CDCl3) δ (ppm): 158.7, 157.3, 155.4, 149.0, 132.0 (d, J = 18.9 Hz, 1C), 129.6, 125.3, 124.0, 123.5 (d, J = 7.8 Hz, 1C), 120.1, 119.0 (d, J = 8.1 Hz, 1C), 115.9 (d, J = 23.4 Hz, 1C), 113.8, 109.3 (d, J = 24.0 Hz, 1C), 79.9, 40.0, 25.8 (three carbons), 25.7, 25.6, 22.9, 18.4, 17.6, -4.2 (two carbons);

[0074] 19 F NMR (376MHz, CDCl3) δ (ppm): -122.6;

[0075] HRMS(ESI)m / z:[M+Na] + Calcd for C 26 H 35 FO2SiNa 449.2283; Found 449.2281.

[0076] Example 4

[0077]

[0078] Biphenyl compound 1d (50 mg, 0.12 mmol, 1.0 equiv) and 2 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (46 mg, 0.36 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (3.1 mg, 0.006 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3d (43 mg, 0.09 mmol), with a yield of 74%.

[0079] Raw material structure characterization data: 1 H NMR (600MHz, CDCl3) δ (ppm): 7.49 (d, J = 8.5Hz, 1H), 7.42 (s, 1H), 7.25 (s, 1H), 7.01 (d, J = 8.5Hz, 1H) ,7.88-7.86(m,1H),5.34(s,1H),5.00(s,1H),5.85(s,1H),1.70(s,3H),0.99(s,9H),0.22(s,6H);

[0080] 13 C NMR (151MHz, CDCl3) δ (ppm): 155.5, 155.4, 144.6, 137.0, 133.7, 128.4, 127.8, 126.5, 124.5, 122.9, 122.2, 120.5, 116.6, 116.0, 25.8 (three carbons),25.8,23.6,18.3,-4.2(two carbons);

[0081] 19F NMR (376MHz, CDCl3) δ (ppm): -61.4;

[0082] HRMS(ESI)m / z:[M+Na] + Calcd for C 22 H 27 F3O2SiNa431.1625; Found431.1627.

[0083] Product structure characterization data: 1 H NMR (600MHz, CDCl3) δ (ppm): 7.86 (s, 1H), 7.45 (d, J = 8.2Hz, 1H), 7.18 (s, 1H), 7.06 (d, J = 8.2Hz, 1H), 7.00 (d, J = 8.3Hz, 1H), 6.81 (d, J = 8.1Hz, 1H), 5.03(t,J=6.0Hz,1H),2.06-2.01(m,2H),1.95-1.88(m,1H),1.79-1.74( m,1H),1.65(s,3H),1.63(s,3H),1.50(s,3H),1.03(s,9H),0.25(s,6H);

[0084] 13 C NMR (151MHz, CDCl3) δ (ppm): 155.7, 155.6, 132.1, 131.5, 129.0, 126.4 (twocarbons), 125.5,124.7,123.8,123.6,122.4,120.3,118.4,113.7,80.8,40.5,26.2,25.9(three carbons),25.8,22.9,18.4,17.6,-4.2(two carbons);

[0085] 19 F NMR (376MHz, CDCl3) δ (ppm): -61.6;

[0086] HRMS(ESI)m / z:[M+Na] + Calcd for C 27 H 35 F3O2SiNa 499.2251; Found 499.2264.

[0087] Example 5

[0088]

[0089] Biphenyl compound 1e (100 mg, 0.26 mmol, 1.0 equiv) and 3 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (100 mg, 0.78 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (6.8 mg, 0.013 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3e (79 mg, 0.17 mmol), with a yield of 66%.

[0090] Raw material structure characterization data: 1 H NMR(600MHz, CDCl3)δ(ppm):8.30-8.28(m,1H),7.84-7.81(m,1H),7.51-7.49(m,2H ),7.45(d,J=8.3Hz,1H),7.30(d,J=8.4Hz,1H),7.28(d,8.4Hz,1H),6.90(dd,8.4Hz and 2.5Hz,1H),6.84(d,J=8.4Hz,1H),5.59(s,1H),5.00(s,1H),4.97(s,1H),1.67(s,3H),1.00(s,9H),0.24(s,6H);

[0091] 13 C NMR (151MHz, CDCl3) δ (ppm): 155.4, 147.9, 145.6, 137.3, 135.6, 134.3, 130.9, 128.1, 127.6, 126.5, 125.5,124.3,122.7,122.6,121.4,120.0,119.9,116.1,25.8(threecarbons),23.5,18.3,-4.2(two carbons);

[0092] HRMS(ESI)m / z:[M+Na] + Calcd for C 25 H 30 O2SiNa 413.1907; Found 413.1906.

[0093] Product structure characterization data: 1H NMR (600MHz, CDCl3) δ (ppm): 8.10-8.09 (m, 1H), 7.59-7.54 (m, 2H), 7.28-7.26 (m, 2H), 7.05-7.04 (m, 2H), 6.88 (d, J = 8.2Hz, 1H), 6.57 (d, J = 8.2Hz, 1H),4.83-4.80(m,1H),1.94-1.90(m,2H),1.86-1.80(m,1H),1.68-1.62 (m,1H),1.53(s,3H),1.39(s,3H),1.25(s,3H),0.83(s,9H),0.06(s,6H);

[0094] 13 C NMR (151MHz, CDCl3) δ (ppm): 115.4, 148.4, 134.6, 131.8, 131.3, 130.7, 127.7, 126.6, 126. 1,125.7,125.1,124.2,122.6,120.8,120.7,119.0,116.1,113.7,80.4,40.13,25.9(four carbons),25.7,22.9,18.4,17.6,-4.1(two carbons);

[0095] HRMS(ESI)m / z:[M+H] + Calcd for C 30 H 38 O2SiH 459.2714; Found 459.2716.

[0096] Example 6

[0097]

[0098] Biphenyl compound 1f (100 mg, 0.25 mmol, 1.0 equiv) and 3 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (96 mg, 0.75 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (6.5 mg, 0.0125 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3f (107 mg, 0.23 mmol), with a yield of 91%.

[0099] Raw material structure characterization data:1 1H NMR (600 MHz, CDCl3) δ (ppm): 7.00 (d, J = 8.3 Hz, 1H), 6.94 (d, J = 8.8 Hz, 1H), 6.86 (d, J = 8.3 Hz, 1H), 6.84 (dd, J = 8.8 Hz and 3.0 Hz, 1H), 6.77 (d, J = 3.0 Hz, 1H), 5.54 (s, 1H), 4.98 (s, 1H), 4.93 (s, 1H), 3.74 (s, 3H), 3.54 (s, 3H), 1.55 (s, 3H), 1.03 (s, 9H), 0.25 (s, 3H), 0.23 (s, 3H);

[0100] 13 13C NMR (151 MHz, CDCl3) δ (ppm): 153.4, 148.2 (two carbons), 147.4, 146.3, 138.8, 129.7, 125.7, 125.6, 120.7, 117.9, 116.5, 115.8, 115.1, 60.9, 55.8, 25.8 (three carbons), 23.2, 18.4, -4.4 (two carbons);

[0101] HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 32 O4SiNa 423.1962; Found 423.1961.

[0102] Product structure characterization data: 1 1H NMR (600 MHz, CDCl3) δ (ppm): 8.12 (d, J = 2.7 Hz, 1H), 6.89 (d, J = 8.7 Hz, 1H), 6.84 - 6.78 (m, 3H), 5.00 (t, J = 6.9 Hz, 1H), 3.84 (s, 3H), 3.72 (s, 3H), 2.08 - 1.97 (m, 2H), 1.86 - 1.81 (m, 1H), 1.65 - 1.63 (m, 1H), 1.61 (s, 6H), 1.50 (s, 3H), 1.05 (s, 9H), 0.25 (s, 3H), 0.23 (s, 3H);

[0103] 13C NMR (151MHz, CDCl3) δ (ppm): 154.2, 148.8, 148.7, 147.1, 134.9, 131.7, 124.2, 123.2, 122.5, 120.3, 119.5, 1 18.3,114.9,112.9,79.0,59.6,55.9,39.2,25.9(threecarbons),25.8,25.1,22.9,18.5,17.6,-4.3,-4.4;

[0104] HRMS(ESI)m / z:[M+Na] + Calcd for C 28 H 40 O4SiNa 491.2588; Found 491.2585.

[0105] Example 7

[0106]

[0107] At room temperature, 1 g (100 mg, 0.39 mmol, 1.0 equiv) of biphenol compound and 3 mL of toluene were added to a dry reaction flask. After stirring, allyl acetate 2 (150 mg, 1.17 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (10 mg, 0.02 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give 3 g (120 mg, 0.37 mmol) of dibenzopyran compound, with a yield of 95%.

[0108] Raw material structure characterization data: 1 H NMR (600MHz, Acetone-d6) δ (ppm): 8.34 (s, 1H), 7.36 (s, 1H), 7.15 (d, J = 9.0Hz, 1H), 6.80-6.78 (m, 2H), 6.75 (dd, J = 8.8Hz and 3.0Hz,1H),6.68(d,J=3Hz,1H),4.88(s,1H),4.78(s,1H),3.70(s,3H),1.75(s,3H);

[0109] 13C NMR (151MHz, Acetone-d6) δ (ppm): 156.7, 153.5, 148.6, 146.5, 138.1, 135.6, 130.3 (two carbons), 118.4, 117.0, 116.7, 114.9 (two carbons), 114.4, 55.7, 23.8;

[0110] HRMS(ESI)m / z:[M+Na] + Calcd for C 16 H 16 O3Na 279.0992; Found 279.0994.

[0111] Product structure characterization data: 1 H NMR (600MHz, CDCl3) δ (ppm): 7.16-7.14 (m, 2H), 7.05 (d, J = 6.5Hz, 1H), 6.91 (d, J = 8.7Hz, 1H), 6.83-6.77 (m, 2H), 6.15 (s, 1H), 5.0 2(t,J=6.4Hz,1H),3.81(s,3H),2.10-2.02(m,2H),1.93-1.87(m,1H),1.73-1.67(m,1H),1.64(s,3H),1.63(s,3H),1.52(s,3H),;

[0112] 13 C NMR (151MHz, CDCl3) δ (ppm): 155.2, 154.2, 146.9, 131.8, 131.7, 130.4, 125.5, 124.0 ,122.9,118.7,115.4,115.1,109.1,108.2,79.6,56.0,39.7,25.7,25.4,22.9,17.6;

[0113] HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 24 O3Na 347.1618; Found 347.1620.

[0114] Example 8

[0115]

[0116] Biphenyl compound 1h (100 mg, 0.41 mmol, 1.0 equiv) and 3 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (158 mg, 1.23 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (10.7 mg, 0.02 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3h (104 mg, 0.34 mmol), with a yield of 82%.

[0117] Raw material structure characterization data: 1 H NMR (600MHz, Acetone-d6) δ (ppm): 8.38 (s, 1H), 7.80 (s, 1H), 7.16 (s, 1H), 7.12 (d, J = 8.2Hz, 1H), 6.78-6.70 (m, 3H), 6.66 (dd, J = 8.7Hz and1.7Hz,1H),6.60(d,J=2.0Hz,1H),4.86(s,1H),4.77(s,1H),1.75(s,3H);

[0118] 13 C NMR (151MHz, Acetone-d6) δ (ppm): 156.7, 150.8, 147.8, 146.5, 138.3, 135.6, 130.5, 130.2, 118.4, 118.0, 117.0, 115.6, 114.8, 114.7, 23.8;

[0119] HRMS(ESI)m / z:[M+Na] + Calcd for C 15 H 14 O3Na 265.0835; Found 265.0838.

[0120] Product structure characterization data: 1H NMR (600MHz, CDCl3) δ (ppm): 7.01 (d, J = 8.4Hz, 1H), 6.99 (d, J = 2.6Hz, 1H), 6.95 (d, J = 2.2Hz, 1H), 6.82 (d, J = 8.6Hz, 1H), 6.77 (dd, J = 8.3Hz and2.2Hz,1H),6.74(dd,J=8.7Hz and 2.6Hz,1H),4.99(t,J=6.6Hz,1H),2.07-1.96(m,2H),1.88-1.82(m,1H),1.67-1.61(m,1H),1.60(s,6H),1.48(s,3H);

[0121] 13 C NMR (151MHz, CDCl3) δ (ppm): 155.1, 149.9, 146.6, 131.9, 131.8, 130.0, 125.6, 124 .0,123.3,119.1,117.1,115.5,109.8,109.2,79.9,39.7,25.7,25.2,22.9,17.6;

[0122] HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 22 O3Na 333.1461; Found 333.1464.

[0123] Example 9

[0124]

[0125] Biphenyl compound 1i (100 mg, 0.42 mmol, 1.0 equiv) and 3 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (161 mg, 1.26 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (10.9 mg, 0.02 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3i (122 mg, 0.39 mmol), with a yield of 94%.

[0126] Raw material structure characterization data: 11H NMR (600 MHz, CDCl3) δ (ppm): 7.27 (d, J = 3.0 Hz, 1H), 7.18 (d, J = 7.4 Hz, 1H), 7.08 (s, 1H), 6.81 (d, J = 8.6 Hz, 1H), 6.73 (dd, J = 8.7 Hz and 3.0 Hz, 1H), 5.26 (s, 1H), 5.03 (s, 1H), 4.94 (s, 1H), 4.84 (s, 1H), 2.38 (s, 3H), 1.74 (s, 3H);

[0127] 13 13C NMR (151 MHz, CDCl3) δ (ppm): 149.1, 146.5, 145.8, 140.8, 137.7, 134.0, 131.6, 129.4, 129.3, 129.2, 117.1, 116.6, 116.2, 115.9, 23.3, 21.1;

[0128] HRMS (ESI) m / z: [M+Na] + Calcd for C 16 H 16 O2Na 263.1043; Found 263.1047.

[0129] Product structure characterization data: 1 1H NMR (600 MHz, Methanol-d4) δ (ppm): 7.48 (br s, 1H), 7.16 (d, J = 2.0 Hz, 1H), 7.09 - 7.07 (m, 2H), 6.72 (d, J = 8.6 Hz, 1H), 6.66 (dd, J = 8.5 Hz and 2.2 Hz, 1H), 5.05 (t, J = 6.7 Hz, 1H), 2.36 (s, 3H), 2.08 - 1.97 (m, 2H), 1.95 - 1.82 (m, 1H), 1.70 - 1.61 (m, 1H), 1.62 (s, 3H), 1.56 (s, 3H), 1.49 (s, 3H);

[0130] 13 13C NMR (151 MHz, Methanol-d4) δ (ppm): 152.1, 146.3, 137.4, 136.7, 131.5, 129.3, 128.8, 124.4, 124.2, 123.5, 122.8, 118.7, 116.4, 109.1, 79.4, 39.9, 25.1, 25.0, 23.1, 20.6, 16.8;

[0131] HRMS (ESI) m / z: [M+Na]+ Calcd for C 21 H 24 O2Na 331.1669; Found 331.1670.

[0132] Example 10

[0133]

[0134] Biphenyl compound 1j (100 mg, 0.42 mmol, 1.0 equiv) and 3 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (161 mg, 1.26 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (10.9 mg, 0.02 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 12 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3j (123 mg, 0.4 mmol), with a yield of 96%.

[0135] Raw material structure characterization data: 1 H NMR (600MHz, CDCl3) δ (ppm): 7.38-7.36 (m, 3H), 7.30-7.29 (m, 1H), 6.88 (d, J = 8.8Hz, 1H), 6.83 (dd, J = 8.8Hz and 2.2Hz,1H),6.74(d,J=2.2Hz,1H),5.08(s,1H),4.98(s,1H),4.71(s,1H),3.76(s,3H),1.76(s,3H);

[0136] 13 C NMR (151MHz, CDCl3) δ (ppm): 153.4, 146.7, 146.1, 143.9, 134.5, 131.0, 129.4, 128.9, 128.5, 127.9, 116.5 (two carbons), 115.7, 114.8, 55.9, 23.3;

[0137] HRMS(ESI)m / z:[M+Na] + Calcd for C 16 H 16 O2Na 263.1043; Found 263.1047.

[0138] Product structure characterization data: 1H NMR (600MHz, CDCl3) δ (ppm): 7.70 (d, J = 7.6Hz, 1H), 7.36-7.33 (m, 1H), 7.32-7.28 (m, 1 H),7.26-7.25(m,1H),7.20(d,J=7.6Hz,1H),6.90(d,J=8.7Hz,1H),6.81(dd,J=8.8Hz and 2.9Hz,1H),5.00(t,J=7.0Hz,1H),3.85(s,3H),2.10-2.07(m,2H),1.99 -1.93(m,1H),1.77-1.71(m,1H),1.66(s,3H),1.64(s,3H),1.53(s,3H);

[0139] 13 C NMR (151MHz, CDCl3) δ (ppm): 154.5, 146.8, 139.2, 131.8, 129.0, 128.0, 127.7, 124.1 ,124.0,123.1,122.4,118.7,115.1,108.1,79.4,55.9,39.7,25.8,25.4,22.9,17.7;

[0140] HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 24 O2Na 331.1669; Found 331.1669.

[0141] Example 11

[0142]

[0143] Biphenyl compound 1k (500 mg, 1.35 mmol, 1.0 equiv) and 10 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (519 mg, 4.05 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (36.4 mg, 0.07 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 24 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3k (574 mg, 1.3 mmol), with a yield of 97%.

[0144] Raw material structure characterization data: 11H NMR (600 MHz, CDCl3) δ (ppm): 7.23 (d, J = 8.3 Hz, 1H), 6.87 (d, J = 8.8 Hz, 1H), 6.85 - 6.80 (m, 2H), 6.76 (d, J = 2.6 Hz, 1H), 6.72 (d, J = 3.0 Hz, 1H), 5.03 - 5.01 (m, 1H), 4.93 - 4.91 (m, 1H), 4.71 (s, 1H), 3.77 (s, 3H), 1.71 (s, 3H), 0.99 (s, 9H), 0.22 (s, 6H);

[0145] 13 13C NMR (151 MHz, CDCl3) δ (ppm) 155.2, 153.3, 146.6, 145.6, 136.7, 135.6, 130.6, 128.8, 122.3, 119.8, 116.5, 116.0, 115.5, 114.6, 55.8, 25.8 (three carbons), 23.4, 18.3, -4.3 (two carbons);

[0146] HRMS (ESI) m / z: [M+Na] + Calcd for C 22 H 30 O3SiNa 393.1856; Found 393.1863.

[0147] Product structure characterization data: 1 1H NMR (600 MHz, CDCl3) δ (ppm): 7.21 - 7.19 (m, 1H), 7.18 - 7.16 (m, 1H), 7.07 (d, J = 8.3 Hz, 1H), 6.91 (d, J = 8.6 Hz, 1H), 6.82 - 6.78 (m, 2H), 5.08 - 5.04 (m, 1H), 3.85 (s, 3H), 2.10 - 2.03 (m, 2H), 1.96 - 1.90 (m, 1H), 1.76 - 1.70 (m, 1H); 1.65 (s, 6H), 1.54 (s, 3H), 1.05 (s, 9H), 0.27 (s, 6H);

[0148] 13C NMR (151MHz, CDCl3) δ (ppm): 155.2, 154.3, 147.0, 132.3, 131.6, 130.3, 125.2, 124.1,123.1,119.5,118.6,114.7,113.7,108.4,79.3,55.8,39.8,25.8(four carbons),25.5,22.9,18.3,17.6,-4.2(two carbons);

[0149] HRMS(ESI)m / z:[M+Na] + Calcd for C 27 H 38 O3SiNa 461.2482; Found 461.2493.

[0150] Example 12

[0151]

[0152] Biphenyl compound 1L (500 mg, 1.29 mmol, 1.0 equiv) and 10 mL of toluene were added to a dry reaction flask at room temperature. After stirring, allyl acetate 2 (496 mg, 3.87 mmol, 3.0 equiv) and palladium hexafluoroacetylacetonate (33.6 mg, 0.06 mmol, 0.05 equiv) were added sequentially. The reaction system was then placed in an oil bath preheated to 60 °C and stirred at this temperature for 24 hours. After the starting material was completely converted, the reaction system was cooled to room temperature, concentrated directly, and purified by silica gel column chromatography (petroleum ether and ethyl acetate as eluents) to give dibenzopyran compound 3L (498 mg, 1.10 mmol), with a yield of 85%.

[0153] Raw material structure characterization data: 1 H NMR (600MHz, CDCl3) δ (ppm): 6.99 (d, J = 8.3Hz, 1H), 6.88-6.85 (m, 2H), 6.74 (d, J = 8.3Hz 1H),6.68(d,J=2.3Hz,1H),5.50-5.48(m,1H),4.95(s,1H),4.89(s,1H),3.52(s,3H),1.56(s,3H),1.02(s,9H),0.24(s,3H),0.22(s,3H); 13C NMR (151MHz, CDCl3) δ (ppm): 149.7, 148.7, 148.6, 147.7, 146.4, 139.1, 129.7, 126.3, 126.1, 121.2, 118.5, 118.4, 116.6, 116.3, 61.3, 26.3 (three carbons),23.7,18.6,-3.9,-4.0;

[0154] HRMS(ESI)m / z:[M+Na] + Calcd for C 22 H 30 O4SiNa 409.1806; Found 409.1807.

[0155] Product structure characterization data: 1 H NMR (600MHz, CDCl3) δ (ppm): 8.02 (d, J = 2.8Hz, 1H), 6.84 (d, J = 8.6Hz, 1H), 6.82 (d, J = 8.3Hz, 1H), 6.79 (d, J = 8.3Hz, 1H), 6.72 (dd, J = 8.6Hz and2.9Hz,1H),5.00(t,J=7.0Hz,1H),3.70(s,3H),2.07-1.97(m,2H),1.84-1.79(m,1H),1.6 3-1.61(m,1H),1.61(s,3H),1.60(s,3H),1.49(s,3H),1.04(s,9H),0.24(s,3H),0.21(s,3H);

[0156] 13 C NMR (151MHz, CDCl3) δ (ppm): 150.0,148.9,148.8,148.7,147.0,134.9,131.7, 124.1,123.0,122.6,119.6,118.6,116.0,114.2,79.1,59.6,39.2,25.9(three carbons),25.8,25.0,22.9,18.5,17.6,-4.4,-4.5;

[0157] HRMS(ESI)m / z:[M+Na] + Calcd for C 27 H 38 O4SiNa 477.2432; Found 477.2441.

[0158] Example 13

[0159] The hexafluoroacetylacetone palladium(II) in Example 11 was reduced to 0.025 equiv, and the rest of the operation was the same as in Example 11, with a yield of 88%.

[0160] Example 14

[0161] The hexafluoroacetylacetone palladium(II) in Example 11 was replaced with palladium(II) trifluoroacetate, and the rest of the operation was the same as in Example 11, with a yield of 40%.

[0162] Example 15

[0163] The palladium(II) hexafluoroacetylacetone in Example 11 was replaced with palladium(II) dichloride, and the rest of the operation was the same as in Example 11, with a yield of 40%.

[0164] Example 16

[0165] In Example 11, after adding palladium hexafluoroacetylacetone, sodium bicarbonate (340 mg, 3 equiv) was added, and the rest of the operation was the same as in Example 11. The yield was 64%, which was 33% lower than that in Example 11.

[0166] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, not all embodiments. People can obtain other embodiments based on the present invention without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method of synthesizing a 7-position quaternary carbon substituted dibenzopyran compound, characterized in that, Includes the following steps: A Wacker-type cross-coupling tandem reaction was carried out with 2'-isopropenyl-1,1'-biphenyl-2-phenolic compounds, allyl acetate derivatives, palladium catalysts and organic solvents to obtain the 7-position quaternary carbon-substituted dibenzopyran compounds. The structural formulas of the 2'-isopropenyl-1,1'-biphenyl-2-phenolic compounds are shown in Formula 1-1 or 1-2, the structural formulas of the allyl acetate derivatives are shown in Formula 2, and the structural formulas of the 7-position quaternary carbon-substituted dibenzopyran compounds are shown in Formula 3-1 or 3-2. Equation 1-1, Equation 1-2, Equation 2, Equation 3-1, Equation 3-2; In Formulas 1-1 and 3-1, R1 is selected from one or more of H, F, F3C, Me, OMe and OH, and R2 is selected from one or more of H, OH, Me, OMe and OTBS. The palladium catalyst is palladium(II) hexafluoroacetylacetone; The molar ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the palladium catalyst is 1:0.05~0.

07.

2. The synthesis method according to claim 1, characterized in that, The molar ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the allyl acetate derivative is 0.12~1.35:0.36~4.

05.

3. The synthesis method according to claim 1, characterized in that, The organic solvent is selected from one or more of toluene, benzene, trifluorotoluene, mesitylene, xylene, monofluorobenzene, hexafluorobenzene, and monochlorobenzene.

4. The synthesis method according to claim 1 or 3, characterized in that, The ratio of the 2'-isopropenyl-1,1'-biphenyl-2-phenol compound to the organic solvent is 0.12~1.35 mmol: 2~10 mL.

5. The synthesis method according to claim 1, characterized in that, The Wacker-type cross-coupled tandem reaction is carried out at a temperature of 50-70°C for 12-24 hours.

6. The synthesis method according to claim 1 or 5, characterized in that, The Wacker-type cross-coupled series reaction is carried out at a temperature of 60°C for 12 to 24 hours.

7. The synthesis method according to claim 1, characterized in that, The Wacker-type cross-coupling tandem reaction is followed by silica gel column purification, in which petroleum ether and ethyl acetate are used as eluents, and the gradient elution ratio of petroleum ether and ethyl acetate is 30 / 1 to 20 / 1.

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