阅读说明：本技术 一种多取代(e)-三氟甲基烯烃的制备方法 (Preparation method of polysubstituted (E) -trifluoromethyl olefin ) 是由 郭武生 刘阳 刘腾 于 2021-10-18 设计创作，主要内容包括：一种多取代(E)-三氟甲基烯烃的制备方法,以烯丙基碳酸酯类化合物、亲核试剂为反应原料,以钯盐、有机磷配体为催化体系,于有机溶剂中反应得到目标物多取代(E)-三氟甲基烯烃化合物,本发明以经济易得的芳胺,芳基亚磺酸钠,苯酚类或水作为亲核试剂,通过烯丙基取代反应合成多取代(E)-三氟甲基烯烃,本发明的合成工艺路线具有底物普适性好、产率高(最高能达到89％)、立体选择性好(E:Z>99:1)、易于实现工业化生产等优点。(A process for preparing polysubstituted (E) -trifluoromethyl olefin from allyl carbonate and nucleophilic reagent includes such steps as reaction between Pd salt and organophosphorus ligand as catalyst system in organic solvent to obtain target polysubstituted (E) -trifluoromethyl olefin, and synthesizing polysubstituted (E) -trifluoromethyl olefin by allyl substitution reaction on arylamine, arylsulfinic acid sodium salt, phenol or water.)

1. a preparation method of polysubstituted (E) -trifluoromethyl olefin is characterized in that allyl carbonate compounds and nucleophilic reagents are used as reaction raw materials, palladium salt and organophosphorus ligand are used as a catalytic system, and the reaction raw materials and the catalytic system react in an organic solvent to obtain a target polysubstituted (E) -trifluoromethyl olefin compound, wherein the reaction general formula is as follows:

in the formula, R¹Is aryl; r²Is H, aryl or alkyl; the nucleophilic reagent is arylamine, aryl sulfinic acid sodium salt, phenol or water.

2. The method for preparing polysubstituted (E) -trifluoromethyl olefin according to claim 1, comprising the following steps:

1) fully and uniformly mixing palladium salt and organic phosphine ligand L1 in an organic solvent;

2) adding an allyl carbonate compound and a nucleophilic reagent into the reaction system in the step 1), carrying out reaction treatment for 2-24 hours, removing the solvent from the reaction product, and carrying out silica gel column chromatographic separation to obtain the polysubstituted (E) -trifluoromethyl olefin.

3. The method according to claim 2, wherein the palladium salt is Pd (dba)₂、Pd₂(dba)₃·CHCl₃、Pd(OAc)₂Or PdCl₂。

4. The method for preparing polysubstituted (E) -trifluoromethyl olefin according to claim 2, wherein the organophosphorus ligand L1 has the following structural formula:

5. the method of claim 2, wherein the organic solvent is 1,1,1,3,3, 3-hexafluoroisopropanol or acetonitrile.

6. The method for preparing polysubstituted (E) -trifluoromethyl olefin according to claim 2, wherein the molar ratio of the palladium salt to the organic phosphine ligand is 1: 1-5;

the molar ratio of the palladium salt to the allyl carbonate compound is 0.025-0.050: 1;

the molar amount of the nucleophilic reagent is 1.0-5.0 times of the molar amount of the allyl carbonate compound.

7. The method for preparing polysubstituted (E) -trifluoromethyl olefin according to claim 2, wherein the reaction temperature in the said operation steps is: room temperature to 60 ℃.

8. The method for preparing polysubstituted (E) -trifluoromethyl olefin according to claim 2, wherein the nucleophile is arylamine, arylsulfinic acid sodium salt, phenol or water.

9. The method of claim 2, wherein the nucleophilic reagent is phenol or water, and an additional inorganic base is added, wherein the inorganic base comprises cesium carbonate, potassium tert-butoxide, and cesium carbonate, and the molar amount of the base used is 1.0-2.0 times that of the allyl carbonate compound.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of polysubstituted (E) -trifluoromethyl olefin, which is suitable for synthesis of various polysubstituted (E) -trifluoromethyl olefins.

Background

Polysubstituted (E) -trifluoromethyl olefin and derivatives thereof are a very important class of organic synthetic intermediates, which are widely present in natural products and bioactive molecules. Besides, partially polysubstituted (E) -trifluoromethylolefins can also be used in photoluminescent materials. At present, the traditional strategy for preparing multi-substituted (E) -trifluoromethyl olefin mainly utilizes trifluoromethyl substituted ketone compound as precursor and phosphate to realize the synthesis of trifluoromethyl olefin through Horner-Wittig reaction. However, this method has significant disadvantages: 1) a large amount of phosphorus-containing byproducts are generated, and the separation is difficult; 2) the trifluoromethyl olefin synthesized by the method belongs to an E/Z mixture, and cannot be synthesized with high stereoselectivity; 3) the method is only suitable for synthesizing tri-substituted olefin compounds, but not suitable for synthesizing tetra-substituted trifluoromethyl olefin; 4) such methods require multiple reactions for subsequent conversion, with lower final yields, higher costs and complex procedures.

Therefore, how to find a universal, simple and effective synthesis method for synthesizing the polysubstituted (E) -trifluoromethyl olefin with stereoselectivity is an unsolved scientific problem.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention aims to provide a preparation method of polysubstituted (E) -trifluoromethyl olefin, which has high yield and good stereoselectivity and is easy for industrial production.

In order to achieve the purpose, the invention adopts the following technical scheme to realize the purpose:

a preparation method of polysubstituted (E) -trifluoromethyl olefin takes allyl carbonate compound and nucleophilic reagent as reaction raw materials, takes palladium salt and organophosphorus ligand as a catalytic system, and reacts in an organic solvent to obtain a target polysubstituted (E) -trifluoromethyl olefin compound, and the reaction general formula is as follows:

in the formula, R¹Is aryl; r²Is H, aryl or alkyl; the nucleophilic reagent is arylamine, aryl sulfinic acid sodium salt, phenol or water.

A method for preparing polysubstituted (E) -trifluoromethyl olefin, comprising the following steps:

1) the palladium salt and the organic phosphine ligand L1 are fully and uniformly mixed in the organic solvent.

2) Adding an allyl carbonate compound and a nucleophilic reagent into the reaction system in the step 1), carrying out reaction treatment for 2-24 hours, removing the solvent from the reaction product, and carrying out silica gel column chromatographic separation to obtain the polysubstituted (E) -trifluoromethyl olefin.

The palladium salt is Pd (dba)₂、Pd₂(dba)₃·CHCl₃、Pd(OAc)₂Or PdCl₂。

The structural formula of the organophosphorus ligand L1 is as follows:

the organic solvent is 1,1,1,3,3, 3-hexafluoroisopropanol or acetonitrile.

The molar ratio of the palladium salt to the organic phosphine ligand is 1: 1-5.

The molar ratio of the palladium salt to the allyl carbonate compound is 0.025-0.050: 1.

The molar amount of the nucleophilic reagent is 1.0-5.0 times of the molar amount of the allyl carbonate compound.

The reaction temperature in the operation steps is as follows: room temperature to 60 ℃.

The nucleophilic reagent is arylamine, aryl sulfinic acid sodium salt, phenol or water.

When the nucleophilic reagent is phenol or water, an additional inorganic base is required to be added, wherein the inorganic base comprises cesium carbonate, potassium tert-butoxide and cesium carbonate, and the molar weight of the base is 1.0-2.0 times that of the allyl carbonate compound.

Compared with the prior art, the invention has the following beneficial effects:

the invention discloses a preparation method of polysubstituted (E) -trifluoromethyl olefin, which takes allyl carbonate as a compound and a nucleophilic reagent as reaction raw materials, and takes palladium salt and an organic phosphine ligand catalytic system to react in an organic solvent to obtain the target polysubstituted (E) -trifluoromethyl olefin. The synthetic process route of the invention has the advantages of good substrate universality, high yield (the highest can reach 89%), good stereoselectivity (E: Z is more than 99:1), easy realization of industrial production and the like.

Drawings

FIG. 1 is a hydrogen spectrum of example 1.

FIG. 2 is a carbon spectrum of example 1.

FIG. 3 is the fluorine spectrum of example 1.

FIG. 4 is a hydrogen spectrum of example 2.

FIG. 5 is a carbon spectrum of example 2.

FIG. 6 is the fluorine spectrum of example 2.

FIG. 7 is a hydrogen spectrum of example 3.

FIG. 8 is a carbon spectrum of example 3.

FIG. 9 is the fluorine spectrum of example 3.

FIG. 10 is a hydrogen spectrum of example 4.

FIG. 11 is a carbon spectrum of example 4.

FIG. 12 is the fluorine spectrum of example 4.

FIG. 13 is a hydrogen spectrum of example 5.

FIG. 14 is a carbon spectrum of example 5.

FIG. 15 is the fluorine spectrum of example 5.

FIG. 16 is a hydrogen spectrum of example 6.

FIG. 17 is a carbon spectrum of example 6.

FIG. 18 is the fluorine spectrum of example 6.

FIG. 19 is a hydrogen spectrum of example 7.

FIG. 20 is a carbon spectrum of example 7.

FIG. 21 is the fluorine spectrum of example 7.

FIG. 22 is a hydrogen spectrum of example 8.

FIG. 23 is a carbon spectrum of example 8.

FIG. 24 is the fluorine spectrum of example 8.

FIG. 25 is a hydrogen spectrum of example 9.

FIG. 26 is a carbon spectrum of example 9.

FIG. 27 is the fluorine spectrum of example 9.

FIG. 28 is a hydrogen spectrum of example 10.

FIG. 29 is a carbon spectrum of example 10.

FIG. 30 is the fluorine spectrum of example 10.

FIG. 31 is a hydrogen spectrum of example 11.

FIG. 32 is a carbon spectrum of example 11.

FIG. 33 is the fluorine spectrum of example 11.

FIG. 34 is a hydrogen spectrum of example 12.

FIG. 35 is a carbon spectrum of example 12.

FIG. 36 is a fluorine spectrum of example 12.

Detailed Description

The present invention is described in further detail below with reference to specific examples.

Example 1

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of 1,1,1,3,3, 3-hexafluoroisopropanol were stirred at room temperature and 39.6mg of allyl carbonate I-1, 11.2mg of aniline II-1 were added. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated by means of a silica gel column (eluent: ethyl acetate/petroleum ether: 1/50) to obtain the purified product (E) -III-1. Yield 85%, E: Z>99:1, pure structure characterization data, see fig. 1-3, below:

¹H NMR(400MHz,CDCl₃)δ7.44(d,J＝4.9Hz,3H),7.35-7.28(m,2H),7.18(t,J＝7.6Hz,2H),6.75(t,J＝7.3Hz,1H),6.53(d,J＝7.5Hz,3H),3.76(d,J＝6.0Hz,3H).

¹³C NMR(100MHz,CDCl₃)δ147.29,134.09(q,³J_C-F＝5.3Hz),133.19(q,²J_C-F＝29.9Hz),131.67,129.49,129.47,129.10,128.79,123.23(q,¹J_C-F＝271.6Hz),118.27,113.10,41.95.

¹⁹F NMR(376MHz,CDCl₃)δ-66.04.IR(neat,cm^-1)3419,3056,3025,2925,2853,1602,1505,1444,1324,1259,1203,1168,1115,751,700.HRMS(ESI):m/z:calcd for C₁₆H₁₅F₃N[M+H]⁺:278.1157,found:278.1160.

example 2

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of 1,1,1,3,3, 3-hexafluoroisopropanol were stirred at room temperature and 41.0mg of allyl carbonate I-2 and 11.2mg of aniline II-1 were added. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated through a silica gel column (eluent: ethyl acetate/petroleum ether: 1/100) to obtain the purified product (E) -III-2. Yield 54%, E: Z>99:1, the pure structure characterization data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.39(q,J＝7.9,7.2Hz,3H),7.21(d,J＝6.7Hz,2H),7.13(t,J＝7.8Hz,2H),6.70(t,J＝7.3Hz,1H),6.45(d,J＝8.3Hz,1H),3.72(s,1H),3.58(s,2H),2.11(q,J＝2.3Hz,3H).

¹³C NMR(100MHz,CDCl₃)δ147.74,144.73(q,³J_C-F＝3.0Hz),134.48(q,³J_C-F＝1.7Hz),129.74,129.37,128.67,128.44,128.33(q,²J_C-F＝33.1Hz),123.83(q,¹J_C-F＝273.7Hz),117.99,112.88,48.31,16.84.

¹⁹F NMR(376MHz,CDCl₃)δ-56.76.IR(neat,cm^-1)3410,3042,2921,2857,1605,1510,1492,1445,1292,1234,1169,1116,993,769,702.HRMS(ESI)m/z:[M+H]⁺calcd for C₁₇H₁₇F₃N292.3252；Found 292.3253.

example 3

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of 1,1,1,3,3, 3-hexafluoroisopropanol were stirred at room temperature and 47.2mg of allyl carbonate I-3 and 11.2mg of aniline II-1 were added. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated through a silica gel column (eluent: ethyl acetate/petroleum ether: 1/100) to obtain the purified product (E) -III-3. Yield 67%, E: Z>99:1, the pure structure characterization data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.48(t,J＝7.3Hz,3H),7.44-7.32(m,5H),7.19(dd,J＝7.1,2.2Hz,2H),7.07(t,J＝7.9Hz,2H),6.68(t,J＝7.3Hz,1H),6.25(d,J＝7.9Hz,2H),3.92-3.81(m,2H).

¹³C NMR(100MHz,CDCl₃)δ147.09,137.53,133.85(q,⁴J_C-F＝1.1Hz),130.69(q,²J_C-F＝29.4Hz),129.93,129.17,128.91,128.74,128.24,128.09,127.82,127.80,123.12(q,¹J_C-F＝273.9Hz),118.15,113.59,48.25.

¹⁹F NMR(376MHz,CDCl₃)δ-56.20.IR(neat,cm^-1)3419,3056,3025,2925,2853,1602,1505,1325,1203,1168,1115,751,700.HRMS(ESI)m/z:[M+H]⁺calcd for C₂₂H₁₉F₃N 354.3882；Found 354.3883.

example 4

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of 1,1,1,3,3, 3-hexafluoroisopropanol were stirred at room temperature and 39.6mg of allyl carbonate I-1, 12.9mg of p-methylaniline II-2 were added. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated through a silica gel column (eluent: ethyl acetate/petroleum ether: 1/100) to obtain the purified product (E) -III-4. Yield 84%, E: Z>99:1, the pure structure characterization data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.43(d,J＝4.8Hz,3H),7.29(d,J＝6.3Hz,2H),6.98(d,J＝7.8Hz,2H),6.53(t,J＝6.0Hz,1H),6.46(d,J＝7.7Hz,2H),3.73(d,J＝5.8Hz,2H),2.24(s,3H).

¹³C NMR(100MHz,CDCl₃)δ145.00,134.3(q,³J_C-F＝5.3Hz),133.03(q,²J_C-F＝29.9Hz),131.72,129.95,129.50,129.06,128.76,127.57,123.25(q,¹J_C-F＝271.7Hz),113.31,42.28,20.51.

¹⁹F NMR(376MHz,CDCl₃)δ-65.97.IR(neat,cm^-1)3408,3023,2922,2859,1617,1521,1292,1170,1118,909,808.HRMS(ESI)m/z:[M+H]⁺Calcd for C₁₇H₁₇F₃N 292.1313；Found292.1317.

example 5

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of 1,1,1,3,3, 3-hexafluoroisopropanol were stirred at room temperature until completion and 39.6mg of allyl carbonate I-1, 14.1mg of o-cyanoaniline II-3 were added. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated through a silica gel column (eluent: ethyl acetate/petroleum ether: 1/50) to obtain the purified product (E) -III-5. Yield 66%, E: Z>99:1, the pure structure characterization data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.48-7.42(m,3H),7.41-7.38(m,1H),7.37-7.27(m,3H),6.71(t,J＝7.5Hz,1H),6.58-6.31(m,2H),4.75(t,J＝5.0Hz,1H),3.85(tt,J＝4.2,2.1Hz,2H).

¹³C NMR(100MHz,CDCl₃)δ149.40,143.45,134.38,133.04,132.53(q,³J_C-F＝5.4Hz),129.38,129.35,128.92,128.80(q,²J_C-F＝57.5Hz),116.84(q,¹J_C-F＝246.7Hz),117.72,117.44,110.66,96.48,41.19.

¹⁹F NMR(376MHz,CDCl₃)δ-66.17.IR(neat,cm^-1)3419,3056,3025,2925,2853,1602,1505,1325,1203,1168,1115,751,700.HRMS(ESI)m/z:[M+H]⁺calcd for C₁₇H₁₄F₃N₂303.3010；Found 303.3012.

example 6

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of 1,1,1,3,3, 3-hexafluoroisopropanol were stirred at room temperature and 39.6mg of allyl carbonate I-1, 11.2mg of sodium II-4 phenylsulfinate were added. The reaction system was stirred at 60 ℃ for 24 hours. Concentrating and spin-drying the reaction solution, and separating by silica gel column (eluent: ethyl acetate/petroleum ether: 1/10) to obtain the purified product (E) -III-6. Yield 89%, E: Z>99:1, the pure structure characterization data are as follows:

¹H(400MHz,CDCl₃)δ7.78(d,J＝7.5Hz,2H),7.73(t,J＝7.5Hz,1H),7.58(t,J＝7.8Hz,2H),7.35(t,J＝7.4Hz,1H),7.26(t,J＝7.6Hz,2H),6.72(d,J＝7.5Hz,2H),6.59-6.36(m,1H),3.85-3.63(m,2H).

¹³C NMR(100MHz,CDCl₃)δ138.77(q,²J_C-F＝30.5Hz),138.10,134.34,129.93,129.48,129.40,129.14,128.74,128.63,122.90(q,³J_C-F＝5.8Hz),122.51(q,¹J_C-F＝272.2Hz),55.94.

¹⁹F NMR(376MHz,CDCl₃)δ-66.99.IR(neat,cm^-1)3065,2925,1669,1594,1490,1400,1299,1172,1131,822,750.HRMS(ESI)m/z:[M+H]⁺Calcd for C₁₆H₁₄F₃O₂S 327.0667；Found 327.0668.

example 7

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of 1,1,1,3,3, 3-hexafluoroisopropanol were stirred at room temperature and 41.0mg of allyl carbonate I-2, 19.7mg of sodium II-4 phenylsulfinate were added. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated through a silica gel column (eluent: ethyl acetate/petroleum ether: 1/10) to obtain the purified product (E) -III-7. Yield 82%, E: Z>95:5, the pure product structure characterization data is as follows:

¹H NMR(400MHz,CDCl₃)δ7.68(dd,J＝15.1,7.5Hz,3H),7.53(t,J＝7.8Hz,2H),7.32-7.25(m,1H),7.21(t,J＝7.4Hz),6.65(d,J＝7.3Hz),3.77,2.35(q,J＝2.6Hz).

¹³C NMR(100MHz,CDCl₃)δ138.89,135.40(q,²J_C-F＝30.2Hz),134.73(q,³J_C-F＝2.9Hz),134.15,133.22(q,⁴J_C-F＝1.7Hz),129.41,128.63,128.56,128.48,123.25(q,¹J_C-F＝274.1Hz),62.78,19.3.

¹⁹F NMR(376MHz,CDCl₃)δ-57.36.IR(neat,cm^-1)3063,2925,1447,1323,1225,1165,1121,1085,766,743.HRMS(ESI)m/z:[M+H]⁺calcd for C₁₇H₁₆F₃O₂S 341.3602；Found 341.3603.

example 8

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of 1,1,1,3,3, 3-hexafluoroisopropanol were stirred at room temperature and then 39.6mg of allyl carbonate I-1, 21.4mg of sodium p-toluenesulfinate II-5 were added. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated through a silica gel column (eluent: ethyl acetate/petroleum ether: 1/10) to obtain the purified product (E) -III-8. Yield 81%, E: Z>99:1, the pure structure characterization data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.66(d,J＝8.3Hz,2H),7.35(t,J＝8.1Hz,3H),7.27(t,J＝7.5Hz,2H),6.77(d,J＝7.4Hz,2H),6.52-6.44(m,1H),3.78-3.71(m,2H),2.49(s,3H).

¹³C NMR(100MHz,CDCl₃)δ145.48,138.60(q,²J_C-F＝30.5Hz),135.33,130.05,129.38,129.21,128.71,128.63,123.07(q,³J_C-F＝5.7Hz),122.58(q,¹J_C-F＝272.1Hz),56.04,21.83.

¹⁹F NMR(376MHz,CDCl₃)δ-66.86.IR(neat,cm^-1)3065,2925,1669,1594,1490,1400,1299,1172,1132,866,822.HRMS(ESI)m/z:[M+H]⁺calcd for C₁₇H₁₆F₃O₂S 341.3120；Found341.3121.

example 9

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of acetonitrile, 39.6mg of allyl carbonate I-1, 11.3mg of phenol II-6, and 65.2mg of cesium carbonate were added after stirring at room temperature. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated through a silica gel column (eluent: ethyl acetate/petroleum ether: 1/100) to obtain the purified product (E) -III-9. Yield 68%, E: Z>99:1, the pure structure characterization data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.35-7.29(m,3H),7.20-7.12(m,4H),6.84(t,J＝7.3Hz,1H),6.68(d,J＝8.2Hz,2H),6.60-6.54(m,1H),4.39(dq,J＝6.4,2.2Hz,2H).

¹³C NMR(100MHz,CDCl₃)δ158.07,133.81(q,²J_C-F＝30.1Hz),131.91(q,³J_C-F＝5.5Hz),131.34,129.67,129.32,128.84,124.40,123.04(q,¹J_C-F＝271.8Hz),121.43,114.69,64.30.

¹⁹F NMR(376MHz,CDCl₃)δ-66.26.IR(neat,cm^-1)3062,2927,1743,1493,1219,1175,1124,754.HRMS(ESI)m/z:[M+H]⁺calcd for C₁₆H₁₄F₃O 279.0977；Found 279.0988.

example 10

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of acetonitrile, 41.0mg of allyl carbonate I-4, 20.8mg of m-bromophenol II-7, 65.2mg of cesium carbonate were added after stirring at room temperature. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated through a silica gel column (eluent: ethyl acetate/petroleum ether: 1/100) to obtain the purified product (E) -III-10. Yield 76%, E: Z>99:1, the pure structure characterization data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.38(d,J＝8.5Hz,2H),7.30(d,J＝8.0Hz,2H),7.26-7.19(m,2H),7.05(d,J＝2.0Hz,1H),6.86(dt,J＝7.6,2.2Hz,1H),6.77-6.70(m,1H),4.64-4.58(m,2H),2.53(s,3H).

¹³C NMR(100MHz,CDCl₃)δ158.84,139.46,134.39(q,²J_C-F＝30.0Hz),130.83(q,³J_C-F＝5.4Hz),130.74,129.63,129.17,124.52,123.02(q,¹J_C-F＝271.7Hz),122.95,117.86,113.86,64.59,21.46.

¹⁹F NMR(376MHz,CDCl₃)δ-66.37.IR(neat,cm^-1)2974,1576,1474,1221,1171,1124,821.HRMS(ESI)m/z:[M]Calcd for C₁₇H₁₅OF₃Br 371.0258；Found 371.0261.

example 11

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of acetonitrile, 39.6mg of allyl carbonate I-1, 18.0mg of water II-8, and 65.2mg of cesium carbonate were added after stirring at room temperature. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated by means of a silica gel column (eluent: ethyl acetate/petroleum ether: 1/10) to obtain the purified product (E) -III-11. Yield 64%, E: Z>99:1, the pure structure characterization data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.47-7.41(m,3H),7.32-7.24(m,2H),6.61-6.54(m,1H),4.88-4.81(m,2H).

¹³C NMR(100MHz,CDCl₃)δ134.80(q,³J_C-F＝5.4Hz),132.57(q,²J_C-F＝30.0Hz),131.46,129.42,129.10,128.68,123.17(q,¹J_C-F＝271.6Hz),59.35.

¹⁹F NMR(376MHz,CDCl₃)δ-66.18.IR(neat,cm^-1)3317,2918,1295,1171,1118,712.HRMS(ESI)m/z:[M+H]⁺calcd for C₁₀H₁₀F₃O 203.0684；Found 203.0674.

example 12

Without nitrogen protection, 1.4mg Pd (dba) was added to a 10mL reaction flask in sequence₂2.7mg of L1 ligand and 0.5mL of acetonitrile, 41.0mg of allyl carbonate I-4, 18.0mg of water II-8, and 65.2mg of cesium carbonate were added after stirring at room temperature. The reaction system was stirred at 60 ℃ for 24 hours. The reaction mixture was concentrated, dried and separated through a silica gel column (eluent: ethyl acetate/petroleum ether: 1/10) to obtain the purified product (E) -III-12. Yield 71%, E: Z>99:1, the pure structure characterization data are as follows:

¹H NMR(400MHz,CDCl₃)δ7.31(d,J＝7.6Hz,2H),7.22(d,J＝7.6Hz,2H),6.62(t,J＝6.0Hz,1H),4.23(d,J＝5.6Hz,2H),2.48(s,3H),2.26(s,1H).

¹³C NMR(100MHz,CDCl3)δ139.06,134.53(q,³J_C-F＝5.3Hz),132.46(q,²J_C-F＝29.9Hz),129.35,129.26,128.43,123.24(q,¹J_C-F＝271.6Hz),59.25,21.30.

¹⁹F NMR(376MHz,CDCl₃)δ-66.18.IR(neat,cm^-1)3310,2997,1774,1176,1123,1015,742.HRMS(ESI)m/z:[M]Calcd for C₁₁H₁₂OF₃ 217.0840；Found 217.0844.