Method for synthesizing (Z)-2-fluoro-1, 3-diaryl propylene derivative through palladium catalysis

Abstract

The invention belongs to the technical field of organic synthesis, and particularly discloses a method for synthesizing a (Z)-2-fluoro-1, 3-diaryl propylene derivative under the catalysis of palladium, which comprises the following steps: in an organic solvent, by taking a gem-difluorocyclopropane derivative and an aryl alkoxy silane compound as initial raw materials and metal palladium salt as a catalyst, reacting at the temperature of 60-80 DEG C for 2-4 hours, thereby obtaining the (Z)-2-fluoro-1, 3-diaryl propylene derivative. And adding an organic phosphorus ligand and an alkaline activator, carrying out heating reflux under stirring, carrying out TLC tracking detection until the reaction is complete, and carrying out post-treatment on the reaction liquid to obtain the (Z)-2-fluoro-1, 3-diaryl propylene derivative as shown in the formula (3). The method is simple to operate, raw materials and reagents are convenient and easy to obtain, a catalytic system is simple, products are easy to separate and purify, the method is suitable for preparing and synthesizing various substituted (Z)-2-fluoro-1, 3-diaryl propylene compounds, and high-purity target compounds can be efficiently prepared with high yield.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a method for synthesizing a (Z)-2-fluoro-1,3-diarylpropene derivative, in particular to a palladium-catalyzed, simple and efficient method for synthesizing a (Z)-2-fluoro-1,3-diarylpropene derivative. Background Art

[0002] As we all know, (Z)-2-fluoro-1,3-diarylpropene is one of the important structural units, which is widely present in many drugs, pesticides, natural products, and active biological molecules, and exhibits extremely excellent physiological activity. Therefore, exploring and developing simple, efficient, and highly selective methods to synthesize structurally diverse (Z)-2-fluoro-1,3-diarylpropene derivatives is one of the important topics in organic synthetic chemistry research. Up to now, the reported catalytic reaction systems have many defects, such as: narrow substrate range, harsh reaction conditions, relatively excessive additives, low yield, etc., and lack broad application prospects. Therefore, it is of great research value to develop a new green, efficient, and practical method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives. Gem-difluorocyclopropane derivatives and phenylalkoxysilane are two common chemical raw materials and are widely used in the field of organic synthesis research. Developing simple and efficient catalytic systems and studying new ring-opening defluorination cross-coupling reactions based on gem-difluorocyclopropane derivatives and phenylalkoxysilanes have important practical value and broad application potential.

[0003] Palladium-catalyzed organic reactions are one of the hot research directions in the field of synthetic chemistry. Various palladium-catalyzed organic synthesis chemical reactions have been reported one after another, such as carbon-carbon coupling reactions, carbon-heteroatom coupling reactions, intramolecular reactions, multi-component reactions, etc. Although the research on organic synthesis under palladium catalysis is relatively mature, there is no literature reporting the use of metal palladium catalysts for novel ring-opening defluorination cross-coupling reactions involving geminal difluorocyclopropane derivatives and phenylalkoxysilanes. If a palladium-catalyzed, highly selective ring-opening defluorination coupling reaction of geminal difluorocyclopropane derivatives and phenylalkoxysilanes can be developed, it will have important significance for promoting the industrialization of the synthesis of (Z)-2-fluoro-1,3-diarylpropene derivatives. Summary of the invention

[0004] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a palladium-catalyzed synthesis method of (Z)-2-fluoro-1,3-diarylpropene derivatives. The present invention uses a metal palladium salt as a catalyst, a geminal difluorocyclopropane derivative and an aryl alkoxysilane compound as starting materials to synthesize the (Z)-2-fluoro-1,3-diarylpropene derivatives. The present invention has high catalytic efficiency and high selectivity, simple reaction operation, mild conditions, and simple and readily available raw materials, and is suitable as a method for large-scale industrial production.

[0005] The present invention is achieved through the following technical solutions:

[0006] A palladium-catalyzed synthesis method of a (Z)-2-fluoro-1,3-diarylpropene derivative comprises the following steps: In an organic solvent, a geminal difluorocyclopropane derivative represented by formula (1) and an aryl alkoxysilane compound represented by formula (2) are used as starting materials, a metal palladium salt is used as a catalyst, an organic phosphorus ligand and an alkaline activator are added, the mixture is heated under reflux under stirring, and the reaction is followed by TLC detection until the reaction is complete, and the reaction solution is post-treated to obtain a (Z)-2-fluoro-1,3-diarylpropene derivative represented by formula (3); the reaction equation is as follows:

[0007]

[0008] Among them, R, R1, and R2 are selected from hydrogen, aryl, alkyl, alkoxy, etc., and can be monosubstituted, disubstituted, or trisubstituted.

[0009] Preferably, the compound of formula (1) is selected from

[0010] The compound of formula (2) is selected from

[0011] A further improvement of the present invention is:

[0012] The metal palladium salt is one or a mixture of two or more of bistriphenylphosphine palladium dichloride, trisdibenzylideneacetone dipalladium, dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium, palladium acetate, palladium chloride or tetrakistriphenylphosphine palladium.

[0013] Preferably, the metal palladium salt is palladium acetate.

[0014] Furthermore, the organic solvent is one or a mixture of two or more of ethanol, tetrahydrofuran, toluene, 1,2-dichloroethane, N,N-dimethylformamide or 1,4-dioxane.

[0015] Preferably, the organic solvent is tetrahydrofuran.

[0016] Furthermore, the organophosphorus ligand is one or a mixture of two or more of triphenylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine, 2-dicyclohexylphosphine-2',6'-diisopropoxy-1,1'-biphenyl, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene or 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl.

[0017] Furthermore, the alkaline activator is one or a mixture of two or more of cesium fluoride, potassium fluoride, copper fluoride, silver fluoride or tetrabutylammonium fluoride.

[0018] Furthermore, the molar ratio of the geminal difluorocyclopropane derivative represented by formula (1), the aryl alkoxysilane compound represented by formula (2), the metal palladium salt, the organic phosphorus ligand and the alkaline activator is 1:2-5:0.04-0.06:0.05-0.15:1-3.

[0019] Preferably, the molar ratio of the geminal difluorocyclopropane derivative represented by formula (1), the aryl alkoxysilane compound represented by formula (2), the metal palladium salt, the organic phosphorus ligand and the alkaline activator is 1:3:0.05:0.1:2.

[0020] Furthermore, 0.2 to 0.8 mL of an organic solvent is required to be added per 1 mmol of the gem-difluorocyclopropane derivative represented by the formula (1).

[0021] Preferably, 0.5 mL of the organic solvent is added per 1 mmol of the gem-difluorocyclopropane derivative represented by formula (1).

[0022] Furthermore, the reaction temperature is 50-80°C.

[0023] Preferably, the reaction temperature is 60°C.

[0024] Furthermore, the post-treatment includes the following steps: after the reaction is completed, pouring the reaction solution into saturated brine, extracting with dichloromethane, backwashing the organic phase with saturated brine, drying with anhydrous sodium sulfate, filtering, and distilling under reduced pressure, and then separating by silica gel column chromatography, distilling the obtained eluate under reduced pressure, and drying to obtain the (Z)-2-fluoro-1,3-diarylpropene derivative shown in formula (3).

[0025] Furthermore, the developing solvent used for TLC tracking of the reaction was petroleum ether:ethyl acetate=20:1, V / V.

[0026] Furthermore, during post-treatment, the eluent used for the silica gel column chromatography is petroleum ether:ethyl acetate=20:1, V / V.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] 1. The present invention uses simple and easy-to-prepare geminal difluorocyclopropane derivatives to react with cheap and readily available aryl alkoxysilanes to efficiently construct structurally diverse (Z)-2-fluoro-1,3-diarylpropene derivatives, enriching the synthesis methods of such compounds; and provides a new preparation method for the precise and efficient synthesis of (Z)-2-fluoro-1,3-diarylpropene compounds.

[0029] 2. The present invention utilizes palladium catalysis to efficiently realize the cross-coupling reaction between geminal difluorocyclopropane derivatives and aryltrialkoxysilanes, and accurately prepares a series of functionalized (Z)-2-fluoro-1,3-diarylpropene compounds.

[0030] 3. The present invention has many characteristics such as easy to obtain raw materials and reagents, simple catalytic system, convenient operation, easy separation of products, etc. It is particularly suitable for preparing various highly functionalized (Z)-2-fluoro-1,3-diarylpropene derivatives and is suitable for large-scale industrial production to obtain (Z)-2-fluoro-1,3-diarylpropene compounds with high efficiency and high yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 For (Z)-2-fluoro-1,3-diarylpropene 3a 1 H-NMR spectrum;

[0032] Figure 2 For (Z)-2-fluoro-1,3-diarylpropene 3a 13 C-NMR spectrum;

[0033] Figure 3 For (Z)-2-fluoro-1,3-diarylpropene 3a 19 F-NMR spectrum;

[0034] Figure 4 For (Z)-2-fluoro-1,3-diarylpropene 3b 1 H-NMR spectrum;

[0035] Figure 5 For (Z)-2-fluoro-1,3-diarylpropene 3b 13 C-NMR spectrum;

[0036] Figure 6 For (Z)-2-fluoro-1,3-diarylpropene 3b 19 F-NMR spectrum;

[0037] Figure 7 For (Z)-2-fluoro-1,3-diarylpropene 3c 1 H-NMR spectrum;

[0038] Figure 8 For (Z)-2-fluoro-1,3-diarylpropene 3c 13 C-NMR spectrum;

[0039] Fig. 9 For (Z)-2-fluoro-1,3-diarylpropene 3c 19 F-NMR spectrum;

[0040] Fig.10 (Z)-2-fluoro-1,3-diarylpropene 3d 1 H-NMR spectrum;

[0041] Fig.11 (Z)-2-fluoro-1,3-diarylpropene 3d 13 C-NMR spectrum;

[0042] Fig.12 (Z)-2-fluoro-1,3-diarylpropene 3d 19 F-NMR spectrum;

[0043] Fig.13 (Z)-2-fluoro-1,3-diarylpropene 3e 1 H-NMR spectrum;

[0044] Fig.14 (Z)-2-fluoro-1,3-diarylpropene 3e 13 C-NMR spectrum;

[0045] Fig.15 (Z)-2-fluoro-1,3-diarylpropene 3e 19 F-NMR spectrum;

[0046] Fig.16 For (Z)-2-fluoro-1,3-diarylpropene 4b 1 H-NMR spectrum;

[0047] Fig.17 For (Z)-2-fluoro-1,3-diarylpropene 4b 13 C-NMR spectrum;

[0048] Fig.18 For (Z)-2-fluoro-1,3-diarylpropene 4b 19 F-NMR spectrum;

[0049] Fig.19 For (Z)-2-fluoro-1,3-diarylpropene 4c 1 H-NMR spectrum;

[0050] Fig. 20 For (Z)-2-fluoro-1,3-diarylpropene 4c 13 C-NMR spectrum;

[0051] Fig.21 For (Z)-2-fluoro-1,3-diarylpropene 4c 19 F-NMR spectrum;

[0052] Fig. 22(Z)-2-fluoro-1,3-diarylpropene 4d 1 H-NMR spectrum;

[0053] Fig.23 (Z)-2-fluoro-1,3-diarylpropene 4d 13 C-NMR spectrum;

[0054] Fig.24 (Z)-2-fluoro-1,3-diarylpropene 4d 19 F-NMR spectrum;

[0055] Fig.25 (Z)-2-fluoro-1,3-diarylpropene 4e 1 H-NMR spectrum;

[0056] Fig.26 (Z)-2-fluoro-1,3-diarylpropene 4e 13 C-NMR spectrum;

[0057] Fig. 27 (Z)-2-fluoro-1,3-diarylpropene 4e 19 F-NMR spectrum;

[0058] Fig.28 For (Z)-2-fluoro-1,3-diarylpropene 4f 1 H-NMR spectrum;

[0059] Fig.29 For (Z)-2-fluoro-1,3-diarylpropene 4f 13 C-NMR spectrum;

[0060] Fig.30 For (Z)-2-fluoro-1,3-diarylpropene 4f 19 F-NMR spectrum. DETAILED DESCRIPTION

[0061] The present invention is described in detail below in conjunction with specific embodiments.

[0062] The present invention utilizes palladium catalysis to efficiently realize the cross-coupling reaction between geminal difluorocyclopropane derivatives and aryltrialkoxysilanes, and accurately prepares a series of functionalized (Z)-2-fluoro-1,3-diarylpropene compounds. The reaction equation is as follows:

[0063]

[0064] Specific:

[0065]

[0066] Example 1: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 3a

[0067]

[0068] In a 35 mL pressure tube with magnetic stirring, add anhydrous tetrahydrofuran (2.0 mL), geminal difluorocyclopropane compound 1a (0.230 g, 1.0 mmol) and phenyltrimethoxysilane 2a (0.594 g, 3.0 mmol), palladium acetate (0.011 g, 0.05 mmol), tricyclohexylphosphine (0.028 g, 0.10 mmol) and copper fluoride (0.202 g, 2.0 mmol) and stir evenly, then place in a 60 ° C oil bath under nitrogen protection and stir for 24 h. Thin layer chromatography (developing solvent V 石油醚 :V 乙酸乙酯 =20:1) to detect the disappearance of the raw material. After the reaction was completed, the reaction solution was poured into saturated brine (15 mL), extracted with dichloromethane (3×10 mL), the organic phases were combined, backwashed with water (3×10 mL), dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain a viscous solid, which was finally chromatographed on a silica gel column (eluent: V 石油醚 :V 乙酸乙酯 =20:1) to obtain an oily liquid, which was determined by NMR to be a (Z)-2-fluoro-1,3-diarylpropene derivative 3a with a yield of 83%.

[0069] Spectral analysis data 3a:

[0070] Oily liquid, 1 H NMR (500MHz, CDCl3) δ7.59–7.55(m,2H),7.53(s,4H),7.40(dd,J=8.5,6.9Hz,2 H),7.32(dt,J=9.0,5.9Hz,6H),5.53(d,J=38.8Hz,1H),3.64(d,J=17.0Hz,2H); 19 FNMR (471MHz,CDCl3)δ-99.40; 13 C NMR (126MHz, CDCl3) δ159.71 (d, J = 267.6Hz), 140.67, 139.52 (d, J = 2.4Hz), 136.12, 132.58 (d, J = 2.8Hz), 128.97, 128.78, 128.73 (d, J = 3.2Hz), 128.65, 127.24, 127.03, 126.98, 126.91, 106.93 (d, J = 8.3Hz), 39.63 (d, J = 27.8Hz).

[0071] Example 2: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 3b

[0072] 1a in Example 1 was replaced by 1b, and other operating conditions were the same as those in Example 1. The yield was 68%.

[0073]

[0074] Spectral analysis data 3b:

[0075] Oily liquid, 1 H NMR (500MHz, CDCl3) δ7.37–7.23(m,7H),7.11(t,J=8.8Hz,2H),5.47(d,J=39.0Hz,1H),3.62(d,J=17.1Hz,2H),2.31(s,3H); 19 F NMR (471MHz, CDCl3) δ-101.15; 13 C NMR (126MHz, CDCl3) δ158.83 (d, J = 266.3Hz), 136.58 (d, J = 2.3Hz), 136.26, 130.62 (d, J = 2.6Hz), 128 .98(d,J=18.7Hz),128.56,128.22(d,J=7.3Hz),126.85,107.11(d,J=8.3Hz),39.41,29.70,21.15.

[0076] Example 3: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 3c

[0077] 1c was used to replace 1a in Example 1. Other operating conditions were the same as those in Example 1. The yield was 74%.

[0078]

[0079] Spectral analysis data 3c:

[0080] Oily liquid, 1 H NMR (500MHz, CDCl3) δ7.42–7.38(m,2H),7.36–7.27(m,5H),6.86–

[0081] 6.82(m,2H),5.45(d,J=39.1Hz,1H),3.79(s,3H),3.62(d,J=17.2Hz,2H); 19 FNMR (471MHz, CDCl3) δ-103.07; 13C NMR (126MHz, CDCl3) δ158.34 (d, J=2.8Hz), 158.06 (d, J=

[0082] 264.6Hz), 136.37, 129.55 (d, J = 7.5Hz), 128.90, 128.56, 126.85, 126.21 (d, J = 2.7Hz), 113.75, 106.66 (d, J = 8.6Hz), 55.16, 39.50 (d, J = 28.1Hz).

[0083] Example 4: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 3d

[0084] 1d was used to replace 1a in Example 1, and other operating conditions were the same as those in Example 1. The yield was 66%.

[0085]

[0086] Spectral analysis data 3d:

[0087] Oily liquid, 1 H NMR(500MHz, CDCl3)δ7.30(m,5H),7.20(t,J=8.0Hz,1H),7.06–7.00(m,2H),6 .78–6.74(m,1H),5.48(d,J=38.5Hz,1H),3.77(s,3H),3.62(d,J=17.0Hz,2H); 19 FNMR (471MHz, CDCl3) δ-99.27; 13 C NMR(126MHz, CDCl3)δ159.65(d,J=267.9Hz),159.49,135.40(d,J=166.0Hz),129.28,128.95,128.62,126.96,1 20.99(d,J=6.9Hz), 113.51(d,J=8.2Hz), 112.84(d,J=2.1Hz), 107.21(d,J=7.8Hz), 55.14, 39.59(d,J=27.8Hz).

[0088] Example 5: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 3e

[0089] 1e was used to replace 1a in Example 1, and other operating conditions were the same as those in Example 1. The yield was 64%.

[0090]

[0091] Spectral analysis data 3e:

[0092] Oily liquid, 1 H NMR(500MHz, CDCl3) δ7.86(s,1H),7.75(dd,J=9.0,4.3Hz,3H),7.62(dd,J=8.7,1.7Hz,1H),7.46– 7.38(m,2H),7.36–7.30(m,4H),7.30–7.24(m,1H),5.63(d,J=38.7Hz,1H),3.66(d,J=16.8Hz,2H), 19 F NMR (471MHz, CDCl3) δ-99.44; 13 C NMR (126MHz, CDCl3) δ159.85 (d, J = 267.6Hz), 136.12, 133.40, 132.28 (d, J = 1.8Hz), 131.06 (d, J = 3.0Hz), 129.01, 128.67, 127.91 (d ,J=10.8Hz),127.49,127.23(d,J=7.4Hz),127.00,126.48(d,J=7.6Hz),126.05,125.78,107.38(d,J=8.1Hz),39.68(d,J=27.9Hz).

[0093] Example 6: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 4b

[0094] 2a in Example 5 was replaced by 2b, and other operating conditions were the same as those in Example 5. The yield was 67%.

[0095]

[0096] Spectral analysis data 4b:

[0097] Oily liquid, 1 H NMR (500MHz, CDCl3) δ7.83(d,J=1.8Hz,1H),7.74(dd,J=9.0,5.4Hz,3H),7.62(dd,J=8.7,1.8Hz,1H),7.45–7.37(m,2H) ,7.10–7.07(m,2H),7.01(dd,J=7.9,1.8Hz,1H),5.48(d,J=39.3Hz,1H),3.64(d,J=13.2Hz,2H),2.32(d,J=3.1Hz,6H); 19 F NMR (471MHz, CDCl3) δ-98.45; 13C NMR (126MHz, CDCl3) δ159.63 (d, J = 268.0Hz), 135.69, 133.90 (d, J = 4.2Hz), 1 33.58,133.40,132.22(d,J=1.8Hz),131.17(d,J=2.7Hz),130.68,130.36,1 27.92(d,J=3.5Hz),127.82,127.47,127.13(d,J=7.4Hz),126.49(d,J=7.7H z),126.02,125.72,106.92(d,J=7.9Hz),37.07(d,J=27.8Hz),20.92,18.91.

[0098] Example 7: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 4c

[0099] 2c was used to replace 2a in Example 5. Other operating conditions were the same as those in Example 5. The yield was 85%.

[0100]

[0101] Spectral analysis data 4c:

[0102] Oily liquid, 1 H NMR (500MHz, CDCl3) δ7.82(d,J=1.7Hz,1H),7.73(dd,J=8.8,6.7Hz,4H),7.61(dd,J=8.7,1.7Hz,1H),7.44–7.38(m, 2H),7.15(d,J=7.5Hz,1H),7.03–6.96(m,2H),5.46(d,J=39.2Hz,1H),3.63(d,J=13.0Hz,2H),2.32(d,J=5.7Hz,6H); 19 FNMR (471MHz, CDCl3) δ-98.51; 13 C NMR (126MHz, CDCl3) δ159.76 (d, J = 268.2Hz), 136.71 (d, J = 33.2Hz), 133.40, 132.21(d,J=1.7Hz),131.30,131.19(d,J=2.7Hz),131.04(d,J=4.6Hz),129. 94,127.91,127.80,127.47,127.11(d,J=7.3Hz),126.90,126.48(d,J=7.7H z),126.01,125.70,106.81(d,J=8.0Hz),36.70(d,J=28.0Hz),20.99,19.32.

[0103] Example 8: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 4d

[0104] 2a in Example 5 was replaced by 2d, and other operating conditions were the same as those in Example 5. The yield was 65%.

[0105]

[0106] Spectral analysis data 4d:

[0107] Oily liquid, 1 H NMR(500MHz, CDCl3) δ7.83(d,J=1.7Hz,1H),7.75(dd,J=9.2,7.0Hz,3H),7.62(dd,J=8.7,1.7Hz,1H),7.45 –7.38(m,2H),7.16–7.07(m,3H),5.45(d,J=39.4Hz,1H),3.71(d,J=12.3Hz,2H),2.32(s,3H),2.26(s,3H); 19 F NMR (471MHz, CDCl3) δ-98.29; 13 C NMR (126MHz, CDCl3) δ159.87 (d, J = 268.0Hz), 137.22, 135.41, 134.01 (d, J = 5 .0Hz),133.40,132.21(d,J=1.5Hz),131.18(d,J=2.7Hz),129.00,128.03,1 27.91,127.81,127.47,127.11(d,J=7.3Hz),126.48(d,J=7.8Hz),126.01,1 25.69(d,J=4.9Hz),106.96(d,J=8.0Hz),37.67(d,J=27.9Hz),20.71,15.24.

[0108] Example 9: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 4e

[0109] 2e was used to replace 2a in Example 5. Other operating conditions were the same as those in Example 5, and the yield was 69%.

[0110]

[0111] Spectral analysis data 4e:

[0112] Oily liquid, 1H NMR (500MHz, CDCl3) δ7.87(d,J=1.7Hz,1H),7.78–7.73(m,3H),7.63(dd,J=8.6,1.8Hz,1H),7.41(qd,J=7.0,3. 4Hz,2H),7.24(t,J=7.5Hz,1H),7.15–7.06(m,3H),5.64(d,J=38.8Hz,1H),3.63(d,J=17.0Hz,2H),2.35(s,3H); 19 FNMR(471MHz, CDCl3)δ-99.38(s); 13 C NMR (126MHz, CDCl3) δ159.97 (d, J = 267.9Hz), 138.30, 136.00 (d, J = 1.7Hz), 133.41, 132.26 (d, J = 1.8Hz), 131.12 (d, J = 2.9Hz), 129.73, 128.53, 127.94,127.85,127.73,127.48,127.21(d,J=7.4Hz),126.50(d,J=7.7 Hz), 126.03, 125.75, 107.27 (d, J = 7.9Hz), 39.60 (d, J = 27.7Hz), 21.37.

[0113] Example 10: Preparation of (Z)-2-fluoro-1,3-diarylpropene derivative 4f

[0114] 2f was used to replace 2a in Example 5. Other operating conditions were the same as those in Example 5. The yield was 78%.

[0115]

[0116] Spectral analysis data 4f:

[0117] Oily liquid, 1 H NMR (500MHz, CDCl3) δ7.83 (d, J=1.8Hz, 1H), 7.74 (dd, J=8.7, 6.2Hz, 3H), 7.61 (dd, J=8.6, 1.7Hz, 1H), 7.41 (qd, J=6 .9,3.4Hz,2H),7.30–7.25(m,1H),7.22–7.15(m,4H),5.47(d,J=39.2Hz,1H),3.68(d,J=13.2Hz,2H),2.37(s,3H); 19 F NMR(471MHz, CDCl3)δ-98.48(s); 13C NMR (126MHz, CDCl3) δ159.48 (d, J = 268.1Hz), 136.78, 134.14 (d, J = 4.4Hz), 1 33.39,132.23(d,J=1.8Hz),131.10(d,J=2.8Hz),130.47,129.96,127.92,1 27.83,127.37(d,J=25.0Hz),127.14(d,J=7.3Hz),126.46(d,J=7.8Hz),126 .14(d,J=28.9Hz),125.73,107.03(d,J=7.9Hz),37.08(d,J=28.1Hz),19.39.

[0118] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent transformation or modification made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis, characterized in that: The method comprises the following steps: in an organic solvent, using a geminal difluorocyclopropane derivative represented by formula (1) and an aryl alkoxysilane compound represented by formula (2) as starting materials, using a metal palladium salt as a catalyst, adding an organic phosphorus ligand and an alkaline activator, heating under reflux reaction under stirring, tracking and detecting by TLC until the reaction is complete, and post-treating the reaction solution to obtain a (Z)-2-fluoro-1,3-diarylpropene derivative represented by formula (3); the reaction equation is as follows: Wherein, the compound of formula (1) is selected from The compound of formula (2) is selected from 2. The method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis according to claim 1, characterized in that: The metal palladium salt is one or a mixture of two or more of bistriphenylphosphine palladium dichloride, trisdibenzylideneacetone dipalladium, dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium, palladium acetate, palladium chloride or tetrakistriphenylphosphine palladium.

3. The method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis according to claim 2, characterized in that: The metal palladium salt is palladium acetate.

4. The method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis according to claim 1, characterized in that: The organic solvent is one or a mixture of two or more of ethanol, tetrahydrofuran, toluene, 1,2-dichloroethane, N,N-dimethylformamide or 1,4-dioxane.

5. The method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis according to claim 4, characterized in that: The organic solvent is tetrahydrofuran.

6. The method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis according to claim 1, characterized in that: The organic phosphorus ligand is one or a mixture of two or more of triphenylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine, 2-dicyclohexylphosphine-2',6'-diisopropoxy-1,1'-biphenyl, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene or 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl.

7. The method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis according to claim 1, characterized in that: The alkaline activator is one or a mixture of two or more of cesium fluoride, potassium fluoride, copper fluoride, silver fluoride or tetrabutylammonium fluoride.

8. The method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis according to claim 1, characterized in that: The molar ratio of the geminal difluorocyclopropane derivative represented by formula (1), the aryl alkoxysilane compound represented by formula (2), the metal palladium salt, the organic phosphorus ligand and the alkaline activator is 1:2-5:0.04-0.06:0.05-0.15:1-3; 0.2-0.8 mL of organic solvent is required for every 1 mmol of the geminal difluorocyclopropane derivative represented by formula (1).

9. The method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis according to claim 1, characterized in that: The reaction temperature is 50-80°C.

10. The method for synthesizing (Z)-2-fluoro-1,3-diarylpropene derivatives by palladium catalysis according to claim 1, characterized in that: The post-treatment comprises the following steps: after the reaction is completed, pouring the reaction solution into saturated brine, extracting with dichloromethane, backwashing the organic phase with saturated brine, drying with anhydrous sodium sulfate, filtering, distilling under reduced pressure, and then separating with silica gel column chromatography, distilling the obtained eluate under reduced pressure, and drying to obtain the (Z)-2-fluoro-1,3-diarylpropene derivative shown in formula (3).

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