Polydifluoroalkylated derivatives of terpene olefins and process for their preparation

Abstract

The application discloses a kind of polydifluoroalkylation derivatives of terpene olefin and preparation method thereof, the preparation method includes under inert gas protection, terpene olefin, photosensitizer, cobalt catalyst, organic reducing agent, base, fluorine reagent and organic solvent are sequentially loaded into reaction container, and the reaction system is obtained;Under inert gas protection, the reaction system is reacted at 40~60 ℃ under light condition;After reaction, the system is filtered, rotary evaporated and chromatographically purified, and the polydifluoroalkylation of terpene olefin is completed.The method of the application can efficiently, high selectivity and high yield realize the polydifluoroalkylation reaction of terpene olefin, without using precious metal catalyst, with good functional group compatibility, high yield, and the highest yield can reach 93%.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a polydifluoroalkylated derivative of terpenoid olefins and its preparation method. Background Technology

[0002] Difluoromethyl (CF2H) has significant applications in medicinal chemistry and materials science. Compared to trifluoromethyl (CF3), difluoromethyl retains the high electronegativity of fluorine atoms and, by using the CH bond as a hydrogen bond donor, can effectively regulate the polarity, solubility, and biocompatibility of molecules. As an isosteric group of hydroxyl or thiol groups, CF2H can maintain the conformation and polarity of molecules essentially unchanged when replacing these functional groups. This allows for the optimization of metabolic stability, lipophilicity, and membrane permeability of compounds without affecting pharmacological activity. Difluoromethylation has become one of the key strategies for lead compound structure optimization and drug performance enhancement (Gouverneur, V. et al. Chem. Soc. Rev. 2021, 50, 8214-8247; Liu, G.-K. et al. Pharmaceuticals 2022, 15, 1552.).

[0003] Given the significant applications of difluoromethyl groups in medicinal chemistry and materials science, researchers are dedicated to developing radical fluoroalkylation reactions as a mild and modular platform to accommodate diverse late-stage modifications of complex skeletons. Visible light photoredox catalysis and transition metal catalysis have enabled the hydrofluoroalkylation and dehydrodifluoroalkylation of terpenoids, while the recently emerging allyl fluoroalkylation reaction has enabled the efficient conversion of simple olefin precursors into single-site fluoroalkylation analogs (Lei, A. et al. Nat. Synth. 2023, 2, 1202-1210; Xie, J. et al. Angew.Chem. Int. Ed. 2023, 62, e202310762; Zhang, X. et al. ACS Catal. 2019, 9, 8224-8229.). However, techniques for systematically introducing multiple difluoroalkyl units within a single carbon skeleton have not yet been reported.

[0004] In the process of realizing this invention, the inventors discovered that a key challenge of polydifluoroalkylation reaction is that after the first difluoroalkylation, the newly formed CF2 substituent fragment has both steric hindrance and strong electron attraction, which significantly reduces the activity of the residual olefin or allyl CH bond for subsequent free radical reactions. Therefore, when performing iterative difluoroalkylation, problems such as slow reaction, loss of selectivity, excessive reduction or breakage, and rapid accumulation of byproducts are usually encountered. Developing a method for efficiently preparing polydifluoroalkylation of terpenoids is of great significance for new drug development. Summary of the Invention

[0005] The technical problem to be solved by this invention is to address the shortcomings of the prior art by providing a polydifluoroalkylated derivative of terpenoids and a method for its preparation. The method of this invention can achieve the polydifluoroalkylation reaction of terpenoids with high efficiency, high selectivity, and high yield. This method does not require the use of expensive metal catalysts, has good functional group compatibility, uses inexpensive and readily available reactants, and achieves high yield.

[0006] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0007] On the one hand, a method for preparing polydifluoroalkylated derivatives of terpenoids is provided, comprising: under inert gas protection, sequentially loading terpenoids, photosensitizers, cobalt catalysts, organic reducing agents, bases, fluorine reagents and organic solvents into a reaction vessel to obtain a reaction system; under inert gas protection, reacting the reaction system at 40-60 °C under light irradiation; and purifying the reaction system by filtration, rotary evaporation and chromatography to complete the polydifluoroalkylation of terpenoids.

[0008] On the other hand, a method for preparing polydifluoroalkylated derivatives of terpenoid olefins using the above method is provided.

[0009] Compared with the prior art, the present invention has the following advantages:

[0010] 1. The method of the present invention can realize the polydifluoroalkylation reaction of terpenoids with high efficiency, high selectivity and high yield, without the need for precious metal catalysts, with good functional group compatibility, and high yield, with a maximum yield of up to 93%.

[0011] 2. The method of the present invention uses inexpensive and readily available raw materials, operates under mild conditions, and has simple and environmentally friendly post-processing, thus having a broad market prospect.

[0012] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0013] Figure 1 For the target product of Example 30 1 H NMR spectrum; Figure 2For the target product of Example 30 13 C NMR spectrum; Figure 3 For the target product of Example 30 19 F NMR spectrum. Detailed Implementation

[0014] The technical solution will now be clearly and completely described with reference to the embodiments of this application. Obviously, the described embodiments are only a part of the embodiments of this application, not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.

[0015] In the following description, the term "and / or" is used to describe the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can mean: A exists alone, B exists alone, and A and B exist simultaneously. A and B can be singular or plural. The terms "including," "containing," "having," and "containing" are all open-ended terms, meaning they include but are not limited to.

[0016] Those skilled in the art should understand that in the following description of the embodiments of this application, the sequence of numbers does not imply the order of execution. Some or all steps may be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of this application. Those skilled in the art should understand that the numerical range in the embodiments of this application should be understood to specifically disclose each intermediate value between the upper and lower limits of the range. Each smaller range between any stated value or intermediate value within a stated range, as well as any other stated value or intermediate value within said range, is also included in this application. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0017] Unless otherwise stated, the technical / scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains. While this application describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this application. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0018] The reaction principle upon which this invention is based is an iterative addition-elimination reaction catalyzed by photo / cobalt, providing a method for preparing polydifluoroalkylated derivatives of terpenoids. This method utilizes continuous free radical addition and elimination under photo / cobalt catalysis to achieve polydifluoroalkylation of terpenoids.

[0019] On the one hand, a method for preparing polydifluoroalkylated derivatives of terpenoids is provided, comprising: under inert gas protection, sequentially loading terpenoids, photosensitizers, cobalt catalysts, organic reducing agents, bases, fluorine reagents and organic solvents into a reaction vessel to obtain a reaction system; under inert gas protection, reacting the reaction system at 40-60 °C under light irradiation; and purifying the reaction system by filtration, rotary evaporation and chromatography to complete the polydifluoroalkylation of terpenoids.

[0020] In some embodiments, the reaction pathway of the method is as follows:

[0021]

[0022] The structural formulas of the terpene olefins are shown in (1) to (4), and the structural formulas of the polydifluoroalkylated derivatives of the terpene olefins are shown in (5) to (7); in some embodiments, when the structural formula of the terpene olefin is (1), the structural formula of the polydifluoroalkylated derivative of the terpene olefin is (5); when the structural formula of the terpene olefin is (2), the structural formula of the polydifluoroalkylated derivative of the terpene olefin is (6); when the structural formula of the terpene olefin is (3) and / or (4), the structural formula of the polydifluoroalkylated derivative of the terpene olefin is (7); R 1 ~R 5 Each is independently selected from hydrogen, halogen, alkyl, alcohol, thiol, alkoxy, ester, acyl, alkenyl, alkynyl, aryl, substituted aryl, fused ring, fused ring, or heterocyclic; the fluorine reagent is selected from fluoroalkanes, fluoroaromatics, selective fluorine reagents, N-fluorobis(benzenesulfonamide), 1-fluoro-4-hydroxy-1,4-diazotized bicyclo2,2,2-octanebis(tetrafluoroborate), pyridine hydrofluoride, triethylamine trihydrofluoride, metal fluorides, fluorinated aldehydes, fluorinated ketones, fluorinated acids, fluorinated esters, fluorinated alkenes, fluorinated alkynes, and Um Emoto reagent, Togni reagent, or Chen Qingyun reagent; the number of fluorine atoms in the fluoroalkane or fluoroaromatic hydrocarbon is ≥1; the selective fluorine reagent is 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate) salt; more preferably, when the terpene olefin polydifluoroalkylation derivative is a terpene olefin bisdifluoroalkylation derivative, the fluorine reagent is BrCF2CO2Et, BrCFHCO2Et, BrCF2PO(OEt)2, or BrCF2COR 6 The BrCF2COR 6 This includes the fluorine reagent described in any of the following Examples 13-29; when the terpene olefin polydifluoroalkylation derivative is a terpene olefin tridifluoroalkylation derivative, the fluorine reagent is ethyl bromodifluoroalkylate. Preferably, when the fluorine reagent is the aforementioned ethyl bromodifluoroalkylate, the activity of the fluorine reagent can be fully utilized, the influence of steric hindrance can be reduced, and tridifluoroalkylation can be achieved.

[0023] In some embodiments, the molar ratio of terpene olefin to fluorine reagent is 1:5 to 1:10. When the molar ratio of terpene olefin to fluorine reagent is 1:5 to 1:10, the yield of the polyfluoroalkylated terpene olefin derivative is higher, it is easier to separate and purify, and it has the characteristics of low cost and environmental friendliness.

[0024] In some embodiments, the volume of organic solvent corresponding to each millimole of fluorine reagent is 1 to 2 mL. The preparation of polydifluoroalkylated derivatives can be achieved with only 1 to 2 mL of organic solvent per millimole of fluorine reagent, resulting in low organic solvent consumption and low cost.

[0025] In some embodiments, the photosensitizer is one or more of Acid Red 87, Rhodamine 6G, and Eosin B; the cobalt catalyst is one or more of cobalt chloride, cobalt bromide, cobalt(II) chloride, and cobalt(II) bromide; the organic reducing agent is one or more of triethylamine, N,N-diisopropylethylamine, and ethylenediamine; the base is an inorganic base, specifically one or more of potassium fluoride, lithium carbonate, sodium bicarbonate, and cesium carbonate; and the organic solvent is carbon tetrachloride, tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, chloroform, toluene, xylene, cyclohexane, n-hexane, n-heptane, dioxane, or acetonitrile. In the reaction system of this invention, the base is an inorganic base. Based on the compatibility of functional groups in the reaction, it is preferred that the inorganic base be one or more of potassium fluoride, lithium carbonate, sodium bicarbonate, and cesium carbonate, which can effectively avoid the influence of strong bases or organic bases on the stability of the functional groups.

[0026] In some embodiments, when the structural formula of the terpene olefin is (1) and the structural formula of the polyfluoroalkylated derivative of the terpene olefin is (5), or when the structural formula of the terpene olefin is (2) and the structural formula of the polyfluoroalkylated derivative of the terpene olefin is (6), the photosensitizer is eosin B, the cobalt catalyst is cobalt chloride, the organic reducing agent is triethylamine, and the base is potassium fluoride; the molar ratio of the terpene olefin, fluorine reagent, photosensitizer, cobalt catalyst, organic reducing agent, and base is 50:250:1:5:100:200; the reaction time under the light condition is 12 h; the reaction diagram is as follows:

[0027] When preparing terpenoid bis(difluoroalkylation) derivatives from terpenoids with structural formulas (1) or (2), the preferred molar ratio of terpenoid, fluorine reagent, photosensitizer, cobalt catalyst, organic reducing agent and base is 50:250:1:5:100:200, which allows the raw materials to react fully and the yield to be high.

[0028] In some embodiments, when the structural formula of the terpene olefin is (3) or (4), and the structural formula of the polyfluoroalkylated derivative of the terpene olefin is (7), the photosensitizer is eosin B, the cobalt catalyst is cobalt dichloride, the organic reducing agent is triethylamine, and the base is potassium fluoride; the molar ratio of the terpene olefin, fluorine reagent, photosensitizer, cobalt catalyst, organic reducing agent and base is 50:500:2.5:10:200:300; and the reaction time under the light conditions is 30 h.

[0029]

[0030] When preparing trifluoroalkylated derivatives of terpenoids from terpenoids with structural formulas (3) or (4), the preferred molar ratio of terpenoid, fluorine reagent, photosensitizer, cobalt catalyst, organic reducing agent and base is 50:500:2.5:10:200:300, which allows the raw materials to react fully and the yield to be high.

[0031] In some embodiments, the chromatographic purification includes thin-layer chromatography or column chromatography, wherein the developing solvent in the chromatographic purification is a mixture of a nonpolar solvent and a polar solvent, wherein the nonpolar solvent is petroleum ether and the polar solvent is ethyl acetate, and the volume ratio of the nonpolar solvent to the polar solvent in the developing solvent is 10:1 to 1:1.

[0032] In some embodiments, the illumination is blue light or violet light, the reaction time under illumination is 12 to 30 hours, and the reaction under illumination is a stirring reaction.

[0033] On the other hand, a polydifluoroalkylated derivative of a terpene olefin prepared by the above method is provided.

[0034] Prior to this application, a series of experiments were conducted. Some of the experimental results are listed below to provide a more detailed description of the invention. The following is a detailed description in conjunction with the embodiments.

[0035] Example 1

[0036] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, and the reaction route is as follows:

[0037]

[0038] The preparation method is as follows: In a 25 mL dry, single-necked, round-bottomed sealed tube equipped with a stirrer, under nitrogen atmosphere, terpenoid olefins (0.2 mmol, 38.0 mg), eosin B (0.004 mmol, 2.5 mg), cobalt dichloride (0.02 mmol, 2.6 mg), triethylamine (0.4 mmol, 40.5 mg), potassium fluoride (0.8 mmol, 46.5 mg), a halofluorinated reagent (1.0 mmol, 203.0 mg), and 2.0 mL of dichloromethane were added as solvent to obtain the reaction system. The eosin B was purchased from Bid Pharmaceuticals, catalog number BD01414312-5g, batch number CLL132. The reaction temperature was 50 °C under a nitrogen atmosphere. o C. Stir and continuously irradiate the reaction system with light at a wavelength of 365 nm for 12 hours to obtain the reaction system; filter the reaction system, remove the organic solvent by rotary evaporation, purify by column chromatography with petroleum ether / ethyl acetate = 10:1 as the developing solvent to obtain the target product;

[0039] The target product is a colorless oily liquid, 48.6 mg (56% yield). The characterization of this compound is as follows: 1 HNMR (500 MHz, Chloroform-d) δ 8.09-7.97 (m, 2H), 7.61-7.52 (m, 1H), 7.47-7.41(m, 2H), 5.97 (t, J = 6.8 Hz, 1H), 4.86 (d, J = 6.8 Hz, 2H), 4.34 (q, J = 7.1Hz, 2H), 4.25 (q, J = 7.2 Hz, 2H), 3.11 (t, J = 17.4 Hz, 2H), 2.98 (t, J =16.1 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 166.2, 163.6 (t, J CF = 32.4 Hz), 163.5 (t, J CF =32.4 Hz), 133.4, 133.1, 129.8, 129.6 (2C), 128.4 (2C), 125.4, 115.5 (t, J CF =252.9 Hz), 115.1 (t, J CF= 252.6 Hz), 63.3, 63.0, 60.9, 41.9 (t, J CF = 23.2Hz), 35.5 (t, J CF = 23.1 Hz), 13.90, 13.88 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -103.6, -104.2 ppm. HRMS (EI): calc.for C 20 H 22 F4O6 (M) + , 434.1353, found,434.1354.

[0040] Table 1 Summary of raw materials (terpenoid olefins) for Examples 1-12

[0041]

[0042] Example 2

[0043] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0044]

[0045] The target product is a yellow oily liquid, 27.8 mg (30% yield). The characterization of this compound is as follows: 1 HNMR (500 MHz, Chloroform-d) δ 7.43-7.29 (m, 5H), 5.75 (t, J = 6.8 Hz, 1H), 5.16 (d, J = 5.5 Hz, 1H), 4.77-4.59 (m, 2H), 4.29 (q, J = 7.1 Hz, 2H), 4.23(q, J = 7.1 Hz, 2H), 3.47 (d, J = 5.8 Hz, 1H), 2.97 (t, J = 17.2 Hz, 2H), 2.90 (t, J = 16.3 Hz, 2H), 1.33 (t, J = 7.1 Hz, 3H), 1.29 (t, J = 7.1 Hz, 3H)ppm. 13 C NMR (126 MHz, Chloroform-d) δ 173.2, 163.44 (t, J CF= 32.4 Hz), 163.36 (t, J CF = 32.3 Hz), 138.0, 132.3, 128.6 (2C), 128.5, 126.5 (2C), 126.1,115.3 (t, J CF = 253.0 Hz), 114.9 (t, J CF = 252.7 Hz), 72.9, 63.3, 63.0, 61.8,41.7 (t, J CF = 23.1 Hz), 35.4 (t, J CF = 23.4 Hz), 13.84, 13.81 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -103.9 (d, J = 17.3 Hz), -104.2 ppm. HRMS (EI):calc.for C 21 H 24 F4O7(M) + , 464.1458, found, 464.1454.

[0046] Example 3

[0047] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0048]

[0049] The target product is a yellow oily liquid, 54.0 mg (40% yield). The characterization of this compound is as follows: 1 HNMR (500 MHz, Chloroform-d) δ 7.66 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.1 Hz, 2H), 6.96-6.85 (m, 2H), 6.70-6.63 (m, 1H), 5.82 (t, J = 6.8 Hz, 1H), 4.63 (d,J = 6.8 Hz, 2H), 4.33-4.28 (m, 2H), 4.26-4.20 (m, 2H), 3.83 (s, 3H), 3.66 (s,2H), 3.01 (t, J = 17.4 Hz, 2H), 2.92 (t, J = 16.3 Hz, 2H), 2.36 (s, 3H), 1.33 (t, J = 6.9 Hz, 3H), 1.29 (t, J = 7.3 Hz, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 170.4, 168.3, 163.5 (t, J CF = 32.5 Hz), 163.4 (t, J CF = 32.6Hz), 156.1, 139.2, 136.0, 133.9, 133.1, 131.1 (2C), 130.8, 130.5, 129.1 (2C),125.4, 115.3 (t, J CF = 253.3 Hz), 115.0 (t, J CF = 253.3 Hz), 114.95, 112.2,111.7, 101.1. 63.2, 63.0, 60.9, 55.7, 41.7 (t, J CF = 23.3 Hz), 35.5 (t, J CF =23.0 Hz), 30.1, 13.9 (2C), 13.3 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -104.1,-104.3 ppm. HRMS (EI): calc.for C 32 H 32 ClF4NO8(M) + , 669.1753, found, 669.1751.

[0050] Example 4

[0051] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0052]

[0053] The target product is a pale yellow oily liquid, 49.2 mg (41% yield). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 7.66-7.59 (m, 2H), 7.59-7.53 (m, 2H), 7.41-7.27 (m, 6H), 5.85 (t, J = 6.7 Hz, 1H), 4.67 (d, J = 6.8 Hz, 2H), 4.36-4.25(m, 4H), 3.18 (t, J = 7.5 Hz, 2H), 3.02 (t, J = 17.3 Hz, 2H), 2.96-2.86 (m,4H), 1.38-1.31 (m, 6H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 171.6, 163.54(t, J CF = 32.3 Hz), 163.47 (t, J CF = 32.3 Hz), 161.5, 145.5, 135.1, 133.3,132.4, 128.9, 128.6 (2C), 128.52 (2C), 128.46, 128.1, 127.9 (2C), 126.5 (2C),125.2, 115.4 (t,J CF = 252.8 Hz), 115.0 (t, J CF = 252.6 Hz), 63.2, 63.0, 60.8,41.8 (t, J CF = 23.3 Hz), 35.5 (t, J CF = 23.1 Hz), 30.9, 23.4, 13.91, 13.87ppm. 19 F NMR (471 MHz, Chloroform-d) δ -103.8, -104.1 ppm. HRMS (EI): calc.forC 31 H 31 F4NO7(M) + , 605.2037, found, 605.2034.

[0054] Example 5

[0055] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0056]

[0057] The target product is a pale yellow oily liquid, 48.0 mg (38% yield). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 8.17 (d, J = 2.3 Hz, 1H), 8.08 (dd, J = 8.9,2.3 Hz, 1H), 7.01 (d, J = 8.9 Hz, 1H), 5.94 (t, J = 6.8 Hz, 1H), 4.82 (d, J =6.8 Hz, 2H), 4.35 (q, J = 7.2 Hz, 2H), 4.29 (q, J = 7.1 Hz, 2H), 3.90 (d, J =6.4 Hz, 2H), 3.09 (t, J = 17.4 Hz, 2H), 2.97 (t, J = 16.2 Hz, 2H), 2.75 (s, 3H), 2.25 –2.15 (m, 1H), 1.37 (t, J = 7.2 Hz, 3H), 1.32 (t, J = 7.1 Hz, 3H), 1.09 (d, J = 6.7 Hz, 6H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 167.5, 163.54(t, J CF = 32.8 Hz), 163.45 (t, J CF = 32.8 Hz), 162.6, 161.7, 161.6, 132.9,132.6, 132.1, 125.9, 125.8, 121.0, 115.4 (t, J CF = 253.0 Hz), 115.3, 115.0 (t,J CF = 252.6 Hz), 112.6, 103.0, 75.7, 63.3, 63.1, 61.1, 41.9 (t, J CF = 23.2Hz), 35.5 (t, J CF = 23.7 Hz), 28.1, 19.0 (2C), 17.5, 13.94, 13.91 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -103.8, -104.2 ppm. HRMS (EI): calc.for C29 H 32 F4N2O7S (M) + , 628.1866, found, 628.1878.

[0058] Example 6

[0059] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0060]

[0061] The target product is a colorless oily liquid, 56.4 mg (53% yield). The characterization of this compound is as follows: 1 HNMR (500 MHz, Chloroform-d) δ 7.38 (s, 1H), 7.20-7.12 (m, 1H), 6.76 (d, J =8.7 Hz, 1H), 5.84 (t, J = 6.9 Hz, 1H), 4.72 (d, J = 6.9 Hz, 2H), 4.68 (s, 2H), 4.35-4.26 (m, 4H), 3.03 (t, J = 17.4 Hz, 2H), 2.93 (t, J = 16.2 Hz, 2H), 1.38-1.29 (m, 6H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 167.8, 163.5 (t, J CF = 32.4 Hz), 163.4 (t, J CF = 32.4 Hz), 152.3, 132.2, 130.3, 127.6, 127.2,126.4, 124.1, 115.3 (t, J CF = 252.9 Hz), 114.9 (t, J CF = 252.6 Hz), 114.8,66.2, 63.3, 63.1, 61.1, 41.8 (t, J CF = 23.2 Hz), 35.5 (t, J CF = 23.4 Hz), 13.88, 13.86 ppm. 19F NMR (471 MHz, Chloroform-d) δ -103.9, -104.4 ppm. HRMS(EI): calc.for C 21 H 22 Cl2F4O7 (M) + , 532.0679, found, 532.0678.

[0062] Example 7

[0063] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0064]

[0065] The target product is a colorless oily liquid, 40.0 mg (32% yield). The characterization of this compound is as follows: 1 HNMR (500 MHz, Chloroform-d) δ 7.76-7.68 (m, 2H), 7.70 (d, J = 8.2 Hz, 2H), 7.44 (d, J = 8.1 Hz, 2H), 6.83 (d, J = 8.3 Hz, 2H), 5.78 (t, J = 6.9 Hz, 1H), 4.70 (d, J = 6.9 Hz, 2H), 4.35-4.23 (m, 4H), 3.03 (t, J = 17.4 Hz, 2H), 2.91 (t, J = 16.6 Hz, 2H), 1.66 (s, 6H), 1.37-1.28 (m, 6H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 194.2, 173.4, 163.5 (t, J CF = 32.3 Hz), 163.4 (t, J CF = 32.3Hz), 159.4, 138.3, 136.3, 132.4, 132.0 (2C), 131.2 (2C), 130.5, 128.5 (2C),126.1, 117.3 (2C), 115.1 (t, J CF = 252.7 Hz), 115.0 (t, J CF= 252.7 Hz), 79.2,63.3, 63.1, 61.5, 41.7 (t, J CF = 23.1 Hz), 35.6 (t, J CF = 23.3 Hz), 25.3 (2C),13.9-13.8 (m, 2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -104.4, -104.5 ppm.HRMS (EI): calc.for C 30 H 31 ClF4O8 (M) + , 630.1644, found, 630.1640.

[0066] Example 8

[0067] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0068]

[0069] The target product is a yellow oily liquid, 38.2 mg (48% yield). The characterization of this compound is as follows: 1 HNMR (500 MHz, Chloroform-d) δ 5.39-5.14 (m, 2H), 4.35-4.23 (m, 4H), 3.72-3.55(m, 2H), 2.94-2.76 (m, 3H), 1.85-1.65 (m, 2H), 1.65-1.59 (m, 1H), 1.56-1.48(m, 2H), 1.42-1.29 (m, 8H), 1.20-1.03 (m, 1H), 0.88 (t, J = 6.3 Hz, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 163.8 (t, J CF = 32.3 Hz), 163.7 (t, J CF =32.3 Hz), 134.2-133.8 (m), 121.44, 121.40, 116.5 (t, J CF = 255.5 Hz), 115.3(t, J CF= 251.7 Hz), 63.0, 62.9, 60.74, 60.72, 50.4 (t, J CF = 21.3 Hz), 50.1(t, J CF = 21.2 Hz), 39.7, 39.3, 39.24 (t, J CF = 23.5 Hz), 39.20 (t, J CF = 23.3Hz), 33.9, 33.7, 29.5, 29.1, 23.8 (t, J CF = 3.2 Hz), 23.6 (t, J CF = 3.4 Hz),19.5, 19.1, 13.8 (2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -102.2 (dd, J =262.8, 12.9 Hz), -104.2 (dd, J = 262.8, 16.1 Hz), -108.5 (dd, J = 255.7,145.3 Hz), -109.9 (dd, J = 255.7, 103.1 Hz) ppm. HRMS (EI): calc.for C 18 H 28 F4O5(M) + , 400.1873, found, 400.1861.

[0070] Example 9

[0071] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0072]

[0073] The target product is a yellow oily liquid, 111.0 mg (81% yield, Z:E = 2.6:1.0). The compound is characterized as follows: 1H NMR (500 MHz, Chloroform-d) δ 5.63-5.46 (t, J = 13.5 Hz, 1H),4.39-4.20 (m, 4H), 3.76 (d, J = 10.7 Hz, 1H), 3.32 (d, J = 10.8 Hz, 1H), 3.18(dd, J = 11.4, 4.6 Hz, 1H), 3.04-2.94 (m, 1H), 2.91-2.78 (m, 2H), 2.01-1.84(m, 3H), 1.73-1.57 (m, 5H), 1.57-1.39 (m, 8H), 1.36-1.31(m, 6H), 1.29-1.16(m, 4H), 1.10-0.98 (m, 6H), 0.98-0.85 (m, 8H), 0.81 (s, 3H), 0.75 (s, 3H),0.67 (d, J = 9.3 Hz, 1H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 164.1 (t, J CF = 35.0 Hz), 163.3 (t, J CF = 32.0 Hz), 148.4-147.9 (m), 119.7 (t, J CF = 27.8Hz), 115.2 (t, J CF = 250.0 Hz), 112.3 (t, J CF = 248.4 Hz), 78.9, 63.2, 63.1,60.3, 55.2, 50.3, 49.4, 47.6, 42.7, 41.9, 40.9, 38.8, 38.7, 37.13, 37.09,36.3 (t, J CF = 24.3 Hz), 34.1, 33.9, 29.1, 28.0, 27.9, 27.3, 26.9, 25.0, 20.8,18.2, 16.1, 15.9, 15.3, 14.8, 13.9, 13.8 ppm. 19F NMR (471 MHz, Chloroform-d)δ -96.0 (d, J = 262.0 Hz), -97.1 (d, J = 262.6 Hz), -98.2 (d, J = 265.8 Hz), -102.0 (d, J = 265.8 Hz) ppm. HRMS (ESI): calc. for C 38 H 58 F4O6Na + (M+Na) + ,709.4062, found, 709.4063.

[0074] Example 10

[0075] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0076]

[0077] The target product is a yellow oily liquid, 66.4 mg (83% yield, Z:E = 2.7:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 5.85-5.66 (m, 1H), 4.36-4.18(m, 4H), 3.53-3.40 (m, 1H), 3.25-2.80 (m, 2H), 2.69-2.56 (m, 1H), 2.12-1.74(m, 3H), 1.68-1.59 (m, 1H), 1.55-1.38 (m, 2H), 1.34-1.27 (m, 6H), 1.02-0.85(m, 5H) ppm. 13 C NMR (126 MHz, CDCl3) δ 164.3 (t, J CF = 34.3 Hz), 163.7 (t, J CF = 34.7 Hz), 163.6 (t, J CF = 32.1 Hz), 163.5 (t, J CF = 32.3 Hz), 146.8-145.1(m), 124.3-123.6 (m), 121.9 (t, J CF= 26.0 Hz), 119.0-110.0 (m, 2C), 74.1,70.1, 63.2 (2C), 63.1 (2C), 52.4, 48.7, 43.8, 43.7, 37.7 (t, J CF = 23.4 Hz), 35.2 (t, J CF = 24.0 Hz), 34.2, 33.5, 31.4, 31.3, 31.2, 28.8, 21.9, 13.7 (2C)ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.3--101.9 (m) ppm. HRMS (EI):calc.for C 18 H 26 F4O5 (M) + , 398.1716, found, 398.1701.

[0078] Example 11

[0079] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0080]

[0081] The target product is a yellow oily liquid, 54.0 mg (68% yield, Z:E = 2.0:1.0). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 5.77-5.62 (m, 1H), 4.38-4.27(m, 4H), 3.29-3.16 (m, 1H), 2.90 (t, J = 16.5 Hz, 2H), 2.43-2.27 (m, 2H),2.26-2.19 (m, 1H), 2.15-2.07 (m, 1H), 1.77-1.66 (m, 2H), 1.48-1.39 (m, 1H),1.38-1.29 (m, 6H), 1.03 (d, J = 6.5 Hz, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 210.0, 163.6 (t, J CF = 34.6 Hz), 163.4 (t, JCF = 32.1 Hz), 144.3-143.9(m), 123.1 (t, J CF = 27.3 Hz), 114.8 (t, J CF = 252.9 Hz), 111.9 (t, J CF = 249.2Hz), 63.4, 63.3, 44.71, 44.67, 41.8, 35.4 (t, J CF = 24.2 Hz), 34.1, 29.4,14.2, 13.9, 13.8 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -97.2 (d, J = 35.5Hz), -101.6 (d, J = 13.0 Hz) ppm. HRMS (EI): calc.for C 18 H 24 F4O5(M) + , 396.1560,found, 396.1555.

[0082] Example 12

[0083] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 1, except that the terpenoid olefin is different. As shown in Table 1, the structural formula of the target product is as follows:

[0084]

[0085] The target product is a yellow oily liquid, 53.8 mg (58% yield, Z:E = 1.9:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 5.79-5.64 (m, 2H), 4.40-4.24(m, 4H), 3.35-3.23 (m, 1H), 2.87-2.75 (m, 2H), 2.58-2.47 (m, 1H), 2.42-2.32(m, 1H), 2.32-2.18 (m, 2H), 2.05-1.94 (m, 1H), 1.78-1.66 (m, 2H), 1.49-1.37(m, 1H), 1.37-1.31 (m, 6H), 1.24-1.08 (m, 4H), 0.98-0.90 (m, 3H) ppm. 13C NMR (126 MHz, CDCl3) δ 199.2, 168.6, 163.9 (t, J CF = 34.7 Hz), 163.4 (t, J CF = 32.1Hz), 146.6-146.0 (m), 125.1, 122.6 (t, J CF = 27.2 Hz), 114.8 (t, J CF = 252.8Hz), 112.2 (t, J CF = 248.9 Hz), 63.21, 63.20, 42.04, 41.96, 40.4, 39.3, 36.0,35.2 (t, J CF = 24.1 Hz), 32.2, 29.8, 16.5, 14.8, 13.87, 13.85 ppm. 19 F NMR (471MHz, Chloroform-d) δ -97.1 (d, J = 82.6 Hz), -101.8 ppm. HRMS (EI): calc.forC 23 H 30 F4O5 (M) + , 462.2029, found, 462.2027.

[0086] Example 13

[0087] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, and the reaction route is as follows:

[0088]

[0089] The preparation method is as follows: In a 25 mL sealed tube equipped with a stir bar and a dry single-necked round-bottom opening, under nitrogen atmosphere, terpenoid olefins (0.2 mmol, 30.9 mg), eosin B (0.004 mmol, 2.5 mg), cobalt dichloride (0.02 mmol, 2.6 mg), triethylamine (0.4 mmol, 40.5 mg), potassium fluoride (0.8 mmol, 46.5 mg), a halofluorinated reagent (1.0 mmol, 202.0 mg), and 2.0 mL of dichloromethane were added as solvent to obtain the reaction system. The eosin B was purchased from Bid Pharmaceuticals, catalog number BD01414312-5g, batch number CLL132. The reaction temperature was 50 °C under a nitrogen atmosphere. oC. Stir and continuously irradiate the reaction system with light at a wavelength of 365 nm for 12 hours to obtain the reaction system; filter the reaction system, remove the organic solvent by rotary evaporation, purify by column chromatography with petroleum ether / ethyl acetate = 3:1 as the developing solvent to obtain the target product;

[0090] The target product is a yellow oily liquid, 72.6 mg (92% yield, Z:E = 1.9:1.0). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.18-6.79 (m, 2H), 5.90-5.50(m, 1H), 3.58-3.44 (m, 1H), 3.37-3.22 (m, 4H), 3.21-2.72 (m, 3H), 2.41 (s,1H), 2.14-1.74 (m, 2H), 1.67-1.50 (m, 2H), 1.50-1.39 (m, 1H), 1.38-1.28 (m,1H), 1.18-1.10 (m, 6H), 1.02-0.95 (m, 1H), 0.92-0.87 (m, 3H) ppm. 13 C NMR (126MHz, Chloroform-d) δ 164.4-163.1 (m, 2C), 146.3-145.6 (m), 123.5 (dd, J CF =31.7, 23.4 Hz), 121.7 (t, J CF = 25.6 Hz), 119.5-111.7 (m, 2C), 73.0, 70.2,52.4, 48.8, 44.0, 43.7, 37.4 (t, J CF = 24.3 Hz), 34.9-34.4 (m, 2C), 34.3,33.5, 31.7, 31.4, 31.3, 28.9, 22.0, 21.9, 14.2-13.9 (m, 2C) ppm. 19 F NMR (471MHz, Chloroform-d) δ -93.5--102.2 (m) ppm. HRMS (ESI): calc. for C 18 H 28 F4N2O3Na + (M+Na) + , 419.1928, found, 419.1931.

[0091] Table 2 Summary of raw materials (fluorine reagents) for Examples 14-29

[0092]

[0093] Example 14

[0094] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0095]

[0096] The target product is a yellow oily liquid, 81.5 mg (90% yield, Z:E = 1.4:1.0). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.13-6.77 (m, 2H), 5.83-5.55(m, 1H), 3.58-3.46 (m, 1H), 3.33-3.14 (m, 4H), 3.08-2.73 (m, 3H), 2.63-2.32(m, 1H), 2.09-1.76 (m, 2H), 1.66-1.59 (m, 1H), 1.58-1.51 (m, 1H), 1.51-1.43(m, 4H), 1.36-1.26 (m, 5H), 1.21-1.06 (m, 1H), 1.02-0.94 (m, 1H), 0.92-0.82 (m, 9H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 164.13 (t, J CF = 30.9 Hz), 164.09 (t, J CF = 30.6 Hz), 163.74 (t, J CF = 28.4 Hz), 163.69 (t, J CF = 28.2Hz), 146.3-145.5 (m), 123.4 (dd, J CF = 31.6, 22.8 Hz), 121.7 (t, J CF= 25.6Hz), 119.6-111.7 (m, 2C), 73.1, 70.2, 52.5, 48.8, 44.0, 43.7, 39.8-39.0 (m,2C), 37.4 (t, J CF = 24.0 Hz), 34.7 (t, J CF = 23.3 Hz), 34.3, 33.5, 31.7, 31.4,31.3, 31.0-30.7 (m, 2C), 28.8, 21.94, 21.90, 20.0-19.6 (m, 2C), 13.7-13.3 (m, 2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -93.4--102.0 (m) ppm. HRMS (ESI):calc. for C 22 H 36 F4N2O3Na + (M+Na) + , 475.2554, found, 475.2556.

[0097] Example 15

[0098] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0099]

[0100] The target product is a yellow oily liquid, 86.5 mg (90% yield, Z:E = 1.7:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.06-6.77 (m, 2H), 5.83-5.55(m, 1H), 3.58-3.46 (m, 1H), 3.30-3.13 (m, 4H), 3.08-2.71 (m, 3H), 2.08-1.76(m, 2H), 1.67-1.59 (m, 1H), 1.58-1.39 (m, 6H), 1.34-1.21 (m, 9H), 1.18-1.06(m, 1H), 1.01-0.94 (m, 1H), 0.91-0.87 (m, 3H), 0.87-0.82 (m, 6H) ppm. 13C NMR (126 MHz, Chloroform-d) δ 164.09 (t, J CF = 31.0 Hz), 164.05 (t, J CF = 30.5Hz), 163.71 (t, J CF = 28.4 Hz), 163.66 (t, J CF = 28.2 Hz), 146.3-145.5 (m), 123.4 (dd, J CF = 31.7, 22.9 Hz), 121.7 (t, J CF = 25.4 Hz), 119.6-111.7 (m,2C), 73.1, 70.2, 52.5, 48.8, 44.0, 43.7, 40.0-39.3 (m, 2C), 37.4 (t, J CF =24.2 Hz), 34.7 (t, J CF = 23.8 Hz), 34.3, 33.5, 31.7, 31.4, 31.3, 28.83, 28.81-28.7 (m, 2C), 28.6-28.4 (m, 2C), 22.2-22.0 (m, 2C), 21.93, 21.89, 13.9-13.7(m, 2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -93.4--102.0 (m) ppm. HRMS(ESI): calc. for C 24 H 40 F4N2O3Na + (M+Na) + , 503.2867, found, 503.2871.

[0101] Example 16

[0102] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0103]

[0104] The target product is a yellow oily liquid, 85.5 mg (89% yield, Z:E = 1.6:1.0). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 7.20-6.83 (m, 2H), 5.82-5.51(m, 1H), 3.57-3.42 (m, 1H), 3.31-3.14 (m, 4H), 3.08-2.66 (m, 3H), 2.09-1.71(m, 2H), 1.64-1.48 (m, 4H), 1.48-1.29 (m, 6H), 1.25-1.03 (m, 1H), 0.99-0.91(m, 1H), 0.88-0.82 (m, 15H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 164.03 (t,J CF = 31.0 Hz), 164.01 (t, J CF = 30.2 Hz), 163.7 (t, J CF = 28.5 Hz), 163.6 (t,J CF = 28.2 Hz), 146.3-145.3 (m), 123.4 (dd, J CF = 31.6, 23.1 Hz), 121.7 (t, J CF = 25.6 Hz), 119.6-111.5 (m, 2C), 73.1, 70.1, 52.4, 48.7, 44.0, 43.6, 38.2-37.8 (m, 2C), 37.7-37.5 (m, 2C), 37.4 (t, J CF = 24.2 Hz), 34.6 (t, J CF = 25.0Hz), 34.2, 33.5, 31.6, 31.34, 31.25, 28.8, 25.8-25.4 (m, 2C), 22.3-22.0 (m,4C), 21.89, 21.86 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -93.3--102.1 (m) ppm.HRMS (ESI): calc. for C 24 H 40 F4N2O3Na + (M+Na) + , 503.2867, found, 503.2870。

[0105] Example 17

[0106] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0107]

[0108] The target product is a yellow oily liquid, 86.5 mg (79% yield, Z:E = 1.6:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.33-7.27 (m, 4H), 7.25-7.20(m, 2H), 7.20-7.13 (m, 4H), 7.03-6.75 (m, 2H), 5.81-5.59 (m, 1H), 3.60-3.43(m, 5H), 3.30-3.15 (m, 1H), 3.07-2.87 (m, 2H), 2.85-2.80 (m, 4H), 2.09-1.78(m, 2H), 1.73-1.54 (m, 2H), 1.52-1.42 (m, 1H), 1.38-1.24 (m, 1H), 1.21-1.08(m, 1H), 1.03-0.96 (m, 1H), 0.95-0.90 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 164.2 (t, J CF = 30.8 Hz), 164.0 (t, J CF = 30.7 Hz), 163.71 (t,J CF = 28.2 Hz), 163.65 (t, J CF = 28.5 Hz), 146.5-145.7 (m), 138.3-137.8 (m,2C), 129.0-128.2 (m, 8C), 126.8-126.4 (m, 2C), 123.3 (dd, J CF = 31.8, 22.7Hz), 121.6 (t, J CF= 25.4 Hz), 119.5-111.7 (m, 2C), 73.1, 70.2, 52.4, 48.8,44.1, 43.7, 41.1-40.4 (m, 2C), 37.4 (t, J CF = 24.2 Hz), 35.2-34.9 (m, 2C), 34.6 (t, J CF = 24.4 Hz), 34.3, 33.5, 31.7, 31.4, 31.3, 28.8, 22.0, 21.9 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -93.7--103.4 (m) ppm. HRMS (ESI): calc. forC 30 H 36 F4N2O3Na + (M+Na) + , 571.2554, found, 571.2556.

[0109] Example 18

[0110] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0111]

[0112] The target product is a yellow oily liquid, 81.2 mg (74% yield, Z:E = 1.6:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.40-7.17 (m, 11H), 7.13-7.03(m, 1H), 5.90-5.57 (m, 1H), 5.19-4.90 (m, 2H), 3.57-3.38 (m, 1H), 3.33-3.17(m, 1H), 3.14-2.82 (m, 2H), 2.75-2.65 (m, 1H), 2.11-1.70 (m, 2H), 1.63-1.54(m, 1H), 1.52-1.39 (m, 7H), 1.33-1.21 (m, 1H), 1.14-0.92 (m, 1H), 0.92-0.81 (m, 3H) ppm. 13C NMR (126 MHz, Chloroform-d) δ 163.6-162.2 (m, 2C), 146.6-145.4 (m, 2C), 142.1-141.2 (m), 128.8-128.4 (m, 4C), 127.8-127.3 (m, 2C),126.3-125.7 (m, 4C), 123.8-121.1 (m), 119.4-111.6 (m, 2C), 73.4-72.7 (m),70.3-69.8 (m), 52.6-51.9 (m), 49.5-49.1 (m, 2C), 49.0-48.7 (m) 44.1-43.3 (m), 37.4 (t, J) CF = 23.4 Hz), 34. 6 (t, J CF = 24.7 Hz), 34.2, 33.6-33.2 (m), 31.8-31.5 (m), 31.4-31.1 (m), 29.0-28.2 (m), 22.0-21.8 (m), 21.3-20.8 (m, 2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -92.4--103.0 (m) ppm. HRMS (ESI): calc. forC 30 H 36 F4N2O3Na + (M+Na) + , 571.2554, found, 571.2557.

[0113] Example 19

[0114] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0115]

[0116] The target product is a yellow oily liquid, 77.2 mg (91% yield, Z:E = 1.3:1.0). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 5.95-5.75 (m, 1H), 3.57-3.29(m, 5H), 3.21-3.09 (m, 2H), 3.09-2.98 (m, 2H), 2.96 (s, 1H), 2.89 (s, 3H),2.86-2.73 (m, 1H), 2.63-2.48 (m, 1H), 2.09-1.78 (m, 2H), 1.65-1.54 (m, 1H),1.51-1.22 (m, 2H), 1.21-1.12 (m, 3H), 1.11-1.02 (m, 4H), 0.99-0.91 (m, 1H), 0.89-0.83 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 164.2-161.5 (m, 2C), 146.5-144.8 (m), 124.3-122.2 (m), 121.2-112.2 (m, 2C), 73.9, 70.1-69.7 (m),52.8-52.2 (m), 49.3-48.7 (m), 44.7-43.9 (m, 2C), 43.6-42.9 (m), 37.7 (q, J CF =24.4 Hz), 34.6-33.3 (m, 3C), 31.33, 31.30, 31.2, 28.6, 21.90, 21.87, 13.7-11.2 (m, 2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -87.5--97.2 (m) ppm. HRMS(ESI): calc. for C 20 H 32 F4N2O3Na + (M+Na) + , 447.2241, found, 447.2243.

[0117] Example 20

[0118] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0119]

[0120] The target product is a yellow oily liquid, 79.1 mg (87% yield, Z:E = 1.3:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 5.93-5.73 (m, 1H), 3.54-3.36(m, 4H), 3.36-3.24 (m, 5H), 3.20-2.78 (m, 3H), 2.64-2.50 (m, 1H), 0.88-0.82 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 163.3 (t, J CF = 30.9 Hz), 162.7 (t, J CF = 30.7 Hz), 162.5 (t,J CF = 28.6 Hz), 162.0 (t, J CF = 28.7 Hz), 146.0-145.1 (m), 123.8 (t, J CF = 27.5Hz), 122.8 (t, J CF = 25.7 Hz), 121.2-112.4 (m, 2C), 73.7, 69.9, 52.5, 49.1,43.4, 43.3, 42.2-41.5 (m, 4C), 37.7 (t, J CF = 23.2 Hz), 34.6 (t, J CF = 23.3Hz), 34.3, 33.5, 31.30, 31.27, 31.2, 28.6, 21.89, 21.87, 14.3-13.7 (m, 2C),12.3 –11.8 (m, 2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -87.9--96.7 (m) ppm.HRMS (ESI): calc. for C 22 H 36 F4N2O3Na + (M+Na)+ , 475.2554, found, 475.2557.

[0121] Example 21

[0122] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0123]

[0124] The target product is a yellow oily liquid, 87.6 mg (86% yield, Z:E = 1.1:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 5.94-5.75 (m, 1H), 3.55-3.45(m, 1H), 3.35-3.13 (m, 9H), 3.11-2.93 (m, 1H), 2.91-2.50 (m, 1H), 2.09-1.93(m, 2H), 1.89-1.79 (m, 1H), 1.65-1.43 (m, 10H), 1.32-1.07 (m, 2H), 1.00-0.93(m, 1H), 0.90-0.80 (m, 15H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 163.6 (t,J CF = 30.8 Hz), 163.1 (t, J CF = 30.6 Hz), 162.8 (t, J CF = 28.4 Hz), 162.3 (t,J CF = 28.6 Hz), 145.8-145.2 (m), 123.8 (t, J CF = 26.7 Hz), 122.9 (t, J CF = 25.5Hz), 121.3-112.6 (m, 2C), 73.8, 70.0, 53.1-48.0 (m, 5C), 43.3, 37.8 (t, J CF=23.0 Hz), 34.4, 33.6, 31.33, 31.31, 31.1, 28.6, 22.2-21.6 (m, 3C), 20.2-19.8(m, 2C), 11.2-11.0 (m, 2C), 10.9-10.7 (m, 2C)ppm. 19 F NMR (471 MHz,Chloroform-d) δ -87.4--97.5 (m) ppm. HRMS (ESI): calc. for C 26 H 44 F4N2O3Na + (M+Na) + , 531.3180, found, 531.3181.

[0125] Example 22

[0126] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0127]

[0128] The target product is a yellow oily liquid, 76.5 mg (91% yield, Z:E = 1.7:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.25-7.03 (m, 2H), 5.82-5.48(m, 1H), 3.60-3.13 (m, 2H), 3.05-2.78 (m, 2H), 2.77-2.62 (m, 3H), 2.07-1.75(m, 2H), 1.65-1.50 (m, 2H), 1.49-1.37 (m, 1H), 1.35-1.06 (m, 1H), 1.01-0.93(m, 1H), 0.92-0.85 (m, 3H), 0.78-0.70 (m, 4H), 0.61-0.53 (m, 4H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 165.7-164.7 (m, 2C), 146.2-145.6 (m), 123.44 (dd,J CF = 31.2, 23.4 Hz), 121.57 (t, J CF= 25.4 Hz), 119.4-111.4 (m, 2C), 73.1,70.1, 52.4, 48.7, 43.9, 43.6, 37.3 (t, J CF = 24.2 Hz), 34.7 (t, J CF = 25.1Hz), 34.2, 33.5, 31.7, 31.4, 31.3, 28.8, 22.9-22.6 (m, 2C), 21.92, 21.88,6.2-5.8 (m, 4C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -93.6--101.8 (m) ppm.HRMS (ESI): calc. for C 20 H 28 F4N2O3Na + (M+Na) + , 443.1928, found, 443.1928.

[0129] Example 23

[0130] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0131]

[0132] The target product is a yellow oily liquid, 83.4 mg (93% yield, Z:E = 1.4:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.25-6.98 (m, 2H), 5.85-5.50(m, 1H), 4.42-4.19 (m, 2H), 3.60-3.15 (m, 2H), 3.06-2.71 (m, 2H), 2.50 (s,1H), 2.35-2.16 (m, 4H), 2.02-1.90 (m, 5H), 1.79-1.52 (m, 6H), 1.50-1.37 (m,1H), 1.35-1.18 (m, 1H), 1.15-0.90 (m, 2H), 0.90-0.85 (m, 3H) ppm. 13C NMR (126MHz, Chloroform-d) δ 163.3-162.3 (m, 2C), 146.3-145.4 (m), 123.5 (dd, J CF =31.5, 23.2 Hz), 121.6 (t, J CF = 25.4 Hz), 119.4-111.4 (m, 2C), 73.1, 70.2,52.4, 48.8, 45.0-44.5 (m, 2C), 44.0, 43.7, 37.4 (t, J CF = 24.2 Hz), 34.7 (t,J CF = 25.3 Hz), 34.2, 33.5, 31.7, 31.4, 31.3, 28.7, 30.5-29.9 (m, 4C), 21.92,21.87, 15.2-14.9 (m, 2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -93.1--102.1(m) ppm. HRMS (ESI): calc. for C 22 H 32 F4N2O3Na + (M+Na) + , 471.2241, found,471.2242.

[0133] Example 24

[0134] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0135]

[0136] The target product is a yellow oily liquid, 95.9 mg (90% yield, Z:E = 1.5:1.0). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 6.84-6.56 (m, 2H), 5.86-5.46(m, 1H), 3.94-3.76 (m, 2H), 3.56-3.14 (m, 2H), 3.08-2.71 (m, 2H), 2.40 (s,1H), 2.06-1.95 (m, 1H), 1.91-1.81 (m, 4H), 1.81-1.74 (m, 1H), 1.67-1.51 (m,10H), 1.49-1.38 (m, 12H), 1.37-1.26 (m, 1H), 1.01-0.92 (m, 1H), 0.90-0.85 (m,3H), 0.84-0.78 (m, 1H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 162.71 (t, J CF =30.8 Hz), 162.68 (t, J CF = 30.6 Hz), 162.4 (t, J CF = 28.3 Hz), 162.3 (t, J CF =28.0 Hz), 146.3-145.6 (m), 123.1 (dd, J CF = 31.0, 23.3 Hz), 121.7 (t, J CF =25.6 Hz), 119.5-111.6 (m, 2C), 73.1, 70.1, 52.4, 51.3-50.6 (m, 2C), 48.9,44.0, 43.6, 37.4 (t, J CF = 24.0 Hz), 34.5-33.2 (m, 5C), 31.6, 31.4, 31.3,28.8, 27.9-27.5 (m, 4C), 24.0-23.6 (m, 4C), 21.93, 21.88 ppm. 19 F NMR (471MHz, Chloroform-d) δ -93.1--101.7 (m) ppm. HRMS (ESI): calc. for C 28 H 44 F4N2O3Na + (M+Na) + , 555.3180, found, 555.3183。

[0137] Example 25

[0138] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0139]

[0140] The target product is a yellow oily liquid, 86.7 mg (91% yield, Z:E = 1.1:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 6.05-5.69 (m, 1H), 3.68-3.54(m, 3H), 3.54-3.45 (m, 4H), 3.44-3.37 (m, 1H), 3.24-3.10 (m, 1H), 3.08-2.78(m, 2H), 2.66-2.53 (m, 1H), 2.29-2.13 (m, 1H), 2.07-1.83 (m, 2H), 1.72-1.47(m, 13H), 1.46-1.34 (m, 1H), 1.31-1.10 (m, 2H), 1.02-0.93 (m, 1H), 0.92-0.84 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 162.4 (t, J CF = 30.5 Hz), 161.8(t, J CF = 30.4 Hz), 161.5 (t, J CF = 28.3 Hz), 160.9 (t, J CF = 28.7 Hz), 146.2-144.9 (m), 124.0 (t, J CF = 26.8 Hz), 123.0 (t, J CF = 25.7 Hz), 121.3-112.1 (m,2C), 74.1, 70.0, 52.7, 49.0, 47.1-46.4 (m, 2C), 44.7-44.1 (m, 2C), 43.4,43.2, 37.9 (t, J CF = 22.8 Hz), 34.6 (t, J CF= 24.2 Hz), 34.4, 33.5, 31.38,31.35, 31.2, 28.7, 26.6-25.8 (m, 2C), 25.6-25.1 (m, 2C), 24.4-24.0 (m, 2C),22.0, 21.9 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -87.7--96.8 (m) ppm. HRMS(ESI): calc. for C 24 H 36 F4N2O3Na + (M+Na) + , 499.2554, found, 499.2557.

[0141] Example 26

[0142] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0143]

[0144] The target product is a yellow oily liquid, 85.4 mg (89% yield, Z:E = 1.4:1.0). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 5.95-5.72 (m, 1H), 3.77-3.53(m, 15H), 3.52-3.43 (m, 2H), 3.25-2.86 (m, 2H), 2.63-2.48 (m, 1H), 2.09-1.79(m, 2H), 1.69-1.35 (m, 3H), 1.30-1.12 (m, 1H), 1.01-0.90 (m, 2H), 0.90-0.85(m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 162.6 (t, J CF = 30.9 Hz), 162.0(t, J CF = 30.8 Hz), 161.6 (t, J CF = 29.5 Hz), 161.1 (t, J CF= 29.4 Hz), 146.7-145.5 (m), 123.6 (t, J CF = 25.1 Hz), 122.5 (t, J CF = 25.6 Hz), 121.0-120.0 (m,2C), 74.3, 70.0, 66.8-66.1 (m, 4C), 52.6, 49.0, 46.7-46.0 (m, 2C), 43.8-42.9(m, 3C), 37.7 (t, J CF = 22.2 Hz), 34.4 (t, J CF = 22.9 Hz), 34.3, 33.4, 31.3,31.0, 28.7, 21.89, 21.85 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -88.0--97.1(m) ppm. HRMS (ESI): calc. for C 22 H 32 F4N2O5Na + (M+Na) + , 503.2140, found, 503.2143.

[0145] Example 27

[0146] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0147]

[0148] The target product is a yellow oily liquid, 107.0 mg (90% yield, Z:E = 1.3:1.0). The compound is characterized as follows: 1H NMR (500 MHz, Chloroform-d) δ 5.92-5.73 (m, 1H), 3.97-3.82(m, 8H), 3.76-3.54 (m, 7H), 3.51-3.38 (m, 2H), 3.25-3.07 (m, 1H), 3.02-2.74(m, 2H), 2.62-2.47 (m, 1H), 2.04-1.75 (m, 2H), 1.70-1.56 (m, 8H), 1.50-1.28(m, 2H), 1.26-1.08 (m, 1H), 0.98-0.86 (m, 2H), 0.86-0.80 (m, 3H) ppm. 13 C NMR(126 MHz, Chloroform-d) δ 162.3 (t, J CF = 30.8 Hz), 161.7 (t, J CF = 30.7 Hz),161.4 (t, J CF = 28.4 Hz), 160.9 (t, J CF = 29.1 Hz), 146.7-145.2 (m), 123.6 (t,J CF = 26.4 Hz), 122.6 (t, J CF = 25.5 Hz), 121.1-111.9 (m, 2C),106.5-105.9 (m,2C), 74.2, 69.8, 64.5-64.0 (m, 4C), 52.5, 48.9, 43.7-43.1 (m, 3C), 41.7-41.2(m, 2C), 37.7 (t, J CF = 22.5 Hz), 35.6-34.9 (m, 2C), 34.7-33.2 (m, 3C), 31.2,31.0, 28.6, 21.83, 21.79 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -87.9--97.0(m) ppm. HRMS (ESI): calc. for C 28 H 40 F4N2O7Na + (M+Na) + , 615.2664, found,615.2665。

[0149] Example 28

[0150] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0151]

[0152] The target product is a yellow oily liquid, 52.0 mg (72% yield, Z:E = 1.3:1.0). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 5.78-5.41 (m, 2H), 5.21-4.96(m, 1H), 4.32-4.15 (m, 4H), 3.61-3.45 (m, 1H), 3.00-2.52 (m, 2H), 2.52-2.11(m, 1H), 2.11-1.74 (m, 3H), 1.72-1.58 (m, 1H), 1.57-1.44 (m, 1H), 1.34-1.21(m, 7H), 1.06-0.85 (m, 5H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 169.5-168.3(m, 2C), 147.3-144.1 (m), 123.8-123.3 (m), 122.7-121.8 (m), 88.8-82.8 (m,2C), 73.2-71.8 (m), 70.2-69.6 (m), 62.2-61.5 (m, 2C), 53.2-52.5 (m), 48.7-48.2 (m), 43.8-42.8 (m), 35.0-33.5 (m, 2C), 31.6-30.8 (m, 2C), 22.0-21.8 (m),14.1-13.7 (m, 2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -176.8--190.4 (m)ppm. HRMS (ESI): calc. for C 18 H 28 F2O5Na + (M+Na) + , 385.1797, found, 385.1801.

[0153] Example 29

[0154] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as in Example 13, except that the fluorine reagent is different. As shown in Table 2, the structural formula of the target product is as follows:

[0155]

[0156] The target product is a yellow oily liquid, 80.0 mg (76% yield, Z:E = 1.0:1.4). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 5.81-5.55 (m, 1H), 4.34-4.05(m, 8H), 3.62-2.66 (m, 5H), 2.08-1.94 (m, 1H), 1.93-1.78 (m, 1H), 1.63-1.51(m, 1H), 1.48-1.20 (m, 14H), 1.20-1.07 (m, 1H), 1.00-0.88 (m, 1H), 0.88-0.80(m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 146.9-146.3 (m), 123.1-120.4(m), 120.3-114.2 (m, 2C), 74.4, 70.7, 65.2-64.3 (m, 4C), 53.2, 48.7, 44.7,43.8, 37.5-36.7 (m), 34.2, 33.5, 31.6, 31.3, 31.0, 29.3, 21.8, 16.3-16.0 (m,4C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -99.4--113.0 (m) ppm. 31 P NMR (202MHz, Chloroform-d) δ 8.6-5.0 (m) ppm. HRMS (ESI): calc. for C 20 H 36 F4O7P2Na + (M+Na) + , 549.1765, found, 549.1771.

[0157] Example 30

[0158] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, and the reaction route is as follows:

[0159]

[0160] The preparation method is as follows: In a 25 mL dry, single-necked, round-bottomed sealed tube equipped with a stirrer, under nitrogen atmosphere, terpenoid olefins (0.2 mmol, 39.7 mg), eosin B (0.01 mmol, 6.2 mg), cobalt dichloride (0.04 mmol, 5.2 mg), triethylamine (0.8 mmol, 81.0 mg), potassium fluoride (1.2 mmol, 69.7 mg), and a halofluorinated reagent (2.0 mmol, 406 mg) were gradually added, with 2.0 mL of dichloromethane as the solvent, to obtain the reaction system; the reaction temperature was 50 °C under a nitrogen atmosphere. o C. Stir and simultaneously irradiate with light at a wavelength of 365 nm for 30 hours to obtain the reaction system; filter the reaction system, remove the organic solvent by rotary evaporation, and obtain the target product by column chromatography with petroleum ether / ethyl acetate = 10:1 as the developing solvent.

[0161] The target product is a pale yellow oily liquid, 67.7 mg (60% yield, Z:E = 1.0:1.1). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 6.14-5.83 (m, 1H), 4.41-4.22(m, 6H), 4.12-3.97 (m, 2H), 3.74-3.33 (m, 1H), 3.20-2.83 (m, 2H), 2.02 (s,3H), 1.70-1.37 (m, 6H), 1.36-1.28 (m, 9H), 1.23-1.04 (m, 1H), 0.92-0.84 (m,3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 171.2-171.1 (m), 163.7-162.7 (m,3C), 137.7-137.0 (m), 127.5 (t, J CF= 26.7 Hz), 118.3-109.3 (m, 3C), 63.4-63.1(m, 3C), 62.6, 49.8-48.7 (m), 45.6-44.8 (m), 37.9-37.1 (m), 35.5-34.8 (m),33.8-33.4 (m), 30.0-29.5 (m), 25.6, 22.7, 20.9, 19.1, 18.9, 13.9-13.6 (m, 3C)ppm. 19 F NMR (471 MHz, Chloroform-d) δ -96.2--111.0 (m) ppm. HRMS (EI):calc.for C 24 H 34 F6O8 (M) + , 564.2158, found, 564.2157.

[0162] The 1H NMR spectrum of the polydifluoroalkylated terpene olefin derivative (target product) obtained in this embodiment ( 1 H NMR, carbon NMR ( 13 C NMR and nuclear magnetic fluorine spectroscopy (C NMR) 19 The spectrum of F NMR is as follows Figures 1-3 As shown.

[0163] Table 3 Summary of raw materials for Examples 30-54 (terpenoids)

[0164]

[0165] Example 31

[0166] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0167]

[0168] The target product is a yellow oily liquid, 54.3 mg (52% yield, Z:E = 1.1:1.0). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 6.14-5.82 (m, 1H), 4.43-4.19(m, 6H), 3.73-3.30 (m, 3H), 3.17-2.82 (m, 2H), 2.02-1.47 (m, 6H), 1.40-1.26(m, 10H), 1.18-0.98 (m, 1H), 0.95-0.75 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 163.8-162.6 (m, 3C), 137.8-136.8 (m), 127.9-126.5 (m), 119.2-109.2 (m, 3C), 63.4-63.0 (m, 3C), 60.8-60.3 (m), 49.8-48.7 (m), 45.8-44.7(m), 39.8-38.8 (m), 37.5 (t, J CF = 22.5 Hz), 35.3 (t, J CF = 23.6 Hz), 33.7-33.3 (m), 29.7-28.0 (m), 25.9-25.3 (m), 22.9-22.4 (m), 19.3, 19.1, 13.9-13.4(m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.5--111.4 (m) ppm. HRMS(EI): calc.for C 22 H 33 F6O7 (M+H) + , 523.2125, found, 523.2112.

[0169] Example 32

[0170] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0171]

[0172] The target product is a pale yellow oily liquid, 52.0 mg (50% yield, Z:E = 1.0:1.2). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 9.68 (d, J = 2.1 Hz, 1H), 6.20-5.74 (m, 1H), 4.33-4.24 (m, 6H), 3.65-3.31 (m, 1H), 3.15-2.80 (m, 2H),2.43-2.16 (m, 3H), 2.06-1.93 (m, 1H), 1.75-1.55 (m, 2H), 1.35-1.27 (m, 10H),0.95-0.86 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 202.2-202.0 (m),164.0-162.4 (m, 3C), 137.6-136.7 (m), 128.0-126.9 (m), 118.2-109.2 (m, 3C),63.5-62.9 (m, 3C), 50.8-50.2 (m), 49.5-48.6 (m), 45.5-44.7 (m), 37.4 (t, J CF =22.6 Hz), 35.3 (t, J CF = 20.2 Hz), 33.6-33.1 (m), 28.2-27.4 (m), 25.5, 22.1,19.7-19.1 (m), 13.9-13.4 (m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.6--110.8 (m) ppm. HRMS (EI): calc.for C 22 H 30 F6O7 (M) + , 520.1896, found,520.1908.

[0173] Example 33

[0174] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0175]

[0176] The target product is a pale yellow oily liquid, 41.1 mg (40% yield, Z:E = 1.0:1.3). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 6.18-5.81 (m, 1H), 4.42-4.22(m, 6H), 3.75-3.35 (m, 1H), 3.20-2.85 (m, 2H), 2.40-2.17 (m, 2H), 1.91-1.64(m, 3H), 1.60-1.42 (m, 1H), 1.41-1.31 (m, 10H), 1.11-1.04 (m, 3H) ppm. 13 C NMR(126 MHz, Chloroform-d) δ 163.6-162.5 (m, 3C), 137.6-136.6 (m), 128.3-127.2(m), 118.4-118.2 (m), 118.1-111.1 (m, 3C), 63.5-63.1 (m, 3C), 49.4-48.5 (m),45.3-44.6 (m), 37.5 (t, J CF = 22.7 Hz), 35.4 (t, J CF = 23.7 Hz), 32.8-32.3(m), 30.3-30.1 (m), 25.6, 24.4-24.0 (m), 22.5, 19.1-18.8 (m), 13.8-13.5 (m,3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.5--110.3 (m) ppm. HRMS (ESI):calc.for C 22 H 29 F6NO6Na + (M+Na) + , 540.1791, found, 540.1792.

[0177] Example 34

[0178] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0179]

[0180] The target product is a colorless oily liquid, 26.5 mg (24% yield, mixture). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 6.21-5.88 (m, 1H), 4.49-4.19 (m, 6H), 4.19-4.05 (m, 2H), 3.63-3.34 (m, 1H), 3.23-2.86 (m, 2H), 1.64-1.56 (m, 1H), 1.46-1.30 (m, 10H), 1.30-1.21 (m, 6H), 1.21-1.09 (m, 3H) ppm. 13 C NMR (126MHz, Chloroform-d) δ 171.1-170.6 (m), 163.5-162.6 (m, 3C), 137.6-137.2 (m), 128.8 (t, J CF = 26.6 Hz), 118.2-109.8 (m, 3C), 63.7-62.9 (m, 3C), 60.6, 60.3,49.4 (t, J CF = 20.7 Hz), 36.1-34.9 (m), 33.8-30.5 (m), 30.0-28.6 (m), 26.9-24.9 (m), 21.6-21.0 (m), 20.6-20.0 (m), 14.4-14.1 (m), 13.9-13.6 (m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.2--114.5 (m) ppm. HRMS (ESI): calc.forC 24 H 32 F6O8 Na + (M+Na) + , 585.1894, found, 585.1899.

[0181] Example 35

[0182] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0183]

[0184] The target product is a pale yellow oily liquid, 45.6 mg (46% yield, Z:E = 1.4:1.0). The compound is characterized as follows:1 H NMR (500 MHz, Chloroform-d) δ 6.20-5.97 (m, 1H), 4.44-4.28(m, 7H), 4.23-4.11 (m, 1H), 3.74-3.36 (m, 1H), 3.17-2.84 (m, 2H), 2.01 (s,3H), 1.41-1.31 (m, 9H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 170.1-169.9 (m), 163.5-162.2 (m, 3C), 135.0-134.3 (m), 129.1 (t, J CF = 26.5 Hz), 128.7 (t, J CF = 26.4 Hz), 114.4 (t, J CF = 253.1 Hz), 111.7 (t, J CF = 250.4 Hz), 111.5 (t, J CF = 250.0 Hz), 63.6-63.2 (m, 3C), 60.6, 59.3, 47.8 (t, J CF = 21.4 Hz), 44.4 (t,J CF = 21.5 Hz), 37.7 (t, J CF = 21.2 Hz), 36.1 (t, J CF = 24.5 Hz), 20.5, 20.4,13.9-13.6 (m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -96.9--111.6 (m) ppm.HRMS (EI): calc.for C 19 H 25 F6O8(M+H) + , 495.1448, found, 495.1436.

[0185] Example 36

[0186] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0187]

[0188] The target product is a pale yellow oily liquid, 61.3 mg (40% yield, Z:E = 1.1:1.0). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.81-7.76 (m, 2H), 7.76-7.72(m, 1H), 7.69-7.64 (m, 1H), 7.62-7.56 (m, 1H), 7.56-7.51 (m, 1H), 7.50-7.46(m, 2H), 7.45-7.41 (m, 1H), 6.12-5.85 (m, 1H), 4.37-4.26 (m, 6H), 4.16-4.02(m, 2H), 3.78 (q, J = 7.2 Hz, 1H), 3.69-3.37 (m, 1H), 3.17-2.82 (m, 2H),1.65-1.56 (m, 2H), 1.52 (d, J = 7.2 Hz, 3H), 1.48-1.37 (m, 2H), 1.37-1.30 (m,10H), 1.23-1.00 (m, 2H), 0.87-0.80 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 196.4, 174.1-173.9 (m), 163.7-162.6 (m, 3C), 140.90, 140.88, 137.8,137.5, 137.4-137.2 (m), 132.5, 131.6-131.3 (m), 130.0 (2C), 129.2, 129.1,128.9, 128.5, 128.3 (2C), 127.5 (t, J CF = 27.0 Hz), 118.3-109.2 (m, 3C), 63.6-62.8 (m, 4C), 45.5-45.2 (m, 2C), 35.7-34.7 (m), 33.8-33.4 (m), 30.0-29.5 (m),25.6, 22.6, 19.1-19.0 (m), 18.9-18.8 (m), 18.5-18.3 (m), 14.0-13.6 (m, 3C)ppm. 19F NMR (471 MHz, Chloroform-d) δ -95.5--110.7 (m) ppm. HRMS (EI):calc.for C 38 H 44 F6O9 (M) + , 758.2890, found, 758.2886.

[0189] Example 37

[0190] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0191]

[0192] The target product is a yellow oily liquid, 77.3 mg (49% yield, Z:E = 1.1:1.0). The compound is characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 8.10 (d, J = 7.9 Hz, 2H), 7.82(d, J = 8.1 Hz, 2H), 6.12-5.77 (m, 1H), 4.41-4.19 (m, 8H), 3.72-3.34 (m, 1H),3.17-2.82 (m, 6H), 1.83-1.43 (m, 10H), 1.36-1.21 (m, 10H), 0.96-0.89 (m, 3H),0.81 (t, J = 7.4 Hz, 6H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 165.1, 163.6-162.6 (m, 3C), 144.0, 137.6-137.0 (m), 133.5, 130.0 (2C), 127.8-127.0 (m), 126.8 (2C), 118.3-109.1 (m, 3C), 63.6, 63.4-63.0 (m, 3C), 49.8 (2C), 49.6-48.7 (m), 45.6-44.7 (m), 37.4 (t, J CF= 21.7 Hz), 35.4-34.8 (m), 33.6-33.3(m), 29.9-29.6 (m), 25.5, 22.6, 21.8 (2C), 19.2-18.7 (m), 13.8-13.5 (m, 3C), 11.0 (2C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.5--110.3 (m) ppm. HRMS(ESI): calc.for C 35 H 49 F6NO 10 SNa + (M+Na) + , 812.2874, found, 812.2878.

[0193] Example 38

[0194] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0195]

[0196] The target product is a yellow oily liquid, 70.9 mg (43% yield, Z:E = 1:1). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.69 (dd, J = 17.0, 8.1 Hz, 4H), 7.41 (d, J = 8.0 Hz, 2H), 6.83 (d, J = 8.3 Hz, 2H), 6.15-5.80 (m, 1H), 4.36-4.23 (m, 6H), 4.21-4.11 (m, 2H), 3.69-3.35 (m, 1H), 3.14-2.82 (m, 2H), 1.76-1.50 (m, 10H), 1.43-1.36 (m, 2H), 1.35-1.26 (m, 9H), 1.18-0.97 (m, 1H), 0.89-0.75 (m, 3H) ppm. 13C NMR (126 MHz, Chloroform-d) δ 194.0, 173.6, 163.7-162.5(m, 3C), 159.6, 138.2, 137.7-137.0 (m), 136.3, 131.9 (2C), 131.1 (2C), 130.3,128.4 (2C), 127.5 (t, J = 26.1 Hz), 117.2 (2C), 118.3-109.1 (m, 3C), 79.3,63.78, 63.75, 63.4-63.0 (m, 3C), 49.6-48.8 (m), 45.6-44.8 (m), 37.5 (t, J CF =22.5 Hz), 35.3 (t, J CF = 22.3 Hz), 35.1 –34.6 (m), 33.51, 33.46, 29.8-29.4(m), 25.7-24.9 (m, 2C), 22.6, 18.9, 18.7, 13.9-13.5 (m, 3C) ppm. 19 F NMR (471MHz, Chloroform-d) δ -95.9--109.9 (m) ppm. HRMS (EI): calc.for C 39 H 45 ClF6O 10 (M) + , 822.2605, found, 822.2608.

[0197] Example 39

[0198] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0199]

[0200] The target product is a colorless oily liquid, 54.1 mg (34% yield, Z:E = 1.0:1.4). The characterization of this compound is as follows: 11H NMR (500 MHz, Chloroform-d) δ 7.16 - 7.02 (m, 2H), 6.82 - 6.69 (m, 2H), 6.11 - 5.80 (m, 1H), 4.39 - 4.22 (m, 6H), 4.20 - 4.08 (m, 2H), 3.65 - 3.35 (m, 1H), 3.16 - 2.86 (m, 2H), 2.84 - 2.76 (m, 1H), 1.95 - 1.86 (m, 1H), 1.79 - 1.72 (m, 1H), 1.70 - 1.50 (m, 9H), 1.42 - 1.35 (m, 2H), 1.35 - 1.27 (m, 9H), 1.24 - 0.98 (m, 2H), 0.87 - 0.77 (m, 3H) ppm. 13 13C NMR (126 MHz, Chloroform-d) δ 174.1, 163.6 - 162.6 (m, 3C), 154.9, 137.8 - 136.8 (m), 129.5 (2C), 128.0, 127.8 - 127.0 (m), 118.5 - 118.3 (m, 2C), 118.8 - 109.3 (m, 3C), 79.0, 63.5, 63.4 - 63.0 (m, 3C), 60.8, 49.3 (t, J CF = 18.8 Hz), 45.3 (t, J CF = 21.7 Hz), 37.5 (t, J CF = 22.6Hz), 35.3 (t, J CF = 24.2 Hz), 35.1 - 34.73 (m), 34.68, 33.5, 29.7 - 29.4 (m), 25.7 (2C), 25.5, 25.6 - 25.0 (m), 22.5, 19.0 - 18.6 (m), 14.0 - 13.5 (m, 3C) ppm. 19 19F NMR(471 MHz, Chloroform-d) δ -95.9--110.1 (m) ppm. HRMS (ESI): calc. for C 35 H 44 Cl2F6O9Na + (M+Na) + , 815.2159, found, 815.2161。

[0201] Example 40

[0202] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0203]

[0204] The target product is a colorless oily liquid, 78.8 mg (55% yield, Z:E = 1.0:1.3). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.23-7.15 (m, 2H), 7.13-7.04(m, 2H), 6.14-5.82 (m, 1H), 4.38-4.25 (m, 6H), 4.13-4.00 (m, 2H), 3.73-3.37(m, 2H), 3.17-2.87 (m, 2H), 2.44 (d, J = 7.2 Hz, 2H), 1.91-1.78 (m, 1H), 1.73-1.52 (m, 4H), 1.47 (d, J = 7.2 Hz, 3H), 1.38-1.30 (m, 10H), 1.24-0.97(m, 2H), 0.89 (d, J = 6.7 Hz, 6H), 0.85-0.78 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 174.7, 163.8-162.6 (m, 3C), 140.4, 137.9-137.7 (m), 137.6-137.2 (m), 129.2 (2C), 127.5 (t, J CF = 26.7 Hz), 127.1 (2C), 118.4-109.2 (m,3C), 63.4-63.1 (m, 3C), 62.9-62.6 (m), 49.3 (t, J CF = 20.8 Hz), 45.3 (t, J CF =22.5 Hz), 45.1, 45.0, 37.5 (t, J CF = 22.6 Hz), 35.5 (d, J CF= 23.8 Hz), 35.3-34.8 (m), 33.6, 30.1, 29.8-29.5 (m), 25.6, 22.7, 22.3 (2C), 19.2-18.2 (m,2C), 14.0-13.6 (m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.5--110.8 (m)ppm. HRMS (ESI): calc.for C 35 H 48 F6O8Na + (M+Na) + , 733.3146, found, 733.3148.

[0205] Example 41

[0206] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0207]

[0208] The target product was a pale yellow oily liquid, 78.5 mg (52% yield, Z:E = 1.0:1.3). The compound was characterized as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.24-7.15 (m, 2H), 7.14-7.06(m, 2H), 6.18-5.84 (m, 1H), 4.39-4.24 (m, 6H), 4.16-3.98 (m, 2H), 3.77-3.37(m, 2H), 3.18-2.84 (m, 3H), 2.55-2.45 (m, 1H), 2.39-2.28 (m, 2H), 2.16-2.03(m, 2H), 2.00-1.90 (m, 1H), 1.79-1.67 (m, 2H), 1.63-1.50 (m, 3H), 1.49-1.44(m, 3H), 1.43-1.30 (m, 11H), 1.23-1.00 (m, 2H), 0.89-0.79 (m, 3H) ppm. 13C NMR(126 MHz, Chloroform-d) δ 220.2, 174.6, 163.7-162.8 (m, 3C), 138.8, 138.4,137.6-137.1 (m), 129.0 (2C), 127.8-126.9 (m), 127.5 (2C), 118.3-106.8 (m,3C), 63.5-63.1 (m, 3C), 63.0-62.7 (m), 60.0, 45.7-45.2 (m), 45.1, 38.1, 35.6-34.8 (m, 3C), 33.6, 30.0-29.5 (m), 29.2, 25.6, 22.7, 20.5, 19.2-18.3 (m, 2C), 14.0-13.5 (m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.5--110.6 (m) ppm.HRMS (EI): calc.for C 37 H 48 F6O9(M) + , 750.3203, found, 750.3200.

[0209] Example 42

[0210] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0211]

[0212] The target product is a colorless oily liquid, 80.4 mg (51% yield, Z:E = 1.1:1.0). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 8.83 (s, 1H), 8.37 (d, J = 7.7Hz, 1H), 8.30-8.14 (m, 2H), 7.68-7.57 (m, 2H), 7.36 (t, J = 7.6 Hz, 1H),7.33-7.27 (m, 1H), 6.22-5.86 (m, 1H), 4.49-4.24 (m, 8H), 3.81-3.41 (m, 1H),3.26-2.82 (m, 2H), 1.91-1.78 (m, 2H), 1.74-1.58 (m, 3H), 1.43-1.30 (m, 10H),1.24-1.13 (m, 1H), 1.07-0.96 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ172.99, 172.95, 168.0, 165.8 (d, J CF = 2.2 Hz), 163.7-162.7 (m, 3C), 160.7 (d,J CF = 260.6 Hz), 137.6-137.0 (m), 134.7 (d, J CF = 8.7 Hz), 132.1, 131.6, 131.2(d, J CF = 1.9 Hz), 130.9, 129.0, 128.6, 127.6-127.0 (m), 127.1, 124.7 (d, J CF = 3.7 Hz), 117.1 (d, J CF = 20.7 Hz), 118.1-109.2 (m, 3C), 112.6 (d, J CF = 11.3Hz), 63.6-63.41 (m), 63.39-63.1 (m, 3C), 45.8-44.8 (m), 35.7-35.0 (m), 35.4,35.3, 33.8-33.5 (m), 30.1-29.7 (m), 25.6, 22.7, 19.2, 19.0, 14.0-13.5 (m, 3C)ppm. 19F NMR (471 MHz, Chloroform-d) δ -95.5--110.5 (m) ppm. HRMS (ESI):calc.for C 37 H 39 F7N2O9Na + (M+Na) + , 811.2436, found, 811.2438.

[0213] Example 43

[0214] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0215]

[0216] The target product is a colorless oily liquid, 64.0 mg (46% yield, Z:E = 1.2:1.0). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.14 (t, J = 8.2 Hz, 1H), 6.56-6.48 (m, 1H), 6.47-6.34 (m, 2H), 6.12-5.83 (m, 1H), 4.81-4.66 (m, 1H), 4.42-4.22 (m, 6H), 4.22-4.08 (m, 2H), 3.75 (s, 3H), 3.66-3.35 (m, 1H), 3.18-2.84(m, 2H), 1.70-1.51 (m, 6H), 1.49-1.29 (m, 11H), 1.24-0.95 (m, 2H), 0.91-0.74 (m, 3H) ppm. 13C NMR (126 MHz, Chloroform-d) δ 172.3-172.0 (m), 163.6-162.7(m, 3C), 160.8, 158.7, 137.8-136.8 (m), 129.9, 127.9-126.9 (m), 118.2-109.2(m, 3C), 107.3-107.0 (m), 106.8-106.5 (m), 101.7-101.3 (m), 72.4, 63.6-62.8(m, 4C), 55.2, 49.8-48.8 (m), 45.8-44.8 (m), 37.5 (t, J CF = 22.7 Hz), 35.3 (d,J CF = 25.9 Hz), 35.2-34.8 (m), 33.8-33.2 (m), 29.9-29.2 (m), 25.6, 22.6, 19.2-18.1 (m, 2C), 14.0-13.4 (m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.5--110.7 (m) ppm. HRMS (EI): calc.for C 32 H 42 F6O 10 (M) + , 700.2682, found, 700.2684.

[0217] Example 44

[0218] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0219]

[0220] The target product is a colorless oily liquid, 52.7 mg (35% yield, Z:E = 1.0:1.3). The characterization of this compound is as follows: 11H NMR (500 MHz, Chloroform-d) δ 8.10 - 8.00 (m, 2H), 7.73 - 7.66 (m, 2H), 7.65 - 7.58 (m, 2H), 7.50 - 7.43 (m, 2H), 7.43 - 7.35 (m, 1H), 6.18 - 5.82 (m, 1H), 4.37 - 4.25 (m, 6H), 4.19 - 4.07 (m, 2H), 3.71 - 3.56 (m, 1H), 3.39 - 3.28 (m, 2H), 3.17 - 2.89 (m, 2H), 2.83 - 2.72 (m, 2H), 1.77 - 1.66 (m, 2H), 1.59 - 1.49 (m, 2H), 1.48 - 1.39 (m, 2H), 1.38 - 1.31 (m, 9H), 1.15 - 1.05 (m, 1H), 0.94 - 0.88 (m, 3H) ppm. 13 13C NMR (126 MHz, Chloroform-d) δ 197.7, 173.0, 163.9 - 162.6 (m, 3C), 145.9, 139.9, 137.6 - 137.1 (m), 135.3, 128.9 (2C), 128.9 - 128.7 (m), 128.6 (2C), 128.2, 127.5 - 127.0 (m, 4C), 118.2 - 109.6 (m, 3C), 63.5 - 63.1 (m, 3C), 62.9, 46.1 - 44.8 (m), 36.2 - 34.9 (m, 2C), 33.8 - 33.3 (m), 33.4, 30.2 - 29.0 (m), 28.3, 25.4, 22.7, 19.2, 19.0, 14.0 - 13.5 (m, 3C) ppm. 19 19F NMR (471 MHz, Chloroform-d) δ -95.2 - -114.6 (m) ppm. HRMS (EI): calc. for C 38 19 44 19F6O9 (M) + , 758.2890, found, 758.2891。

[0221] Example 45

[0222] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0223]

[0224] The target product is a colorless oily liquid, 76.6 mg (52% yield, Z:E = 1:1). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.26-7.21 (m, 2H), 7.12 (d, J = 8.2Hz, 2H), 6.17-5.86 (m, 1H), 4.44-4.20 (m, 6H), 4.19-4.03 (m, 2H), 3.77-3.37(m, 1H), 3.23-2.86 (m, 2H), 2.55-2.43 (m, 1H), 2.39-2.26 (m, 1H), 2.14-2.04(m, 2H), 2.01-1.89 (m, 2H), 1.81-1.71 (m, 1H), 1.68-1.38 (m, 9H), 1.38-1.27(m, 9H), 1.22-1.03 (m, 1H), 0.97-0.85 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 175.81, 175.79, 163.8-162.6 (m, 3C), 145.3, 137.5-137.0 (m), 131.6, 128.4 (2C), 128.1 (2C), 127.8-127.0 (m), 118.2-109.1 (m, 3C), 63.5-63.0 (m, 3C), 62.4, 45.8-44.9 (m), 42.93, 42.87, 35.8-34.8 (m, 2C), 33.8-33.4(m), 33.2(2C), 30.0-29.8(m), 29.1 (2C), 25.7, 22.7, 19.1, 19.0, 14.0-13.5(m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.4--110.9 (m) ppm. HRMS(EI): calc.for C 35 H 45ClF6O8 (M) + , 742.2707, found, 742.2705.

[0225] Example 46

[0226] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0227]

[0228] The target product is a pale yellow oily liquid, 63.7 mg (39% yield, Z:E = 1.0:1.7). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 8.21-8.15 (m, 1H),8.13-8.05(m, 1H), 7.00 (d, J = 8.9 Hz, 1H), 6.23-5.80 (m, 1H), 4.37-4.18 (m, 8H), 3.89(d, J = 6.5 Hz, 2H), 3.72-3.38 (m, 1H), 3.21-2.83 (m, 2H), 2.75 (d, J = 2.2Hz, 3H), 2.27-2.14 (m, 1H), 1.84-1.67 (m, 2H), 1.64-1.48 (m, 3H), 1.43-1.28(m, 11H), 1.08 (d, J = 6.7 Hz, 6H), 0.99-0.92 (m, 3H) ppm. 13C NMR (126 MHz, Chloroform-d) δ 167.2, 163.7-162.7 (m, 3C), 162.5, 162.0, 161.2-161.0 (m), 137.5-137.0 (m), 132.6, 132.1, 127.8-127.0 (m), 126.0, 121.8-121.7 (m),118.1-109.2 (m, 3C), 115.4, 112.6, 102.9, 75.7, 63.7-63.0 (m, 4C), 45.8-44.8(m), 35.5-35.0 (m), 33.8-33.4 (m), 30.1-29.8 (m), 28.1, 25.7, 22.7, 19.2,19.0 (3C), 17.4, 14.0-13.6 (m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.4--110.3 (m) ppm. HRMS (EI): calc.for C 38 H 46 F6N2O9S (M) + , 820.2828, found,820.2829.

[0229] Example 47

[0230] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0231]

[0232] The target product is a yellow oily liquid, 86.6 mg (50% yield, Z:E = 1.0:1.2). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 7.62 (d, J = 8.1 Hz, 2H), 7.35(d, J = 8.1 Hz, 2H), 7.07 (d, J = 7.9 Hz, 2H), 6.77 (d, J = 8.0 Hz, 2H),6.37-6.20 (m, 1H), 6.13-5.81 (m, 1H), 4.40-4.23 (m, 6H), 4.21-4.11 (m, 2H),3.69-3.34 (m, 3H), 3.16-2.77 (m, 4H), 2.55-2.04 (m, 1H), 1.71-1.59 (m, 3H),1.59-1.53 (m, 6H), 1.46-1.37 (m, 3H), 1.36-1.27 (m, 9H), 0.93-0.71 (m, 3H)ppm. 13 C NMR (126 MHz, Chloroform-d) δ 174.2, 166.3, 163.7-162.7 (m, 3C),154.1, 137.5, 137.4-137.1 (m), 133.0, 132.4-132.2 (m), 129.4 (2C), 128.7(2C), 128.2 (2C), 127.8-127.0 (m), 119.5-119.1 (m, 2C), 118.3-109.3 (m, 3C),79.1, 63.6-63.4 (m), 63.4-63.1 (m, 3C), 49.3 (t, J CF = 19.8 Hz), 45.3 (t, J CF = 20.1 Hz), 41.2, 37.5 (t, J CF = 22.4 Hz), 35.3 (t, J CF = 27.0 Hz), 35.2-34.8(m), 34.6, 33.8-33.4 (m), 29.8-29.4 (m), 25.6, 25.5-25.1 (m, 2C), 22.6, 19.0-18.7 (m), 14.0-13.5 (m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.9--110.6 (m) ppm. HRMS (ESI): calc. for C 41 H50 ClF6NO 10 Na + (M+Na) + , 888.2920, found, 888.2921.

[0233] Example 48

[0234] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0235]

[0236] The target product is a colorless oily liquid, 64.2 mg (43% yield, Z:E = 1.1:1.0). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.36-7.30 (m, 2H), 7.30-7.24(m, 1H), 7.13-7.07 (m, 1H), 7.06-6.95 (m, 4H), 6.90-6.84 (m, 1H), 6.15-5.88(m, 1H), 4.39-4.25 (m, 6H), 4.14-4.02 (m, 2H), 3.75-3.37 (m, 2H), 3.17-2.88(m, 2H), 1.76-1.52 (m, 3H), 1.47 (d, J = 7.2 Hz, 3H), 1.45-1.39 (m, 1H),1.39-1.21 (m, 11H) 1.20-1.01 (m, 1H), 0.90-0.80 (m, 3H) ppm. 13C NMR (126 MHz, Chloroform-d) δ 174.1, 163.7-162.7 (m, 3C), 157.3, 157.0, 142.6-142.4 (m), 137.7-136.9 (m), 129.8-129.6 (m, 3C), 127.8-126.9 (m), 123.2, 122.4-122.1(m), 118.8 (2C), 118.2-118.0 (m), 117.3-117.2 (m), 117.9-109.3 (m, 3C), 63.4-63.1 (m, 3C), 63.0-62.8 (m), 49.6-48.9 (m), 45.7-44.9 (m), 37.5 (t, J CF = 23.1Hz), 35.3 (t, J CF = 24.1 Hz), 35.2-34.8 (m), 33.8-33.3 (m), 30.0-29.4 (m), 25.6, 22.6, 19.1-18.7 (m), 18.4-18.1 (m), 14.0-13.5 (m, 3C) ppm. 19 F NMR (471MHz, Chloroform-d) δ -95.4--110.8 (m) ppm. HRMS (EI): calc.for C 37 H 44 F6O9 (M) + ,746.2890, found, 746.2884.

[0237] Example 49

[0238] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0239]

[0240] The target product is a colorless oily liquid, 77.5 mg (58% yield, Z:E = 1.1:1.0). The characterization of this compound is as follows: 1H NMR (500 MHz, Chloroform-d) δ 7.21-7.15 (m, 2H), 7.15-7.07(m, 2H), 6.19-5.82 (m, 1H), 4.41-4.23 (m, 6H), 4.14-3.99 (m, 2H), 3.72-3.36(m, 2H), 3.17-2.87 (m, 2H), 2.32 (s, 3H), 1.69-1.50 (m, 3H), 1.49-1.44 (m,3H), 1.43-1.30 (m, 11H), 1.25-1.15 (m, 1H), 1.11-0.98 (m, 1H), 0.88-0.78 (m,3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 174.66, 174.65, 163.8-162.8 (m,3C), 137.7-137.6 (m), 137.5-137.1 (m), 136.6, 129.2 (2C), 127.8-126.9 (m),127.3 (2C), 118.2-109.2 (m, 3C), 63.5-63.0 (m, 3C), 62.9-62.6 (m), 45.6-45.16(m), 45.07, 35.8-34.8 (m, 2C), 33.9-33.3 (m), 29.9-29.4 (m), 25.6, 22.6,20.9, 19.1-18.8 (m), 18.5-18.3 (m), 14.0-13.5 (m, 3C) ppm. 19 F NMR (471 MHz,Chloroform-d) δ -95.3--110.9 (m) ppm. HRMS (EI): calc.for C 32 H 42 F6O8(M) + ,668.2784, found, 668.2781.

[0241] Example 50

[0242] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0243]

[0244] The target product is a colorless oily liquid, 49.3 mg (55% yield, E:Z > 20.0:1.0). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 6.00 (t, J = 15.2 Hz, 1H), 4.38-4.19 (m, 6H), 3.30 (t, J = 17.9 Hz, 2H), 1.41-1.30 (m, 15H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 163.6 (t, J CF = 32.9 Hz), 163.13 (t, J CF = 34.3 Hz), 163.08 (t, J CF = 32.6 Hz), 141.2-140.8 (m), 127.1 (t, J CF = 25.3 Hz), 117.6(t, J CF = 260.4 Hz), 113.7 (t, J CF = 253.4 Hz), 112.5 (t, J CF = 249.9 Hz), 63.2, 63.1, 62.9, 46.4 (t, J CF = 20.8 Hz), 33.0 (t, J CF = 23.8 Hz), 21.3 (s,2C), 13.9-13.6 (m, 3C) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -100.1, -100.8,-109.9 ppm. HRMS (EI): calc.for C 18 H 24 F6O6(M) + , 450.1477, found, 450.1463.

[0245] Example 51

[0246] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0247]

[0248] The target product is a colorless oily liquid, 39.2 mg (45% yield, Z:E = 1.0:1.6). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 6.13-5.77 (m, 1H), 4.42-4.23(m, 6H), 3.87-3.37 (m, 1H), 3.27-2.87 (m, 2H), 1.43-1.25 (m, 11H), 1.23-1.19(m, 1H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 163.7-162.7 (m, 3C), 139.8-139.4 (m), 139.3-138.9 (m), 126.9 (t, J CF = 26.7 Hz), 126.1 (t, J CF = 27.1Hz), 118.3-109.3 (m, 3C), 63.5-62.9 (m, 3C), 43.6 (t, J CF = 21.9 Hz), 39.8 (t,J CF = 22.5 Hz), 37.6 (t, J CF = 23.3 Hz), 35.5 (t, J CF = 23.9 Hz), 14.0-13.6 (m,3C), 13.5-13.2 (m), 11.3-10.9 (m) ppm. 19 F NMR (471 MHz, Chloroform-d) δ -96.3--111.9 (m) ppm. HRMS (EI): calc.for C 17 H 23 F6O6(M+H) + , 437.1393, found, 437.1410.

[0249] Example 52

[0250] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0251]

[0252] The target product is a colorless oily liquid, 48.6 mg (54% yield, Z:E = 1.0:1.2). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 6.16-5.84 (m, 1H), 4.38-4.25(m, 6H), 3.67-3.38 (m, 1H), 3.16-2.86 (m, 2H), 1.80-1.65 (m, 1H), 1.62-1.52(m, 1H), 1.38-1.31 (m, 9H), 1.00-0.85 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 163.7-162.8 (m, 3C), 137.5-136.7 (m), 127.9-126.9 (m), 118.5-109.3 (m, 3C), 63.5-63.0 (m, 3C), 50.5 (t, J CF = 20.7 Hz), 46.5 (t, J CF = 21.6Hz), 37.6 (t, J CF = 22.8 Hz,), 35.3 (t, J CF = 24.0 Hz), 21.4, 18.4, 13.9-13.6(m, 3C), 11.1, 10.9 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -95.7--111.4 (m)ppm. HRMS (EI): calc.for C 18 H 24 F6O6(M) + , 450.1477, found, 450.1480.

[0253] Example 53

[0254] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0255]

[0256] The target product is a colorless oily liquid, 23.1 mg (27% yield). The characterization of this compound is as follows: 1HNMR (500 MHz, Chloroform-d) δ 5.90 (t, J = 13.8 Hz, 1H), 4.31 (q, J = 7.1 Hz, 6H), 3.21 (t, J = 16.9 Hz, 2H), 3.04 (t, J = 16.1 Hz, 2H), 1.39-1.28 (m, 9H)ppm. 13 C NMR (126 MHz, Chloroform-d) δ 163.12 (t, J CF = 34.0 Hz), 163.11 (t,J CF = 34.0 Hz), 163.05 (t, J CF = 32.1 Hz), 133.7-133.3 (m), 129.2 (t, J CF =26.6 Hz), 114.9 (d, J CF = 253.5 Hz), 114.5 (t, J CF = 253.6 Hz), 111.4 (t, J CF =250.0 Hz), 63.4, 63.28, 63.26, 41.6 (t, J CF = 23.3 Hz), 36.0 (t, J CF = 23.4Hz), 13.82, 13.77, 13.7 ppm. 19 F NMR (471 MHz, Chloroform-d) δ -99.5 (t, J =3.5 Hz), -102.6, -103.8 ppm. HRMS (EI): calc.for C 16 H 20 F6O6 (M) + , 422.1164,found, 422.1152.

[0257] Example 54

[0258] This embodiment provides a method for preparing polydifluoroalkylated derivatives of terpenoid olefins, which is the same as that in Example 30, except that the terpenoid olefin is different. As shown in Table 3, the structural formula of the target product is as follows:

[0259]

[0260] The target product is a colorless oily liquid, 20.4 mg (20% yield, Z:E = 1.0:1.5). The characterization of this compound is as follows: 1 H NMR (500 MHz, Chloroform-d) δ 7.36-7.13 (m, 5H), 6.24-5.85(m, 1H), 4.41-4.18 (m, 5H), 4.01-3.87 (m, 2H), 3.24-2.68 (m, 4H), 1.39-1.27(m, 6H), 1.25-1.14 (m, 3H) ppm. 13 C NMR (126 MHz, Chloroform-d) δ 163.7-162.3(m, 3C), 137.6-137.2 (m), 136.2, 129.3 (2C), 128.4 (2C), 127.0, 126.5 (t, J CF = 26.6 Hz), 117.9-109.3 (m, 3C), 63.5-62.9 (m, 3C), 46.3 (t, J CF = 21.2 Hz), 36.0 (t, J CF = 23.6 Hz), 32.9, 14.0-13.3 (m, 3C) ppm. 19 F NMR (471 MHz,Chloroform-d) δ -96.0--112.1 (m) ppm. HRMS (EI): calc.for C 23 H 26 F6O6(M) + ,512.1634, found, 512.1636.

Claims

1. A method for preparing a polydifluoroalkylated derivative of a terpene olefin, characterized in that, include: Under inert gas protection, terpenoid olefins, photosensitizers, cobalt catalysts, organic reducing agents, bases, fluorine reagents, and organic solvents are sequentially loaded into a reaction vessel to obtain the reaction system; Under inert gas protection, the reaction system was carried out at 40~60 °C under light irradiation. The reaction system was purified by filtration, rotary evaporation and chromatography to complete the polydifluoroalkylation of terpenoid olefins.

2. The method for preparing polydifluoroalkylated derivatives of terpenoid olefins according to claim 1, characterized in that, The reaction pathway of the method is shown below: ； The structural formulas of the terpene olefins are shown in (1) to (4), and the structural formulas of the polydifluoroalkylated derivatives of the terpene olefins are shown in (5) to (7). ； R 1 ~R 5 Each is independently selected from hydrogen, halogen, alkyl, alcohol, thiol, alkoxy, ester, acyl, alkenyl, alkynyl, aryl, substituted aryl, fused ring, fused ring, or heterocyclic; the fluorine reagent is selected from fluoroalkanes, fluoroaromatics, selective fluorine reagents, N-fluorobis(benzenesulfonamide), 1-fluoro-4-hydroxy-1,4-diazotized bicyclo2.2.2-octanebis(tetrafluoroborate), pyridine hydrofluoric acid, triethylamine trihydrofluoric acid, metal fluorides, fluorinated aldehydes, fluorinated ketones, fluorinated acids, fluorinated esters, fluorinated alkenes, fluorinated alkynes, Umemoto reagent, Togni reagent, or Chen Qingyun reagent.

3. The method for preparing polydifluoroalkylated derivatives of terpenoid olefins according to claim 1, characterized in that, The molar ratio of the terpene olefin to the fluorine reagent is 1:5 to 1:10; the volume of organic solvent corresponding to each millimole of fluorine reagent is 1 to 2 mL.

4. The method for preparing polydifluoroalkylated derivatives of terpenoid olefins according to claim 1, characterized in that, The photosensitizer is one or more of Acid Red 87, Rhodamine 6G, and Eosin B.

5. The method for preparing polydifluoroalkylated derivatives of terpenoid olefins according to claim 1, characterized in that, The cobalt catalyst is one or more of cobalt chloride, cobalt bromide, cobalt chloride, and cobalt bromide.

6. The method for preparing polydifluoroalkylated derivatives of terpenoid olefins according to claim 1, characterized in that, The organic reducing agent is one or more of triethylamine, N,N-diisopropylethylamine, and ethylenediamine.

7. The method for preparing polydifluoroalkylated derivatives of terpenoid olefins according to claim 1, characterized in that, The base is an inorganic base.

8. The method for preparing polydifluoroalkylated derivatives of terpenoid olefins according to claim 1, characterized in that, The organic solvent is carbon tetrachloride, tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, chloroform, toluene, xylene, cyclohexane, n-hexane, n-heptane, dioxane, or acetonitrile.

9. The method for preparing polydifluoroalkylated derivatives of terpenoid olefins according to claim 1, characterized in that, The light source is blue or violet light, and the reaction time under the light conditions is 12 to 30 hours.

10. A polydifluoroalkylated derivative of a terpenoid olefin prepared by the method described in any one of claims 1 to 9.

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