Method for synthesizing difluoroolefin by catalyzing alcohol derivative through eosin Y

Abstract

The invention discloses a method for synthesizing difluoroolefin by catalyzing an alcohol derivative through eosin Y. Compared with the prior art, the invention provides a reaction method for realizing difluoroallylation through beta-cracking of an alcohol derivative without transition metal catalysis. The method has the advantages of simple operation steps, good substrate universality, coverage of polycyclic and heterocyclic substituted alpha-trifluoromethyl olefins such as naphthalene, dibenzothiophene, dibenzofuran, modified primary, secondary and tertiary alcohols, bioactive molecules and natural products, wide functionality tolerance, mild reaction conditions, high yield and simple post-treatment, and is suitable for industrial production. The method is a green chemical synthesis method with a good application prospect.

Description

Technical Field

[0001] The invention relates to a method for synthesizing difluoroolefins from alcohol derivatives by using eosin Y as a catalyst without transition metal, mildly and efficiently. Background Art

[0002] The introduction of fluorine into target molecules can significantly change their physicochemical and biochemical properties, including dipole moment, hydrogen bonding, lipophilicity and metabolic stability. Many anticancer drugs and antibiotics are enhanced in efficacy by fluorination. Currently, about 20% of drugs and 30-40% of pesticides on the market contain fluorine. Among various organic fluorine entities, geminal-difluoroolefins are particularly important and commonly found in biologically active molecules. Due to their unique electronic and stereo effects, they are important core skeletons of many pharmacologically and agromedically active molecules and have received extensive attention in the field of drug design and development. They have diverse synthesis methods and rich reactivity, making them an important research direction for fluorine-containing compounds.

[0003] In addition, alcohols are one of the most abundant raw material chemicals, with low cost, stability, non-toxicity, structural diversity, and a wide range of renewable sources, including biomass and other natural resources. These characteristics make alcohols excellent precursors of alkyl radicals. In this context, one-step modification of alcohols can yield N-alkoxyphthalimides, which can serve as versatile alkyl radical precursors. Under light induction, using the cheap and readily available eosin Y photocatalyst, the abundant and inexpensive chemical raw materials can be converted into high-value-added compounds, which will have broad application prospects. Summary of the invention

[0004] Purpose of the invention: In order to break the limitations of the prior art methods, as a supplement to the existing methods for studying the visible light catalytic synthesis of difluoroolefins from alcohol derivatives, the present invention provides a transition metal-free, mild and efficient method for synthesizing difluoroolefins from alcohol derivatives using Eosin Y as a catalyst.

[0005] To solve the above technical problems, the present invention provides the following technical solutions.

[0006] One of the technical solutions of the present invention is a method for synthesizing difluoroolefins using alcohol derivatives catalyzed by eosin Y, the structural formula of which is:

[0007]

[0008] Among them, R is any one of hydrogen, phenyl, methyl, tert-butyl, methoxy, benzyloxy, cyano, halogen atom, polycyclic aromatic group, and heterocyclic group, and R1 is various alkyl groups.

[0009] The second technical solution of the present invention provides a reaction method of the above-mentioned α-trifluoromethyl olefin and N-alkoxyphthalimide, comprising the following steps:

[0010]

[0011] Among them, R 1 , R 2 It is hydrogen, methyl, and phenyl.

[0012] The α-trifluoromethyl olefin shown in Formula 1, the N-alkoxyphthalimide shown in Formula 2, a base, a reducing agent and a photocatalyst are dissolved in an organic solvent, and reacted at room temperature for 12 h or 16 h under 456 nm blue light irradiation. After the reaction, the reaction system is separated and purified to obtain the target product, that is, the target product of Formula 3 is synthesized.

[0013] The photocatalyst is EosinY, 4CzIPN, Me-Acr-Mes, fac-[Ir(ppy) 3 ].

[0014] The reducing agent is Hantzsch ester.

[0015] The inorganic base is potassium phosphate, sodium phosphate, potassium carbonate, sodium carbonate, and cesium carbonate.

[0016] The organic solvent is acetonitrile, toluene, tetrahydrofuran, and N,N-dimethylacetamide.

[0017] The visible light is blue light with a wavelength of 456nm.

[0018] The molar ratio of the compound represented by Formula 1 to the compound represented by Formula 2 may be 1:1.2 or 1:2.

[0019] The molar ratio of the compound shown in Formula 1 to the photocatalyst is 1:0.01.

[0020] The reaction is carried out under an inert gas environment, and the inert gas atmosphere may be nitrogen.

[0021] In the eluent, the volume ratio of petroleum ether to ethyl acetate is 1000:1 to 5:1.

[0022] The progress of the reaction can be monitored by conventional monitoring methods in the art (eg, TLC).

[0023] The steps of separating and purifying the reaction system of the reaction are as follows: the reaction system is directly concentrated under reduced pressure, the obtained concentrate is separated and purified by column chromatography on silica gel, the eluent is petroleum ether or a mixture of petroleum ether and ethyl acetate, the eluent is collected and the solvent is evaporated to obtain the target product.

[0024] In a certain embodiment of the present invention, the difluoroolefin product as shown in Formula 3 includes but is not limited to any of the following structures:

[0025]

[0026] The beneficial effects of the present invention are as follows: the present invention provides a transition metal-free, mild and efficient method for synthesizing difluoroolefins from alcohol derivatives using eosin Y as a catalyst, the raw materials are stable and easy to prepare, the reaction conditions are mild, the experimental operation is simple, the production capacity is high, the functional group tolerance is wide, and the chemical selectivity is good. The method is a green chemical synthesis method with good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative labor. Among them:

[0028] Figure 1 is the reaction formula of α-trifluoromethyl olefin and N-alkoxyphthalimide;

[0029] Figure 2 The H NMR spectrum of compound 3a prepared in Example;

[0030] Figure 3-1 The H NMR spectrum of compound 3b prepared in Example;

[0031] Figure 3-2 The carbon NMR spectrum of compound 3b prepared in Example;

[0032] Figure 4-1 This is the hydrogen nuclear magnetic resonance spectrum of compound 3c prepared in Example;

[0033] Figure 4-2 The carbon NMR spectrum of compound 3c prepared in Example;

[0034] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of compound 3h prepared in Example;

[0035] Figure 6 This is the hydrogen nuclear magnetic resonance spectrum of compound 3i prepared in Example;

[0036] Figure 7 The H NMR spectrum of compound 3k prepared in Example;

[0037] Figure 8-1 is the hydrogen nuclear magnetic resonance spectrum of compound 31 prepared in Example;

[0038] Figure 8-2 The carbon NMR spectrum of compound 31 prepared in Example;

[0039] Figure 9-1 The H NMR spectrum of compound 3n prepared in Example;

[0040] Figure 9-2 The carbon NMR spectrum of compound 3n prepared in Example;

[0041] Fig.10 This is the H NMR spectrum of compound 3o prepared in Example;

[0042] Fig.11 The H NMR spectrum of compound 3p prepared in Example;

[0043] Figure 12-1 The H NMR spectrum of compound 3r prepared in Example;

[0044] Figure 12-2 The carbon NMR spectrum of compound 3r prepared in Example;

[0045] Figure 13-1 The H NMR spectrum of compound 3t prepared in Example;

[0046] Figure 13-2 The carbon NMR spectrum of compound 3t prepared in Example;

[0047] Figure 14-1 The H NMR spectrum of compound 3g' prepared in Example;

[0048] Figure 14-2 The carbon NMR spectrum of compound 3g' prepared in Example;

[0049] Fig.15 The H NMR spectrum of compound 3k' prepared in Example;

[0050] Figure 16-1 The H NMR spectrum of compound 31′ prepared in Example;

[0051] Figure 16-2 The carbon NMR spectrum of compound 31' prepared in Example; DETAILED DESCRIPTION

[0052] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation of the present invention is described in detail below in conjunction with the embodiment of the specification.

[0053] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0054] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0055] Example 1: Preparation of tert-butyl (R)-2-(2-((1,1′-biphenyl)-4-yl)-3,3-difluoroallyl)pyrrolidine-1-carboxylic acid 3a, the formula is as follows:

[0056]

[0057] 4-phenyl-α-trifluoromethylene (0.2 mmol), Eosin Y (1 mol%), tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate (1.2 equiv), Hantzsch ester (1.2 equiv) and potassium phosphate (1.2 equiv) were added to a Shrek tube equipped with a stirrer, replaced with nitrogen three times, and acetonitrile (2.0 mL) was added under a nitrogen atmosphere. The reaction mixture was sealed, irradiated with a 40W blue LED lamp with a wavelength of 456 nm, and stirred at room temperature for 12 hours. After the reaction was completed, the system was concentrated under reduced pressure to remove the solvent to obtain a crude product, which was then purified by column chromatography using petroleum ether: ethyl acetate (10:1-5:1) as the eluent to obtain 64.7 mg of the product with a yield of 81%.

[0058] NMR analysis: 1 H NMR (400 MHz, CDCl 3 )δ7.65-7.56(m, 4H), 7.56-7.41(m, 4H), 7.39-7.32(m, 1H), 4.04-3.65(m, 1H), 3.48-3.1 6(m, 2H), 3.14-2.78(m, 1H), 2.55-2.32(m, 1H), 1.95-1.61(m, 4H), 1.53-1.40(m, 9H).At RT, this compound appears as an~1.9:1mixture of rotamers.

[0059] Example 2: Preparation of tert-butyl (S)-(5-(1,1′-biphenyl)-4-yl)-6,6-difluoro-2-methylhex-5-en-3-yl)carbamate 3b, except that the tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate in Example 1 was replaced with an equal molar amount of tert-butyl ((R)-(1-((1,3-dioxolan-2-yl)oxy)-3-methylbutan-2-yl)carbamate. The same method as Example 1 was used to obtain 60.0 mg of the target compound with a yield of 75%.

[0060] NMR analysis: 1 H NMR (400 MHz, CDCl 3 )δ7.68-7.57(m, 4H), 7.54-7.30(m, 5H), 4.37-4.08(m, 1H), 3.64-3.38(m, 1H), 2 .61-2.43(m, 2H), 1.89-1.74(m, 1H), 1.50-1.33(m, 9H), 0.93(t, J=6.7Hz, 6H).At RT,this compound appears as an~4:1 mixture of rotamers. 13 C NMR (101 MHz, CDCl 3 )δ155.7, 154.4 (dd, J=290.7, 286.6Hz), 140.8, 140.3, 132.5, 128.9, 127.4, 127 .3, 127.2, 90.2 (dd, J=21.4, 14.6Hz), 79.0, 54.2, 31.8, 31.5, 28.5, 19.4, 17.4.

[0061] Example 3: Preparation of tert-butyl-(R)-(4-((1,1′-biphenyl)-4-yl)-5,5-difluoro-1-phenylpent-4-en-2-yl)carbamate 3c, the formula is as follows:

[0062]

[0063] 4-Phenyl-α-trifluoromethylene (0.2 mmol), Eosin Y (1 mol%), tert-butyl-(R)-(1-((1,3-dioxolan-2-yl)oxy)-3-phenylpropane-2-yl)carbamate (2.0 equiv), Hantzsch ester (1.2 equiv) and potassium phosphate (1.2 equiv)) were added to a Shrek tube equipped with a stirrer, and the atmosphere was replaced with nitrogen three times. Acetonitrile (2.0 mL) was added under a nitrogen atmosphere. The reaction mixture was sealed, irradiated with a 40W blue LED lamp with a wavelength of 456 nm, and stirred at room temperature for 12 hours. After the reaction was completed, the system was concentrated under reduced pressure to remove the solvent to obtain a crude product, which was then purified by column chromatography using petroleum ether: ethyl acetate (10:1-5:1) as the eluent to obtain 76.2 mg of the product with a yield of 85%.

[0064] NMR analysis: 1 H NMR (400 MHz, CDCl 3 )δ7.69-7.52(m, 4H), 7.53-7.42(m, 2H), 7.42-7.18(m, 6H), 7.19-7.05(m, 2H), 4.46-4.0 6(m, 1H), 4.06-3.59(m, 1H), 2.90-2.72(m, 2H), 2.70-2.49(m, 2H), 1.49-1.16(m, 9H).At RT,this compound 8ppears as an~4:1mixture of rotamers. 13 C NMR (101 MHz, CDCl 3 ) δ155.3, 154.5 (dd, J = 291.6, 287.5Hz), 140.7, 140.4, 137.9, 132.1, 129.4, 128.9, 128.8 (t, J = 3. 0Hz) ​​128.5, 127.5, 127.3, 127.2, 126.6, 89.8 (dd, J=20.7, 15.6Hz), 79.3, 50.5, 40.9, 32.8, 28.4.

[0065] Example 4: Preparation of 4-(1,1-difluoro-4,4-dimethylpent-1-en-2-yl)-1,1′-biphenyl 3h. The same method as in Example 1 was used, except that the tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate in Example 1 was replaced with an equal molar amount of 2-(neopentyloxy)isoindolin-1,3-dione to obtain 46 mg of the target compound with a yield of 80%.

[0066] NMR analysis: 1H NMR (400 MHz, CDCl 3 )δ7.73-7.54(m, 4H), 7.53-7.31(m, 5H), 2.40(m, 2H), 1.59(s, 1H), 0.86(s, 9H).

[0067] Example 5: Preparation of 4-(1,1-difluoro-4-methylpent-1-en-2-yl)-1,1′-biphenyl 3i. The same method as in Example 1 was used, except that the tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate in Example 1 was replaced with an equal molar amount of 2-((3-methylbutan-2-yl)oxy)isoindole-1,3-dione to obtain 25.1 mg of the target compound with a yield of 46%.

[0068] NMR analysis 1 H NMR (400 MHz, CDCl 3 )δ7.70-7.55(m, 4H), 7.54-7.29(m, 5H), 2.33(d, J=7.3Hz, 2H), 1.76-1.58(m, 1H), 0.93(d, 6H).

[0069] Example 6: Preparation of 4-(1,1-difluoro-4-phenylbut-1-en-2-yl)-1,1′-biphenyl 3k, except that the tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate in Example 1 was replaced with an equal molar amount of 2-((2-methyl-1-phenylpropane-2-yl)oxy)isoindole-1,3-dione. The preparation was carried out in the same manner as Example 1 to obtain 22.4 mg of the target compound with a yield of 35%.

[0070] NMR analysis: 1 H NMR (400 MHz, CDCl 3 )δ7.70-7.59(m, 4H), 7.53-7.35(m, 5H), 7.35-7.28(m, 2H), 7.25-7.16(m, 3H), 3.00-2.50(m, 4H).

[0071] Example 7: Preparation of 7-((1,1′-biphenyl)-4-yl)-8,8-difluorooct-7-en-2-one 3l, using the same method as Example 1, except that tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate 2-(1-methylcyclobutyloxy)isoindole-1,3-dione in Example 1 was used to obtain 61.5 mg of the target compound with a yield of 98%.

[0072] NMR analysis: 1 H NMR (600 MHz, CDCl 3 )δ7.67-7.59(m, 4H), 7.50-7.45(m, 2H), 7.45-7.33(m, 3H), 2.51-2.45(m, 2H ), 2.43 (t, J=7.4Hz, 2H), 2.13 (s, 3H), 1.68-1.61 (m, 2H), 1.48-1.39 (m, 2H). 13 C NMR (101 MHz, CDCl 3 )δ209.0, 153.8 (dd, J=290.3, 287.6Hz), 140.6, 140.2, 128.7 (t, J=3.3Hz), 128.9, 128.7 (t, J=3 .4Hz), 127.5, 127.2, 127.1, 91.9 (dd, J=20.3, 14.4Hz), 43.4, 33.7, 30.0, 27.4-27.3 (m), 23.1.

[0073] Example 8: Preparation of 6-((1,1'-biphenyl)-4-yl)-7,7-difluorohept-6-ene-1-carboxylate 3n, except that the tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate in Example 1 was replaced with an equal molar amount of 2-((tetrahydro-2H-pyran-2-yl)oxy)isoindole-1,3-dione. The same method as Example 1 was used to obtain 39.4 mg of the target compound with a yield of 59%.

[0074] NMR analysis: 1 H NMR (400 MHz, CDCl 3 )δ8.05 (s, 1H), 7.66-7.54 (m, 4H), 7.50-7.31 (m, 5H), 4.14 (t, J = 6.6Hz, 2H), 2.46 (s, 2H), 1.71-1.61 (m, 2H), 1.50-1.36 (m, 4H). 13 C NMR (101 MHz, CDCl 3 )δ161.3, 153.8 (dd, J=289.5, 288.1Hz), 140.7, 140.2, 132.6, 128.9, 128.7 (t, J= 3.2Hz), 127.5, 127.3, 127.1, 91.98 (dd, J=19.3, 15.5Hz), 64.0, 28.3, 27.5, 25.4.

[0075] Example 9: Preparation of 2-((4-((1,1′-biphenyl)-4-yl)-5,5-difluoro-2-methylpent-4-en-2-yl)oxy)ethanol-1-ol 3o, except that the tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate in Example 1 was replaced with an equal molar amount of 2-(2-isopropoxyethoxy)isoindolin-1,3-dione. The target compound 55.4 mg was obtained in a yield of 83%.

[0076] NMR analysis: 1 H NMR (400 MHz, CDCl 3 )δ7.67-7.55(m, 4H), 7.51-7.39(m, 4H), 7.39-7.31(m, 1H), 3.42-3.35(m, 2H), 3.35-3.26(m, 2H), 2.67(s, 2H), 1.79(s, 1H), 1.17(s, 6H).

[0077] Example 10. Preparation of tert-butyl 2-(3,3-difluoro-2-phenylallyl)pyrrolidine-1-carboxylate 3p, except that the 4-phenyl-α-trifluoromethyl olefin in Example 1 was replaced with an equal molar amount of (3,3,3-trifluoroprop-1-en-2-yl)benzene, and the same method as Example 1 was used to obtain 55.6 mg of the target compound with a yield of 78%.

[0078] NMR analysis: 1 H NMR (400 MHz, CDCl 3 )δ7.50-7.19(m, 4H), 3.80(m, 1H), 3.30(m, 1H), 2.94(m, 2H), 2.39(m, 1H), 1.92-1.70(m, 3H), 1.66(m, 1H), 1.45(s, 9H). At RT, this compound appears as an ~ 1.6: 1 mixture of rotamers.

[0079] Example 11: Preparation of tert-butyl 2-(2-(4-(tert-butyl)phenyl)-3,3-difluoroallyl)pyrrolidine-1-carboxylate 3r. The same method as Example 1 was used, except that the 4-phenyl-α-trifluoromethyl olefin in Example 1 was replaced with an equal molar amount of 1-(tert-butyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene to obtain 42.3 mg of the target compound with a yield of 56%.

[0080] NMR analysis: 1 H NMR (400 MHz, CDCl 3)67.45-7.27(m, 4H), 4.04-3.60(m, 1H), 3.55-3.13(m, 2H), 3.11-2.72(m, 1H), 2.5 5-2.23(m, 1H), 1.94-1.71(m, 1H), 1.71-1.62(m, lH), 1.45(s, 9H), 1.32(s, 9H).At RT,this compound appears as an~1.3:1 mixture of rotamers. 13 C NMR (101 MHz, CDCl 3 )δ154.7 (dd, J=291.9, 287.9Hz), 154.5, 151.78, 150.4, 130.0, 127.9, 125.4, 90.1 (dd, J=19.7, 15.1Hz), 79.6, 55.6, 46.8, 34.6, 31.7, 31.4, 29.6, 28.7, 22.7.Peaks corresponding to the minor rotamer are present at δ150.1, 79.0, 46.3, 29.8, 23.6.

[0081] Example 12: Preparation of tert-butyl 2-(2-(4-(benzyloxy)phenyl)-3,3-difluoroallyl)pyrrolidine-1-carboxylate 3t. The same method as Example 1 was used, except that 4-phenyl-α-trifluoromethyl olefin in Example 1 was replaced with 1-(benzyloxy)-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene, to obtain 76.3 mg of the target compound with a yield of 85%.

[0082] NMR analysis: 1 H NMR (400 MHz, CDCl 3 )δ7.63-7.30 (m, 7H), 7.12-6.90 (m, 2H), 5.09 (s, 2H), 4.08-3.62 (m, 1H), 3.64-3.1 8(m, 2H), 3.17-2.71(m, 1H), 2.60-2.24(m, 1H), 2.02-1.61(m, 4H), 1.51(s, 9H).At RT,this compound appears as an~1.5:1 mixture of rotamers. 13 C NMR (151 MHz, CDCl 3)δ158.1, 156.4-152.5 (m), 154.4, 136.9, 129.3, 128.6, 128.1, 127.5, 125.4, 11 4.88, 89.7 (dd, J = 17.3Hz), 79.5, 70.0, 55.6, 46.3, 31.7, 29.5, 28.6, 22.6.Peaks corresponding to the minor rotamer are present at δ158.0, 137.0, 78.9, 46.7, 30.7, 29.0, 23.6.

[0083] Example 13: Preparation of tert-butyl 2-(2-(dibenzo(b,d)thiophene-4-yl)-3,3-difluoroallyl)pyrrolidine-1-carboxylate 3g', except that the 4-phenyl-α-trifluoromethyl olefin in Example 1 was replaced with an equal molar amount of 4-(3,3,3-trifluoroprop-1-en-2-yl)dibenzo(b,d)thiophene, and the target compound 81.6 mg was obtained with a yield of 95%.

[0084] NMR analysis: 1 H NMR (400 MHz, CDCl 3 )δ8.20-8.03(m, 2H), 7.92-7.77(m, 1H), 7.58-7.29(m, 4H), 4.05-3.54(m, 1H), 3.55-3.2 3(m, 2H), 3.24-2.85(m, 1H), 2.70-2.41(m, 1H), 2.00-1.63(m, 4H), 1.55-1.16(m, 9H).At RT, this compound appears as an~2.3:1mixture of rotamers. 13 C NMR (101 MHz, CDCl 3 )δ154.3, 154.0 (t, J=290.9Hz), 139.8, 139.1, 136.1, 135.8, 128.4, 127.5, 127.1, 124.8, 124.5, 122 .7, 121.8, 121.2, 89.70, 89.5 (dd, J=23.2, 16.7Hz), 79.3, 55.9, 46.3, 32.7, 30.1, 28.3, 22.8.Peaks corresponding to the minor rotamer are present at δ78.9, 46.7, 31.9, 29.8, 29.7, 28.5, 23.6.

[0085] Example 14: Preparation of 4-(7-(2,5-dimethylphenoxy)-1,1-difluoro-4,4-dimethylhept-1-en-2-yl)-1,1′-biphenyl 3k′, except that the tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate in Example 1 was replaced with an equal molar amount of 2-((5-(2,5-dimethylphenoxy)-2,2-dimethylpentyl)oxy)isoindolin-1,3-dione, and the target compound (64.7 mg) was obtained in a yield of 74%.

[0086] NMR analysis: 1 H NMR (600 MHz, CDCl 3 )δ7.67(d, J=7.9Hz, 4H), 7.55-7.47(m, 4H), 7.43(t, J=7.3Hz, 1H), 7.11(d, J=7.4Hz, 1H), 6.76(d, J=7.3Hz, 1H), 6.65(s , 1H), 3.82 (t, J = 6.4Hz, 2H), 2.53 (s, 2H), 2.37 (s, 3H), 2.29 (s, 3H), 1.84-1.76 (m, 2H), 1.45-1.40 (m, 2H), 0.96 (s, 6H).

[0087] Example 15: Preparation of (1S, 2S, 4aR, 8aR)-1-(3-((1, 1′-biphenyl)-4-yl)-4, 4-difluorobut-3-en-1-yl)-2,5,5,8a-tetramethyldecahydronaphthalene-2-ol 3l, by the same method as in Example 1, except that the tert-butyl (R)-2-(((1,3-dioxoisoindolin-2-yl)oxy)methyl)pyrrolidine-1-carboxylate in Example 2 was replaced with an equal molar amount of 2-(((3aS, 5aR, 9aR, 9bS)-3a, 6,6,9a-tetramethyldodecahydronaphtho(2,1-b)furan-2-yl)oxy)isoindolin-1,3-dione to obtain 40.7 mg of the target compound in a yield of 45%.

[0088] NMR analysis: 1 H NMR (400 MHz, CDCl 3)δ7.67-7.56(m, 4H), 7.49-7.42(m, 2H), 7.42-7.32(m, 3H), 2.60-2.42(m, 1H), 2.34-2.12(m, 1H), 1.67-1 .49 (m, 2H), 1.46-1.01 (m, 9H), 0.83 (s, 3H), 0.81 (s, 3H), 0.79 (s, 3H), 0.77 (s, 3H), 0.73 (d, J=6.9Hz, 4H). 13 C NMR (101 MHz, CDCl 3 ) 6154.5 (dd, J=289.2, 288.1Hz), 140.7, 139.7, 135.1 (q, J=2.4Hz), 129.1 (t, J=2.4Hz), 128.9, 127.5, 127.1, 127.0, 90.5 (dd, J= 21.3, 13.1Hz), 56.6, 52.8, 42.1, 41.9, 40.5, 40.4, 39.6 (t, J=2.2Hz), 38.4, 33.6, 33.4, 21.8, 20.3, 18.8 (d, J=3.7Hz), 15.4, 8.4.

[0089] Embodiment 16:

[0090] The description of the above embodiments is only used to help understand the method of the present invention and its core concept. It should be pointed out that for ordinary technicians in this technical field, any modifications, equivalent substitutions and improvements made without departing from the principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for synthesizing difluoroolefins by using eosin Y as a catalyst for alcohol derivatives, characterized in that The α-trifluoromethyl olefin shown in Formula 1, the N-alkoxyphthalimide shown in Formula 2, a base, a reducing agent and a photocatalyst are dissolved in an organic solvent, and reacted at room temperature for 12 hours under visible light irradiation. After the reaction is completed, the reaction system is separated and purified to obtain the target product, that is, the geminal difluoroolefin and its derivatives shown in Formula 3 are synthesized, and the reaction formula is as follows:

2. The method for synthesizing difluoroolefins by using eosin Y as catalyst for alcohol derivatives according to claim 1, characterized in that The photocatalysts are Eosin Y, 4CzIPN, Me-Acr-Mes, and fac-[Ir(ppy)3].

3. The method for synthesizing difluoroolefins by using eosin Y as catalyst for alcohol derivatives according to claim 1, characterized in that The reducing agent is Hantzsch ester.

4. The method for synthesizing difluoroolefins by using eosin Y as catalyst for alcohol derivatives according to claim 1, characterized in that The inorganic base is potassium phosphate, sodium phosphate, potassium carbonate, sodium carbonate, and cesium carbonate.

5. The method for synthesizing difluoroolefins by using eosin Y as catalyst for alcohol derivatives according to claim 1, characterized in that The organic solvent is acetonitrile, toluene, tetrahydrofuran, and N,N-dimethylacetamide.

6. The method for synthesizing difluoroolefins by using eosin Y as a catalyst for alcohol derivatives according to claim 1, characterized in that The visible light is blue light.

7. The method for synthesizing difluoroolefins by using eosin Y as catalyst for alcohol derivatives according to claim 1, characterized in that The molar ratio of the α-trifluoromethyl olefin shown in Formula 1 to the N-alkoxyphthalimide shown in Formula 2 is 1:1.2 or 1:

2.

8. The method for synthesizing difluoroolefins by using eosin Y as catalyst for alcohol derivatives according to claim 1, characterized in that The molar ratio of the -trifluoromethyl olefin shown in Formula 1 to the photocatalyst is 1:0.

01.

9. The method for synthesizing difluoroolefins by using eosin Y as catalyst for alcohol derivatives according to claim 1, characterized in that The reaction is preferably carried out under an inert atmosphere, which may be nitrogen.

10. The method for synthesizing difluoroolefins using eosin Y as a catalyst for alcohol derivatives according to claim 1, characterized in that The steps of separating and purifying the reaction system are as follows: the reaction system is directly concentrated under reduced pressure, the obtained concentrate is separated and purified by column chromatography on silica gel, the eluent is petroleum ether or a mixture of petroleum ether and ethyl acetate, the eluate is collected and the solvent is evaporated to obtain the target product.

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