Gem-difluorocyclopentane compounds and their synthesis methods

Abstract

Embodiments of the present invention provide a geminal difluorocyclopentane compound and its synthesis method, belonging to the field of fluorine-containing cyclic compound synthesis technology. A geminal difluorocyclopentane compound with the following structural formula is provided, wherein Ar... 1 Selected from one of phenyl, 4-methylphenyl, 3,5-dimethylphenyl, 4-chlorophenyl, 4-bromophenyl, 3,5-ditrifluoromethylphenyl, 2-methyl-4-methoxyphenyl, and 2-naphthyl; Ar 2 This compound is selected from one of the following: phenyl, 4-tert-butylphenyl, 4-methylphenyl, 4-phenylphenyl, 4-methoxyphenyl, 4-methylthiophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 4-methoxycarbonylphenyl, 4-cyanophenyl, 2-methylphenyl, 2-fluorophenyl, 3,5-dimethylphenyl, 1-naphthyl, 3-thienyl, 3-benzothienyl, and 2-benzofuranyl. This compound exhibits higher lipophilicity, chemical stability, and the ability to form hydrogen bonds, making it widely applicable in drug design.

Description

Technical Field

[0001] This invention belongs to the field of fluorine-containing cyclic compound synthesis technology, specifically relating to a geminal difluorocyclopentane compound and its synthesis method. Background Technology

[0002] Introducing fluorine atoms or fluorine-containing functional groups into organic compounds can often alter their physical, chemical, and biological properties. The synthesis of fluorine-containing organic molecules has wide applications in new drug development and drug structure modification. With the increasing demands for green and low-carbon chemistry, developing synthetic methods for fluorine-containing organic compounds that are mild, low-cost, and widely applicable has become an important goal in the field of organic synthesis. Difluoromethylene (CF2) is considered a bioisostere of ether, methylene, carbonyl, phosphinate, and sulfonyl functional groups, which can improve the lipophilicity, binding affinity, and hydrogen bonding ability of compounds, and is widely used in drug design. Introducing difluoromethylene into cyclic hydrocarbons to obtain geminitrofluorocyclic hydrocarbons is an effective method in drug design; however, geminitrofluorocyclic hydrocarbons are difficult to obtain directly from cyclic hydrocarbons through fluorination. Therefore, developing synthetic methods for geminitrofluorocyclic hydrocarbons is a significant challenge in the field of medicinal chemistry.

[0003] Currently, the main methods for synthesizing geminitrofluorocyclic hydrocarbons are as follows:

[0004] 1. The gemini difluorocyclopropane compounds were obtained by cyclization of alkenes with a series of difluorocarbene reagents (Beilstein J. Org. Chem. 2021, 17, 245-272.), as shown below.

[0005]

[0006] The reaction of alkenes with difluorocarbene reagents to produce gem-difluorocyclopropanes can rapidly prepare gem-difluorocyclic hydrocarbons, and the preparation method is relatively simple. However, it is only applicable to the synthesis of gem-difluorocyclopropanes and cannot be applied to the synthesis of other gem-difluorocyclic hydrocarbons.

[0007] 2. Cyclic ketone raw materials are reacted with diethylaminosulfur trifluoride (DAST) or sulfuromorpholine trifluoride (Morph-DAST) via a deoxyfluorination reaction to prepare geminal difluorocyclic hydrocarbon compounds (ChemMedChem 2022,17,e202200365.), as shown below.

[0008]

[0009] This route can be used to synthesize various geminifluorocyclic hydrocarbons, but its disadvantages are: the use of highly toxic fluorinated reagents is not conducive to simplifying the process; cyclic ketone raw materials are not easy to obtain and it is necessary to prepare cyclic ketone raw materials with the same structure in advance.

[0010] 3. Another method is to prepare gemdifluorocyclopentene or gemdifluorocyclopentane compounds by cyclizing easily synthesized gemdifluorocyclopropene or gemdifluorocyclopropane with an olefin. As shown in reaction (1) below, gemdifluorocyclopropene and an olefin are first added under palladium catalysis to generate alkenyl gemdifluorocyclopropane, which is then cyclized at high temperature to obtain gemdifluorocyclopentene (J.Am.Chem.Soc.2022,144,20875-20883.); in reaction (2) below, gemdifluorocyclopentane is prepared by cycloaddition reaction of gemdifluorocyclopropane with an olefin catalyzed by the transition metal rhodium (Angew.Chem.Int.Ed.2023,62,e202307129.).

[0011]

[0012] In this method, although a series of gemdifluorocyclopentanes or gemdifluorocyclopentenes can be prepared by cyclization reactions of gemdifluorocyclopropanes or gemdifluorocyclopropenes with olefins, it generally requires the use of noble metal catalysts and ligands, and the reaction conditions are relatively complex, which is not conducive to industrial synthesis.

[0013] In summary, the development of a novel synthetic method for geminal difluorocyclopentane compounds is of great significance in addressing the problems of high cost of raw materials and reagents, narrow applicability of the reaction, and complex operation in the synthesis of geminal difluorocycloanes. Summary of the Invention

[0014] In view of this, the technical problem to be solved by the present invention is to provide a geminal difluorocyclopentane compound and a method for synthesizing the same. This synthetic method uses readily available raw materials, is simple to operate, has mild reaction conditions, and yields a high product.

[0015] The technical solution adopted in this invention is as follows:

[0016] In a first aspect of the invention, a geminitrofluorocyclopentane compound with the following structural formula is provided.

[0017]

[0018] Among them, Ar 1 Selected from one of phenyl, 4-methylphenyl, 3,5-dimethylphenyl, 4-chlorophenyl, 4-bromophenyl, 3,5-ditrifluoromethylphenyl, 2-methyl-4-methoxyphenyl, and 2-naphthyl; Ar 2 It is selected from one of phenyl, 4-tert-butylphenyl, 4-methylphenyl, 4-phenylphenyl, 4-methoxyphenyl, 4-methylthiophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 4-methoxycarbonylphenyl, 4-cyanophenyl, 2-methylphenyl, 2-fluorophenyl, 3,5-dimethylphenyl, 1-naphthyl, 3-thienyl, 3-benzothienyl, and 2-benzofuranyl.

[0019] In a second aspect of the present invention, a method for synthesizing the above-described geminal difluorocyclopentane compound is provided, the method comprising:

[0020] The geminal difluorocyclopentane compound was synthesized by using N-arylcyclopropylamine and 1,1-difluoro-2-arylethylene as raw materials under blue light irradiation and catalytic synthesis with an iridium photocatalyst.

[0021] In some embodiments, the synthesis method is as follows: using N-arylcyclopropylamine and 1,1-difluoro-2-arylethylene as raw materials, the geminal difluorocyclopentane compound is synthesized by iridium photocatalysis under blue light irradiation.

[0022] In some embodiments, the aryl group in the N-arylcyclopropylamine is one of phenyl, 4-methylphenyl, 3,5-dimethylphenyl, 4-chlorophenyl, 4-bromophenyl, 3,5-ditrifluoromethylphenyl, 2-methyl-4-methoxyphenyl, and 2-naphthyl.

[0023] In some embodiments, the aryl group in the 1,1-difluoro-2-arylethylene is one of phenyl, 4-tert-butylphenyl, 4-methylphenyl, 4-phenylphenyl, 4-methoxyphenyl, 4-methylthiophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 4-methoxycarbonylphenyl, 4-cyanophenyl, 2-methylphenyl, 2-fluorophenyl, 3,5-dimethylphenyl, 1-naphthyl, 3-thienyl, 3-benzothienyl, and 2-benzofuranyl.

[0024] In some embodiments, the iridium photocatalyst is bis[2-(4,6-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium (hexafluorophosphate) salt (Ir[dF(CF3)ppy]2(dtbbpy)PF6), bis[2-(4,6-difluorophenyl)-5-trifluoromethylpyridine](2-2'-bipyridine)iridium (hexafluorophosphate) salt (Ir[dF(CF3)ppy]2(bpy)PF6), bis(2-phenylpyridine)(2-2'-bipyridine)iridium (hexafluorophosphate) salt (Ir(ppy)2(bpy)PF6), bis[2-(4,6-difluorophenyl)-5-trifluoromethylpyridine](2-2'-bipyridine)iridium ( Ir[dF(CF3)ppy]2(bpy)PF6, bis[2-(4,6-difluorophenyl)pyridine][2-2'-bi(4-tert-butylpyridine)]iridium(hexafluorophosphate) (Ir(dFppy)2(dtbbpy)PF6), bis[2-(4-methylphenyl)-4-methylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium(hexafluorophosphate) (Ir[Me(Me)ppy]2(dtbbpy)PF6), bis[2-(4-fluorophenyl)-5-methylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium(hexafluorophosphate) (Ir[F(Me)ppy]2(dtbbpy)PF6), tri[2 -(4-trifluoromethylphenyl)pyridine]iridium(Ir(p-CF3ppy)3), tris[2-(4-fluorophenyl)pyridine]iridium(Ir(p-Fppy)3), di(2-phenylpyridine)(pyridine-2-carboxylic acid)iridium(Ir(ppy)2(pic)), di(2-(4,6-difluorophenyl)pyridine](pyridine-2-carboxylic acid)iridium(Ir(dFppy)2(pic)), di(2-(4,6-difluorophenyl)-5-trifluoromethylpyridine](pyridine-2-carboxylic acid)iridium(Ir[dF(CF3)ppy]2(pic)), di(2-phenylpyridine)(4-trifluoromethylpyridine-2-carboxylic acid)iridium(Ir(ppy)2[(4-CF3)p ic]), bis(2-phenylpyridine)(5-methoxypyridine-2-carboxylic acid) iridium (Ir(ppy)2[(5-OMe)pic]), bis(2-phenylpyridine)(6-methylpyridine-2-carboxylic acid) iridium (Ir(ppy)2[(6-Me)pic]), bis(2-phenylpyridine)(5-fluoropyridine-2-carboxylic acid) iridium (Ir(ppy)2[(5-F)pic]), bis(2-phenylpyridine)(5-chloropyridine-2-carboxylic acid) iridium (Ir(ppy)2[(5-Cl)pic]), bis(2-phenylpyridine)(4,5-difluoropyridine-2-carboxylic acid) iridium (Ir(ppy)2[(4,5-dF)pic]), bis[2-(4,One of the following: [6-difluorophenyl)pyridine](5-fluoropyridine-2-carboxylic acid) iridium (Ir(dFppy)2[(5-F)pic]), bis[2-(4,6-difluorophenyl)pyridine](4-trifluoromethylpyridine-2-carboxylic acid) iridium (Ir(dFppy)2[(4-CF3)pic]), bis[2-(4,6-difluorophenyl)pyridine](5-methoxypyridine-2-carboxylic acid) iridium (Ir(dFppy)2[(5-OMe)pic]), and bis[2-(4,6-difluorophenyl)pyridine](5-chloropyridine-2-carboxylic acid) iridium (Ir(dFppy)2[(5-Cl)pic]).

[0025] In some embodiments, the synthetic route of the synthesis method is as follows:

[0026]

[0027] In some embodiments, the synthesis method specifically includes:

[0028] N-arylcyclopropylamine 1 and 1,1-difluoro-2-arylethylene 2 were mixed in a solvent, and an iridium photocatalyst was added to obtain a mixed solution;

[0029] The mixed solution was subjected to a room temperature reaction under continuous blue light irradiation to obtain gem-difluorocyclopentane compound 3.

[0030] In some embodiments, the solvent is any one or a mixture of dichloromethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methanol, ethanol, isopropanol, and ethylene glycol, more preferably methanol.

[0031] In some embodiments, in the above synthesis method, the molar ratio of N-arylcyclopropylamine, 1,1-difluoro-2-arylethylene to iridium photocatalyst is 1:(1-10):(0.005-0.05), more preferably 1:6:0.02.

[0032] In some embodiments, in the above synthesis method, the concentration of N-arylcyclopropylamine in the mixed solution is 0.05-0.3 mol / L, more preferably 0.1 mol / L.

[0033] In some embodiments, the blue light irradiation specifically refers to continuous irradiation using a blue light lamp with a wavelength of 410–480 nm, more preferably 450–465 nm. The power of the blue light lamp is 3–30 W, more preferably 10–20 W.

[0034] In some embodiments, the reaction time in the above synthesis method is 12 to 30 hours.

[0035] The post-processing operations of this invention are simple. After the reaction for synthesizing the geminidiafluorocyclopentane compound is completed, a purification operation for the geminidiafluorocyclopentane compound is included.

[0036] In some specific embodiments of the present invention, the purification steps are as follows: the reaction solution is transferred from the reaction tube to a round-bottom flask, the solvent is removed under reduced pressure, and the crude product is separated by silica gel column chromatography to obtain a high-purity geminal difluorocyclopentane compound. Simultaneously, unreacted 1,1-difluoro-2-arylethylene feedstock can be recovered. The separated geminal difluorocyclopentane compound contains two isomers, cis and trans, and the ratio of the two isomers is determined by gas chromatography-mass spectrometry (GC-MS). The column chromatography separation operation uses 300-400 mesh silica gel, and the eluent is a 1:10 volume ratio mixture of ethyl acetate and petroleum ether.

[0037] The geminal difluorocyclopentane compound and its synthesis method according to embodiments of the present invention have at least one of the following advantages:

[0038] (1) The present invention provides a novel gem-difluorocyclopentane compound with higher ester affinity, chemical stability and ability to form hydrogen bonds, which can be widely used in drug design.

[0039] (2) The method for synthesizing gem-difluorocyclopentane compounds provided by this invention uses raw materials derived from inexpensive and readily available chemical reagents such as aryl bromides, 1-aminocyclopropane, aryl formaldehyde, and sodium difluorochloroacetate. The synthesis conditions are simple, requiring only the addition of a photocatalyst and continuous blue light irradiation in addition to the two reaction raw materials. The reaction cost is low, the amount of photocatalyst used is small, and there is no need to use large quantities of expensive precious metal catalysts and ligands, thus avoiding the use of strong acids, strong bases, unstable or difficult-to-obtain additives. The reaction operation is simple, requiring no anhydrous or oxygen-free reaction conditions, and can be carried out at room temperature. There are few reaction byproducts, the yield is high, and a wide range of gem-difluorocyclopentane compounds can be synthesized, making it suitable for large-scale production. Attached Figure Description

[0040] These and / or other aspects and advantages of the present invention will become apparent and readily understood from the following description of preferred embodiments taken in conjunction with the accompanying drawings, in which:

[0041] Figure 1 The 1H NMR spectrum of cis-3-(N-phenylamino)-2-(4-tert-butylphenyl)-1,1-difluorocyclopentane (cis-3a) prepared in Example 1;

[0042] Figure 2 The carbon NMR spectrum of cis-3-(N-phenylamino)-2-(4-tert-butylphenyl)-1,1-difluorocyclopentane (cis-3a) prepared in Example 1;

[0043] Figure 3 The nuclear magnetic resonance fluorine spectrum of cis-3-(N-phenylamino)-2-(4-tert-butylphenyl)-1,1-difluorocyclopentane (cis-3a) prepared in Example 1;

[0044] Figure 4 The 1H NMR spectrum of trans-3-(N-phenylamino)-2-(4-tert-butylphenyl)-1,1-difluorocyclopentane (trans-3a) prepared in Example 1;

[0045] Figure 5 The carbon NMR spectrum of trans-3-(N-phenylamino)-2-(4-tert-butylphenyl)-1,1-difluorocyclopentane (trans-3a) prepared in Example 1;

[0046] Figure 6 The nuclear magnetic resonance fluorine spectrum of trans-3-(N-phenylamino)-2-(4-tert-butylphenyl)-1,1-difluorocyclopentane (trans-3a) prepared in Example 1;

[0047] Figure 7 The 1H NMR spectrum of cis-3-(N-phenylamino)-2-(4-methylphenyl)-1,1-difluorocyclopentane (cis-3b) prepared in Example 2;

[0048] Figure 8 The carbon NMR spectrum of cis-3-(N-phenylamino)-2-(4-methylphenyl)-1,1-difluorocyclopentane (cis-3b) prepared in Example 2;

[0049] Figure 9 The nuclear magnetic resonance fluorine spectrum of cis-3-(N-phenylamino)-2-(4-methylphenyl)-1,1-difluorocyclopentane (cis-3b) prepared in Example 2;

[0050] Figure 10 The 1H NMR spectrum of trans-3-(N-phenylamino)-2-(4-methylphenyl)-1,1-difluorocyclopentane (trans-3b) prepared in Example 2;

[0051] Figure 11 The carbon NMR spectrum of trans-3-(N-phenylamino)-2-(4-methylphenyl)-1,1-difluorocyclopentane (trans-3b) prepared in Example 2;

[0052] Figure 12 The nuclear magnetic resonance fluorine spectrum of trans-3-(N-phenylamino)-2-(4-methylphenyl)-1,1-difluorocyclopentane (trans-3b) prepared in Example 2. Detailed Implementation

[0053] The technical solution of the present invention will be further described in detail below through embodiments and in conjunction with the accompanying drawings. In this specification, the same or similar reference numerals indicate the same or similar components. The following description of the embodiments of the present invention with reference to the accompanying drawings is intended to explain the overall inventive concept of the present invention and should not be construed as a limitation thereof.

[0054] To further illustrate the present invention, the method for synthesizing gem-difluorocyclopentane provided by the present invention will be described in detail below with reference to embodiments.

[0055] In the synthesis steps of the geminitrocyclopentane compounds in the following embodiments of the present invention, N-arylcyclopropylamine was synthesized from aryl bromide and 1-aminocyclopropane using a known synthetic method (J. Org. Chem. 2024, 89, 57-67). 1,1-Difluoro-2-arylethylene was synthesized from aryl formaldehyde and sodium difluorochloroacetate using a known synthetic method (Angew. Chem. Int. Ed. 2019, 58, 4690-4694).

[0056] Example 1

[0057] Preparation of 3-(N-phenylamino)-2-(4-tert-butylphenyl)-1,1-difluorocyclopentane (3a)

[0058] Add 2.6 mg (0.004 mmol) of bis[2-(4,6-difluorophenyl)pyridine](pyridine-2-carboxylic acid)iridium, 26.6 mg (0.2 mmol) of N-phenylcyclopropylamine, 235.2 mg (1.2 mmol) of 2-(4-tert-butylphenyl)-1,1-difluoroethylene, and 2 mL of methanol to a 10 mL dry Schlenk tube. Tighten the Schlenk stopcock and stir at room temperature under blue light for 24 h. After the reaction is complete, transfer the reaction solution to a round-bottom flask, remove the solvent under reduced pressure, and separate the crude product by column chromatography (using 300-400 mesh silica gel as the column and a 1:10 mixture of ethyl acetate and petroleum ether as the eluent). 56.5 mg of white solid products cis-3a and trans-3a were obtained, with a yield of 86% (cis:trans = 32:68). 186.2 mg of 2-(4-tert-butylphenyl)-1,1-difluoroethylene was recovered.

[0059] The structure and NMR spectral data of compound 3a are as follows:

[0060]

[0061] See Figure 1 , 1H NMR (400MHz, CDCl3) δ7.35(d,J=8.2Hz,2H),7.27–7.19(m,2H),7.16(t,J=7.8Hz,2H),6.71(t,J=7.4Hz,1H),6.52(d,J=8 .0Hz,2H),4.40–4.27(m,1H),3.77–3.64(m,2H),2.57–2.33(m,2H),2.33–2.19(m,1H),2.08–1.96(m,1H),1.32(s,9H).See Figure 2 , 13 C NMR (101MHz, CDCl3) δ 150.2, 146.7, 131.3 (dd, J = 255.2, 250.4Hz), 129.3 (t, J = 2.4Hz), 129.2, 129.1, 125.4, 117.5, 113.1, 54.4 (d, J = 5.4Hz), 54.2 (dd, J = 23.9, 21.5Hz), 34.4, 33.9 (t, J = 25.1Hz), 31.2, 28.1 (t, J = 4.0Hz). See also Figure 3 , 19 F NMR (376MHz, CDCl3) δ -87.47 (d, J = 232.3Hz), -94.35 (d, J = 232.4Hz).

[0062]

[0063] See Figure 4 , 1 H NMR (400MHz, CDCl3) δ7.37(d,J=8.3Hz,2H),7.24(d,J=8.2Hz,2H),7.15(t,J=7.9Hz,2H),6.72(t,J=7.3Hz,1H),6.57(d,J=7.9Hz,2H),4.17 See Figure 5 , 13C NMR (101MHz, CDCl3) δ 150.7, 147.1, 130.3 (d, J = 1.6Hz), 129.3, 128.8, 128.3 (dd, J = 253.2, 251.0Hz), 125.5, 117.9, 113.4, 57.9 (t, J = 23.0Hz), 55.9 (d, J = 7.4Hz), 34.5, 33.5 (t, J = 25.0Hz), 31.3, 29.0 (dd, J = 4.4, 3.0Hz). See also Figure 6 , 19 F NMR (376MHz, CDCl3) δ -95.5 (d, J = 228.2Hz), -97.3 (d, J = 228.2Hz).

[0064] Example 2

[0065] Preparation of 3-(N-phenylamino)-2-(4-methylphenyl)-1,1-difluorocyclopentane (3b)

[0066] Add 2.6 mg (0.004 mmol) of bis[2-(4,6-difluorophenyl)pyridine](pyridine-2-carboxylic acid)iridium, 26.6 mg (0.2 mmol) of N-phenylcyclopropylamine, 184.8 mg (1.2 mmol) of 2-(4-methylphenyl)-1,1-difluoroethylene, and 2 mL of methanol to a 10 mL dry Schlenk tube. Tighten the Schlenk stopcock and stir at room temperature under blue light for 24 h. After the reaction is complete, transfer the reaction solution to a round-bottom flask, remove the solvent under reduced pressure, and separate the crude product by column chromatography (using 300-400 mesh silica gel as the column and a 1:10 mixture of ethyl acetate and petroleum ether as the eluent). This yields 39.1 mg of colorless oily liquid products cis-3b and trans-3b, with a yield of 68% (cis:trans = 47:53). 150.9 mg of 2-(4-methylphenyl)-1,1-difluoroethylene was recovered.

[0067] The structure and NMR spectral data of compound 3b are as follows:

[0068]

[0069] See Figure 7 , 1¹H NMR (400MHz, CDCl₃) δ 7.21–7.08 (m, 6H), 6.70 (t, J = 7.3Hz, 1H), 6.55–6.47 (m, 2H), 4.37–4.29 (m, 1H), 3.77–3.64 (m, 2H), 2.55–2.35 (m, 2H), 2.33 (s, 3H), 2.32–2.21 (m, 1H), 2.05–1.93 (m, 1H). See also Figure 8 , 13 C NMR (101MHz, CDCl3) δ 146.7, 137.1, 131.2 (dd, J = 255.7, 250.0Hz), 129.4, 129.3 (d, J = 2.5Hz), 129.2, 129.2, 117.6, 113.2, 54.41 (d, J = 5.3Hz), 54.38 (dd, J = 24.0, 21.5Hz), 33.8 (t, J = 25.2Hz), 28.3 (t, J = 4.0Hz), 21.0. See also Figure 9 , 19 F NMR (376MHz, CDCl3) δ-87.2 (d, J = 232.8Hz), -95.0 (d, J = 232.9Hz).

[0070]

[0071] See Figure 10 , 1 H NMR (400MHz, CDCl3) δ7.17(p,J=8.3Hz,6H),6.71(t,J=7.3Hz,1H),6.56(d,J=7.9Hz,2H),4.16(q,J=8 .3Hz,1H),3.74(s,1H),3.35–3.18(m,1H),2.65–2.53(m,1H),2.50–2.23(m,5H),1.77–1.64(m,1H).See Figure 11 , 13 C NMR (101MHz, CDCl3) δ 147.1, 137.6, 130.4 (d, J = 1.6Hz), 129.30, 129.27, 129.0, 128.2 (dd, J = 253.6, 252.2Hz), 117.9, 113.4, 58.1 (t, J = 23.1Hz), 56.0 (d, J = 7.2Hz), 33.5 (dd, J = 25.2, 24.3Hz), 29.0 (dd, J = 4.7, 2.9Hz), 21.1. See also Figure 12 , 19F NMR (376MHz, CDCl3) δ -95.4 (d, J = 228.6Hz), -97.3 (d, J = 228.4Hz).

[0072] Example 3

[0073] Preparation of 3-(N-phenylamino)-2-(4-phenylphenyl)-1,1-difluorocyclopentane (3c)

[0074] Add 2.6 mg (0.004 mmol) of bis[2-(4,6-difluorophenyl)pyridine](pyridine-2-carboxylic acid)iridium, 26.6 mg (0.2 mmol) of N-phenylcyclopropylamine, 259.2 mg (1.2 mmol) of 2-(4-phenylphenyl)-1,1-difluoroethylene, and 2 mL of methanol to a 10 mL dry Schlenk tube. Tighten the Schlenk stopcock and stir at room temperature under blue light for 24 h. After the reaction is complete, transfer the reaction solution to a round-bottom flask, remove the solvent under reduced pressure, and separate the crude product by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a mixture of ethyl acetate and petroleum ether at a volume ratio of 1:10). 48.9 mg of white solid products cis-3c and trans-3c were obtained, with a yield of 70% (cis:trans = 40:60). 209.5 mg of 2-(4-phenylphenyl)-1,1-difluoroethylene was recovered.

[0075] The 3c structure and NMR spectral data of the compound are as follows:

[0076]

[0077] 1 H NMR (400MHz, CDCl3) δ7.57(dd,J=13.1,7.8Hz,4H),7.44(t,J=7.6Hz,2H),7.40–7.31(m,3H),7.16(t,J=7.8Hz,2H),6.71(t,J=7.3Hz,1H),6.54(d,J= 8.0Hz,2H),4.40(p,J=7.4,6.7Hz,1H),3.79(td,J=14.2,6.9Hz,1H),3.67 (d,J=7.7Hz,1H),2.61–2.37(m,2H),2.37–2.24(m,1H),2.11–1.97(m,1H). 13C NMR (101MHz, CDCl3) δ146.6, 140.5, 140.2, 131.2 (dd, J = 256.4, 251.9Hz), 131.5 (d, J = 2.0Hz), 129.9, 129.3, 128.8, 12 7.4,127.1,127.0,117.7,113.2,54.5(d,J=5.4Hz),54.4(dd,J=23.7,21.6Hz),33.9(t,J=25.2Hz),28.3(t,J=3.9Hz). 19 F NMR (376MHz, CDCl3) δ -87.3 (d, J = 233.0Hz), -94.5 (d, J = 233.0Hz).

[0078]

[0079] 1 H NMR (400MHz, CDCl3) δ7.59(d,J=8.1Hz,4H),7.49–7.31(m,5H),7.17(dd,J=8.5,7.4Hz,2H),6.74(t,J=7.3Hz,1H),6.60(d,J=7.7Hz,2H),4 .25(q,J=8.1Hz,1H),3.78(d,J=9.2Hz,1H),3.35(ddd,J=18.2,13.2,10.5Hz,1H),2.69–2.27(m,3H),1.76(ddt,J=13.1,10.3,8.2Hz,1H). 13 C NMR (101MHz, CDCl3) δ147.0, 140.8, 140.7, 132.6 (d, J = 1.7Hz), 129.5, 129.3, 128.7, 128.3 (dd, J = 253.0, 251.4Hz), 12 7.3, 127.1, 118.1, 113.5, 58.3 (t, J = 22.9Hz), 56.3 (d, J = 7.2Hz), 33.6 (dd, J = 25.4, 24.5Hz), 29.1 (dd, J = 4.5, 2.9Hz). 19 F NMR (376MHz, CDCl3) δ -95.0 (d, J = 228.8Hz), -97.1 (d, J = 228.8Hz).

[0080] Example 4

[0081] Preparation of 3-(N-phenylamino)-2-(4-methoxyphenyl)-1,1-difluorocyclopentane (3d)

[0082] Add 2.6 mg (0.004 mmol) of bis[2-(4,6-difluorophenyl)pyridine](pyridine-2-carboxylic acid)iridium, 26.6 mg (0.2 mmol) of N-phenylcyclopropylamine, 204 mg (1.2 mmol) of 2-(4-methoxyphenyl)-1,1-difluoroethylene, and 2 mL of methanol to a 10 mL dry Schlenk tube. Tighten the Schlenk stopcock and stir at room temperature under blue light for 24 h. After the reaction is complete, transfer the reaction solution to a round-bottom flask, remove the solvent under reduced pressure, and separate the crude product by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a mixture of ethyl acetate and petroleum ether at a volume ratio of 1:10). A total of 45.4 mg of colorless oily liquid products cis-3d and trans-3d were obtained, with a yield of 75% (cis:trans = 40:60). 171.2 mg of 2-(4-methoxyphenyl)-1,1-difluoroethylene was recovered.

[0083] The 3d structure and NMR spectral data of the compound are as follows:

[0084]

[0085] 1 H NMR (400MHz, CDCl3) δ7.20(d,J=8.5Hz,2H),7.14(t,J=7.8Hz,2H),6.86(d,J=8.7Hz,2H),6.69(t,J=7.3Hz,1H),6.50(d, J=7.9Hz,2H),4.37–4.25(m,1H),3.79(s,3H),3.74–3.56(m,2H),2.56–2.21(m,3H),1.98(ddt,J=16.7,11.0,5.8Hz,1H). 13 C NMR (101MHz, CDCl3) δ158.8, 146.7, 131.2 (dd, J = 255.2, 250.3Hz), 130.6, 129.2, 124.4 (d, J = 2.1Hz), 117.6 ,113.9,113.1,55.2,54.4(d,J=5.5Hz),54.0(dd,J=23.9,21.4Hz),33.8(t,J=25.2Hz),28.3(t,J=3.9Hz). 19 F NMR (376MHz, CDCl3) δ -87.8 (d, J = 232.3Hz), -95.1 (d, J = 232.3Hz).

[0086]

[0087] 1H NMR (400MHz, CDCl3) δ7.24(d,J=8.6Hz,2H),7.16(t,J=7.8Hz,2H),6.90(d,J=8.6Hz,2H),6.72(t,J=7.3Hz,1H),6.57(d,J=8.1Hz,2H),4.13(q,J=7.9 Hz,1H),3.80(s,3H),3.73(brs,1H),3.24(ddd,J=18.5,13.0,10.7Hz,1H) ,2.58(ddt,J=16.9,8.7,4.5Hz,1H),2.49–2.22(m,2H),1.78–1.65(m,1H). 13 C NMR (101MHz, CDCl3) δ159.2,147.1,130.2,129.3,128.2(dd,J=253.5,251.8Hz),125.4(d,J=1.7Hz),117.9,1 14.0, 113.4, 57.7 (t, J = 23.0Hz), 56.1 (d, J = 7.3Hz), 55.2, 33.4 (dd, J = 25.5, 24.4Hz), 29.0 (dd, J = 4.7, 2.9Hz). 19 F NMR (376MHz, CDCl3) δ -95.8 (d, J = 228.3Hz), -97.4 (d, J = 228.3Hz).

[0088] Example 5

[0089] Preparation of 3-(N-phenylamino)-2-(4-methylthiophenyl)-1,1-difluorocyclopentane (3e)

[0090] Add 2.6 mg (0.004 mmol) of bis[2-(4,6-difluorophenyl)pyridine](pyridine-2-carboxylic acid)iridium, 26.6 mg (0.2 mmol) of N-phenylcyclopropylamine, 223.2 mg (1.2 mmol) of 2-(4-methylthiophenyl)-1,1-difluoroethylene, and 2 mL of methanol to a 10 mL dry Schlenk tube. Tighten the Schlenk stopcock and stir at room temperature under blue light for 24 h. After the reaction is complete, transfer the reaction solution to a round-bottom flask, remove the solvent under reduced pressure, and separate the crude product by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a mixture of ethyl acetate and petroleum ether at a volume ratio of 1:10). A total of 49.7 mg of colorless oily liquid products cis-3e and trans-3e were obtained, with a yield of 78% (cis:trans = 56:44). 178.5 mg of 2-(4-methylthiophenyl)-1,1-difluoroethylene was recovered.

[0091] The structure and NMR spectral data of compound 3e are as follows:

[0092]

[0093] 1 H NMR (400MHz, CDCl3) δ7.23–7.18(m,4H),7.18–7.10(m,2H),6.70(t,J=7.3Hz,1H),6.50(d,J=7.8Hz,2H),4.38– 4.29(m,1H),3.75–3.64(m,1H),3.60(d,J=6.5Hz,1H),2.55–2.33(m,5H),2.33–2.22(m,1H),2.05–1.92(m,1H). 13 C NMR (101MHz, CDCl3) δ146.6,137.7,131.1(dd,J=255.3,250.8Hz),130.0,129.3,129.2(d,J=2.4Hz),126.5 ,117.7,113.2,54.5(d,J=4.7Hz),54.2(dd,J=23.9,21.2Hz),33.8(t,J=25.1Hz),28.3(t,J=3.9Hz),15.7. 19 F NMR (376MHz, CDCl3) δ-87.6 (d, J = 233.1Hz), -94.8 (d, J = 232.9Hz).

[0094]

[0095] 1 H NMR (400MHz, CDCl3) δ7.23 (s, 4H), 7.15 (t, J = 7.9Hz, 2H), 6.72 (t, J = 7.3Hz, 1H), 6.55 (d, J = 7.8Hz, 2H), 4.14 (q, J = 8.1Hz, 1H),3.71(brs,1H),3.33–3.17(m,1H),2.65–2.53(m,1H),2.47(s,3H),2.46–2.21(m,2H),1.71(dq,J=13.1,8.4Hz,1H). 13C NMR (101MHz, CDCl3) δ147.0,138.2,130.3(d,J=1.8Hz),129.6,129.3,128.1(dd,J=253.1,251.4Hz),126.7,1 18.1, 113.4, 58.1 (t, J = 22.9Hz), 56.2 (d, J = 7.3Hz), 33.5 (dd, J = 25.3, 24.3Hz), 29.1 (dd, J = 4.5, 3.0Hz), 15.7. 19 F NMR (376MHz, CDCl3) δ -95.3 (d, J = 228.6Hz), -97.3 (d, J = 228.7Hz).

[0096] Example 6

[0097] Preparation of 3-(N-phenylamino)-2-(4-chlorophenyl)-1,1-difluorocyclopentane (3f)

[0098] Add 2.6 mg (0.004 mmol) of iridium di(2-phenylpyridine)(5-fluoropyridine-2-carboxylic acid), 26.6 mg (0.2 mmol) of N-phenylcyclopropylamine, 208.8 mg (1.2 mmol) of 2-(4-chlorophenyl)-1,1-difluoroethylene, and 2 mL of methanol to a 10 mL dry Schlenk tube. Tighten the Schlenk stopcock and stir at room temperature under blue light for 24 h. After the reaction is complete, transfer the reaction solution to a round-bottom flask, remove the solvent under reduced pressure, and separate the crude product by column chromatography (using 300-400 mesh silica gel as the column and a 1:10 mixture of ethyl acetate and petroleum ether as the eluent). 51.0 mg of white solid products cis-3f and trans-3f were obtained, with a yield of 83% (cis:trans = 53:47). 160.1 mg of 2-(4-chlorophenyl)-1,1-difluoroethylene was recovered.

[0099] The structure and NMR spectral data of compound 3f are as follows:

[0100]

[0101] 1H NMR(400MHz,CDCl3)δ7.27(d,J=9.1Hz,2H),7.21(d,J=8.4Hz,2H),7.14(t,J=7.8Hz,2H),6.70(t,J=7.3Hz,1H),6.49(d,J=7.9Hz,2H),4.35(q,J=5.8Hz,1H),3.77–3.64(m,1H),3.58(brs,1H),2.54–2.33(m,2H),2.34–2.22(m,1H),2.05–1.92(m,1H). 13 CNMR(101MHz,CDCl3)δ146.4,133.3,131.0(d,J=1.6Hz),130.9,129.3,128.5,117.8,113.0,54.3(d,J=5.6Hz),54.0(dd,J=23.6,21.3Hz),33.7(t,J=25.0Hz),28.3(t,J=4.0Hz). 19 F NMR(376MHz,CDCl3)δ-88.2(d,J=233.2Hz),-94.5(d,J=233.2Hz).

[0102]

[0103] 1 H NMR(400MHz,CDCl3)δ7.32(d,J=8.4Hz,2H),7.24(d,J=8.5Hz,2H),7.15(t,J=7.8Hz,2H),6.73(t,J=7.3Hz,1H),6.55(d,J=7.9Hz,2H),4.15(q,J=8.5Hz,1H),3.68(s,1H),3.26(ddd,J=18.2,13.1,10.5Hz,1H),2.63–2.53(m,1H),2.51–2.21(m,2H),1.71(dq,J=13.1,8.4Hz,1H). 13 C NMR(101MHz,CDCl3)δ146.8,133.8,132.2(d,J=1.8Hz),130.5,129.3,128.8,128.0(dd,J=253.3,251.6Hz),118.2,113.4,58.0(t,J=22.9Hz),56.3(d,J=7.2Hz),33.5(dd,J=25.3,24.2Hz),29.0(dd,J=4.6,2.9Hz). 19F NMR (376MHz, CDCl3) δ -95.2 (d, J = 229.5Hz), -97.2 (d, J = 229.0Hz).

[0104] Example 7

[0105] Preparation of 3-(N-phenylamino)-2-(4-bromophenyl)-1,1-difluorocyclopentane (3g)

[0106] Add 2.6 mg (0.004 mmol) of iridium di(2-phenylpyridine)(5-fluoropyridine-2-carboxylic acid), 26.6 mg (0.2 mmol) of N-phenylcyclopropylamine, 262.8 mg (1.2 mmol) of 2-(4-bromophenyl)-1,1-difluoroethylene, and 2 mL of methanol to a 10 mL dry Schlenk tube. Tighten the Schlenk stopcock and stir at room temperature under blue light for 24 h. After the reaction is complete, transfer the reaction solution to a round-bottom flask, remove the solvent under reduced pressure, and separate the crude product by column chromatography (using 300-400 mesh silica gel as the column and a 1:10 mixture of ethyl acetate and petroleum ether as the eluent). This yields 55.0 mg of white solid products cis-3g and trans-3g, with a yield of 78% (cis:trans = 43:57). 194.9 mg of 2-(4-bromophenyl)-1,1-difluoroethylene was recovered.

[0107] The structure and NMR spectral data of compound 3g are as follows:

[0108]

[0109] 1 H NMR (400MHz, CDCl3) δ7.43(d,J=8.4Hz,2H),7.19–7.11(m,4H),6.72(t,J=7.3Hz,1H),6.50(d,J=7.9Hz,2H),4.36 (s,1H),3.69(td,J=15.4,14.5,6.7Hz,1H),3.59(s,1H),2.56–2.34(m,2H),2.34–2.22(m,1H),2.05–1.92(m,1H). 13 C NMR (101MHz, CDCl3) δ146.4,131.5(d,J=1.4Hz),131.5,131.2,130.9(dd,J=254.8,251.7Hz),129.3,12 1.5, 117.9, 113.1, 54.4 (d, J = 5.8Hz), 54.1 (dd, J = 23.7, 21.3Hz), 33.8 (t, J = 25.1Hz), 28.3 (t, J = 3.9Hz).19 F NMR (376MHz, CDCl3) δ -88.2 (d, J = 233.2Hz), -94.5 (d, J = 233.2Hz).

[0110]

[0111] 1 H NMR (400MHz, CDCl3) δ7.48(d,J=8.4Hz,2H),7.17(dd,J=15.5,8.1Hz,4H),6.73(t,J=7.3Hz,1H),6.55(d,J=8.0Hz,2H),4.15(q,J=8.2 Hz,1H),3.69(s,1H),3.25(ddd,J=18.2,12.9,10.7Hz,1H),2.59(ddt,J=16.9,8.2,4.5Hz,1H),2.51–2.23(m,2H),1.78–1.65(m,1H). 13 C NMR(101MHz, CDCl3)δ146.8,132.6(d,J=1.8Hz),131.7,130.8,129.3,128.0(dd,J=254.3,252.4Hz),122.0 ,118.2,113.4,58.0(t,J=22.9Hz),56.1(d,J=7.2Hz),33.5(dd,J=25.3,24.4Hz),29.0(dd,J=4.6,2.8Hz). 19 F NMR (376MHz, CDCl3) δ-95.2 (d, J = 229.0Hz), -97.1 (d, J = 229.3Hz).

[0112] Example 8

[0113] Preparation of 3-(N-phenylamino)-2-(4-iodophenyl)-1,1-difluorocyclopentane (3h)

[0114] Add 2.6 mg (0.004 mmol) of bis(2-phenylpyridine)(5-fluoropyridine-2-carboxylic acid)iridium, 26.6 mg (0.2 mmol) of N-phenylcyclopropylamine, 319.2 mg (1.2 mmol) of 2-(4-iodophenyl)-1,1-difluoroethylene, and 2 mL of methanol to a 10 mL dry Schlenk tube. Tighten the Schlenk stopcock and stir at room temperature under blue light for 24 h. After the reaction is complete, transfer the reaction solution to a round-bottom flask, remove the solvent under reduced pressure, and separate the crude product by column chromatography (using 300-400 mesh silica gel as the column and a 1:10 mixture of ethyl acetate and petroleum ether as the eluent). 55.8 mg of white solid products cis-3h and trans-3h were obtained, with a yield of 70% (cis:trans = 60:40). 234.1 mg of 2-(4-iodophenyl)-1,1-difluoroethylene was recovered.

[0115] The structure and NMR spectral data of compound 3h are as follows:

[0116]

[0117] 1 H NMR (400MHz, CDCl3) δ7.63(d,J=8.4Hz,2H),7.15(t,J=7.9Hz,2H),7.03(d,J=8.2Hz,2H),6.71(t,J=7.3Hz,1H),6.50(d,J=7.9 Hz,2H),4.35(s,1H),3.67(td,J=14.4,13.7,6.8Hz,1H),3.57(s,1H),2.56–2.33(m,2H),2.33–2.20(m,1H),2.04–1.93(m,1H). 13 C NMR (101MHz, CDCl3) δ146.4, 137.4, 132.2 (d, J = 2.2Hz), 131.5, 130.9 (dd, J = 254.8, 251.6Hz), 129.3, 11 7.9, 113.1, 93.1, 54.4 (d, J = 6.0Hz), 54.2 (dd, J = 23.7, 21.4Hz), 33.8 (t, J = 25.1Hz), 28.3 (t, J = 3.9Hz). 19 F NMR (376MHz, CDCl3) δ -88.0 (d, J = 233.6Hz), -94.5 (d, J = 233.6Hz).

[0118]

[0119] 1H NMR (400MHz, CDCl3) δ7.68(d,J=8.4Hz,2H),7.20–7.11(m,2H),7.06(d,J=8.2Hz,2H),6.73(t,J=7.3Hz,1H),6.55(d,J=7.8Hz,2H), 4.15(q,J=8.0Hz,1H),3.68(s,1H),3.23(ddd,J=18.1,13.0,10.6Hz,1H),2.64–2.51(m,1H),2.50–2.22(m,2H),1.78–1.65(m,1H). 13 C NMR (101MHz, CDCl3) δ146.8,137.7,133.3(d,J=1.7Hz),131.0,129.3,127.9(dd,J=253.5,251.5Hz),1 18.2, 113.4, 93.6, 58.1 (t, J = 23.0Hz), 56.0 (d, J = 7.1Hz), 33.5 (d, J = 24.8Hz), 29.0 (dd, J = 4.6, 2.8Hz). 19 F NMR (376MHz, CDCl3) δ -95.1 (d, J = 229.0Hz), -97.0 (d, J = 229.3Hz).

[0120] Example 9

[0121] Preparation of 3-[N-(4-chlorophenyl)amino]-2-(4-tert-butylphenyl)-1,1-difluorocyclopentane (3i)

[0122] Add 2.6 mg (0.004 mmol) of iridium di(2-phenylpyridine)(5-fluoropyridine-2-carboxylic acid), 33.4 mg (0.2 mmol) of N-(4-chlorophenyl)cyclopropylamine, 235.2 mg (1.2 mmol) of 2-(4-tert-butylphenyl)-1,1-difluoroethylene, and 2 mL of methanol to a 10 mL dry Schlenk tube. Tighten the Schlenk stopcock and stir at room temperature under blue light for 24 h. After the reaction is complete, transfer the reaction solution to a round-bottom flask, remove the solvent under reduced pressure, and separate the crude product by column chromatography (using 300-400 mesh silica gel as the column and a 1:10 mixture of ethyl acetate and petroleum ether as the eluent). This yields 61.8 mg of white solid products cis-3i and trans-3i, with a yield of 85% (cis:trans = 43:57). 199.9 mg of 2-(4-tert-butylphenyl)-1,1-difluoroethylene was recovered.

[0123] The structure and NMR spectral data of compound 3i are as follows:

[0124]

[0125] 1 H NMR(400MHz,CDCl3)δ7.33(d,J=8.4Hz,2H),7.18(d,J=8.1Hz,2H),7.07(d,J=8.8Hz,2H),6.41(d,J=8.8Hz,2H),4.28(p,J=6.1Hz,1H),3.75–3.62(m,2H),2.57–2.20(m,3H),2.02–1.91(m,1H),1.31(s,9H). 13 C NMR(101MHz,CDCl3)δ150.3,145.3,131.1(dd,J=255.1,250.6Hz),129.11(d,J=1.7Hz),129.07,129.0,125.4,122.1,114.2,54.6(d,J=5.6Hz),54.2(dd,J=23.9,21.4Hz),34.4,33.8(t,J=25.3Hz),31.2,28.1(t,J=3.9Hz). 19 F NMR(376MHz,CDCl3)δ-88.0(d,J=232.8Hz),-94.9(d,J=232.6Hz).

[0126]

[0127] 1 H NMR(400MHz,CDCl3)δ7.41–7.35(m,2H),7.23(d,J=8.1Hz,2H),7.15–7.06(m,2H),6.52–6.44(m,2H),4.15(d,J=14.0Hz,1H),3.76(s,1H),3.26(ddd,J=18.3,13.1,10.4Hz,1H),2.62–2.23(m,3H),1.70(ddt,J=13.1,10.2,8.2Hz,1H),1.32(s,9H). 13 C NMR(101MHz,CDCl3)δ150.8,145.6,130.2(d,J=1.7Hz),129.0,128.7,128.2(t,J=253.1Hz),125.6,122.5,114.5,58.0(t,J=23.1Hz),56.2(d,J=7.3Hz),34.5,33.5(t,J=25.0Hz),31.3,28.8(dd,J=4.7,2.8Hz). 19F NMR (376MHz, CDCl3) δ-95.4 (d, J = 228.6Hz), -97.4 (d, J = 228.4Hz).

[0128] In summary, the preparation method described in this invention is characterized by mild conditions and simple operation. The synthesis reaction of gem-difluorocyclopentane compounds according to this invention involves few side reactions, high yields, simple post-processing, and low production costs, significantly improving the synthesis efficiency of gem-difluorocyclopentane compounds and facilitating large-scale industrial production.

[0129] The geminal difluorocyclopentane compound and its synthesis method according to embodiments of the present invention have at least one of the following advantages:

[0130] (1) The present invention provides a novel gem-difluorocyclopentane compound with higher ester affinity, chemical stability and ability to form hydrogen bonds, which can be widely used in drug design.

[0131] (2) The method for synthesizing gem-difluorocyclopentane compounds provided by this invention uses raw materials derived from inexpensive and readily available chemical reagents such as aryl bromides, 1-aminocyclopropane, aryl formaldehyde, and sodium difluorochloroacetate. The synthesis conditions are simple, requiring only the addition of a photocatalyst and continuous blue light irradiation in addition to the two reaction raw materials. The reaction cost is low, the amount of photocatalyst used is small, and there is no need to use large quantities of expensive precious metal catalysts and ligands, thus avoiding the use of strong acids, strong bases, unstable or difficult-to-obtain additives. The reaction operation is simple, requiring no anhydrous or oxygen-free reaction conditions, and can be carried out at room temperature. There are few reaction byproducts, the yield is high, and a wide range of gem-difluorocyclopentane compounds can be synthesized, making it suitable for large-scale production.

[0132] While some embodiments of the present general inventive concept have been shown and described, those skilled in the art will understand that changes may be made to these embodiments without departing from the principles and spirit of the present general inventive concept, the scope of which is defined by the claims and their equivalents.

Claims

1. A method for synthesizing a geminitrofluorocyclopentane compound, characterized in that, The structural formula of the gem-difluorocyclopentane compound is shown below: Among them, Ar 1 Selected from one of phenyl, 4-methylphenyl, 3,5-dimethylphenyl, 4-chlorophenyl, 4-bromophenyl, 3,5-ditrifluoromethylphenyl, 2-methyl-4-methoxyphenyl, and 2-naphthyl; Ar 2 It is selected from one of phenyl, 4-tert-butylphenyl, 4-methylphenyl, 4-phenylphenyl, 4-methoxyphenyl, 4-methylthiophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 4-methoxycarbonylphenyl, 4-cyanophenyl, 2-methylphenyl, 2-fluorophenyl, 3,5-dimethylphenyl, 1-naphthyl, 3-thienyl, 3-benzothienyl and 2-benzofuranyl; The synthesis method is as follows: The geminal difluorocyclopentane compound was synthesized by using N-arylcyclopropylamine and 1,1-difluoro-2-arylethylene as raw materials under blue light irradiation and catalytic synthesis with an iridium photocatalyst.

2. The synthesis method according to claim 1, characterized in that, The aryl group in the N-arylcyclopropylamine is one of phenyl, 4-methylphenyl, 3,5-dimethylphenyl, 4-chlorophenyl, 4-bromophenyl, 3,5-ditrifluoromethylphenyl, 2-methyl-4-methoxyphenyl, and 2-naphthyl.

3. The synthesis method according to claim 1, characterized in that, The aryl group in the 1,1-difluoro-2-arylethylene is one of phenyl, 4-tert-butylphenyl, 4-methylphenyl, 4-phenylphenyl, 4-methoxyphenyl, 4-methylthiophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 4-methoxycarbonylphenyl, 4-cyanophenyl, 2-methylphenyl, 2-fluorophenyl, 3,5-dimethylphenyl, 1-naphthyl, 3-thienyl, 3-benzothienyl, and 2-benzofuranyl.

4. The synthesis method according to claim 1, characterized in that, The iridium photocatalyst is bis[2-(4,6-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium (hexafluorophosphate) salt (Ir[dF(CF3)ppy]2(dtbbpy)PF6), bis[2-(4,6-difluorophenyl)-5-trifluoromethylpyridine](2-2'-bipyridine)iridium (hexafluorophosphate) salt (Ir[dF(CF3)ppy]2(bpy)PF6), bis(2-phenylpyridine)(2-2'-bipyridine)iridium (hexafluorophosphate) salt (Ir(ppy)2(bpy)PF6), bis[2-(4,6-difluorophenyl)-5-trifluoromethylpyridine](2-2'-bipyridine)iridium (hexafluorophosphate) salt (Ir[dF(CF3)ppy]2(bpy)PF6), bis[2-(4,6-difluorophenyl)pyridine][2-2'-bi(4-tert-butylpyridine)]iridium (hexafluorophosphate) salt (Ir(dFppy)2(dtbbpy)PF6), bis[2-(4-methylphenyl)-4-methylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium (hexafluorophosphate) salt (Ir[Me(Me)ppy]2(dtbbpy)PF6), bis[2-(4-fluorophenyl)-5-methylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium (hexafluorophosphate) salt (Ir[F(Me)ppy]2(dtbbpy)PF6), tri[2-(4- [Trifluoromethylphenyl]pyridine]iridium (Ir(p-CF3ppy)3), tri[2-(4-fluorophenyl)pyridine]iridium (Ir(p-Fppy)3), di(2-phenylpyridine)(pyridine-2-carboxylic acid)iridium (Ir(ppy)2(pic)), di[2-(4,6-difluorophenyl)pyridine](pyridine-2-carboxylic acid)iridium (Ir(dFppy)2(pic)), di[2-(4,6-difluorophenyl)-5-trifluoromethylpyridine](pyridine-2-carboxylic acid)iridium (Ir[dF(CF3)ppy]2(pic)), di(2-phenylpyridine)(4-trifluoromethylpyridine-2-carboxylic acid)iridium (Ir(ppy)2[(4-CF3)pic) ]), bis(2-phenylpyridine)(5-methoxypyridine-2-carboxylic acid) iridium (Ir(ppy)2[(5-OMe)pic]), bis(2-phenylpyridine)(6-methylpyridine-2-carboxylic acid) iridium (Ir(ppy)2[(6-Me)pic]), bis(2-phenylpyridine)(5-fluoropyridine-2-carboxylic acid) iridium (Ir(ppy)2[(5-F)pic]), bis(2-phenylpyridine)(5-chloropyridine-2-carboxylic acid) iridium (Ir(ppy)2[(5-Cl)pic]), bis(2-phenylpyridine)(4,5-difluoropyridine-2-carboxylic acid) iridium (Ir(ppy)2[(4,5-dF)pic]), bis[2-(4,One of the following: [6-difluorophenyl)pyridine](5-fluoropyridine-2-carboxylic acid) iridium (Ir(dFppy)2[(5-F)pic]), bis[2-(4,6-difluorophenyl)pyridine](4-trifluoromethylpyridine-2-carboxylic acid) iridium (Ir(dFppy)2[(4-CF3)pic]), bis[2-(4,6-difluorophenyl)pyridine](5-methoxypyridine-2-carboxylic acid) iridium (Ir(dFppy)2[(5-OMe)pic]), and bis[2-(4,6-difluorophenyl)pyridine](5-chloropyridine-2-carboxylic acid) iridium (Ir(dFppy)2[(5-Cl)pic]).

5. The synthesis method according to claim 1, characterized in that, The specific synthesis method is as follows: N-arylcyclopropylamine and 1,1-difluoro-2-arylethylene were mixed in a solvent, and an iridium photocatalyst was added to obtain a mixed solution. The mixed solution was subjected to a reaction at room temperature under continuous blue light irradiation to obtain a gem-difluorocyclopentane compound; The solvent is one or more selected from dichloromethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, methanol, ethanol, isopropanol, and ethylene glycol.

6. The synthesis method according to claim 1, characterized in that, The molar ratio of N-arylcyclopropylamine, 1,1-difluoro-2-arylethylene to iridium photocatalyst is 1:(1-10):(0.005-0.05).

7. The synthesis method according to claim 6, characterized in that, The concentration of N-arylcyclopropylamine in the mixed solution is 0.05-0.3 mol / L.

8. The synthesis method according to any one of claims 1-7, characterized in that, The conditions for blue light irradiation are: wavelength of 410-480nm and power of 3-30W.

9. The synthesis method according to claim 5, characterized in that, The reaction time is 12–30 h.

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