Synthesis method of novel fluorine-containing allyl tertiary nitro alkane compound

Abstract

The invention discloses a synthesis method of a novel fluorine-containing allyl tertiary nitro alkane compound, which comprises the following steps: by taking a gem-difluorocyclopropane derivative and sec-nitro alkane as raw materials, carrying out ring opening on gem-difluorocyclopropane under the catalysis of transition metal to generate a fluorine allyl-metal complex; and then reacting with sec-nitro alkane to obtain the straight-chain fluorine-containing allyl tert-nitro alkane compound. The method has obvious advantages in the aspects of synthesis conditions and practicability, has the advantages of simple synthesis steps, simplicity and convenience in operation, cheap and easily available raw materials, good compatibility to functional groups, high chemical selectivity, high reaction efficiency and the like, and is more in line with green and sustainable chemistry concepts; and reference and reliable technical support are provided for efficient synthesis of the fluorine-containing allyl tertiary nitro alkane compound.

Description

Technical Field

[0001] This invention relates to the field of fluorine-containing compounds and chemical synthesis technology, specifically to a method for synthesizing fluorine-containing allyl tertiary nitroalkane compounds. Background Technology

[0002] The unique properties exhibited by fluorine or fluorine-containing groups—including electronic effects, permeation effects, barrier effects, and mimicry effects—are collectively referred to as the "fluorine effect." The introduction of these groups can significantly modulate the physicochemical properties and biological activities of organic molecules, thus fluorinated organic compounds have significant application value in pharmaceuticals, pesticides, and functional materials. In drug design, fluorine or fluorine-containing fragments are often considered bioisosteres of classic pharmacophores such as hydrogen atoms, carbonyl groups, and sulfonyl groups, earning them the reputation of being the "universal key to molecular modification." The unique properties brought about by fluorine atoms have attracted widespread attention from chemists. Related research has not only promoted the development of various novel fluorinating reagents but has also gradually established diversified strategies for fluorination and the introduction of fluorine-containing functional groups, significantly expanding the research scope of organofluorine chemistry. Currently, one of the research focuses in this field is to utilize widely available and structurally simple raw materials, combined with efficient and highly selective synthetic methods, to achieve the precise construction of fluorine-containing molecules. Furthermore, since the introduction of fluorinated groups at different sites in a molecule often leads to significant differences in properties, achieving site-specific and controllable fluorination of complex skeletons (such as different carbon sites in alkenes) has become a highly valuable and challenging research direction in this field. Among these, the fluoroallyl skeleton, as an important structural unit, has been proven in medicinal chemistry and materials science to serve as a highly efficient enzyme inhibitor, isosteric amide, or enol mimic, exhibiting unique structural advantages and broad application prospects.

[0003] Nitroalkanes, as key functional building blocks, play an irreplaceable role in various fields such as pharmaceuticals, agrochemicals, energetic materials, and critical structural building blocks. Their structural diversity and reactivity make them indispensable synthetic building blocks for constructing complex functional molecules. Among them, tertiary nitroalkanes and their reduction products, α-tertiary amines, not only serve as key synthetic precursors in drug discovery but also frequently as the final structural units of target molecules, playing a crucial role in improving drug metabolic stability and bioavailability. The importance of these compounds and the challenges they present in synthetic methods have jointly promoted the development of various efficient synthetic strategies. Given that introducing fluorine atoms into organic molecules can powerfully alter their various properties, synthetic methods for fluorinated allyl tertiary nitroalkanes have not yet been reported. Summary of the Invention

[0004] The technical problem to be solved by this invention is to develop a method for synthesizing novel fluorinated allyl tertiary nitroalkane compounds.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: a novel method for synthesizing fluorinated allyl tertiary nitroalkanes, using gem-difluoropropane and secondary nitroalkanes as raw materials, under the catalysis of transition metals / ligands, generating fluorinated allyl-metal complexes through ring opening of gem-difluorocyclopropane, and then reacting with secondary nitroalkanes to obtain fluorinated allyl tertiary nitroalkanes. Attached Figure Description

[0006] This method conforms to the following reaction equation:

[0007]

[0008] Figure 1 The reaction equation is: gem-difluorocyclopropane with secondary nitroalkanes.

[0009]

[0010] Figure 2 It is a gemdifluorocyclopropane derivative.

[0011]

[0012] Figure 3 Secondary nitroalkanes

[0013] Among them, R 1 Represents a hydrogen atom or an alkyl, alkoxy, phenyl, nitrile, trifluoromethyl, ester, or halogen group containing one or more substituted groups; R 2 Represents hydrogen atom, alkyl group, phenyl group; R 3 It represents hydrogen atoms and alkyl groups. Detailed Implementation

[0014] The above-mentioned method for synthesizing a novel fluorinated allyl tert-nitro alkane compound is carried out according to the following steps: In a reaction tube, a geminitrocyclopropane derivative, a secondary nitro alkane, a metal catalyst, a ligand, a base, and a solvent are added, and the reaction is carried out at 75 °C under a nitrogen atmosphere for 24 hours. After cooling to room temperature, the mixture is filtered, and the solvent is removed under reduced pressure to obtain a crude product. The crude product is purified by column chromatography to obtain the fluorinated allyl tert-nitro alkane compound.

[0015] The metal catalysts are Co(OAc)2, Co(acac)3, Pd(dba)2, and Pd(P t One or more of the following: Bu3)2, [Pd(allyl)Cl]2, Pd(cod)Cl2, Pd(PPh3)4, Pd-PEPPSI-SIPr.

[0016] The ligand is tritert-butylphosphine ( tBu3P), 2-(dicyclohexylphosphine)-3,6-dimethoxy-2'-4'-6'-tris-isopropyl-1,1'-biphenyl (BrettPhos), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos), 2-di-tert-butylphosphine-2',4',6'-triisopropylbiphenyl ( t Bu-XPhos), tricyclohexylphosphine (PCy3), tri(1-adamantyl)phosphine (PAd3), 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphine)ferrocene (QPhos) or a mixture of two or more of these.

[0017] The base is one or a mixture of two or more of cesium hydroxide monohydrate, cesium hydroxide, potassium hydroxide, cesium carbonate, potassium phosphate, cesium fluoride, triethylamine, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

[0018] The solvent is one or a mixture of two or more of the following: 1,4-dioxane, tetrahydrofuran, cyclopentylmethyl ether, ethylene glycol dimethyl ether, trifluorotoluene, n-heptane, N,N-dimethylacetamide, and acetonitrile.

[0019] The molar ratio of geminitrocyclopropane derivatives to secondary nitroalkanes is 2:3.

[0020] The reaction tubes are Schlenk tubes.

[0021] The eluent in column chromatography is a mixture of petroleum ether, petroleum ether and ethyl acetate in a volume ratio of (2-100):1, or a mixture of dichloromethane and methanol in a volume ratio of (2-100):1.

[0022] The inventors have established a novel synthetic method for fluorinated allyl tert-nitroalkanes. Using gem-difluorocyclopropane and secondary nitroalkanes as raw materials, the method achieves ring-opening of gem-difluorocyclopropane and allyl alkylation of secondary nitroalkanes via transition metal catalysis to obtain fluorinated allyl tert-nitroalkanes. This invention has significant advantages in terms of synthetic conditions and practicality. It features simple synthetic steps, convenient operation, inexpensive and readily available raw materials, good compatibility with functional groups, high chemoselectivity, and high reaction efficiency. It also aligns better with the principles of green and sustainable chemistry, providing a reference and reliable technical support for the efficient synthesis of fluorinated allyl tert-nitroalkanes. Detailed Implementation

[0023] Example 1

[0024] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. tBu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 100:1 mixture of petroleum ether and ethyl acetate.

[0025] The structural characterization data of the obtained product are as follows:

[0026] 1 H NMR (600 MHz, CDCl3) δ 7.90 (d, J = 1.8 Hz, 1H), 7.83-7.79 (m, 3H), 7.63 (dd, J = 8.6, 1.8 Hz, 1H), 7.50-7.46 (m, 2H), 5.74 (d, J = 38.5 Hz, 1H), 3.04 (s, 1H), 3.01 (s, 1H), 1.73 (s, 6H).

[0027] 13 C NMR (151 MHz, CDCl3) δ 155.5 (d, J = 266.9 Hz), 133.4, 132.6,130.2 (d, J = 3.1 Hz), 128.1, 128.0, 127.9 (d, J = 7.5 Hz), 127.6, 126.4 (d, J = 7.7 Hz), 126.3, 126.2, 111.1 (d, J = 7.7 Hz), 87.2 (d, J = 3.9 Hz), 44.2 (d, J = 25.9 Hz), 25.9.

[0028] 19 F NMR (565 MHz, CDCl3) δ -98.50.

[0029] HRMS (APCI) m / z: [M+H + calcd for C 16 H 17 FNO2 + 274.1238; found: 274.1217.

[0030] Based on the above data, the structure of the product is inferred as follows:

[0031]

[0032] Example 2

[0033] Add 0.20 mmol of 1-(2,2-difluorocyclopropyl)-4-methoxybenzene, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 100:1 mixture of petroleum ether and ethyl acetate.

[0034] The structural characterization data of the obtained product are as follows:

[0035] 1 H NMR (600 MHz, CDCl3) δ 7.37-7.34 (m, 2H), 7.14 (d, J = 8.0 Hz, 2H), 5.55 (d, J = 38.8 Hz, 1H), 2.98 (s, 1H), 2.94 (s, 1H), 2.34 (s, 3H), 1.70 (s, 6H).

[0036] 13 C NMR (151 MHz, CDCl3) δ 154.5 (d, J = 264.8 Hz), 137.4 (d, J = 2.5Hz), 129.8 (d, J = 3.1 Hz), 129.2, 128.5 (d, J = 7.6 Hz), 110.8 (d, J = 8.2Hz), 87.2 (d, J = 4.1 Hz), 44.1 (d, J = 26.0 Hz), 25.8 (d, J = 1.8 Hz), 21.2.

[0037] 19 F NMR (565 MHz, CDCl3) δ -99.89.

[0038] HRMS (APCI) m / z: [M+H + calcd for C 13 H 17 FNO3 + 254.1187; found: 254.1182.

[0039] Based on the above data, the structure of the product is inferred as follows:

[0040]

[0041] Example 3

[0042] Add 0.20 mmol of 4-(2,2-difluorocyclopropyl)-N,N-dimethylaniline, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 20:1 mixture of petroleum ether and ethyl acetate.

[0043] The structural characterization data of the obtained product are as follows:

[0044] 1 H NMR (600 MHz, CDCl3) δ 7.39-7.34 (m, 2H), 6.70-6.65 (m, 2H), 5.47(d, J = 39.5 Hz, 1H), 2.96 (s, 6H), 2.96 (s, 1H), 2.92 (s, 1H), 1.68 (s, 6H).

[0045] 13 C NMR (151 MHz, CDCl3) δ 152.5 (d, J = 261.2 Hz), 149.7 (d, J = 2.4Hz), 129.6 (d, J = 7.3 Hz), 121.0, 112.1, 110.7 (d, J = 8.8 Hz), 87.3 (d, J =4.1 Hz), 44.2 (d, J = 26.3 Hz), 40.3, 25.7.

[0046] 19 F NMR (565 MHz, CDCl3) δ -103.72.

[0047] HRMS (APCI) m / z: [M+H + calcd for C 14 H 20 FN2O2 +267.1503; found: 267.1499.

[0048] Based on the above data, the structure of the product is inferred as follows:

[0049]

[0050] Example 4

[0051] Add (4-(2,2-difluorocyclopropyl)phenyl)methyl sulfide (0.20 mmol), 2-nitropropane (0.30 mmol), and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 30:1.

[0052] The structural characterization data of the obtained product are as follows:

[0053] 1 H NMR (600 MHz, CDCl3) δ 7.37 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5Hz, 2H), 5.53 (d, J = 38.5 Hz, 1H), 2.98 (s, 1H), 2.94 (s, 1H), 2.48 (s, 3H), 1.69 (s, 6H).

[0054] 13 C NMR (151 MHz, CDCl3) δ 154.9 (d, J = 265.6 Hz), 138.0 (d, J = 2.7Hz), 129.4 (d, J = 2.9 Hz), 128.9 (d, J = 7.7 Hz), 126.3, 110.4 (d, J = 7.8Hz), 87.1 (d, J = 4.1 Hz), 44.1 (d, J = 25.9 Hz), 25.8, 15.6.

[0055] 19 F NMR (565 MHz, CDCl3) δ -98.96.

[0056] HRMS (APCI) m / z: [M+H +calcd for C 13 H 17 FNO2S + 270.0959; found: 270.0953.

[0057] Based on the above data, the structure of the product is inferred as follows:

[0058]

[0059] Example 5

[0060] Add 0.20 mmol of 4'-(2,2-difluorocyclopropyl)-1,1'-biphenyl, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0061] The structural characterization data of the obtained product are as follows:

[0062] 1 H NMR (600 MHz, CDCl3) δ 7.61-7.53 (m, 6H), 7.44 (t, J = 7.7 Hz, 2H), 7.37-7.33 (m, 1H), 5.63 (d, J = 38.5 Hz, 1H), 3.02 (s, 1H), 2.98 (s, 1H), 1.72 (s, 6H).

[0063] 13 C NMR (151 MHz, CDCl3) δ 155.3 (d, J = 266.5 Hz), 140.5, 140.3,131.7, 129.0 (d, J = 7.7 Hz), 128.8, 127.4, 127.1, 127.0, 110.6 (d, J = 7.8Hz), 87.2 (d, J = 3.9 Hz), 44.1 (d, J = 25.8 Hz), 25.8.

[0064] 19 F NMR δ -98.35.

[0065] HRMS (APCI) m / z: [M+H + calcd for C 18 H 19 FNO2 + 300.1394; found: 300.1385.

[0066] Based on the above data, the structure of the product is inferred as follows:

[0067]

[0068] Example 6

[0069] Add 0.20 mmol of 1-(2,2-difluorocyclopropyl)-4-(trifluoromethyl)benzene, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 100:1 mixture of petroleum ether and ethyl acetate.

[0070] The structural characterization data of the obtained product are as follows:

[0071] 1 H NMR (600 MHz, CDCl3) δ 7.59-7.53 (m, 4H), 5.63 (d, J = 37.7 Hz,1H), 3.02 (s, 1H), 2.98 (s, 1H), 1.71 (s, 6H).

[0072] 13 C NMR (151 MHz, CDCl3) δ 156.8 (d, J = 269.2 Hz), 136.1, 128.8,128.7, 125.4 (q, J = 3.7 Hz), 124.9 (q, J = 272.1 Hz), 109.7 (d, J = 7.5 Hz), 87.0 (d, J = 3.9 Hz), 44.0 (d, J = 25.4 Hz), 25.7.

[0073] 19 F NMR (565 MHz, CDCl3) δ -62.68, -95.60.

[0074] HRMS (APCI) m / z: [M+H + calcd for C 13 H 14 F4NO2 + 292.0955; found: 292.0940.

[0075] Based on the above data, the structure of the product is inferred as follows:

[0076]

[0077] Example 7

[0078] Add 0.20 mmol of 4-(2,2-difluorocyclopropyl)benzonitrile, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75°C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 20:1.

[0079] The structural characterization data of the obtained product are as follows:

[0080] 1 H NMR (600 MHz, CDCl3) δ 7.60 (d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.5Hz, 2H), 5.62 (d, J = 37.4 Hz, 1H), 3.02 (s, 1H), 2.98 (s, 1H), 1.70 (s, 6H).

[0081] 13 C NMR (151 MHz, CDCl3) δ 157.7 (d, J = 271.6 Hz), 137.2 (d, J = 2.9Hz), 132.3, 129.1 (d, J = 8.1 Hz), 118.8, 110.9 (d, J = 3.1 Hz), 109.8 (d, J= 7.2 Hz), 87.0 (d, J = 4.1 Hz), 44.0 (d, J = 25.2 Hz), 25.91.

[0082] 19F NMR (565 MHz, CDCl3) δ -93.46.

[0083] HRMS (APCI) m / z: [M+H + calcd for C 13 H 14 FN2O2 + 249.1034; found: 249.1016.

[0084] Based on the above data, the structure of the product is inferred as follows:

[0085]

[0086] Example 8

[0087] 4-(2,2-difluorocyclopropyl)benzoate (0.20 mmol), 2-nitropropane (0.30 mmol), and Pd(P) were added to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75°C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 20:1.

[0088] The structural characterization data of the obtained product are as follows:

[0089] 1 H NMR (600 MHz, CDCl3) δ 8.00-7.96 (m, 2H), 7.52-7.49 (m, 2H), 5.63(d, J = 37.9 Hz, 1H), 3.91 (s, 3H), 3.01 (s, 1H), 2.98 (s, 1H), 1.71 (s, 6H).

[0090] 13C NMR (151 MHz, CDCl3) δ 166.7, 156.8 (d, J = 270.0 Hz), 137.1 (d, J= 2.8 Hz), 129.7, 128.9 (d, J = 2.7 Hz), 128.5 (d, J = 7.7 Hz), 110.3 (d, J =7.6 Hz), 87.0 (d, J = 4.0 Hz), 52.1, 44.0 (d, J = 25.6 Hz), 25.9.

[0091] 19 F NMR (565 MHz, CDCl3) δ -95.12.

[0092] HRMS (APCI) m / z: [M+H + calcd for C 14 H 17 FNO4 + 282.1136; found: 282.1135.

[0093] Based on the above data, the structure of the product is inferred as follows:

[0094]

[0095] Example 9

[0096] Add 0.20 mmol of 1-(2,2-difluorocyclopropyl)-4-fluorobenzene, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75°C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 100:1 mixture of petroleum ether and ethyl acetate.

[0097] The structural characterization data of the obtained product are as follows:

[0098] 1H NMR (600 MHz, CDCl3) δ 7.43 (dd, J = 8.8, 5.5 Hz, 2H), 7.01 (t, J =8.7 Hz, 2H), 5.54 (d, J = 38.2 Hz, 1H), 2.98 (s, 1H), 2.94 (s, 1H), 1.70 (s,6H).

[0099] 13 C NMR (151 MHz, CDCl3) δ 161.9 (dd, J = 247.9, 3.5 Hz), 154.8 (dd, J= 265.4, 2.6 Hz), 130.3 (t, J = 7.8 Hz), 128.7 (t, J = 3.1 Hz), 115.4 (d, J =21.5 Hz), 109.8 (d, J = 8.2 Hz), 87.1 (d, J = 4.1 Hz), 44.0 (d, J = 25.7 Hz), 25.8 (d, J = 2.0 Hz).

[0100] 19 F NMR (565 MHz, CDCl3) δ -100.12, -113.54.

[0101] HRMS (APCI) m / z: [M+Na + calcd for C 12 H 13 F2NNaO2 + 264.0807; found: 264.0802.

[0102] Based on the above data, the structure of the product is inferred as follows:

[0103]

[0104] Example 10

[0105] Add 0.20 mmol of 1-(2,2-difluorocyclopropyl)-4-(phenylethynyl)benzene, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. tBu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 100:1 mixture of petroleum ether and ethyl acetate.

[0106] The structural characterization data of the obtained product are as follows:

[0107] 1 H NMR (600 MHz, CDCl3) δ 7.56-7.53 (m, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.39-7.33 (m, 3H), 5.58 (d, J = 38.3 Hz, 1H), 3.00(s, 1H), 2.97 (s, 1H), 1.71 (s, 6H).

[0108] 13 C NMR (151 MHz, CDCl3) δ 155.8 (d, J = 268.1 Hz), 132.5 (d, J = 2.9Hz), 131.7, 131.6, 128.5 (d, J = 7.7 Hz), 128.3, 128.3, 123.1, 122.3 (d, J =2.7 Hz), 110.5 (d, J = 7.7 Hz), 90.2, 89.3, 87.1 (d, J = 4.1 Hz), 44.1 (d, J= 25.6 Hz), 25.8.

[0109] 19 F NMR (565 MHz, CDCl3) δ -97.02.

[0110] HRMS (APCI) m / z: [M+H + calcd for C 20 H 19 FNO2 + 324.1394; found: 324.1390.

[0111] Based on the above data, the structure of the product is inferred as follows:

[0112]

[0113] Example 11

[0114] Add 0.20 mmol of 1-(3-(2,2-difluorocyclopropyl)phenyl)ethyl ketone, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 20:1 mixture of petroleum ether and ethyl acetate.

[0115] The structural characterization data of the obtained product are as follows:

[0116] 1 H NMR (600 MHz, CDCl3) δ 8.00 (s, 1H), 7.83 (dd, J = 7.8, 1.4 Hz, 1H), 7.66 (dt, J = 7.8, 1.4 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 5.64 (d, J =37.9 Hz, 1H), 3.01 (s, 1H), 2.98 (s, 1H), 2.60 (s, 3H), 1.71 (s, 6H).

[0117] 13 C NMR (151 MHz, CDCl3) δ 197.9, 156.0 (d, J = 268.0 Hz), 137.3,133.1 (d, J = 2.7 Hz), 133.0 (d, J = 8.2 Hz), 128.8, 128.4 (d, J = 7.0 Hz), 127.3 (d, J = 2.2 Hz), 110.1 (d, J = 7.7 Hz), 87.0 (d, J = 4.0 Hz), 44.0 (d, J = 25.8 Hz), 26.6, 25.8.

[0118] 19 F NMR (565 MHz, CDCl3) δ -97.27.

[0119] HRMS (APCI) m / z: [M+H + calcd for C 14 H 17FNO3 + 266.1187; found: 266.1180.

[0120] Based on the above data, the structure of the product is inferred as follows:

[0121]

[0122] Example 12

[0123] Add 0.20 mmol of 4-(2,2-difluorocyclopropyl)-1,2-dimethoxybenzene, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 20:1 mixture of petroleum ether and ethyl acetate.

[0124] The structural characterization data of the obtained product are as follows:

[0125] 1 H NMR (600 MHz, CDCl3) δ 7.06 (d, J = 2.0 Hz, 1H), 6.96 (dd, J = 8.3,2.0 Hz, 1H), 6.80 (d, J = 8.4 Hz, 1H), 5.49 (d, J = 38.7 Hz, 1H), 3.86 (s,6H), 2.95 (s, 1H), 2.92 (s, 1H), 1.68 (s, 6H).

[0126] 13 C NMR (151 MHz, CDCl3) δ 153.8 (d, J = 263.9 Hz), 148.6, 148.5 (d, J= 2.8 Hz), 125.6 (d, J = 2.8 Hz), 121.5 (d, J = 6.7 Hz), 111.5 (d, J = 8.9Hz), 110.9, 110.5 (d, J = 8.0 Hz), 87.1 (d, J = 3.9 Hz), 55.8, 55.7, 44.0 (d,J = 26.0 Hz), 25.7.

[0127] 19F NMR (565 MHz, CDCl3) δ -101.63.

[0128] HRMS (APCI) m / z: [M+H + calcd for C 14 H 19 FNO4 + 284.1293; found: 284.1284.

[0129] Based on the above data, the structure of the product is inferred as follows:

[0130]

[0131] Example 13

[0132] Add 0.20 mmol of 1-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0133] The structural characterization data of the obtained product are as follows:

[0134] 1 H NMR (600 MHz, CDCl3) δ 7.95 (d, J = 8.3 Hz, 1H), 7.87 (d, J = 7.9Hz, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.72 (d, J = 7.3 Hz, 1H), 7.58-7.48 (m,2H), 7.48 (t, J = 7.7 Hz, 1H), 6.25 (d, J = 36.0 Hz, 1H), 3.12 (s, 1H), 3.08(s, 1H), 1.76 (s, 6H).

[0135] 13C NMR (151 MHz, CDCl3) δ 155.7 (d, J = 265.3 Hz), 133.6, 131.2,128.7, 128.7, 128.2, 127.4 (d, J = 7.9 Hz), 126.4, 125.8, 125.4, 123.8, 107.9(d, J = 9.9 Hz), 87.3 (d, J = 4.1 Hz), 44.1 (d, J = 26.0 Hz), 25.9 (d, J =1.7 Hz).

[0136] 19 F NMR (565 MHz, CDCl3) δ -99.88.

[0137] HRMS (APCI) m / z: [M+H + calcd for C 16 H 17 FNO2 + 274.1238; found: 274.1266.

[0138] Based on the above data, the structure of the product is inferred as follows:

[0139]

[0140] Example 14

[0141] Add 0.20 mmol of 3-(2,2-difluorocyclopropyl)-1-methyl-2-phenyl-1H-indole, 0.30 mmol of 2-nitropropane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0142] The structural characterization data of the obtained product are as follows:

[0143] 1 H NMR (600 MHz, CDCl3) δ 7.82 (dd, J = 8.0, 3.5 Hz, 1H), 7.56-7.53(m, 2H), 7.51-7.48 (m, 1H), 7.43-7.41 (m, 2H), 7.38 (dt, J = 8.2, 0.9 Hz,1H), 7.32 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 7.24 (ddd, J = 8.0, 7.0, 1.1 Hz,1H), 5.60 (d, J = 41.7 Hz, 1H), 3.66 (s, 3H), 2.97 (s, 1H), 2.93 (s, 1H),1.70 (s, 6H).

[0144] 13 C NMR (151 MHz, CDCl3) δ 152.0 (d, J = 259.8 Hz), 139.6, 137.4,131.2, 130.8, 128.4, 125.8, 122.2, 121.4, 121.3, 120.2 (d, J = 2.2 Hz), 109.5, 106.4, 103.9 (d, J = 12.8 Hz), 87.3 (d, J = 4.3 Hz), 44.0 (d, J = 26.5Hz), 31.0, 25.7 (d, J = 1.9 Hz).

[0145] 19 F NMR (565 MHz, CDCl3) δ -98.27.

[0146] HRMS (APCI) m / z: [M+H + calcd for C 21 H 22 FN2O2 + 353.1660; found: 353.1655.

[0147] Based on the above data, the structure of the product is inferred as follows:

[0148]

[0149] Example 15

[0150] 2-(2,2-difluorocyclopropyl)benzofuran (0.20 mmol), 2-nitropropane (0.30 mmol), and Pd(P) were added to the reaction tube. tBu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75°C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0151] The structural characterization data of the obtained product are as follows:

[0152] 1 H NMR (600 MHz, CDCl3) δ 7.55 (dt, J = 7.6, 0.9 Hz, 1H), 7.44 (dd, J= 8.0, 1.1 Hz, 1H), 7.29-7.26 (m, 1H), 7.22 (td, J = 7.5, 1.0 Hz, 1H), 6.90(s, 1H), 5.82 (d, J = 36.7 Hz, 1H), 3.05 (s, 1H), 3.01 (s, 1H), 1.72 (s, 6H).

[0153] 13 C NMR (151 MHz, CDCl3) δ 156.5 (d, J = 270.7 Hz), 154.0, 149.3 (d, J= 2.8 Hz), 128.7, 124.6, 123.0, 121.0, 111.0, 106.5 (d, J = 11.1 Hz), 101.8 (d, J = 10.5 Hz), 86.9 (d, J = 4.1 Hz), 43.5 (d, J = 24.3 Hz), 25.8.

[0154] 19 F NMR (565 MHz, CDCl3) δ -90.69.

[0155] HRMS (APCI) m / z: [M+H + calcd for C 14 H 15 FNO3 + 264.1030; found: 264.1028.

[0156] Based on the above data, the structure of the product is inferred as follows:

[0157]

[0158] Example 16

[0159] 2-(2,2-difluorocyclopropyl)benzo[b]thiophene (0.20 mmol), 2-nitropropane (0.30 mmol), and Pd(P) were added to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0160] The structural characterization data of the obtained product are as follows:

[0161] 1 H NMR (600 MHz, CDCl3) δ 7.83-7.78 (m, 1H), 7.73 (dd, J = 7.1, 1.8Hz, 1H), 7.33 (pd, J = 7.2, 1.4 Hz, 2H), 7.26 (d, J = 2.5 Hz, 1H), 5.99 (d, J= 37.2 Hz, 1H), 3.05 (s, 1H), 3.01 (s, 1H), 1.72 (s, 6H).

[0162] 13 C NMR (151 MHz, CDCl3) δ 155.2 (d, J = 268.1 Hz), 140.1 (d, J = 7.7Hz), 139.0, 134.8 (d, J = 4.4 Hz), 124.6, 124.4, 123.7 (d, J = 4.4 Hz), 123.4, 122.0, 106.0 (d, J = 11.4 Hz), 87.1 (d, J = 4.2 Hz), 43.4 (d, J = 24.8Hz), 25.8.

[0163] 19 F NMR (565 MHz, CDCl3) δ -94.28.

[0164] HRMS (APCI) m / z: [M+H + calcd for C 14 H 15 FNO2S+ 280.0802; found: 280.0799.

[0165] Based on the above data, the structure of the product is inferred as follows:

[0166]

[0167] Example 17

[0168] Add (3aR,5R,6S,6aR)-6-((4-(2,2-difluorocyclopropyl)benzyl)oxy)-5-((S)-2,2-dimethyl-1,3-dioxolane-4-yl)-2,2-dimethyltetrahydrofurano[2,3-d][1,3]dioxolane (0.20 mmol), 2-nitropropane (0.30 mmol), and Pd(P t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 2:1 mixture of petroleum ether and ethyl acetate.

[0169] The structural characterization data of the obtained product are as follows:

[0170] 1 H NMR (600 MHz, CDCl3) δ 7.43 (d, J = 7.9 Hz, 2H), 7.30 (d, J = 7.9Hz, 2H), 5.89 (d, J = 3.7 Hz, 1H), 5.57 (d, J = 38.5 Hz, 1H), 4.67-4.60 (m,2H), 4.58 (d, J = 3.7 Hz, 1H), 4.35 (dt, J = 7.8, 6.0 Hz, 1H), 4.15-4.09 (m,2H), 4.02-3.97 (m, 2H), 2.99 (s, 1H), 2.95 (s, 1H), 1.69 (s, 6H), 1.49 (s,3H), 1.42 (s,3H), 1.37 (s, 3H), 1.31 (s, 3H).

[0171] 13C NMR (151 MHz, CDCl3) δ 148.2 (d, J = 266.4 Hz), 130.0 (d, J = 2.2Hz), 125.2 (d, J = 2.6 Hz), 121.7, 121.6, 120.8, 104.8, 103.6 (d, J = 8.0Hz), 102.0, 98.3, 80.1 (d, J = 3.9 Hz), 75.6, 74.7, 74.3, 65.5, 65.0, 60.4,37.1 (d, J = 25.9 Hz), 19.8 (d, J = 7.3 Hz), 19.2, 18.8, 18.4.

[0172] 19 F NMR (565 MHz, CDCl3) δ -98.53.

[0173] HRMS (APCI) m / z: [M+H + calcd for C 25 H 35 FNO8 + 496.2341; found: 496.2318.

[0174] Based on the above data, the structure of the product is inferred as follows:

[0175]

[0176] Example 18

[0177] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 3-nitropentane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0178] The structural characterization data of the obtained product are as follows:

[0179] 1 H NMR (600 MHz, CDCl3) δ 7.90 (d, J = 1.8 Hz, 1H), 7.83-7.78 (m, 3H), 7.62 (dd, J = 8.6, 1.7 Hz, 1H), 7.50-7.44 (m, 2H), 5.74 (d, J = 38.7 Hz, 1H), 3.08 (d, J = 22.0 Hz, 2H), 2.11 (q, J = 7.4 Hz, 4H).

[0180] 13 C NMR (151 MHz, CDCl3) δ 155.6 (d, J = 266.9 Hz), 133.3, 132.5,130.2 (d, J = 2.8 Hz), 128.0, 128.0, 127.7 (d, J = 7.5 Hz), 127.5, 126.4 (d, J = 7.6 Hz), 126.2, 126.1, 110.8 (d, J = 8.3 Hz), 94.5 (d, J = 3.9 Hz), 38.0 (d, J = 25.5 Hz), 28.8, 8.1.

[0181] 19 F NMR (565 MHz, CDCl3) ) δ -99.56.

[0182] HRMS (APCI) m / z: [M+H + calcd for C 18 H 21 FNO2 + 302.1551; found: 302.1528.

[0183] Based on the above data, the structure of the product is inferred as follows:

[0184]

[0185] Example 19

[0186] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 4-nitropentanone, and Pd(P) to the reaction tube. tBu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 5:1 mixture of petroleum ether and ethyl acetate.

[0187] The structural characterization data of the obtained product are as follows:

[0188] 1 H NMR (600 MHz, CDCl3) δ 7.90 (s, 1H), 7.81 (dd, J = 7.7, 2.9 Hz,3H), 7.61 (dd, J = 8.6, 1.8 Hz, 1H), 7.51-7.45 (m, 2H), 5.77 (d, J = 38.6 Hz,1H), 3.12-2.96 (m, 2H), 2.61-2.54 (m, 1H), 2.47-2.41 (m, 2H), 2.34-2.27 (m,1H), 1.74 (s, 3H).

[0189] 13 C NMR (151 MHz, CDCl3) δ 153.9 (d, J = 265.8 Hz), 133.2, 132.7,129.6 (d, J = 2.9 Hz), 128.1, 128.1, 128.0, 127.5, 126.4, 126.4, 126.2 (d, J = 7.7 Hz), 118.1, 112.0 (d, J = 7.7 Hz), 88.8 (d, J = 4.0 Hz), 43.1 (d, J =26.0 Hz), 34.0, 22.2, 12.6.

[0190] 19 F NMR (565 MHz, CDCl3) δ -99.45.

[0191] HRMS (APCI) m / z: [M+H + calcd for C 18 H 18 FN2O2 + 313.1347; found: 313.1326.

[0192] Based on the above data, the structure of the product is inferred as follows:

[0193]

[0194] Example 20

[0195] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of ethyl 2-nitropropionate, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75°C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 10:1.

[0196] The structural characterization data of the obtained product are as follows:

[0197] 1 H NMR (600 MHz, CDCl3) ) δ 7.89 (d, J = 1.7 Hz, 1H), 7.83-7.77 (m,3H), 7.61 (dd, J = 8.6, 1.7 Hz, 1H), 7.55-7.41 (m, 2H), 5.81 (d, J = 38.4 Hz,1H), 4.33 (qq, J = 7.2, 3.6 Hz, 2H), 3.39 (ddd, J = 71.1, 21.3, 15.2 Hz, 2H), 1.95 (s, 3H), 1.32 (t, J = 7.1 Hz, 3H).

[0198] 13 C NMR (151 MHz, CDCl3) δ 166.6, 153.7 (d, J = 265.9 Hz), 133.3,132.72, 129.9 (d, J = 2.9 Hz), 128.1, 128.1, 128.00, 127.6, 126.4, 126.3,111.9 (d, J = 7.6 Hz), 91.2 (d, J = 4.2 Hz), 63.3, 40.5 (d, J = 26.1 Hz), 21.1 (d, J = 1.9 Hz), 13.8.

[0199] 19F NMR (565 MHz, CDCl3) δ -99.87.

[0200] HRMS (APCI) m / z: [M+H + calcd for C 18 H 19 FNO4 + 332.1293; found: 332.1281.

[0201] Based on the above data, the structure of the product is inferred as follows:

[0202]

[0203] Example 21

[0204] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of methyl 4-nitrohexanoate, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75°C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 5:1 mixture of petroleum ether and ethyl acetate.

[0205] The structural characterization data of the obtained product are as follows:

[0206] 1 H NMR (600 MHz, CDCl3) δ 7.89 (d, J = 1.7 Hz, 1H), 7.82-7.77 (m, 3H), 7.61 (dd, J = 8.6, 1.7 Hz, 1H), 7.50-7.44 (m, 2H), 5.76 (d, J = 38.8 Hz, 1H), 3.70 (s, 3H), 3.14 – 3.01 (m, 2H), 2.47-2.34 (m, 4H), 2.11 (hept, J = 7.4 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H).

[0207] 13C NMR (151 MHz, CDCl3) δ 172.3, 154.9 (d, J = 266.4 Hz), 133.3,132.6, 130.0 (d, J = 3.1 Hz), 128.0, 127.9 (d, J = 7.6 Hz), 127.5, 126.3 (d,J = 7.6 Hz), 126.3, 126.2, 111.3 (d, J = 8.1 Hz), 93.0 (d, J = 3.9 Hz), 52.0,38.5 (d, J = 25.6 Hz), 30.7, 29.2, 28.6, 8.2.

[0208] 19 F NMR (565 MHz, CDCl3) δ -99.99.

[0209] HRMS (APCI) m / z: [M+H + calcd for C 20 H 23 FNO4 + 360.1606; found: 360.1630.

[0210] Based on the above data, the structure of the product is inferred as follows:

[0211]

[0212] Example 22

[0213] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of N,N-dimethyl-4-nitrohexanamide, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 5:1 mixture of petroleum ether and ethyl acetate.

[0214] The structural characterization data of the obtained product are as follows:

[0215] 1H NMR (600 MHz, CDCl3) δ 7.90-7.86 (m, 1H), 7.81-7.75 (m, 3H), 7.59(dd, J = 8.6, 1.7 Hz, 1H), 7.48-7.41 (m, 2H), 5.76 (d, J = 38.8 Hz, 1H),3.18-3.01 (m, 2H), 2.96 (s, 3H), 2.93 (s, 3H), 2.44-2.39 (m, 2H), 2.39-2.33(m, 1H), 2.32-2.26 (m, 1H), 2.18 (dd, J = 14.8, 7.4 Hz, 1H), 2.10 (dd, J =14.7, 7.4 Hz, 1H), 1.00 (t, J = 7.4 Hz, 3H).

[0216] 13 C NMR (151 MHz, CDCl3) δ 170.70, 155.0 (d, J = 266.5 Hz), 133.2,132.5, 130.0 (d, J = 2.9 Hz), 128.0, 128.0, 127.8 (d, J = 7.6 Hz), 127.5,126.3 (d, J = 7.5 Hz), 126.2, 126.1, 111.2 (d, J = 7.9 Hz), 93.4 (d, J = 3.8Hz), 38.7 (d, J = 25.5 Hz), 37.0, 35.5, 31.6, 28.8, 27.6, 8.3.

[0217] 19 F NMR (565 MHz, CDCl3) δ -99.67.

[0218] HRMS (APCI) m / z: [M+H + calcd for C 21 H 26 FN2O3 + 373.1922; found: 373.1911.

[0219] Based on the above data, the structure of the product is inferred as follows:

[0220]

[0221] Example 23

[0222] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 1-(3-nitropentyl)sulfonylbenzene, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 3:1 mixture of petroleum ether and ethyl acetate.

[0223] The structural characterization data of the obtained product are as follows:

[0224] 1 H NMR (600 MHz, CDCl3) δ 7.91-7.89 (m, 2H), 7.82-7.77 (m, 4H), 7.61-7.58 (m, 1H), 7.53-7.46 (m, 5H), 5.70 (d, J = 38.9 Hz, 1H), 3.22-3.11 (m,2H), 3.07-2.95 (m, 2H), 2.49-2.43 (m, 2H), 2.05 (q, J = 7.5 Hz, 2H), 0.93 (t,J = 7.4 Hz, 3H).

[0225] 13 C NMR (151 MHz, CDCl3) δ 154.0 (d, J = 265.8 Hz), 138.2, 134.1,133.2, 132.7, 129.6 (d, J = 2.9 Hz), 129.4, 128.1, 128.0, 128.0, 127.5,126.3, 126.3 (d, J = 7.6 Hz), 111.7 (d, J = 7.9 Hz), 92.1 (d, J = 3.9 Hz), 51.2, 38.9 (d, J = 25.8 Hz), 29.7, 28.4, 8.0.

[0226] 19 F NMR (565 MHz, CDCl3) δ -100.44.

[0227] HRMS (APCI) m / z: [M+H + calcd for C 24 H25 FNO4S + 442.1483; found: 442.1472.

[0228] Based on the above data, the structure of the product is inferred as follows:

[0229]

[0230] Example 24

[0231] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 1-(4-nitropentyl)benzene, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75°C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0232] The structural characterization data of the obtained product are as follows:

[0233] 1 H NMR (600 MHz, CDCl3) δ 7.89 (d, J = 1.7 Hz, 1H), 7.83-7.79 (m, 3H), 7.61 (dd, J = 8.5, 1.8 Hz, 1H), 7.50-7.46 (m, 2H), 7.31 (t, J = 7.6 Hz, 2H), 7.24-7.21 (m, 1H), 7.20-7.17 (m, 2H), 5.71 (d, J = 38.6 Hz, 1H), 3.15 (dd, J= 21.6, 15.1 Hz, 1H), 2.89 (dd, J = 22.3, 15.0 Hz, 1H), 2.70-2.63 (m, 2H),2.16 (ddd, J = 14.2, 12.3, 4.4 Hz, 1H), 1.95 (ddd, J = 14.2, 12.3, 4.5 Hz, 1H), 1.75-1.67 (m, 4H), 1.63 (ddt, J = 12.6, 6.8, 2.4 Hz, 1H).

[0234] 13C NMR (151 MHz, CDCl3) δ 155.3 (d, J = 266.9 Hz), 141.1, 133.3,132.6, 130.1 (d, J = 3.1 Hz), 128.5, 128.3, 128.0, 128.0, 127.8 (d, J = 7.3Hz), 127.5, 126.4 (d, J = 7.6 Hz), 126.2, 126.2, 126.1, 111.1 (d, J = 7.8Hz), 90.3 (d, J = 3.9 Hz), 43.0 (d, J = 25.6 Hz), 39.1, 35.5, 25.6, 22.2.

[0235] 19 F NMR (565 MHz, CDCl3) δ -98.30.

[0236] HRMS (APCI) m / z: [M+H + calcd for C 24 H 25 FNO2 + 378.1864; found: 378.1835.

[0237] Based on the above data, the structure of the product is inferred as follows:

[0238]

[0239] Example 25

[0240] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 1-methoxy-4-(2-nitropropyl)benzene, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 100:1 mixture of petroleum ether and ethyl acetate.

[0241] The structural characterization data of the obtained product are as follows:

[0242] 1H NMR (600 MHz, CDCl3) δ 7.91 (d, J = 1.7 Hz, 1H), 7.81 (ddd, J =8.6, 5.8, 3.5 Hz, 3H), 7.64 (dd, J = 8.6, 1.7 Hz, 1H), 7.55-7.41 (m, 2H),7.07 (d, J = 8.7 Hz, 2H), 6.88-6.85 (m, 2H), 5.76 (d, J = 38.7 Hz, 1H), 3.80(s, 3H), 3.39 (d, J = 14.1 Hz, 1H), 3.30 (dd, J = 21.9, 15.1 Hz, 1H), 3.10 (d, J= 14.1 Hz, 1H), 2.85 (dd, J = 21.5, 15.1 Hz, 1H), 1.65 (d, J = 1.3 Hz, 3H).

[0243] 13 C NMR (151 MHz, CDCl3) δ 159.1, 155.3 (d, J = 266.9 Hz), 133.3,132.5, 131.1, 130.3, 130.1 (d, J = 2.8 Hz), 128.0, 128.0, 127.8 (d, J = 7.6Hz), 127.5, 126.4 (d, J = 7.5 Hz), 126.2, 126.1, 125.9, 114.0, 111.2 (d, J =7.7 Hz), 90.9 (d, J = 3.9 Hz), 55.1, 45.2, 42.9 (d, J = 25.6 Hz), 21.2.

[0244] 19 F NMR (565 MHz, CDCl3) δ -98.23.

[0245] HRMS (APCI) m / z: [M+Na + calcd for C 23 H 22 FNNaO3 + 402.1476; found: 402.1471.

[0246] Based on the above data, the structure of the product is inferred as follows:

[0247]

[0248] Example 26

[0249] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 1-nitro-4-(2-nitropropyl)benzene, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 3:1 mixture of petroleum ether and dichloromethane.

[0250] The structural characterization data of the obtained product are as follows:

[0251] 1 H NMR (600 MHz, CDCl3) δ 8.20-8.16 (m, 2H), 7.91 (d, J = 1.7 Hz, 1H), 7.83-7.79 (m, 3H), 7.63 (dd, J = 8.6, 1.7 Hz, 1H), 7.50-7.45 (m, 2H), 7.31(d, J = 8.7 Hz, 2H), 5.79 (d, J = 38.7 Hz, 1H), 3.60 (d, J = 14.0 Hz, 1H), 3.26 (dd, J = 22.2, 14.7 Hz, 2H), 2.96 (dd, J = 20.9, 15.0 Hz, 1H), 1.66 (s, 3H).

[0252] 13 C NMR (151 MHz, CDCl3) δ 154.5 (d, J = 266.0 Hz), 147.6, 141.4,133.3, 132.67, 131.1, 129.8 (d, J = 3.0 Hz), 128.1, 128.1, 128.0 (d, J = 7.6Hz), 127.6, 126.4, 126.3 (d, J = 7.6 Hz), 123.8, 111.9 (d, J = 7.7 Hz), 90.3 (d, J = 4.0 Hz), 45.0, 43.4 (d, J = 25.6 Hz), 21.5.

[0253] 19F NMR (565 MHz, CDCl3) delta -98.79.

[0254] HRMS (APCI) m / z: [M+H + calcd for C 22 H 19 FN2NaO4 + 417.1221; found: 417.1223.

[0255] Based on the above data, the structure of the product is inferred as follows:

[0256]

[0257] Example 27

[0258] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 1-(2-nitropropyl)ferrocene, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0259] The structural characterization data of the obtained product are as follows:

[0260] 1 H NMR (600 MHz, CDCl3) δ 7.91-7.88 (m, 1H), 7.83-7.78 (m, 3H), 7.63(dd, J = 8.6, 1.7 Hz, 1H), 7.50-7.44 (m, 2H), 5.72 (d, J = 38.7 Hz, 1H), 4.16-4.12 (m, 9H), 3.24-3.14 (m, 2H), 3.02 (d, J = 14.3 Hz, 1H), 2.81 (dd, J= 21.5, 15.1 Hz, 1H), 1.60 (s, 3H).

[0261] 13C NMR (151 MHz, CDCl3) δ 155.4 (d, J = 266.9 Hz), 133.3, 132.6,130.2 (d, J = 2.9 Hz), 128.0, 128.0, 127.8 (d, J = 7.5 Hz), 127.5, 126.4 (d,J = 7.4 Hz), 126.2, 126.2, 111.1 (d, J = 7.8 Hz), 90.8 (d, J = 4.0 Hz), 80.1,70.1, 69.7, 68.9, 68.6, 68.4, 42.5 (d, J = 25.7 Hz), 41.3, 21.8.

[0262] 19 F NMR (565 MHz, CDCl3) ) δ -98.34.

[0263] HRMS (APCI) m / z: [M+H + calcd for C 26 H 24 FFeNNaO2 + 480.1033; found: 480.1025.

[0264] Based on the above data, the structure of the product is inferred as follows:

[0265]

[0266] Example 28

[0267] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 1-methyl-3-(2-nitropropyl)-2-phenyl-1H-indole, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0268] The structural characterization data of the obtained product are as follows:

[0269] 1 H NMR (600 MHz, CDCl3) δ 7.84-7.82 (m, 1H), 7.82-7.78 (m, 2H), 7.77(d, J = 8.7 Hz, 1H), 7.68 (dt, J = 8.0, 0.9 Hz, 1H), 7.58-7.54 (m, 3H), 7.53-7.50 (m, 1H), 7.49-7.45 (m, 2H), 7.41 (ddd, J = 8.1, 5.4, 1.3 Hz, 3H), 7.34(ddd, J = 8.2, 7.0, 1.1 Hz, 1H), 7.26 (td, J = 7.5, 7.0, 1.1 Hz, 1H), 5.61(d, J = 38.8 Hz, 1H), 3.65 (d, J = 14.7 Hz, 1H), 3.61 (s, 3H), 3.55 (d, J =14.7 Hz, 1H), 3.27 (dd, J = 21.9, 15.2 Hz, 1H), 2.64 (dd, J = 21.7, 15.2 Hz,1H), 1.49 (s, 3H).

[0270] 13 C NMR (151 MHz, CDCl3) δ 155.5 (d, J = 267.2 Hz), 140.5, 136.7,133.2, 132.4, 131.4, 130.7, 130.2 (d, J = 2.6 Hz), 128.8, 128.7, 127.9,127.8, 127.6 (d, J = 7.4 Hz), 127.4, 126.3 (d, J = 7.6 Hz), 126.1, 126.0,122.1, 120.1, 119.0, 110.7 (d, J = 7.5 Hz), 109.6, 105.6, 91.6 (d, J = 3.7Hz), 42.7 (d, J = 25.4 Hz), 36.2, 30.8, 21.1.

[0271] 19 F NMR (565 MHz, CDCl3) δ -97.87.

[0272] HRMS (APCI) m / z: [M+H + ] calcd for C 31 H 28 FN2O2 +479.2129; found: 479.2119.

[0273] Based on the above data, the structure of the product is inferred as follows:

[0274]

[0275] Example 29

[0276] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 1-methyl-4-(1-nitroethyl)benzene, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 100:1 mixture of petroleum ether and ethyl acetate.

[0277] The structural characterization data of the obtained product are as follows:

[0278] 1 H NMR (600 MHz, CDCl3) δ 7.85 (d, J = 1.7 Hz, 1H), 7.81-7.76 (m, 3H), 7.57 (dd, J = 8.5, 1.7 Hz, 1H), 7.46 (tt, J = 5.6, 4.5 Hz, 2H), 7.37-7.34 (m,2H), 7.23 (d, J = 8.0 Hz, 2H), 5.69 (d, J = 38.7 Hz, 1H), 3.75 (dd, J = 21.2,15.0 Hz, 1H), 3.25 (dd, J = 21.3, 15.0 Hz, 1H), 2.37 (s, 3H), 2.13 (s, 3H).

[0279] 13C NMR (151 MHz, CDCl3) δ 155.1 (d, J = 267.0 Hz), 139.2, 136.0,133.3, 132.5, 130.2 (d, J = 2.8 Hz), 129.6, 128.0, 128.0, 127.8 (d, J = 7.3Hz), 127.5, 126.4 (d, J = 7.6 Hz), 126.2, 126.1, 125.2, 111.5 (d, J = 7.7Hz), 91.9 (d, J = 3.8 Hz), 43.6 (d, J = 25.2 Hz), 23.6 (d, J = 2.2 Hz), 21.0.

[0280] 19 F NMR (565 MHz, CDCl3) δ -97.70.

[0281] HRMS (APCI) m / z: [M+H + calcd for C 22 H 21 FNO2 + 350.1551; found: 350.1571.

[0282] Based on the above data, the structure of the product is inferred as follows:

[0283]

[0284] Example 30

[0285] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of N,N-dimethyl-3-(1-nitropropyl)aniline, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 20:1 mixture of petroleum ether and ethyl acetate.

[0286] The structural characterization data of the obtained product are as follows:

[0287] 1 H NMR (600 MHz, CDCl3) ) δ 7.82 (d, J = 1.7 Hz, 1H), 7.80-7.76 (m,3H), 7.55 (dd, J = 8.6, 1.7 Hz, 1H), 7.48-7.44 (m, 2H), 7.27-7.24 (m, 1H),6.74 (dd, J = 8.3, 2.5 Hz, 1H), 6.71 (dd, J = 7.7, 1.9 Hz, 1H), 6.63 (t, J =2.2 Hz, 1H), 5.56 (d, J = 38.8 Hz, 1H), 3.69 (dd, J = 20.2, 14.9 Hz, 1H),3.39 (dd, J = 22.5, 14.9 Hz, 1H), 2.95 (s, 6H), 2.61 (qd, J = 7.2, 4.2 Hz, 2H), 0.98 (t, J = 7.3 Hz, 3H).

[0288] 13 C NMR (151 MHz, CDCl3) δ 155.2 (d, J = 267.0 Hz), 150.6, 139.1,133.3, 132.5, 130.3 (d, J = 2.7 Hz), 129.3, 128.0, 127.9, 127.7 (d, J = 7.5Hz), 127.5, 126.4 (d, J = 7.5 Hz), 126.2, 126.1, 113.5, 113.0, 111.2 (d, J =7.9 Hz), 109.2, 96.5 (d, J = 3.5 Hz), 40.4, 39.3 (d, J = 25.2 Hz), 28.7, 8.7.

[0289] 19 F NMR (565 MHz, CDCl3) δ -99.13.

[0290] HRMS (APCI) m / z: [M+H + calcd for C 24 H 26 FN2O2 + 393.1973; found: 393.1969.

[0291] Based on the above data, the structure of the product is inferred as follows:

[0292]

[0293] Example 31

[0294] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 1-(4-(1-nitropropyl)phenyl)ethyl ketone, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 5:1 mixture of petroleum ether and ethyl acetate.

[0295] The structural characterization data of the obtained product are as follows:

[0296] 1 H NMR (600 MHz, CDCl3 ) δ 8.00-7.96 (m, 2H), 7.81-7.73 (m, 4H), 7.50(dd, J = 8.6, 1.7 Hz, 1H), 7.48-7.40 (m, 4H), 5.54 (d, J = 38.6 Hz, 1H), 3.65(dd, J = 20.1, 14.9 Hz, 1H), 3.40 (dd, J = 21.9, 14.9 Hz, 1H), 2.68-2.58 (m,5H), 0.99 (t, J = 7.3 Hz, 3H).

[0297] 13 C NMR (151 MHz, CDCl3) δ 197.1, 154.3 (d, J = 266.8 Hz), 142.9,137.3, 133.2, 132.6, 129.9 (d, J = 2.9 Hz), 128.7, 128.0, 127.8 (d, J = 7.6Hz), 127.5, 126.3, 126.2, 126.1, 111.7 (d, J = 7.8 Hz), 95.9 (d, J = 3.9 Hz), 39.7 (d, J = 25.1 Hz), 28.8, 26.6, 8.5.

[0298] 19 F NMR (565 MHz, CDCl3) δ -99.50.

[0299] HRMS (APCI) m / z: [M+H + calcd for C 24 H 23 FNO3 + 392.1656; found: 392.1646.

[0300] Based on the above data, the structure of the product is inferred as follows:

[0301]

[0302] Example 32

[0303] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of nitrocyclopentane, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75 °C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a petroleum ether:ethyl acetate mixture with a volume ratio of 50:1.

[0304] The structural characterization data of the obtained product are as follows:

[0305] 1 H NMR (600 MHz, CDCl3) ) δ 7.88 (d, J = 1.7 Hz, 1H), 7.81-7.77 (m,3H), 7.61 (dd, J = 8.5, 1.8 Hz, 1H), 7.48-7.44 (m, 2H), 5.71 (d, J = 38.6 Hz,1H), 3.10 (d, J = 21.1 Hz, 2H), 2.70-2.65 (m, 2H), 2.04-1.99 (m, 2H), 1.84-1.78 (m, 4H).

[0306] 13C NMR (151 MHz, CDCl3) δ 155.6 (d, J = 266.9 Hz), 133.3, 132.5,130.2 (d, J = 3.2 Hz), 128.0, 128.0, 127.8 (d, J = 7.4 Hz), 127.5, 126.4 (d, J = 7.6 Hz), 126.2, 126.1, 110.5 (d, J = 7.7 Hz), 98.2 (d, J = 3.4 Hz), 42.4 (d, J = 25.7 Hz), 36.9, 23.9.

[0307] 19 F NMR (565 MHz, CDCl3) δ -100.33.

[0308] HRMS (APCI) m / z: [M+H + calcd for C 18 H 19 FNO2 + 300.1394; found: 300.1366.

[0309] Based on the above data, the structure of the product is inferred as follows:

[0310]

[0311] Example 33

[0312] Add 0.20 mmol of 2-(2,2-difluorocyclopropyl)naphthalene, 0.30 mmol of 4-nitrotetrahydro-2H-pyran, and Pd(P) to the reaction tube. t Bu3)2 (5.0 mol%), cesium hydroxide monohydrate (0.20 mmol), and 1,4-dioxane (1.5 mL) were reacted at 75°C under nitrogen protection for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the target product. The column chromatography eluent was a 5:1 mixture of petroleum ether and ethyl acetate.

[0313] The structural characterization data of the obtained product are as follows:

[0314] 1H NMR (600 MHz, CDCl3) δ 7.88 (d, J = 1.7 Hz, 1H), 7.79 (dd, J = 9.1,5.5 Hz, 3H), 7.60 (dd, J = 8.6, 1.7 Hz, 1H), 7.53-7.41 (m, 2H), 5.70 (d, J =38.3 Hz, 1H), 3.90 (dt, J = 12.4, 4.1 Hz, 2H), 3.55 (ddd, J = 12.7, 10.6, 2.4Hz, 2H), 2.95 (d, J = 22.1 Hz, 2H), 2.56 (dq, J = 15.0, 2.7 Hz, 2H), 2.07(ddd, J = 15.0, 10.7, 4.7 Hz, 2H).

[0315] 13 C NMR (151 MHz, CDCl3) δ 154.1 (d, J = 266.4 Hz), 133.3, 132.6,129.8 (d, J = 3.1 Hz), 128.1, 128.0, 127.9 (d, J = 7.3 Hz), 127.5, 126.3 (d, J = 7.3 Hz), 126.3, 126.2, 111.4 (d, J = 7.5 Hz), 88.1 (d, J = 4.0 Hz), 64.0, 44.3 (d, J = 26.0 Hz), 33.7.

[0316] 19 F NMR (565 MHz, CDCl3) δ -98.30.

[0317] HRMS (APCI) m / z: [M+H + calcd for C 18 H 19 FNO3 + 316.1343; found: 316.1318.

[0318] Based on the above data, the structure of the product is inferred as follows:

[0319]

Claims

1. A method for synthesizing a novel fluorinated allyl tert-nitro alkane compound, characterized in that: Using gem-difluorocyclopropane and secondary nitroalkanes as raw materials, a ring-opening reaction of gem-difluorocyclopropane and allyl alkylation of secondary nitroalkanes is achieved through transition metal / ligand catalysis to obtain straight-chain fluorinated allyl tertiary nitroalkanes.

2. The method for synthesizing a novel fluorinated allyl tert-nitro alkane compound according to claim 1, characterized in that... This method conforms to the following reaction equation: The gem-difluorocyclopropane derivative is Secondary nitroalkanes are , where R 1 Represents a hydrogen atom or an alkyl, alkoxy, phenyl, nitrile, trifluoromethyl, ester, or halogen group containing one or more substituted groups; R 2 Represents hydrogen atom, alkyl group, phenyl group; R 3 It represents hydrogen atoms and alkyl groups.

3. The method for synthesizing a novel fluorinated allyl tert-nitro alkane compound according to claim 1, characterized in that... The following steps were performed: In a reaction tube, geminitropropane derivative, secondary nitroalkanes, metal catalyst, ligand, base and solvent were added, and the reaction was carried out at 75 °C under a nitrogen atmosphere for 24 hours. After cooling to room temperature, the mixture was filtered, and the solvent was removed under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain a fluorinated allyl tertiary nitroalkan compound.

4. The method for synthesizing a novel fluorinated allyl tert-nitro alkane compound according to claim 3, characterized in that: The metal catalyst is Cu(OAc)₂, Co(acac)₃, Pd(dba)₂, Pd(P t One or more of the following: Bu3)2, [Pd(allyl)Cl]2, Pd(cod)Cl2, Pd(PPh3)4, Pd-PEPPSI-SIPr.

5. The method for synthesizing a novel fluorinated allyl tert-nitro alkane compound according to claim 3, characterized in that: The ligand is tri-tert-butylphosphine ( t Bu3P), 2-(dicyclohexylphosphine)-3,6-dimethoxy-2'-4'-6'-tris-isopropyl-1,1'-biphenyl (BrettPhos), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos), 2-di-tert-butylphosphine-2',4',6'-triisopropylbiphenyl ( t Bu-XPhos), tricyclohexylphosphine (PCy3), tri(1-adamantyl)phosphine (PAd3), 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphine)ferrocene (QPhos) or a mixture of two or more of these.

6. The method for synthesizing a novel fluorinated allyl tert-nitro alkane compound according to claim 3, characterized in that: The alkali is one or a mixture of two or more of the following: cesium hydroxide monohydrate, cesium hydroxide, potassium hydroxide, cesium carbonate, potassium phosphate, cesium fluoride, triethylamine, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

7. The method for synthesizing a novel fluorinated allyl tert-nitro alkane compound according to claim 3, characterized in that: The solvent is one or a mixture of two or more of the following: 1,4-dioxane, tetrahydrofuran, cyclopentylmethyl ether, ethylene glycol dimethyl ether, trifluorotoluene, n-heptane, N,N-dimethylacetamide, and acetonitrile.

8. The method for synthesizing a novel fluorinated allyl tert-nitro alkane compound according to claim 3, characterized in that: The molar ratio of the geminocyclopropane derivative to the secondary nitroalkane is 2:

3.

9. The method for synthesizing a novel fluorinated allyl tert-nitro alkane compound according to claim 3, characterized in that: The reaction tube is a Schlenk tube.

10. The method for synthesizing a novel fluorinated allyl tert-nitro alkane compound according to claim 3, characterized in that: The eluent in the column chromatography is a mixture of petroleum ether, petroleum ether and ethyl acetate in a volume ratio of (2-100):1, or a mixture of dichloromethane and methanol in a volume ratio of (2-100):1.

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