A bromo gem-difluoroallylic bicyclo[1,1,1]pentane compound and a method of preparing the same

Abstract

The application discloses a preparation method of a bromo gem-difluoro allyl bicyclo[1,1,1]pentane compound in the technical field of organic synthesis, and the method takes [1,1,1] spiropropyl, alpha, alpha, alpha-trifluoromethyl aryl olefin or a derivative thereof and potassium bromide as starting materials, and under the conditions of 2,4,5,6-tetrakis(9 H Under the conditions of taking 2,4,6-trimethylpyridine as an organic photocatalyst, 2,4,6-trimethylpyridine as a base and acetone as a solvent, bromide is oxidized into bromine free radicals under visible light excitation, then the free radicals are added to [1,1,1] spiropropyl through tension ring release, to form bromo bicyclo[1,1,1] pentane free radicals, and then the free radicals are added to alpha, alpha, alpha-trifluoromethyl aryl olefin, and through reduction and defluorination, the bromo gem-difluoro allyl bicyclo[1,1,1] pentane compound is obtained, the optimized reaction condition of the application is mild and green, the substrate has good universality, and the reaction yield is high, so that the application is a new method for preparing the bromo gem-difluoro allyl bicyclo[1,1,1]pentan compound.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing a brominated geminal difluoroallyl bicyclo[1,1,1]pentane compound. Background Technology

[0002] Bicyclic [1.1.1]pentane (BCP), with its linear, rigid, and sp3-enriched structure, is widely considered a bioisomer of the para-substituted aromatic ring. Its unique molecular structure makes it an ideal candidate for designing bioactive molecules. Utilizing its stability and unique stereochemical properties, BCP is frequently used in the pharmacophore design of drug molecules, particularly in the design of novel therapeutics; in this case, its structure can improve the stability, bioavailability, and pharmacological properties of the drug molecule. On the other hand, as bioelectronic components of carbonyl and amide functional groups, gem-difluoroenes possess the ability to modulate the structure and function of biomolecules through interactions. Their introduction may alter the electronic structure and spatial configuration of biomolecules, thereby affecting their interactions with other biomolecules. Given its practicality and importance, the synthesis of compounds containing 1,3-disubstituted BCP and gem-difluoroene functional groups is at the forefront of organic chemistry.

[0003]

[0004] [1.1.1] Propellane has important research value in chemical synthesis.

[0005] [1.1.1]Propellane is a compound with unique structure and properties. Its stability and stereoconfiguration make it an important intermediate and building block in organic synthesis. In recent years, research on the synthesis of bicyclic [1.1.1]pentane compounds from [1.1.1]propellane has attracted much attention. By introducing different functional groups or substituents, bicyclic [1.1.1]pentane compounds with specific functions can be designed and synthesized, such as drug molecules and functional materials, thereby expanding their applications in biomedicine and materials science. Although significant progress has been made in this field, reports on the synthesis of 1-bromo-3-substituted BCPs are relatively few. For example, Anderson's team reported a method using triethylboron to promote the 1,3-bromoalkylation of alkyl bromides with strong electron-attracting groups with [1,1,1]propellane. In addition, Gutierrez's team also developed a method for synthesizing 1-bromo-3-alkyl BCPs from difluoroalkyl bromides via bisphosphine-iron catalysis. Anderson's team also reported a photocatalytic method for the 1,3-bromoalkylation of [1.1.1]spiroline, although its substrates were limited to electron-deficient alkyl bromides. Mechanistic studies showed that the above three transformations were mainly initiated by the formation of alkyl radicals. Recently, Jiang's team reported a new visible light-driven method for the synthesis of 1-bromo-3-sulfonamide BCPs, involving nitrogen radical addition to [1.1.1]spiroline. To date, no method has been reported for the synthesis of 1-bromo-3-substituted BCPs via bromine radical addition to [1.1.1]spiroline.

[0006] As is well known, bromine radicals are widely recognized for their significant reactivity. In complex reactions involving alkanes, bromine radicals always act as hydrogen atom extractors. However, the introduction of bromine radicals into alkanes, especially into strained ring structures such as [1.1.1]spiroline, remains an unexplored area. Given the widespread use of gem-difluoroolefins in modifying bioactive compounds, the construction of brominated gem-difluoroallyl bicyclic [1.1.1]pentane (BCP) compounds through the bifunctionalization of [1.1.1]spiroline has become a pressing issue in this field. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this invention provides a brominated geminal difluoroallyl bicyclo[1,1,1]pentane compound and its preparation method. It uses inexpensive potassium bromide as the bromine source, requires no addition of any transition metal catalysts or strong bases, has mild reaction conditions, good substrate versatility, and high reaction yield.

[0008] The object of this invention is achieved as follows: a brominated geminitrodifluoroallyl bicyclo[1,1,1]pentane compound, characterized in that it comprises:

[0009] Compound A, [1,1,1]spiroalkyl;

[0010] Compound B, α,α,α-trifluoromethylaryl olefin or its derivative.

[0011] Furthermore, compound B comprises any of the following structural formulas:

[0012]

[0013] in, t Bu represents tert-butyl, and Ph represents benzene ring.

[0014] Furthermore, pentane compounds include any of the following structural formulas:

[0015] .

[0016] A method for preparing a brominated geminal difluoroallyl bicyclic [1,1,1]pentane compound includes the following steps:

[0017] Starting materials, including compound A, compound B, and potassium bromide, were used to obtain brominated gem-difluoroallyl bicyclo[1,1,1]pentane under photocatalyst and alkaline conditions.

[0018] The reaction formula is as follows:

[0019]

[0020] Ar represents aryl.

[0021] In this invention, bromide anions are oxidized to bromine radicals under visible light excitation, which then add to the free radicals released from the strained ring of [1,1,1]spiroalkane to form brominated bicyclic [1,1,1]pentane radicals. These radicals then add to α,α,α-trifluoromethylaryl olefins, followed by reduction and defluorination, to obtain brominated gem-difluoroallyl bicyclic [1,1,1]pentane compounds. This optimized method features mild and green reaction conditions, good substrate versatility, and high reaction yield, making it a novel approach for preparing brominated gem-difluoroallyl bicyclic [1,1,1]pentane compounds.

[0022] Furthermore, the molar ratio of compound A to compound B is 1:1.5-1:3, preferably 1:2.

[0023] Furthermore, the molar ratio of compound A to potassium bromide is 1:1.2-1:2, preferably 1:1.5.

[0024] Furthermore, the base includes a weak base, comprising at least one of dipotassium hydrogen phosphate, potassium acetate, pyridine, and 2,4,6-trimethylpyridine. Preferably, it is 2,4,6-trimethylpyridine.

[0025] Furthermore, the molar ratio of compound A to alkali is 1:0.5-1:2, preferably 1:1.

[0026] Furthermore, the molar ratio of compound A to the photocatalyst is 1:0.02-1:0.04, preferably 1:0.03.

[0027] Furthermore, the photocatalyst comprises at least one of 2,4,5,6-tetra(9H-carbazole-9-yl)isophthalonitrile, succinate Y, and bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium hexafluorophosphate; preferably 2,4,5,6-tetra(9H-carbazole-9-yl)isophthalonitrile.

[0028] The reaction solvent includes any one of acetone, acetonitrile, dichloromethane, and tetrahydrofuran. The reaction light source is blue light, the reaction gas atmosphere is argon, and the reaction time is 10-15 hours. Acetone is preferred.

[0029] Compared with the prior art, the beneficial effects of the present invention are as follows: the present invention uses inexpensive potassium bromide as bromine source, does not require the use of transition metal catalyst, has mild reaction conditions, good substrate universality, and high reaction yield, and is a new method for synthesizing brominated geminal difluoroallyl bicyclo[1,1,1]pentane compounds. Detailed Implementation

[0030] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention. Example

[0031] This invention proposes a method for preparing a brominated gem-difluoroallyl bicyclic [1,1,1]pentane compound, comprising: using [1,1,1]spiroalkyl, α,α,α-trifluoromethylaryl olefin or its derivatives, and potassium bromide as starting materials, in a 2,4,5,6-tetra(9 H Using 9-carbazole isophthalonitrile and other organic photocatalysts, and 2,4,6-trimethylpyridine and other bases, and acetone as solvent, brominated geminal difluoroallyl bicyclo[1,1,1]pentane compounds were obtained.

[0032] Example 1: Preparation of Compound 3

[0033]

[0034] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 2 (49.6 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), 2,4,5,6-tetra(9H-carbazole-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0035] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 3 (26.2 mg, 70%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0036] The product structure characterization data are as follows:

[0037] 1 H NMR (400 MHz, CCCl3): δ 7.63 – 7.58 (m, 4H), 7.46 (t, J = 7.6 Hz, 2H),7.40 – 7.35 (m, 3H), 2.73 (t, J = 2.3 Hz, 2H), 2.04 (s, 6H) ppm.

[0038] 13 C NMR (101 MHz, CDCl3): δ 154.3 (dd, J C-F = 290.2, 294.7 Hz), 140.3,140.2, 132.2 (t, J C-F = 4.4 Hz), 128.8, 128.3 (t, J C-F = 3.7 Hz), 127.5, 127.1,127.0, 89.7 (dd, J C-F =13.5 Hz, 22.3 Hz), 58.8, 39.8 (dd, J C-F= 2.6 Hz, 4.4 Hz),36.3, 29.4 (d, J C-F = 2 Hz) ppm.

[0039] 19 F NMR (377 MHz, CDCl3): δ -89.37 (d, J C-F = 38.9 Hz, 1F), -90.29 (d, J =38.9 Hz, 1F) ppm.

[0040] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 20 H 18 BrF2 + 375.0555; Found 375.0589.

[0041] Example 2: Preparation of Compound 5

[0042]

[0043] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 4 (41.2 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetrakis(9H-carbazol-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0044] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 5 (22.6 mg, 68%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0045] The product structure characterization data are as follows:

[0046] 1 H NMR (400 MHz, CDCl3): δ 7.35 – 7.30 (m, 2H), 7.23 – 7.19 (m, 2H), 2.66 (t, J= 2.4 Hz, 2H), 1.99 (s, 6H) ppm.

[0047] 13 C NMR (101 MHz, CDCl3) δ 154.2 (dd, J C-F = 289.9, 293.9 Hz), 133.3,131.7 (t, J C-F = 4.0 Hz), 129.2 (t, J C-F = 4.0 Hz), 128.8, 89.2 (dd, J C-F = 13.0, 22.2Hz), 58.7, 39.6 (dd, J C-F = 3.0, 4.0 Hz), 36.2, 29.4 (d, J C-F = 2 Hz) ppm.

[0048] 19 F NMR (377 MHz, CDCl3): δ -89.13 (d, J C-F = 37.7 Hz, 1F), -90.05 (d, J =37.7 Hz, 1F) ppm.

[0049] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 14 H 13 BrClF2 + 332.9852; Found332.9853.

[0050] Example 3: Preparation of Compound 7

[0051]

[0052] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 6 (50.0 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0053] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 7 (24.1 mg, 64%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0054] The product structure characterization data are as follows:

[0055] 1 H NMR (400 MHz, CDCl3): δ 7.50 – 7.46 (m, 2H), 7.17 – 7.13 (m, 2H), 2.66 (t, J = 2.4 Hz, 2H), 1.99 (s, 6H) ppm.

[0056] 13 C NMR (101 MHz, CDCl3) δ 154.4 (dd, J C-F = 289.9, 292.9 Hz), 132.4 (t, J C-F = 4.0 Hz), 131.9, 129.7 (t, J C-F = 3.0 Hz), 121.6, 89.4 (dd, J C-F = 13.5, 22.2Hz), 58.7, 39.7 (dd, J C-F = 2.0, 4.0 Hz), 36.1, 29.4 (d, J C-F = 1.0 Hz) ppm.

[0057] 19 F NMR (377 MHz, CDCl3): δ -88.97 (d,J C-F = 37.7 Hz, 1F), -89.90 (d, J =37.7 Hz, 1F) ppm.

[0058] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 14 H 13 Br2F2 + 376.9347; Found 376.9353.

[0059] Example 4: Preparation of Compound 9

[0060]

[0061] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 8 (46.0 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0062] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 9 (17.8 mg, 50%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 10:1).

[0063] The product structure characterization data are as follows:

[0064] 1 H NMR (400 MHz, CDCl3): δ 8.03 – 8.00 (m, 2H), 7.38 – 7.35 (m, 2H), 3.92 (s, 3H), 2.71 (t, J = 2.3 Hz, 2H), 1.98 (s, 6H) ppm.

[0065] 13 C NMR (101 MHz, CDCl3) δ 166.5, 154.5 (dd, J C-F= 290.8, 295.9 Hz), 138.1 (t, J C-F = 4.0 Hz), 129.8, 129.2 (d, J C-F = 5.0 Hz), 127.9 (t, J C-F = 4.0 Hz), 89.7 (dd, J C-F = 13.1, 22.2 Hz), 58.7, 52.2, 39.7 (dd, J C-F = 2.0, 4.0 Hz), 36.1(d, J C-F = 1.0 Hz), 29.3 ppm.

[0066] 19 F NMR (377 MHz, CDCl3): δ -87.64 (d, J C-F = 37.7 Hz, 1F), -88.58 (d, J =37.7 Hz, 1F) ppm.

[0067] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 16 H 16 BrF2O2 + 357.0297; Found357.0297.

[0068] Example 5: Preparation of Compound 11

[0069]

[0070] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 10 (48.8 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0071] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 11 (20.4 mg, 55%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0072] The product structure characterization data are as follows:

[0073] 1 H NMR (400 MHz, CDCl3): δ 7.51 – 7.48 (m, 2H), 7.27 – 7.24 (m, 2H), 2.69 (t, J = 2.4 Hz, 2H), 2.01 (s, 6H), 0.27 (s, 9H) ppm.

[0074] 13 C NMR (101 MHz, CDCl3) δ 154.3 (dd, J C-F = 288.9, 293.9 Hz), 139.9,133.6 (t, J C-F = 4.0 Hz), 133.5, 127.1 (t, J C-F = 3.0 Hz), 89.9 (dd, J C-F = 13.1, 22.2Hz), 58.8, 39.8 (dd, J C-F = 2.0, 4.0 Hz), 36.4 (d, J C-F = 1.0 Hz), 29.4 (d, J C-F = 2.0Hz), -1.18 ppm.

[0075] 19 F NMR (377 MHz, CDCl3): δ -89.46 (d, J C-F = 41.5 Hz, 1F), -90.46 (d, J =37.7 Hz, 1F) ppm.

[0076] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 17 H 22 BrF2Si +371.0637; Found371.0639.

[0077] Example 6: Preparation of Compound 13

[0078]

[0079] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 12 (37.2 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetra(9H-carbazole-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0080] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 13 (16.2 mg, 52%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0081] The product structure characterization data are as follows:

[0082] 1 H NMR (400 MHz, CDCl3): δ 7.19 – 7.13 (m, 4H), 2.67 (t, J = 2.3 Hz, 2H), 2.35 (s, 3H), 1.99 (s, 6H) ppm.

[0083] 13 C NMR (101 MHz, CDCl3) δ 154.1 (dd, J C-F = 287.9, 292.9 Hz), 137.3,130.2 (t, J C-F = 4.0 Hz), 129.2, 127.8 (t, J C-F = 3.0 Hz), 89.7 (dd, J C-F = 14.1, 21.2Hz), 58.9, 39.8 (dd, J C-F = 2.0, 4.0 Hz), 36.4 (d,J C-F = 1.0 Hz), 29.5 (d, J C-F = 2.0Hz), 21.1 ppm.

[0084] 19 F NMR (377 MHz, CDCl3): δ -90.63 (d, J C-F = 41.5 Hz, 1F), -91.39 (d, J =41.5 Hz, 1F) ppm.

[0085] HRMS (ESI-TOF) m / z: [M+K] + Calcd for C 15 H 15 BrF2K + 350.9957; Found350.9971.

[0086] Example 7: Preparation of Compound 15

[0087]

[0088] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 14 (45.6 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0089] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 15 (21.6 mg, 61%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0090] The product structure characterization data are as follows:

[0091] 1 H NMR (400 MHz, CDCl3): δ 7.38 – 7.35 (m, 2H), 7.23 – 7.19 (m, 2H), 2.67 (t, J= 2.4 Hz, 2H), 2.01 (s, 6H), 1.32 (s, 9H) ppm.

[0092] 13 C NMR (101 MHz, CDCl3) δ 154.2 (dd, J C-F = 287.9, 293.9 Hz), 150.5,130.2 (t, J C-F = 4.0 Hz), 127.5 (t, J C-F = 3.0 Hz), 125.4, 89.6 (dd, J C-F = 14.1, 21.2Hz), 58.8, 39.8 (dd, J C-F = 2.0, 4.0 Hz), 36.5 (d, J C-F = 1.0 Hz), 34.5, 31.2, 29.5(d, J C-F = 2.0 Hz) ppm.

[0093] 19 F NMR (377 MHz, CDCl3): δ -90.16 (d, J C-F = 41.5 Hz, 1F), -91.06 (d, J =41.5 Hz, 1F) ppm.

[0094] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 18 H 22 BrF2 + 357.0847; Found 357.0842.

[0095] Example 8. Preparation of Compound 17

[0096]

[0097] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 16 (43.6 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetrakis(9H-carbazol-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0098] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 17 (20.0 mg, 58%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0099] The product structure characterization data are as follows:

[0100] 1 H NMR (400 MHz, CDCl3): δ 7.23 – 7.17 (m, 4H), 2.66 (t, J = 2.3 Hz, 2H), 2.49 (s, 3H), 1.99 (s, 6H) ppm.

[0101] 13 C NMR (101 MHz, CDCl3) δ 154.2 (dd, J C-F = 288.9, 292.9 Hz), 137.9,129.8 (t, J C-F = 4.0 Hz), 128.3 (t, J C-F = 4.0 Hz), 126.3, 89.5 (dd, J C-F = 13.1, 21.2Hz), 58.7, 39.7 (dd, J C-F = 2.0, 4.0 Hz), 36.3 (d, J C-F = 1.0 Hz), 29.3 (d, J C-F = 1.0Hz), 15.5 ppm.

[0102] 19F NMR (377 MHz, CDCl3): δ -89.86 (d, J C-F = 41.5 Hz, 1F), -90.67 (d, J =41.5 Hz, 1F) ppm.

[0103] HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 15 H 16 BrF2S + 347.0099; Found 347.009.

[0104] Example 9: Preparation of Compound 19

[0105]

[0106] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 18 (40.4 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0107] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 19 (25.6 mg, 78%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 20:1).

[0108] The product structure characterization data are as follows:

[0109] 1 H NMR (400 MHz, CDCl3): δ 7.22 – 7.17 (m, 2H), 6.90 – 6.86 (m, 2H), 3.81 (s, 3H), 2.65 (t, J = 2.4 Hz, 2H), 1.99 (s, 6H) ppm.

[0110] 13 C NMR (101 MHz, CDCl3) δ 158.8, 154.0 (dd,J C-F = 288.9, 291.9 Hz), 129.1 (t, J C-F = 4.0 Hz), 125.3 (t, J C-F = 4.0 Hz), 113.9, 89.4 (dd, J C-F = 14.1, 22.2Hz), 58.8, 55.2, 39.7 (dd, J C-F = 2, 4 Hz), 36.4 (d, J C-F = 1.0 Hz), 29.5 (d, J C-F =2.0 Hz) ppm.

[0111] 19 F NMR (377 MHz, CDCl3): δ -91.25 (d, J C-F = 41.5 Hz, 1F), -92.04 (d, J =41.5 Hz, 1F) ppm.

[0112] HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 15 H 15 BrF2ONa + 351.0167; Found351.0147.

[0113] Example 10: Preparation of Compound 21

[0114]

[0115] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 20 (64.8 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0116] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 21 (27.0 mg, 60%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0117] The product structure characterization data are as follows:

[0118] 1 H NMR (400 MHz, CDCl3): δ 7.74 – 7.71 (m, 1H), 7.66 – 7.62 (m, 4H), 7.52 – 7.47 (m, 6H), 7.43 – 7.38 (m, 2H), 2.79 (t, J = 2.4 Hz, 2H), 2.08 (s, 6H) ppm.

[0119] 13 C NMR (101 MHz, CDCl3) δ 154.5 (dd, J C-F = 289.9, 294.9 Hz), 142.1,140.7, 134.4 (t, J C-F = 4.0 Hz), 128.9, 127.7, 127.3, 125.7 (t, J C-F = 3.0 Hz), 125.4, 90.0 (dd, J C-F = 14.1, 22.2 Hz), 58.8, 39.9 (dd, J C-F = 2.0, 4.0 Hz), 36.3(d, J C-F = 2.0 Hz), 29.7 (d, J C-F = 2.0 Hz) ppm.

[0120] 19 F NMR (377 MHz, CDCl3): δ -91.69 (d, J C-F = 37.7 Hz, 1F), -92.41 (d, J =37.7 Hz, 1F) ppm.

[0121] HRMS (ESI-TOF) m / z: [M+Na]+ Calcd for C 26 H 21 BrF2Na + 473.0687; Found473.0675.

[0122] Example 11. Preparation of compound 23

[0123]

[0124] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. α,α,α-trifluoromethylaryl olefin 22 (72.8 mg, 0.2 mmol), potassium bromide (18.2 mg, 0.15 mmol), and 2,4,5,6-tetrakis(9H-carbazol-9-yl)isophthalonitrile (2.4 mg, 0.003 mmol, 1 mol%) were added. After purging with argon three times, 4 mL of acetone, 2,4,6-trimethylpyridine (12.1 mg, 0.1 mmol), and [1,1,1]spiropropane 1 (0.1 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature under blue light irradiation for 12 hours.

[0125] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 23 (20 mg, 40%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 10:1).

[0126] The product structure characterization data are as follows:

[0127] 1 H NMR (400 MHz, CDCl3): δ 8.02 – 7.98 (m, 2H), 7.37 – 7.34 (m, 2H), 5.38 – 5.36 (m, 1H), 4.35 – 4.31 (m, 2H), 2.71 (t, J = 2.4 Hz, 2H), 2.47 – 2.35(m, 4H), 2.27 – 2.22 (m, 2H), 2.12 – 2.10 (m, 1H), 1.98 (s, 6H), 1.79 – 1.75(m, 1H), 1.27 (s, 3H), 0.84 (s, 3H) ppm.

[0128] 13 C NMR (101 MHz, CDCl3) δ 166.0, 154.5 (dd, J C-F= 289.9, 294.9 Hz), 144.1 (d, J C-F = 5.0 Hz), 138.0 (t, J C-F = 4.0 Hz), 129.9, 129.7, 127.8 (t, J C-F = 4.0Hz), 119.0 (d, J C-F = 3.0 Hz), 89.7 (dd, J C-F = 13.1, 22.2 Hz), 63.4, 58.7, 48.6(dd, J C-F = 27.3, 55.6 Hz), 45.7, 40.7, 39.7 (dd, J C-F = 2.0, 4.0 Hz), 38.0, 36.0,31.66, 31.4, 29.3, 26.2 ppm.

[0129] 19 F NMR (377 MHz, CDCl3): δ -87.67 (d, J C-F = 37.7 Hz, 1F), -88.62 (d, J =33.9 Hz, 1F) ppm.

[0130] HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 26 H 29 BrF2O2Na + 513.1212; Found513.1202.

[0131] The examples provided above demonstrate that the present invention provides a method for preparing brominated geminodifluoroallyl bicyclo[1,1,1]pentane compounds. The reaction conditions are mild, the use of transition metals is avoided, the substrate compatibility is broad, and the reaction yield is generally high.

[0132] The above description of the embodiments is only for the purpose of helping to understand the method and core ideas of the present invention. It should be noted that those skilled in the art can make several improvements and modifications to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. A process for the preparation of a bromo gem-difluoroallyl bicyclo[l,l,l]pentane compound, characterized in that, The method comprises the following steps: The starting materials including compound A, compound B and potassium bromide are subjected to the condition of a photocatalyst 2,4,5,6-tetrakis(9H-carbazole-9-yl)isophthalonitrile and a base 2,4,6-trimethylpyridine to obtain a bromo gem difluoro allyl bicyclo[1,1,1]pentane compound; The reaction formula is as follows: ； The compound B is any one of the following structural formulae: wherein t Bu represents a tert-butyl group, and Ph represents a phenyl ring.

2. The production method according to claim 1, characterized by, The molar ratio of the compound A to the compound B is 1:1.5-1:

3.

3. The preparation method according to claim 1, characterized in that, The molar ratio of the compound A to potassium bromide is 1:1.2-1:

2.

4. The method of claim 1, wherein, The molar ratio of the compound A to the base is 1:0.5-1:

2.

5. The preparation method according to claim 1, characterized in that, The molar ratio of the compound A to the photocatalyst is 1:0.02-1:0.

04.

6. The method of claim 1, wherein, The reaction solvent comprises any one of acetone, acetonitrile, dichloromethane and tetrahydrofuran, the reaction light source is blue light, the reaction gas atmosphere is argon, and the reaction time is 10-15 hours.

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