A method for preparing a 1-aryl-3-ynylbicyclic [1.1.1]pentane compound

Abstract

This invention discloses a visible light / copper dual-catalyzed method for preparing 1-aryl-3-ynylbicyclo[1.1.1]pentane. Using arylthionium trifluoromethanesulfonate, [1.1.1]spiroline, and terminal alkynes as starting materials, under the conditions of tris(2-phenylpyridine)iridium as a photocatalyst, copper acetylacetonate as a metal catalyst, 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl as a ligand, 1,8-diazabicyclo[5.4.0]undec-7-ene as a base, and acetonitrile as a solvent, the arylthionium salt is reduced to an aryl radical, which then undergoes ring-strained radical addition with [1.1.1]spiroline. Finally, the radical is captured by the in-situ generated ynyl copper intermediate and reduced to obtain the 1-aryl-3-ynylbicyclo[1.1.1]pentane compound. The optimized method features mild reaction conditions and good substrate versatility, solving the problem of multiple steps required in previous syntheses. It is a new method for preparing 1-aryl-3-ynthylbicyclic [1,1,1]pentane compounds.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing a 1-aryl-3-ynylbicyclo[1.1.1]pentane compound. Background Technology

[0002] Bicyclic [1.1.1]pentanes (BCPs) are an important class of organic compounds that have attracted widespread attention in medicinal chemistry and materials science due to their unique three-dimensional structure and high stability. These compounds are designed to replace traditional aromatic structures, providing similar electronic and stereochemical properties while exhibiting better biocompatibility and chemical stability. In medicinal chemistry, the study of BCPs as bioisomers is gaining increasing importance. Compared to conventional aromatic rings, BCPs can maintain similar electronic and stereochemical environments within a smaller molecular framework, giving them an advantage in improving molecular specificity and biocompatibility. Furthermore, the synthesis of BCPs is not only involved in drug development but also has potential applications in the design of new materials, especially in the fields of polymers and nanomaterials.

[0003]

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

[0005] [1.1.1]Propellane is a uniquely attractive compound. Its distinctive structure and properties endow it with excellent stability and stereoconfiguration, making it an indispensable 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 increasing attention. By cleverly introducing different functional groups or substituents, scientists have been able to design and synthesize bicyclic [1.1.1]pentane compounds with specific functions. These compounds have shown broad application prospects in drug development and functional materials, greatly promoting the progress of biomedicine and materials science. Although significant progress has been made in this field, reports on the synthesis of 1-aryl-3-ynthyl bicyclic [1.1.1]pentane compounds are relatively few, and they are still mainly multi-step reactions. These methods usually require complex reaction steps, such as the preparation of reactive organometallic reagents, addition, and subsequent oxidation, to achieve the synthesis of the target product. This not only requires a strictly anhydrous and oxygen-free environment but also easily leads to side reactions and low yields. Furthermore, the selectivity of the substrate, the complexity of post-reaction processing, and the separation and purification processes also limit the expansion of its applications. Therefore, developing an efficient and simple synthetic method can significantly improve the synthetic efficiency of 1-aryl-3-ynthyl BCP and promote its application in drug development and new materials. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides 1-aryl-3-ynylbicyclo[1.1.1]pentane compounds and their preparation methods. Under visible light / copper dual-catalysis, this invention achieves one-step efficient synthesis of such compounds with mild reaction conditions and good substrate versatility.

[0007] The object of this invention is achieved as follows: a method for preparing a 1-aryl-3-ynylbicyclic [1.1.1]pentane compound, characterized in that the substrate of the method comprises:

[0008] Compound A, arylthionium trifluoromethanesulfonate,

[0009] Compound B, [1.1.1]spiroalkyl, and

[0010] Compound C is a terminal alkyne.

[0011] The method includes the following steps: starting materials including compound A, compound B, and compound C are used to obtain 1-aryl-3-ynylbicyclo[1.1.1]pentane compound under visible light-promoted iridium / copper dual catalysis.

[0012] Furthermore, compound A comprises any of the following structural formulas:

[0013]

[0014] In this context, OMe represents methoxy, Me represents methyl, and OTf represents trifluoromethanesulfonate.

[0015] Furthermore, compound C comprises any of the following structural formulas:

[0016]

[0017] in, t Bu represents tert-butyl, OMe represents methoxy, CF3 represents trifluoromethyl, and CN represents cyano.

[0018] Furthermore, it includes any of the following structural formulas:

[0019] .

[0020] Furthermore, the reaction equation is as follows:

[0021]

[0022] Ar represents aryl.

[0023] Furthermore, the molar ratio of compound C to compound A is 1:1.2-1:2, preferably 1:1.5; the molar ratio of compound C to compound B is 1:1.5-1:3, preferably 1:3; the molar ratio of compound C to photocatalyst is 1:0.02-1:0.04, preferably 1:0.03; the molar ratio of compound C to copper catalyst is 1:0.2-1:0.4, preferably 1:0.3; the molar ratio of compound C to alkali is 1:1-1:3; and the molar ratio of compound C to ligand is 1:0.2-1:0.4, preferably 1:0.3.

[0024] Furthermore, the photocatalyst includes at least one of the following: Y-red, bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)], 2,4,5,6-tetra(9H-carbazole-9-yl)isophthalonitrile, and tri(2-phenylpyridine)iridium, preferably tri(2-phenylpyridine)iridium.

[0025] Furthermore, the copper catalyst includes at least one of copper acetate, cuprous acetate, cuprous iodide, and copper acetylacetonate, preferably copper acetylacetonate.

[0026] Furthermore, the ligand includes at least one of 2,2'-bipyridine, 4,4-di-tert-butyl-2,2-bipyridine, 2,2'-bis(diphenylphosphine)-1,1'-naphthyl, and 2,2'-bis(dicyclohexylphosphine)-1,1'-biphenyl, preferably 2,2'-bis(dicyclohexylphosphine)-1,1'-biphenyl.

[0027] Furthermore, the base includes at least one of triethylamine, 2,4,6-trimethylpyridine, tetramethylguanidine, and 1,8-diazabicyclo[5.4.0]undec-7-ene; preferably 1,8-diazabicyclo[5.4.0]undec-7-ene. The reaction solvent includes any one of acetone, dichloromethane, tetrahydrofuran, and acetonitrile. The reaction light source is blue light, the reaction gas atmosphere is argon, and the reaction time is 2-6 hours, preferably acetonitrile.

[0028] In this invention, aryl thioonium salts are reduced to aryl radicals by an excited-state photocatalyst, which then undergo addition with the radicals released from the strained ring of [1.1.1]spiroane to form aryl bicyclic [1.1.1]pentane radicals. These radicals then undergo addition with an alkynyl copper intermediate followed by reductive elimination to obtain 1-aryl-3-alkynyl bicyclic [1.1.1]pentane compounds. This optimized method features mild and environmentally friendly reaction conditions, good substrate versatility, and high one-step synthesis efficiency, making it a novel method for preparing 1-aryl-3-alkynyl bicyclic [1.1.1]pentane compounds.

[0029] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0030] High efficiency: The dual catalytic system of photocatalysis and copper catalysis used in this invention allows the reaction to proceed under mild conditions, which greatly improves the reaction efficiency and yield.

[0031] Simplified steps: By introducing arylthioonium salt as an intermediate, this invention achieves the single-step synthesis of 1-aryl-3-ynylbicyclo[1.1.1]pentane, which significantly simplifies the traditional multi-step synthesis process.

[0032] Broad substrate compatibility: This method is well applicable to a wide range of aryl and alkynyl compounds, expanding the range of compounds that can be synthesized.

[0033] Reduced side reactions: Compared with traditional synthesis methods, the reaction steps in this invention are milder, reducing the occurrence of side reactions and thus improving the purity and selectivity of the product.

[0034] Green chemistry: Using mild conditions and fewer harmful reagents in reactions, in accordance with the principles of green chemistry, contributes to environmental protection and sustainable development.

[0035] These advantages give the present invention significant technical advantages and application potential in the synthesis of 1-aryl-3-ynylbicyclo[1.1.1]pentane compounds. Detailed Implementation

[0036] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. 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 skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] This invention proposes a method for preparing a 1-aryl-3-ynylbicyclo[1.1.1]pentane compound, comprising: using aryl thioonium trifluoromethanesulfonate, [1.1.1]spiroalkyl and terminal alkynes as starting materials, and obtaining the 1-aryl-3-ynylbicyclo[1.1.1]pentane compound under the following conditions: using tri(2-phenylpyridine)iridium as a photocatalyst, copper acetylacetonate as a metal catalyst, 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl as a ligand, 1,8-diazabicyclo[5.4.0]undec-7-ene as a base, and acetonitrile as a solvent.

[0038] Example 1: Preparation of Compound 16

[0039]

[0040] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0041] After the reaction was completed, the solvent was removed by rotary evaporation, and compound 16 (37.4 mg, 65%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0042] The product structure characterization data are as follows:

[0043] 1 H NMR (400 MHz, Chloroform-d) δ 7.33 (d, J = 8.1 Hz, 2H), 7.16 –7.09 (m, 4H), 6.85 (d, J = 8.6 Hz, 2H), 3.80 (s, 3H), 2.37 (s, 6H), 2.34 (s,3H).

[0044] 13 C NMR (101 MHz, Chloroform-d) δ 158.4, 138.0, 132.5, 131.6, 129.0,127.1, 120.0, 113.6, 88.2, 80.1,56.6, 55.3, 43.7, 27.8, 21.5 ppm.

[0045] Example 2: Preparation of Compound 17

[0046]

[0047] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 2 (136.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0048] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 17 (31.5 mg, 58%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0049] The product structure characterization data are as follows:

[0050] 1 H NMR (400 MHz, Chloroform-d) δ 7.35 (d, J = 8.1 Hz, 2H), 7.15 –7.09 (m, 6H), 2.40 (s, 6H), 2.35 (s, 6H) ppm.

[0051] 13 C NMR (101 MHz, Chloroform-d) δ 138.0, 137.2, 136.3, 131.6, 129.0,128.8, 125.9, 120.1, 88.2, 80.2, 56.6, 44.0, 28.0, 21.4, 21.1 ppm.

[0052] Example 3: Preparation of Compound 18

[0053]

[0054] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 3 (142.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0055] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 18 (26.8 mg, 46%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0056] The product structure characterization data are as follows:

[0057] 1 H NMR (400 MHz, Chloroform-d) δ 7.34 (d, J = 7.9 Hz, 2H), 7.28 –7.24 (m, 2H), 7.16 – 7.07 (m, 4H), 2.39 (s, 6H), 2.35 (s, 3H) ppm.

[0058] 13 C NMR (101 MHz, Chloroform-d) δ 138.6, 138.1, 132.5, 131.6, 129.0,128.3, 127.5, 120.0, 87.8, 80.4,56.6, 43.6, 28.0, 21.4 ppm.

[0059] Example 4: Preparation of Compound 19

[0060]

[0061] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 4 (141.0 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0062] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 19 (25.7 mg, 45%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

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

[0064] 1 H NMR (400 MHz, Chloroform-d) δ 7.36 (d, J = 8.1 Hz, 2H), 7.12 (d, J= 8.2 Hz, 2H), 7.04 – 6.93 (m, 3H), 2.52 (s, 6H), 2.38 (d, J = 11.0 Hz, 6H),2.32 (s, 3H) ppm.

[0065] 13 C NMR (101 MHz, Chloroform-d) δ 138.0, 136.7, 134.6, 131.6, 131.4,130.4, 129.0, 127.6, 126.3, 120.1, 88.1, 80.2, 56.5, 44.9, 29.1, 21.4, 20.9,20.5 ppm.

[0066] Example 5: Preparation of Compound 20

[0067]

[0068] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 5 (164.9 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0069] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 20 (43.9 mg, 60%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0070] The product structure characterization data are as follows:

[0071] 1 H NMR (400 MHz, Chloroform-d) δ 7.39 (d, J = 2.0 Hz, 1H), 7.34 (d, J= 8.0 Hz, 2H), 7.10 (d, J = 8.1 Hz, 3H), 6.82 (d, J = 8.4 Hz, 1H), 3.88 (s,3H), 2.37 (s,6H), 2.34 (s,3H) ppm.

[0072] 13 C NMR (101 MHz, Chloroform-d) δ 154.7, 138.0, 134.0, 131.6, 131.1,129.0, 126.1, 120.0, 111.6, 111.4, 87.8, 80.4, 56.6, 56.3, 43.1, 27.9, 21.4ppm.

[0073] Example 6: Preparation of Compound 21

[0074]

[0075] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-tert-butylphenylacetylene 7 (31.6 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0076] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 21 (42.9 mg, 65%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0077] The product structure characterization data are as follows:

[0078] 1 H NMR (400 MHz, Chloroform-d) δ 7.36 (d, J = 8.5 Hz, 2H), 7.30 (d, J= 8.4 Hz, 2H), 7.14 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.6 Hz, 2H), 3.79 (s,3H), 2.36 (s,6H), 1.30 (s,9H) ppm.

[0079] 13 C NMR (101 MHz, Chloroform-d) δ 158.5, 151.1, 132.5, 131.4, 127.2,125.2, 120.1, 113.6, 88.2, 80.1, 56.6, 55.3, 43.7, 34.7, 31.2, 27.9ppm.

[0080] Example 7: Preparation of Compound 22

[0081]

[0082] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-methoxyphenylacetylene 8 (26.4 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0083] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 22 (36.5 mg, 60%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0084] The product structure characterization data are as follows:

[0085] 1 H NMR (400 MHz, Chloroform-d) δ 7.38 (d, J = 8.8 Hz, 2H), 7.14 (d, J= 8.7 Hz, 2H), 6.83 (t, J = 8.7 Hz, 4H), 3.80 (d, J = 4.2 Hz, 6H), 2.37 (s,6H) ppm.

[0086] 13 C NMR (101 MHz, Chloroform-d) δ 159.3, 158.5, 133.1, 132.5, 127.1,115.3, 113.8, 113.6, 87.4, 79.9, 56.6, 55.3, 55.2, 43.7, 27.9 ppm.

[0087] Example 8: Preparation of Compound 23

[0088]

[0089] A 10 mL Shrek tube with a side arm and a magnetic stir bar was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-methoxyphenylacetylene 9 (34.0 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0090] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 23 (37.6 mg, 55%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0091] The product structure characterization data are as follows:

[0092] 1 H NMR (400 MHz, Chloroform-d) δ 7.54 (d, J = 2.9 Hz, 4H), 7.15 (d, J = 8.7 Hz, 2H), 6.86 (d, J = 8.6 Hz, 2H), 3.80 (s, 3H), 2.40 (s, 6H) ppm.

[0093] 13 C NMR (101 MHz, Chloroform-d) δ 158.6, 132.2, 131.9, 129.6 (q, J =32.3 Hz), 127.1, 125.1 (q, J = 4.0 Hz), 123.9 (q, J = 272.7 Hz), 113.6, 91.6, 78.9, 56.6, 55.3, 43.9, 27.7 ppm.

[0094] Example 9: Preparation of Compound 24

[0095]

[0096] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-methoxyphenylacetylene 10 (25.4 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0097] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 24 (31.7 mg, 53%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0098] The product structure characterization data are as follows:

[0099] 1 H NMR (400 MHz, Chloroform-d) δ 7.58 (d, J = 8.5 Hz, 2H), 7.50 (d, J= 8.4 Hz, 2H), 7.14 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 3.80 (s,3H), 2.39 (s,6H) ppm.

[0100] 13 C NMR (101 MHz, Chloroform-d) δ 158.6, 133.3, 132.2, 131.9, 128.3,127.1, 118.5, 113.6, 111.2, 93.7, 78.7, 56.6, 55.3, 44.0, 27.6 ppm.

[0101] Example 10: Preparation of Compound 25

[0102]

[0103] A 10 mL Shrek tube with a side arm and a magnetic stir bar was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-chlorophenylacetylene 11 (27.2 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0104] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 25 (34.4 mg, 56%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0105] The product structure characterization data are as follows:

[0106] 1 H NMR (400 MHz, Chloroform-d) δ 7.35 (d, J = 8.7 Hz, 2H), 7.26 (d, J= 8.6 Hz, 2H), 7.13 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 3.79 (s,3H), 2.37 (s,6H) ppm.

[0107] 13 C NMR (101 MHz, Chloroform-d) δ 158.5, 133.9, 133.0, 132.3, 128.5, 127.1, 121.8, 113.6, 90.0, 79.0, 56.6, 43.8, 29.7 ppm.

[0108] Example 11: Preparation of Compound 26

[0109]

[0110] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-bromophenylacetylene 12 (36.0 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0111] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 26 (29.5 mg, 42%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0112] The product structure characterization data are as follows:

[0113] 1 H NMR (400 MHz, Chloroform-d) δ 7.43 (d, J = 8.5 Hz, 2H), 7.30 (d, J= 8.5 Hz, 2H), 7.14 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 3.80 (s,3H), 2.38 (s,6H) ppm.

[0114] 13 C NMR (101 MHz, Chloroform-d) δ 158.5, 133.2, 132.3, 131.5, 127.1, 122.2, 122.1, 113.6, 90.2, 79.1, 56.6, 55.3, 43.9, 27.8 ppm.

[0115] Example 12: Preparation of Compound 27

[0116]

[0117] A 10 mL Shrek tube with a side arm and a magnetic stir bar was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and p-fluorophenylacetylene 13 (24.0 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0118] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 27 (30.9 mg, 53%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0119] The product structure characterization data are as follows:

[0120] 1 H NMR (400 MHz, Chloroform-d) δ 7.43 – 7.39 (m, 2H), 7.14 (d, J =8.6 Hz, 2H), 6.99 (t, J = 8.7 Hz, 2H), 6.84 (d, J = 8.6 Hz, 2H), 3.80 (s,3H), 2.37 (s, 6H) ppm.

[0121] 13 C NMR (101 MHz, Chloroform-d) δ 162.2 (d, J = 249.5 Hz), 158.5,133.6 (d, J = 9.8 Hz), 132.3, 127.13, 119.2 (d, J = 4.0 Hz), 115.5 (d, J =22.2 Hz), 113.6, 88.6, 79.0, 56.6, 55.3, 43.8, 27.7 ppm.

[0122] Example 13: Preparation of Compound 28

[0123]

[0124] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroalkyl B (0.6 mmol), and 2-ethynylpyridine 14 (20.6 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0125] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 28 (28.1 mg, 51%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

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

[0127] 1 H NMR (400 MHz, Chloroform-d) δ 8.56 (s, 1H), 7.64 (t, J = 7.7 Hz,1H), 7.42 (d, J = 7.8 Hz, 1H), 7.24 – 7.19 (m, 1H), 7.13 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 3.79 (s, 3H), 2.39 (s, 6H) ppm.

[0128] 13 C NMR (101 MHz, Chloroform-d) δ 158.5, 149.7, 143.1, 136.3, 132.2,127.1, 127.0, 122.6, 113.6, 89.5,79.3,56.6, 55.3, 44.0, 27.5 ppm.

[0129] Example 14: Preparation of Compound 29

[0130]

[0131] A 10 mL Shrek tube equipped with a magnetic stir bar and a side arm was selected. Arylthiotrifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tri(2-phenylpyridinium)iridium (4.0 mg, 0.006 mmol), copper acetylacetonate (16.0 mg, 0.06 mmol), 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl (35 mg, 0.06 mmol) were added. After purging with argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]spiroline B (0.6 mmol), and 2-ethynylnaphthalene 15 (30.4 mg, 0.2 mmol) were added under an argon atmosphere. The reaction was then carried out at room temperature for 6 hours under blue light irradiation.

[0132] After the reaction was completed, the solvent was removed by rotary evaporation in a rotary evaporator, and compound 29 (32.4 mg, 50%) was obtained by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1).

[0133] The product structure characterization data are as follows:

[0134] 1 H NMR (400 MHz, Chloroform-d) δ 7.97 (s, 1H), 7.84 – 7.73 (m, 3H), 7.48 (t, J = 6.1 Hz, 3H), 7.20 – 7.11 (m, 2H), 6.90 – 6.81 (m, 2H), 3.80 (s,3H), 2.42 (s,6H) ppm.

[0135] 13 C NMR (101 MHz, Chloroform-d) δ 158.5, 133.0, 132.6, 132.4, 131.5,128.6, 127.8, 127.7, 127.6, 127.2, 126.5, 126.4, 120.5, 113.6, 89.3, 80.5,56.7, 55.3, 43.8, 27.9 ppm.

[0136] The examples provided above demonstrate that this invention provides a method for preparing 1-aryl-3-ynthylbicyclic [1,1,1]pentane compounds. This method features mild reaction conditions, good substrate versatility, and high one-step synthesis efficiency, giving it significant technical advantages and application potential in the synthesis of 1-aryl-3-ynthylbicyclic [1.1.1]pentane compounds. The descriptions of the above embodiments are merely illustrative and are intended to aid in understanding the method and core concepts of this invention. It should be noted that those skilled in the art can make various improvements and modifications to this invention without departing from its principles, and these improvements and modifications also fall within the scope of protection of the claims of this invention.

Claims

1. A 1-aryl-3-ynyl bicyclic [ 1.1.1] A method for preparing pentane compounds, characterized in that, The substrates of the method include: Compound A, arylthionium trifluoromethanesulfonate, Compound B, [1.1.1]spiroalkyl, and Compound C is a terminal alkyne. The method includes the following steps: starting materials including compound A, compound B, and compound C are used to obtain 1-aryl-3-ynylbicyclo[1.1.1]pentane compound under visible light-promoted iridium / copper dual catalysis; The reaction conditions are as follows: tris(2-phenylpyridine)iridium is used as a photocatalyst, copper acetylacetonate is used as a copper catalyst, 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl is used as a ligand, 1,8-diazabicyclo[5.4.0]undec-7-ene is used as a base, acetonitrile is used as a solvent, blue light is used as the reaction light source, argon is used as the reaction gas atmosphere, and the reaction time is 2-6 hours. The molar ratio of compound C to compound A is 1:1.2-1:2, the molar ratio of compound C to compound B is 1:1.5-1:3, the molar ratio of compound C to photocatalyst is 1:0.02-1:0.04, the molar ratio of compound C to copper catalyst is 1:0.2-1:0.4, the molar ratio of compound C to base is 1:1-1:3, and the molar ratio of compound C to ligand is 1:0.2-1:0.

4. Compound A has any of the following structural formulas: ； Where OMe represents methoxy, Me represents methyl, and OTf represents trifluoromethanesulfonate; The compound C has any of the following structural formulas: ； in, t Bu represents tert-butyl, OMe represents methoxy, CF3 represents trifluoromethyl, and CN represents cyano.

2. The preparation method according to claim 1, characterized in that, 1-Aryl-3-ynylbicyclic [ [1.1.1] Pentane compounds have any of the following structural formulas: 。

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