Preparation method of 1-aryl-3-alkynyl bicyclo [1.1. 1] pentane compound

Abstract

The invention discloses a preparation method of a visible light / copper dual-catalysis 1-aryl-3-alkynyl bicyclo [1.1. 1] pentane compound, which comprises the following steps: taking trifluoromethanesulfonic acid aryl sulfonium salt, [1.1. 1] propeller alkane and terminal alkyne as initial raw materials, taking tris (2-phenylpyridine) iridium and the like as photocatalysts, taking copper acetylacetonate and the like as metal catalysts, taking 2, 2 '-bis (dicyclohexylphosphino)-1, 1'-pentane as a catalyst, and taking 2, 2 '-bis (dicyclohexylphosphino)-1, 1'-pentane as a catalyst to prepare the visible light / copper dual-catalysis 1-aryl-3-alkynyl bicyclo [1.1. 1] pentane compound. The method comprises the following steps: under the conditions that 1, 1 '-biphenyl and the like are used as ligands, 1, 8-diazabicyclo [5.4. 0] undec-7-alkene and the like are used as alkali, and acetonitrile and the like are used as solvents, reducing aryl hexane salt into aryl free radicals, and then carrying out ring tension released free radical addition with [1.1. 1] propeller alkane, so as to obtain the aryl hexane compound. And finally, capturing by an alkynyl copper intermediate generated in situ, and carrying out reduction elimination to obtain the 1-aryl-3-alkynyl bicyclo [1.1. 1] pentane compound. After the method is optimized, the reaction condition is mild, the substrate universality is good, the problem that synthesis needs multiple steps in the prior art is solved, and the method is a novel method for preparing the 1-aryl-3-alkynyl bicyclo [1, 1, 1] pentane compound.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing a 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compound. Background Art

[0002] Bicyclo[1.1.1]pentane (BCP) is an important class of organic compounds that have attracted extensive 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 stereo properties while having better biocompatibility and chemical stability. In medicinal chemistry, the study of BCP as a bioisomer has received increasing attention. Compared with conventional aromatic rings, BCP is able to maintain similar electronic and stereo environments in a smaller molecular framework, which gives it an advantage in improving molecular specificity and biocompatibility. In addition, the synthesis of BCP is not only related to drug development, but also has potential applications in the design of new materials, especially in the field of polymers and nanomaterials.

[0003]

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

[0005] [1.1.1]propellerane is a unique compound. Its unique structure and properties give it excellent stability and stereo configuration, making it an indispensable intermediate and building block in organic synthesis. In recent years, research on the synthesis of bicyclo[1.1.1]pentane compounds from [1.1.1]propellerane has attracted more and more attention. By cleverly introducing different functional groups or substituents, scientists have been able to design and synthesize bicyclo[1.1.1]pentane compounds with specific functions. These compounds have shown broad application prospects in the fields of drug development and functional materials, greatly promoting the progress of biomedicine and materials science. Although great progress has been made in this field, there are relatively few reports on the synthesis of 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compounds, and they are still mainly multi-step reactions. These methods usually require complex reaction steps, such as preparing active organometallic reagents, addition and subsequent oxidation, to achieve the synthesis of the target product. This not only requires a strict anhydrous and oxygen-free environment, but also easily leads to side reactions and low yields. In addition, the selectivity of substrates, the complexity of post-reaction treatment and separation and purification processes also restrict the expansion of its application. Therefore, the development of an efficient and simple synthesis method can significantly improve the synthesis efficiency of 1-aryl-3-alkynyl BCP and promote its application in drug development and new materials. Summary of the invention

[0006] In view of the deficiencies in the prior art, the present invention provides 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compounds and a preparation method thereof, which realize a one-step efficient synthesis of such compounds under a visible light / copper dual catalytic system, with mild reaction conditions and good substrate universality.

[0007] The object of the present invention is achieved by: a method for preparing a 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compound, characterized in that the substrate of the method comprises:

[0008] Compound A, arylsulfonium trifluoromethanesulfonate,

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

[0010] Compound C, terminal alkyne;

[0011] The method comprises the following steps: using starting materials including compound A, compound B and compound C under visible light-promoted iridium / copper dual catalytic conditions to obtain a 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compound.

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

[0013]

[0014] Among them, OMe represents methoxy, Me represents methyl, and OTf represents trifluoromethanesulfonate.

[0015] Further, the compound C includes any one of the following structural formulas:

[0016]

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

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

[0019] .

[0020] Further, the reaction formula is as follows:

[0021]

[0022] Here, Ar represents an aryl group.

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

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

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

[0026] Further, the ligand includes at least one of 2,2'-bipyridine, 4,4-di-tert-butyl-2,2-bipyridine, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, and 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl, preferably 2,2'-bis(dicyclohexylphosphino)-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 the present invention, an aryl sulfonium salt is reduced to an aryl free radical by an excited-state photocatalyst, and then reacts with a free radical released by a strained ring of [1.1.1] propellerane to form an aryl bicyclo[1.1.1]pentane free radical; then the free radical is added to an alkynyl copper intermediate and undergoes reduction elimination to obtain a 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compound; after the method is optimized, the reaction conditions are mild and green, the substrate has good universality, and the one-step synthesis efficiency is high, and the method is a new method for preparing 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compounds.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] High efficiency: The dual catalytic system of photocatalysis and copper catalysis adopted in the present invention enables the reaction to be carried out under mild conditions, greatly improving the reaction efficiency and yield.

[0031] Simplified steps: By introducing an arylsulfonium salt as an intermediate, the present invention realizes a single-step synthesis of 1-aryl-3-alkynylbicyclo[1.1.1]pentane, which significantly simplifies the traditional multi-step synthesis process.

[0032] Broad substrate compatibility: This method has good applicability to a variety of aromatic and alkynyl compounds, expanding the scope of synthesizable compounds.

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

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

[0035] These advantages make the present invention have significant technical advantages and application potential in the synthesis of 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compounds. DETAILED DESCRIPTION

[0036] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0037] The invention provides a preparation method of a 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compound, comprising: taking arylsulfonium trifluoromethanesulfonate, [1.1.1] propellerane and terminal alkyne as starting materials, and obtaining the 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compound under the conditions that tri(2-phenylpyridine)iridium or the like is used as a photocatalyst, copper acetylacetonate or the like is used as a metal catalyst, 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl or the like is used as a ligand, 1,8-diazabicyclo[5.4.0]undec-7-ene or the like is used as a base, and acetonitrile or the like is used as a solvent.

[0038] Example 1: Preparation of Compound 16

[0039]

[0040] A 10 mL Shrek tube with a branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 with a branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 2 (136.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

[0048] After the reaction, the solvent was removed by rotary evaporation, and then the product was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1) to obtain compound 17 (31.5 mg, 58%).

[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 with a branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 3 (142.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 with a branch tube equipped with a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 4 (141.0 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 with a branch tube equipped with a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 5 (164.9 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-methylphenylacetylene 6 (23.2 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 with a branch tube equipped with a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-tert-butylphenylacetylene 7 (31.6 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

[0076] After the reaction, the solvent was removed by rotary evaporation, and then the product was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1) to obtain compound 21 (42.9 mg, 65%).

[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 with a branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-methoxyphenylacetylene 8 (26.4 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-methoxyphenylacetylene 9 (34.0 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 with a branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-methoxyphenylacetylene 10 (25.4 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-chlorophenylacetylene 11 (27.2 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 with a branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-bromophenylacetylene 12 (36.0 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propellerane B (0.6 mmol) and p-fluorophenylacetylene 13 (24.0 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

[0118] After the reaction, the solvent was removed by rotary evaporation, and then the product was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1) to obtain compound 27 (30.9 mg, 53%).

[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 with a branch tube equipped with a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propane B (0.6 mmol) and 2-ethynylpyridine 14 (20.6 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

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

[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 with a branch tube and a magnetic stirrer was selected, and arylsulfonium trifluoromethanesulfonate 1 (141.8 mg, 0.30 mmol), tris(2-phenylpyridine)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 respectively. After replacing argon three times, 2 mL of acetonitrile, 1,8-diazabicyclo[5.4.0]undec-7-ene (59 µL, 0.2 mmol), [1.1.1]propane B (0.6 mmol) and 2-ethynylnaphthalene 15 (30.4 mg, 0.2 mmol) were added under argon atmosphere; then the reaction was carried out at room temperature under blue light irradiation for 6 hours.

[0132] After the reaction, the solvent was removed by rotary evaporation, and then the product was purified by rapid silica gel column chromatography (eluent: petroleum ether: ethyl acetate volume ratio = 50:1) to obtain compound 29 (32.4 mg, 50%).

[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 show that the present invention provides a method for preparing a 1-aryl-3-alkynyl bicyclo [1,1,1] pentane compound, the reaction conditions are mild, the substrate is universal, and the one-step synthesis efficiency is high, so that the present invention has significant technical advantages and application potential in the synthesis of 1-aryl-3-alkynyl bicyclo [1.1.1] pentane compounds. The description of the above embodiments is only used to help understand the method of the present invention and its core idea. It should be pointed out that for ordinary technicians in this technical field, without departing from the principle of the present invention, the present invention can also be improved and modified in a number of ways, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A 1-aryl-3-alkynyl bicyclic [ 1.1.1] A method for preparing a pentane compound, characterized in that: The substrates of the method include: Compound A, arylsulfonium trifluoromethanesulfonate, Compound B, [1.1.1]propane, and Compound C, terminal alkyne; The method comprises the following steps: using starting materials including compound A, compound B and compound C under visible light-promoted iridium / copper dual catalytic conditions to obtain a 1-aryl-3-alkynyl bicyclo[1.1.1]pentane compound.

2. The method according to claim 1, characterized in that The compound A includes any of the following structural formulas: ； Among them, OMe represents methoxy, Me represents methyl, and OTf represents trifluoromethanesulfonate.

3. The method according to claim 1, characterized in that The compound C includes any of the following structural formulas: ； in, t Bu represents tert-butyl, OMe represents methoxy, CF3 represents trifluoromethyl, and CN represents cyano.

4. The preparation method according to any one of claims 1 to 3, characterized in that Includes any of the following structural formulas: 。 5. The preparation method according to any one of claims 1 to 3, characterized in that: The reaction formula is as follows: ； Here, Ar represents an aryl group.

6. The preparation method according to any one of claims 1 to 3, characterized in that: 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.

7. The preparation method according to any one of claims 1 to 3, characterized in that: The photocatalyst includes at least one of red Y, bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)], 2,4,5,6-tetra(9H-carbazole-9-yl)isophthalonitrile, and tris(2-phenylpyridine)iridium.

8. The preparation method according to any one of claims 1 to 3, characterized in that: The copper catalyst includes at least one of cupric acetate, cuprous acetate, cuprous iodide, and copper acetylacetonate.

9. The preparation method according to any one of claims 1 to 3, characterized in that: The ligand includes at least one of 2,2'-bipyridine, 4,4-di-tert-butyl-2,2-bipyridine, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, and 2,2'-bis(dicyclohexylphosphino)-1,1'-biphenyl.

10. The preparation method according to any one of claims 1 to 3, characterized in that: The base includes at least one of triethylamine, 2,4,6-trimethylpyridine, tetramethylguanidine, and 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.

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