A preparation method of bicyclo[1.1.1]pentanesulfonamide

Abstract

The invention discloses a method for preparing bicyclo[1.1.1]pentanesulfonamide, which comprises taking N-substituted sulfonamide shown in formula (1), [1.1.1] propellerane shown in formula (2), and hydrogen / iodine / sulfur source reagent as raw materials, reacting in a solvent under the action of light and photocatalyst to obtain bicyclo[1.1.1]pentanesulfonamide shown in formula (3), and the reaction equation thereof is as follows: wherein, R 1 and R 2 The electron withdrawing group is a halogen, trifluoromethyl, nitro or cyano group, the electron donating group is an alkyl, alkenyl, alkynyl, alkoxy or aryl group, the Ar group is a phenyl, a substituted phenyl or pyridine, and the substituent of the substituted phenyl is an alkoxy or a halogen. The present invention uses cheap and readily available N-nitrososulfonamide as a nitrogen source, and has the advantages of simple operation, good substrate universality, high atomic utilization, etc.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical organic synthesis, and particularly relates to a method for preparing bicyclo[1.1.1]pentanesulfonamide. Background Art

[0002] In 1908, German scientist Paul Gelmo synthesized sulfonamide for the first time. Twenty-four years later, Prontosil et al. discovered the first sulfonamide antibacterial drug, in which sulfonanilide molecules have broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. As a key building block for many bioactive molecules, sulfonanilide building blocks are of great significance in drug development. For example, the pKa value of the molecule can be adjusted, thereby affecting permeability and solubility, and the hydrolytic stability of the molecule can be effectively improved. Therefore, the design and synthesis of sulfonanilide building block bioisosteres have received extensive attention in the fields of medicinal chemistry and medicine.

[0003] Bicyclo[1.1.1]pentylamines (BCPAs) have gotten rid of the planarity of aniline, have a three-dimensional structure and a shorter para-spatial distance, and exhibit good physical and chemical properties. In addition, bicyclo[1.1.1]pentylamines have been shown to be bioisosteres of aniline, which can improve the lipid solubility, cell membrane permeability and metabolic stability of drug molecules. In this regard, the efficient preparation of para-substituted bicyclo[1.1.1]pentylsulfonamide building blocks as alternatives to para-substituted sulfonylanilide building blocks has become one of the research hotspots in the field of medicinal chemistry. The method reported by Baran's group to synthesize monosubstituted bicyclo[1.1.1]pentylamines using [1.1.1]propellerane and "Turbo" amine nucleophiles cannot prepare bicyclo[1.1.1]pentylsulfonamide compounds. The research group of Daniele Leonori reported that the use of reagents such as 2-phenylmalononitrile and Nphth-SPh can only achieve the mono-substituted amidation and thioamidation of [1.1.1] propellerane (Angew. Chem. Int. Ed. 2020, 59, 8225-8231). At the same time, this method not only requires the use of toxic nitrile reagents and complex precursors, but also cannot prepare iodobicyclo [1.1.1] pentanesulfonamide. The research group of Edward A. Anderson reported a method of synthesizing 3-iodobicyclo [1.1.1] pentanesulfonamide by atom transfer radical addition (ATRA) mechanism using triethyl boron to catalyze α-iodoaziridine and [1.1.1] propellerane, but cannot synthesize other bicyclo [1.1.1] pentanesulfonamide compounds (J. Am. Chem. Soc. 2021, 143, 9729-9736). Summary of the invention

[0004] In view of the above problems existing in the prior art, the object of the present invention is to provide a simple, efficient and low-cost method for preparing bicyclo[1.1.1]pentanesulfonamide.

[0005] In order to solve these problems, this method uses cheap and readily available N-substituted sulfonamides, hydrogen / iodine / sulfur source reagents and [1.1.1] propellerane as raw materials, and successfully achieves the efficient preparation of bicyclo[1.1.1]pentanesulfonamide through a photocatalytic three-component free radical tandem strategy. This method is simple to operate and avoids the limitations of previous synthetic methods that require multi-step synthesis. At the same time, it has the advantages of good substrate universality, high atomic utilization and wide application value. It provides a preparation method for the efficient synthesis of monosubstituted bicyclo[1.1.1]pentanesulfonamide, 3-iodobicyclo[1.1.1]pentanesulfonamide and 3-thiobicyclo[1.1.1]pentanesulfonamide, and also lays a foundation for the application research of bicyclo[1.1.1]pentanesulfonamide drug molecules in the fields of medicinal chemistry and organic synthesis.

[0006] The specific technical solutions are as follows:

[0007] A method for preparing bicyclo[1.1.1]pentanesulfonamide, using N-substituted sulfonamide represented by formula (1), [1.1.1] propellerane represented by formula (2), and hydrogen / iodine / sulfur source reagent as raw materials, reacting in a solvent under the action of light and photocatalyst to obtain bicyclo[1.1.1]pentanesulfonamide represented by formula (3), wherein the reaction equation is as follows:

[0008]

[0009] In the formula, R 1 and R 2 It is an electron withdrawing group or an electron donating group, the electron withdrawing group is halogen, trifluoromethyl, nitro or cyano, the electron donating group is alkyl, alkenyl, alkynyl, alkoxy or aryl, the Ar group is phenyl, substituted phenyl or pyridine, and the substituent of the substituted phenyl is alkoxy or halogen.

[0010] Furthermore, the aryl group includes a five-membered or six-membered aromatic heterocycle containing nitrogen, oxygen or sulfur atoms, a benzyl group or a substituted phenyl group, wherein the substituent of the substituted phenyl group is an alkyl group, an alkoxy group, a halogen group, a cyano group, a nitro group, a trifluoromethyl group or a phenyl group.

[0011] Furthermore, the hydrogen source reagent is one of hydrogen peroxide I, II, III, IV, V, VI, VII, and VIII with a mass concentration of 10-50%, preferably hydrogen peroxide I with a mass concentration of 30%,

[0012]

[0013] Further, the iodine source reagent is one of IX, X, XI, XII, XIII, XIV, XV, and XVI, preferably IX,

[0014]

[0015] Furthermore, the sulfur source reagent is a diaryl disulfide compound XVII,

[0016]

[0017] In the formula, the Ar group is phenyl, substituted phenyl or pyridine, and the substituent of the substituted phenyl is alkoxy or halogen.

[0018] Furthermore, the photocatalyst is an iridium catalyst (including: Ir(ppy)3(tris(2-phenylpyridine)iridium), Ir(dtbbpy)(ppy)2PF6((4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III)hexafluorophosphate), Ir[dF(CF3)ppy)]2(dtbbpy)PF6((4,4'-di-tert-butyl-2,2'-bipyridine)bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl]phenyl]iridium(III)hexafluorophosphate), ruthenium catalyst (including: Ru(bpy)3[PF6]2(tris(2,2' -bipyridyl)ruthenium(II)bis(hexafluorophosphate)salt), Ru(bpy)3Cl2(tris(2,2'-bipyridyl)ruthenium(II)dichloride), Ru(dtbbpy)3[PF6]2(tris[4,4'-bis(tert-butyl)-2,2'-bipyridyl]ruthenium(II)hexafluorophosphate), Ru(bpy)3Cl2·6H2O(tris(2,2'-bipyridyl)ruthenium(II)chloride hexahydrate) or organic photocatalysts (including: 4-CZIPN(2,4,5,6-tetrakis(carbazole-9-yl)-1,3-dicyanobenzene), 4-DPAIPN(2,4,5,6-tetrakis(diphenylamino)isophthalonitrile), MesAcrMe + ClO4 - (9-mesityl-10-methylacridine perchlorate), Eosin Y (tetrabromofluorescein), Eosin Y·2Na (tetrabromofluorescein disodium), Rose Bengal (Rose Bengal) or Thioxanthen-9-one (9-thioxanthenone), preferably a ruthenium catalyst (Ru(bpy)3Cl2 (tris(2,2'-bipyridine) dichloride ruthenium).

[0019]

[0020] Furthermore, the light source is a purple lamp, a blue lamp, a green lamp or a yellow lamp with a wattage of 5W to 60W, preferably a 10W to 20W blue lamp; the reaction solvent is one or more of acetonitrile, N,N-dimethylacetamide, dimethyl sulfoxide, methanol, dichloromethane, ether, nitromethane, toluene, and water, preferably acetonitrile, and the reaction is carried out under argon, nitrogen or air, preferably under argon.

[0021] Furthermore, the reaction temperature is 0°C to 60°C, preferably 25°C to 35°C, and the reaction time is 1 to 24 hours, preferably 8 to 13 hours when preparing monosubstituted bicyclo[1.1.1]pentanesulfonamide and 3-thiobicyclo[1.1.1]pentanesulfonamide, and preferably 20 to 24 hours when preparing 3-iodobicyclo[1.1.1]pentanesulfonamide.

[0022] Further, the molar ratio of the N-substituted sulfonamide represented by formula (1), the [1.1.1] propeller alkane represented by formula (2) and the hydrogen / iodine / sulfur source reagent is 1 to 3:1 to 5:1 to 3. When preparing monosubstituted bicyclo [1.1.1] pentanesulfonamide, the molar ratio of the N-substituted sulfonamide represented by formula (1), the [1.1.1] propeller alkane represented by formula (2) and the hydrogen source reagent I is preferably 1:2:2. When preparing 3-iodobicyclo [1.1.1] pentanesulfonamide, the molar ratio of the N-substituted sulfonamide represented by formula (1), the [1.1.1] propeller alkane represented by formula (2) and the iodine source reagent IX is preferably 1:5:2. When preparing 3-thiobicyclo [1.1.1] pentanesulfonamide, the molar ratio of the N-substituted sulfonamide represented by formula (1), the [1.1.1] propeller alkane represented by formula (2) and the sulfur source reagent XVII is preferably 2:1:2.

[0023] Preferably, the specific operation is as follows: in a reaction tube, N-substituted sulfonamide represented by formula (1), [1.1.1] propeller alkane represented by formula (2), and hydrogen / iodine / sulfur source reagent are added in sequence according to the molar ratio of the feed, a solvent is added, 10W to 20W, 456nm blue light is irradiated, and the reaction is carried out under the action of a photocatalyst for 8 to 24 hours. After the reaction is complete, the organic phase is collected, dried by rotation, and separated by a column to obtain bicyclo[1.1.1]pentanesulfonamide.

[0024] By adopting the above technology, compared with the prior art, the beneficial effects of the present invention are embodied in:

[0025] The invention uses N-substituted sulfonamide, hydrogen / iodine / sulfur source reagent and [1.1.1] propellerane as raw materials, and realizes the efficient preparation of bicyclo[1.1.1]pentanesulfonamide through a photocatalytic three-component free radical tandem strategy. The preparation method defined in the invention uses cheap and readily available N-nitrososulfonamide as a nitrogen source, and has the advantages of simple operation, good substrate universality, high atomic utilization rate, etc. DETAILED DESCRIPTION

[0026] The synthesis scheme of the present invention is described below in conjunction with specific examples, but the protection scope of the present invention is not limited thereto.

[0027] Example 1 N-(Bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0028]

[0029] Under argon atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (42.9 mg, 0.2 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (4 mL) were added to the reaction tube in sequence, and finally hydrogen source reagent I (30% hydrogen peroxide solution, 41.0 μL, 0.4 mmol) and [1.1.1] propeller alkane (0.6 mL, 0.67 M, 0.4 mmol) were added. The resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 35.9 mg of colorless oil N-(bicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide with a yield of 70%. 1 H NMR (400MHz, Chloroform-d) δ7.68(d,J=8.4Hz,2H),7.29(d,J=8.4Hz,2H),2.80(s,3H),2.42(s,3H),2.36(s,1H),1.92(s,6H). 13 C NMR(100MHz,Chloroform-d)δ143.16,136.52,129.48,127.39,53.68,51.79,33.13,22.96,21.49.HRMS(ESI)m / z:calcd for C 13 H 17 NNaO2S[M+Na] + 274.0872,found:274.0875.

[0030] Example 2 N-(Bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0031]

[0032] Under argon atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (1724.5 mg, 8.0 mmol), Ru(bpy)3Cl2 (120.0 mg, 2 mol%), anhydrous acetonitrile (160 mL) were added to the reaction tube in sequence, and finally hydrogen source reagent I (30% hydrogen peroxide solution, 1.6 mL, 16.0 mmol) and [1.1.1] propeller alkane (23.9 mL, 0.67 M, 16.0 mmol) were added. The resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain a colorless oil N-(bicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide 1389.9 mg, with a yield of 69%.

[0033] Example 3 N-(Bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0034]

[0035] Under air atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (42.9 mg, 0.2 mmol), Ru(bpy)3[PF6]2 (3.0 mg, 2 mol%), anhydrous acetonitrile (4 mL) were added to the reaction tube in sequence, and finally hydrogen source reagent I (30% hydrogen peroxide solution, 31.0 μL, 0.3 mmol) and [1.1.1] propeller alkane (0.45 mL, 0.67 M, 0.3 mmol) were added. The resulting solution was irradiated with a green light lamp (30 W, 510 nm) and stirred at 40 ° C for 15 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 26.5 mg of colorless oil N-(bicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide with a yield of 52%.

[0036] Example 4 N-(Bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0037]

[0038] Under argon atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (42.9 mg, 0.2 mmol), hydrogen source reagent II (tert-butyl hydroperoxide, 41.0 μL, 0.3 mmol), Ir(ppy)3 (1.4 mg, 2 mol%), nitromethane (3 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.90 mL, 0.67 M, 0.6 mmol) was added. The resulting solution was irradiated with a yellow light lamp (40 W, 590 nm) and stirred at 45 ° C for 21 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 22.2 mg of colorless oil N-(bicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide with a yield of 44%.

[0039] Example 5 N-(Bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0040]

[0041] Under nitrogen atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (42.9 mg, 0.2 mmol), hydrogen source reagent IV (N-hydroxysuccinimide, 34.5 mg, 0.3 mmol), Ir(dtbbpy)(ppy)2PF6 (1.8 mg, 1 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.36 mL, 0.67 M, 0.24 mmol) was added. The resulting solution was irradiated with a blue light lamp (40 W, 456 nm) and stirred at 20 ° C for 6 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 23.3 mg of colorless oil N-(bicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide with a yield of 47%.

[0042] Example 6 N-(Bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0043]

[0044] Under air atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (42.9 mg, 0.2 mmol), hydrogen source reagent V (triethylsilane, 34.9 mg, 0.3 mmol), Eosin Y (6.5 mg, 5 mol%), dichloromethane (1 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.45 mL, 0.67 M, 0.3 mmol) was added. The resulting solution was irradiated with a violet lamp (30 W, 390 nm) and stirred at 50 ° C for 9 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 20.6 mg of colorless oil N-(bicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide with a yield of 41%.

[0045] Example 7 N-(Bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0046]

[0047] Under argon atmosphere, N-methyl-N-nitroso-toluenesulfonamide (42.9 mg, 0.2 mmol), hydrogen source reagent VI (phenylsilane, 43.3 mg, 0.4 mmol), 4-CZIPN (8.0 mg, 5 mol%), isopropyl acetate (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.6 mL, 0.67 M, 0.4 mmol) was added. The resulting solution was irradiated with a blue lamp (10 W, 456 nm) and stirred at 35 ° C for 24 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 26.0 mg of colorless oil N-(bicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide with a yield of 50%.

[0048] Example 8 N-(3-iodobicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0049]

[0050] Under argon atmosphere, N-methyl-N-nitroso-toluenesulfonamide (42.9 mg, 0.2 mmol), iodine source reagent IX (iodoform, 157.5 mg, 0.4 mmol), Ru(bpy)3[PF6]2 (3.4 mg, 2 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (1.5 mL, 0.67 M, 1.0 mmol) was added. The resulting solution was irradiated with a blue lamp (10 W, 456 nm) and stirred at 30 ° C for 24 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 52.9 mg of N-(3-iodobicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide as a yellow oil with a yield of 70%. 1 H NMR (400MHz, Chloroform-d) δ7.65 (d, J = 8.2Hz, 2H), 7.31 (d, J = 7.6Hz, 2H), 2.79 (s, 3H), 2.43 (s, 3H), 2.36 (s, 6H). 13 CNMR(100MHz,Chloroform-d)δ143.74,135.65,129.70,127.33,60.87,56.24,33.68,21.52,-0.63.HRMS(ESI)m / z:calcd for C 13 H 17 INO2S[M+H] + 378.0019,found:278.0030.

[0051] Example 9 N-(3-iodobicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0052]

[0053] Under air atmosphere, N-methyl-N-nitroso-toluenesulfonamide (42.9 mg, 0.2 mmol), iodine source reagent XIII (iodomethane, 157.5 mg, 0.4 mmol), Thioxanthen-9-one (10.6 mg, 5 mol%), anhydrous ether (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.3 mL, 0.67 M, 0.2 mmol) was added. The resulting solution was irradiated with a blue lamp (35 W, 456 nm) and stirred at 25 ° C for 16 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 31.7 mg of yellow oil N-(3-iodobicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide with a yield of 42%.

[0054] Example 10 N-(3-iodobicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0055]

[0056] Under argon atmosphere, N-methyl-N-nitroso-toluenesulfonamide (42.9 mg, 0.2 mmol), iodine source reagent XV (trifluoroiodomethane, 470.3 mg, 0.6 mmol), Ir[dF(CF3)ppy)]2(dtbbpy)PF6 (2.4 mg, 2 mol%), toluene (1 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.6 mL, 0.67 M, 0.4 mmol) was added. The resulting solution was irradiated with a purple lamp (40 W, 390 nm) and stirred at 50 ° C for 6 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 34.7 mg of yellow oil N-(3-iodobicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide with a yield of 46%.

[0057] Example 11 N-(3-iodobicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0058]

[0059] Under nitrogen atmosphere, N-methyl-N-nitroso-toluenesulfonamide (42.9 mg, 0.2 mmol), iodine source reagent XVI (1,3-diiodo-5,5-dimethylhydantoin, 152.0 mg, 0.4 mmol), Rose Bengal (10.2 mg, 5 mol%), dimethyl sulfoxide (3 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (1.2 mL, 0.67 M, 0.8 mmol) was added. The resulting solution was irradiated with a green lamp (50 W, 510 nm) and stirred at 60 ° C for 9 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 30.2 mg of yellow oil N-(3-iodobicyclo[1.1.1]pentane-1-yl)-N,4-dimethylbenzenesulfonamide with a yield of 40%.

[0060] Example 12 N,4-dimethyl-N-(3-(phenylthio)bicyclo[1.1.1]pentan-1-yl)benzenesulfonamide

[0061]

[0062] Under argon atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (85.8 mg, 0.4 mmol), sulfur source reagent XVII (diphenyl disulfide, 87.3 mg, 0.4 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propane (0.3 mL,

[0063] 0.67M, 0.2mmol), the resulting solution was irradiated with a blue lamp (20W, 456nm) at 30°C

[0064] The mixture was stirred for 12 hours. The reaction was monitored by TLC analysis to completion. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to give 48.6 mg of N,4-dimethyl-N-(3-(phenylthio)bicyclo[1.1.1]pentane-1-yl)benzenesulfonamide as a light yellow oil in a yield of 68%.

[0065] 1 H NMR(400MHz,Chloroform-d)δ7.64(d,J=8.2Hz,2H),7.43-7.37(m,

[0066] 2H),7.33-7.27(m,5H),2.77(s,3H),2.42(s,3H),2.03(s,6H). 13C NMR(100MHz,Chloroform-d)δ143.50,135.94,133.75,133.03,129.61,128.91,128.00,

[0067] 127.33,55.37,51.92,38.85,33.53,21.51.HRMS(ESI)m / z:calcd forC 19 H 21 NNaO2S2[M+Na] + 382.0906,found:382.0909.

[0068] Example 13 N,4-dimethyl-N-(3-(phenylthio)bicyclo[1.1.1]pentan-1-yl)benzenesulfonamide

[0069]

[0070] Under air atmosphere, N-methyl-N-nitroso-toluenesulfonamide (42.9 mg, 0.2 mmol), sulfur source reagent XVII (diphenyl disulfide, 87.3 mg, 0.4 mmol), Eosin Y·2Na (7.1 mg, 5 mol%), dichloromethane (3 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.45 mL, 0.67 M, 0.3 mmol) was added. The resulting solution was irradiated with a purple lamp (30 W, 390 nm) and stirred at 45 ° C for 6 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 39.6 mg of light yellow oily N, 4-dimethyl-N-(3-(phenylthio)bicyclo[1.1.1]pentane-1-yl)benzenesulfonamide with a yield of 55%.

[0071] Example 14 N-(Bicyclo[1.1.1]pentan-1-yl)-2-methoxy-N-methylbenzenesulfonamide

[0072]

[0073] Under argon atmosphere, 2-methoxy-N-methyl-N-nitrosobenzenesulfonamide (46.6 mg, 0.2 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (4 mL) were added to the reaction tube in sequence, and finally hydrogen source reagent I (30% hydrogen peroxide solution, 41.0 μL, 0.4 mmol) and [1.1.1] propeller alkane (0.6 mL, 0.67 M, 0.4 mmol) were added. The resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 34.6 mg of N-(bicyclo[1.1.1]pentane-1-yl)-2-methoxy-N-methylbenzenesulfonamide as a yellow oil with a yield of 64%. 1 HNMR(400MHz,Chloroform-d)δ7.73(d,J=8.8Hz,2H),6.96(d,J=8.8Hz,2H),3.87(s,3H),2.79(s,3H),2.36(s,1H),1.92(s,6H). 13 C NMR(100MHz,Chloroform-d)δ162.72,131.09,129.44,114.01,55.54,53.71,51.77,33.11,22.97.HRMS(ESI)m / z:calcd for C 13 H 18 NO3S[M+H] + 268.1002,found:268.1019.

[0074] Example 15 N-(Bicyclo[1.1.1]pentan-1-yl)-N-methyl-3-(trifluoromethyl)benzenesulfonamide

[0075]

[0076] Under argon atmosphere, N-methyl-N-nitroso-3-(trifluoromethyl)benzenesulfonamide (55.6 mg, 0.2 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (4 mL) were added to the reaction tube in sequence, and finally hydrogen source reagent I (30% hydrogen peroxide solution, 41.0 μL, 0.4 mmol) and [1.1.1] propeller alkane (0.6 mL, 0.67 M, 0.4 mmol) were added, and the resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 32.9 mg of colorless oil N-(bicyclo[1.1.1]pentane-1-yl)-N-methyl-3-(trifluoromethyl)benzenesulfonamide with a yield of 52%. 1 H NMR (400MHz, Chloroform-d) δ8.07(s,1H),8.00(d,J=8.0Hz,1H),7.83(d,J=8.0Hz,1H),7.67(t,J=7.8Hz,1H),2.84(s,3H),2.41(s,1H),1.95(s,6H). 13 C NMR(100MHz,Chloroform-d)δ140.77,131.63(q,J=33.4Hz),130.46,129.72,129.06( q, J=3.6Hz), 124.36 (q, J=3.8Hz), 123.21 (q, J=273.0Hz), 53.50, 51.90, 33.17, 23.01. 19 FNMR(376MHz,Chloroform-d)δ-62.85.HRMS(ESI)m / z:calcd for C 13 H 15 F3NO2S[M+H] + 306.0770,found:306.0777.

[0077] Example 16 N-(Bicyclo[1.1.1]pentan-1-yl)-N-methylthiophene-2-sulfonamide

[0078]

[0079] Under argon atmosphere, N-methyl-N-nitrosothiophene-2-sulfonamide (42.8 mg, 0.2 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (4 mL) were added to the reaction tube in sequence, and finally hydrogen source reagent I (30% hydrogen peroxide solution, 41.0 μL, 0.4 mmol) and [1.1.1] propeller alkane (0.6 mL, 0.67 M, 0.4 mmol) were added. The resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 28.3 mg of colorless oil N-(bicyclo[1.1.1]pent-1-yl)-N-methylthiophene-2-sulfonamide with a yield of 56%. 1 H NMR (400MHz, Chloroform-d) δ7.60-7.54(m,2H),7.12-7.08(m,1H),2.83(s,3H),2.39(s,1H),1.98(s,6H). 13 CNMR(100MHz,Chloroform-d)δ139.80,132.04,131.51,127.19,53.64,51.76,33.17,22.93.HRMS(ESI)m / z:calcd for C 10 H 14 NO2S2[M+H] + 244.0460,found:244.0473.

[0080] Example 17 N-Benzyl-N-(bicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide

[0081]

[0082] Under argon atmosphere, N-benzyl-4-methyl-N-nitrosobenzenesulfonamide (59.5 mg, 0.2 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (4 mL) were added to the reaction tube in sequence, and finally hydrogen source reagent I (30% hydrogen peroxide solution, 41.0 μL, 0.4 mmol) and [1.1.1] propeller alkane (0.6 mL, 0.67 M, 0.4 mmol) were added. The resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 31.9 mg of colorless oil N-benzyl-N-(bicyclo[1.1.1]pentane-1-yl)-4-methylbenzenesulfonamide with a yield of 48%. 1 H NMR (400MHz, Chloroform-d) δ7.72 (d, J = 8.2Hz, 2H), 7.39-7.25 (m, 7H), 4.47 (s, 2H), 2.43 (s, 3H), 2.24 (s, 1H), 1.82 (s, 6H). 13 C NMR(100MHz,Chloroform-d)δ143.10,138.37,138.05,129.54,128.35,127.36,127.27,127.11,53.37,52.88,51.01,23.57,21.51.HRMS(ESI)m / z:calcdfor C 19 H 22 NO2S[M+H] + 328.1366,found:328.1379.

[0083] Example 18 N-(Bicyclo[1.1.1]pent-1-yl)-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide

[0084]

[0085] Under argon atmosphere, 4-methyl-N-nitroso-N-(prop-2-yn-1-yl)benzenesulfonamide (49.0 mg, 0.2 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (4 mL) were added to the reaction tube in sequence, and finally hydrogen source reagent I (30% hydrogen peroxide solution, 41.0 μL, 0.4 mmol) and [1.1.1] propeller alkane (0.6 mL, 0.67 M, 0.4 mmol) were added, and the resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1 v / v) to give 19.6 mg of colorless oily N-(bicyclo[1.1.1]pent-1-yl)-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide in a yield of 35%. 1 H NMR(400MHz,Chloroform-d)δ7.79(d,J=8.4Hz,2H),7.28(d,J=8.0Hz,2H),4.16 (d,J=2.4Hz,2H),2.42(s,3H),2.37(s,1H),2.15(t,J=2.4Hz,1H),2.04(s,6H). 13 CNMR(100MHz,Chloroform-d)δ143.37,137.75,129.31,127.72,79.35,72.78,53.05,52.94,36.27,23.48,21.54.HRMS(ESI)m / z:calcd for C 15 H 18 NO2S[M+H] +

[0086] 276.1053,found:276.1068.

[0087] Example 19 N-(Bicyclo[1.1.1]pentan-1-yl)-1-(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)-N-methylmethanesulfonamide

[0088]

[0089] Under argon atmosphere, 1-(7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-yl)-N-methyl-N-nitrosomethylsulfonamide (56.2 mg, 0.2 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (4 mL) were added to the reaction tube in sequence, and finally hydrogen source reagent I (30% hydrogen peroxide solution, 41.0 μL, 0.4 mmol) and [1.1.1] propeller alkane (0.6 mL, 0.67 M, 0.4 mmol) were added, and the resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1 v / v) to give 35.1 mg of white solid N-(bicyclo[1.1.1]pentan-1-yl)-1-(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)-N-methylmethanesulfonamide in a yield of 55%. 1 H NMR(400MHz,Chloroform-d)δ3.35(d,J=14.4Hz,1H),2.86(s,3H),2.77(d,J=14.4Hz,1H),2.59-2.50(m,1H),2.46(s,1H),2.41-2. 33(m,1H),2.09(s,6H),2.09-1.98(m,2H),1.92(d,J=18.4Hz,1H),1.65-1.58(m,1H),1.44-1.36(m,1H),1.14(s,3H),0.88(s,3H). 13 C NMR(100MHz,Chloroform-d)δ215.31,58.44,53.60,52.06,47.65,46.76,42.78,42.55,32.93,26.85,25.13,22.89,20.14,19.78.HRMS(ESI)m / z:calcd for C 16 H 26 NO3S[M+H] + 312.1628,found:312.1642.

[0090] Example 20 3-Chloro-4-fluoro-N-(3-iodobicyclo[1.1.1]pentan-1-yl)-N-toluenesulfonamide

[0091]

[0092] Under argon atmosphere, 3-chloro-4-fluoro-N-methyl-N-nitrosobenzenesulfonamide (50.9 mg, 0.2 mmol), iodine source reagent IX (iodoform, 157.7 mg, 0.4 mmol), Ru(bpy)3[PF6]2 (3.4 mg, 2 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (1.5 mL, 0.67 M, 1.0 mmol) was added. The resulting solution was irradiated with a blue lamp (10 W, 456 nm) and stirred at 30 ° C for 24 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 42.7 mg of white solid 3-chloro-4-fluoro-N-(3-iodobicyclo[1.1.1]pentane-1-yl)-N-toluenesulfonamide in a yield of 51%. 1 H NMR (400MHz, Chloroform-d) δ7.89-7.81(m,1H),7.73-7.64(m,1H),7.35-7.25(m,1H),2.81(s,3H),2.40(s,6H). 13 C NMR(100MHz,Chloroform-d)δ160.62(d,J=257.8Hz),135.96(d,J=4.0Hz),130.12,127.6 7(d,J=8.4Hz),122.51(d,J=18.6Hz),117.45(d,J=22.4Hz),60.96,56.07,33.70,-1.43. 19 F NMR(376MHz,Chloroform-d)δ-106.73.HRMS(ESI)m / z:calcd for C 12 H 13 ClFINO2S[M+H] + 415.9379,found:415.9397.

[0093] Example 21 N-(3-iodobicyclo[1.1.1]pentan-1-yl)-N-methylpyridine-3-sulfonamide

[0094]

[0095] Under argon atmosphere, N-methyl-N-nitrosopyridine-3-sulfonamide (39.9 mg, 0.2 mmol), iodine source reagent IX (iodoform, 157.7 mg, 0.4 mmol), Ru(bpy)3[PF6]2 (3.4 mg, 2 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (1.5 mL, 0.67 M, 1.0 mmol) was added. The resulting solution was irradiated with a blue lamp (10 W, 456 nm) and stirred at 30 ° C for 24 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 26.6 mg of yellow solid N-(3-iodobicyclo[1.1.1]pent-1-yl)-N-methylpyridine-3-sulfonamide with a yield of 37%. 1 H NMR (400MHz, Chloroform-d) δ9.01 (s, 1H), 8.83 (d, J = 3.6Hz, 1H), 8.13-8.03 (m, 1H), 7.54-7.45 (m, 1H), 2.85 (s, 3H), 2.40 (s, 6H). 13 C NMR(100MHz,Chloroform-d)δ153.26,147.98,135.66,135.03,123.82,60.96,56.05,33.65,-1.56.HRMS(ESI)m / z:calcd for C 11 H 14 IN2O2S[M+H] + 364.9815,found:364.9830.

[0096] Example 22 N-(3-iodobicyclo[1.1.1]pentan-1-yl)-N-methyl-1-phenylmethanesulfonamide

[0097]

[0098] Under argon atmosphere, N-methyl-N-nitroso-1-phenylmethanesulfonamide (43.3 mg, 0.2 mmol), iodine source reagent IX (iodoform, 157.7 mg, 0.4 mmol), Ru(bpy)3[PF6]2 (3.4 mg, 2 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (1.5 mL, 0.67 M, 1.0 mmol) was added, and the resulting solution was irradiated with a blue lamp (10 W, 456 nm) and stirred at 30 ° C for 24 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated, and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 40.5 mg of white solid N-(3-iodobicyclo[1.1.1]pent-1-yl)-N-methyl-1-phenylmethanesulfonamide in a yield of 53%. 1 H NMR(400MHz,Chloroform-d)δ7.46-7.30(m,5H),4.19(s,2H),2.66(s,3H),2.31(s,6H). 13 CNMR(100MHz,Chloroform-d)δ130.68,128.91,128.83,128.70,61.32,58.35,56.32,33.73,-0.98.HRMS(ESI)m / z:calcd for C 13 H 17 INO2S[M+H] + 378.0019,found:378.0030.

[0099] Example 23 N-allyl-N-(3-iodobicyclo[1.1.1]pent-1-yl)-4-nitrobenzenesulfonamide

[0100]

[0101] Under argon atmosphere, N-allyl-4-nitro-N-nitroisobenzenesulfonamide (53.9 mg, 0.2 mmol), iodine source reagent IX (iodoform, 157.7 mg, 0.4 mmol), Ru(bpy)3[PF6]2 (3.4 mg, 2 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (1.5 mL, 0.67 M, 1.0 mmol) was added. The resulting solution was irradiated with a blue lamp (10 W, 456 nm) and stirred at 30 ° C for 24 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30: 1 v / v) to obtain 24.2 mg of white solid N-allyl-N-(3-iodobicyclo[1.1.1]pent-1-yl)-4-nitrobenzenesulfonamide in a yield of 28%. 1 H NMR (400MHz, Chloroform-d) δ8.36(d,J=8.8Hz,2H),7.98(d,J=8.8Hz,2H),5.85-5.70(m,1H),5.29-5.19(m,2H),3.96-3.92(m,2H),2.44(s,6H). 13 C NMR(100MHz,Chloroform-d)δ150.04,146.64,133.65,128.32,124.41,118.53,62.07,55.67,50.55,-1.48.HRMS(ESI)m / z:calcd for C 14 H 16 IN2O4S[M+H] + 434.9870,found:434.9881.

[0102] Example 24 N-(3-((4-methoxyphenyl)thio)bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0103]

[0104] Under argon atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (85.7 mg, 0.4 mmol), sulfur source reagent XVII (1,2-bis(4-methoxyphenyl)disulfane, 111.4 mg, 0.4 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.3 mL, 0.67 M, 0.2 mmol) was added, and the resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated, and the crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate=5:1 v / v) to give 36.4 mg of light yellow oily N-(3-((4-methoxyphenyl)thio)bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide in a yield of 47%. 1 H NMR(400MHz,Chloroform-d)δ7.64(d,J=8.2Hz,2H),7.33(d,J=8.6Hz,2H),7.28(d,J= 8.4Hz,2H),6.83(d,J=8.6Hz,2H),3.80(s,3H),2.76(s,3H),2.42(s,3H),1.96(s,6H). 13 C NMR(100MHz,Chloroform-d)δ159.89,143.46,136.11,135.97,129.60,127.34, 123.35,114.48,55.30,55.08,51.82,39.30,33.52,21.52.HRMS(ESI)m / z:calcd for C 20 H 24 NO3S2[M+H] + 390.1192,found:390.1202.

[0105] Example 25 N-(3-((2-fluorophenyl)thio)bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide

[0106]

[0107] Under argon atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (85.7 mg, 0.4 mmol), sulfur source reagent XVII (1,2-bis(2-fluorophenyl)disulfane, 101.7 mg, 0.4 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.3 mL, 0.67 M, 0.2 mmol) was added, and the resulting solution was irradiated with a blue lamp (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate=5:1 v / v) to give 43.6 mg of white oily N-(3-((2-fluorophenyl)thio)bicyclo[1.1.1]pentan-1-yl)-N,4-dimethylbenzenesulfonamide in a yield of 58%. 1 H NMR (400MHz, Chloroform-d) δ7.64(d,J=8.2Hz,2H),7.48-7.39(m,1H),7.37-7.25(m,3H),7.13-7.04(m,2H),2.76(s,3H),2.42(s,3H),2.03(s,6H). 13 C NMR(100MHz,Chloroform-d)δ162.62(d,J=246.8Hz),143.52,136.74,135.89,130.71(d,J=8.0Hz),129.62,1 27.32, 124.46 (d, J = 3.9Hz), 119.65 (d, J = 19.0Hz), 115.96 (d, J = 23.4Hz), 55.55, 51.52, 38.62, 33.52, 21.51. 19 F NMR(565MHz,Chloroform-d)δ-107.26.HRMS(ESI)m / z:calcd for C 19 H 21 FNO2S2[M+H] + 378.0992,found:378.1004.

[0108] Example 26 N,4-dimethyl-N-(3-(pyridin-4-ylthio)bicyclo[1.1.1]pentan-1-yl)benzenesulfonamide

[0109]

[0110] Under argon atmosphere, N-methyl-N-nitroso-p-toluenesulfonamide (85.7 mg, 0.4 mmol), sulfur source reagent XVII (1,2-di(pyridin-4-yl)disulfane, 88.1 mg, 0.4 mmol), Ru(bpy)3Cl2 (3.0 mg, 2 mol%), anhydrous acetonitrile (2 mL) were added to the reaction tube in sequence, and finally [1.1.1] propeller alkane (0.3 mL, 0.67 M, 0.2 mmol) was added. The resulting solution was irradiated with blue (20 W, 456 nm) and stirred at 30 ° C for 12 hours. The reaction was monitored by TLC analysis. The reaction mixture was evaporated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1 v / v) to obtain 21.0 mg of white solid N, 4-dimethyl-N-(3-(pyridin-4-ylthio)bicyclo[1.1.1]pentan-1-yl)benzenesulfonamide in a yield of 34%. 1 HNMR(400MHz,Chloroform-d)δ8.47(s,2H),7.70(d,J=8.2Hz,2H),7.34(d,J=8.0Hz,2H),7.28(s,2H),2.86(s,3H),2.46(s,3H),2.28(s,6H). 13 C NMR(150MHz,Chloroform-d)δ149.44,146.50,143.71,136.04,129.71,127.34,124.30,56.05,52.56,37.24,33.55,21.52.HRMS(ESI)m / z:calcd for C 18 H 21 N2O2S2[M+H] + 361.1039,found:361.1051.

Claims

1. A method for preparing bicyclo[1.1.1]pentanesulfonamide, characterized in that N-substituted sulfonamide represented by formula (1), [1.1.1] propellerane represented by formula (2), and hydrogen / iodine / sulfur source reagent are used as raw materials, and under the action of light and photocatalyst, a bicyclo[ 1.1.1] Pentylsulfonamide, the reaction equation is as follows: In the formula, R 1 and R 2 is an electron withdrawing group or an electron donating group, the electron withdrawing group is halogen, trifluoromethyl, nitro or cyano, the electron donating group is alkyl, alkenyl, alkynyl, alkoxy or aryl, the Ar group is phenyl, substituted phenyl or pyridine, and the substituent of the substituted phenyl is alkoxy or halogen; The hydrogen source reagent is one of hydrogen peroxide I, II, III, IV, V, VI, VII, VIII with a mass concentration of 10-50%, The iodine source reagent is one of IX, X, XI, XII, XIII, XIV, XV, and XVI, The sulfur source reagent is a diaryl disulfide compound XVII, The photocatalyst is an iridium catalyst, a ruthenium catalyst or an organic photocatalyst, wherein the iridium catalyst is: Ir(ppy)3, Ir[dF(CF3)ppy)]2(dtbbpy)PF6 or Ir(dtbbpy)(ppy)2PF6, the ruthenium catalyst is Ru(dtbbpy)3[PF6]2, Ru(bpy)3[PF6]2, Ru(bpy)3Cl2 or Ru(bpy)3Cl2·6H2O, and the organic photocatalyst is 4-CZIPN, 4-DPAIPN, MesAcrMe + ClO4 - , Eosin Y, Eosin Y·2Na, Rose Bengal or Thioxanthen-9-one.

2. The method for preparing bicyclo[1.1.1]pentanesulfonamide according to claim 1, characterized in that: Aryl includes a five-membered or six-membered aromatic heterocyclic ring containing nitrogen, oxygen or sulfur atoms, benzyl or substituted phenyl, wherein The substituent of the substituted phenyl group is alkyl, alkoxy, halogen, cyano, nitro, trifluoromethyl or phenyl.

3. The method for preparing bicyclo[1.1.1]pentanesulfonamide according to claim 1, characterized in that: The light source is a violet lamp, a blue lamp, a green lamp or a yellow lamp, and the wattage of the blue lamp is 5W to 60W; the reaction solvent is one or more of acetonitrile, N,N-dimethylacetamide, dimethyl sulfoxide, methanol, dichloromethane, ether, nitromethane, toluene, and water, and the reaction is carried out under argon, nitrogen or air.

4. The method for preparing bicyclo[1.1.1]pentanesulfonamide according to claim 3, characterized in that: The light source is a blue light lamp with a wattage of 10W to 20W, the reaction solvent is acetonitrile, and the reaction is carried out under argon.

5. The method for preparing bicyclo[1.1.1]pentanesulfonamide according to claim 1, characterized in that: The reaction temperature is 0°C to 60°C, and the reaction time is 1 to 24 hours.

6. The method for preparing bicyclo[1.1.1]pentanesulfonamide according to claim 5, characterized in that: The reaction temperature is 25°C to 35°C, and the reaction time is 8 to 13 hours when preparing monosubstituted bicyclo[1.1.1]pentanesulfonamide and 3-thiobicyclo[1.1.1]pentanesulfonamide, and 20 to 24 hours when preparing 3-iodobicyclo[1.1.1]pentanesulfonamide.

7. The method for preparing bicyclo[1.1.1]pentanesulfonamide according to claim 5, characterized in that: The N-substituted sulfonamide represented by formula (1), the [ 1.1.1] The molar ratio of propellerane to hydrogen / iodine / sulfur source reagent is 1-3:1-5:1-3.

8. The method for preparing bicyclo[1.1.1]pentanesulfonamide according to claim 7, characterized in that: When preparing monosubstituted bicyclo[1.1.1]pentanesulfonamide, the N-substituted sulfonamide represented by formula (1), the [ 1.1.1] propeller alkane and hydrogen source reagent I have a molar ratio of 1:2:

2. When preparing 3-iodobicyclo[1.1.1]pentanesulfonamide, the N-substituted sulfonamide represented by formula (1) and the [ 1.1.1] propeller alkane and iodine source reagent IX are used in a molar ratio of 1:5:

2. When preparing 3-thiobicyclo[1.1.1]pentanesulfonamide, the N-substituted sulfonamide represented by formula (1) and the [ 1.1.1] The molar ratio of propellerane to sulfur source reagent XVII is 2:1:

2.

9. The method for preparing bicyclo[1.1.1]pentanesulfonamide according to claim 7, characterized in that: The specific operation is as follows: in a reaction tube, N-substituted sulfonamide represented by formula (1), [1.1.1] propeller alkane represented by formula (2), and hydrogen / iodine / sulfur source reagent are added in sequence according to the molar ratio of the feed, and a solvent is added, 10W to 20W, 456nm blue light is irradiated, and the reaction is carried out under the action of a photocatalyst for 8 to 24 hours. After the reaction is complete, the organic phase is collected, dried in a rotary evaporator, and separated by a column to obtain bicyclo[1.1.1]pentanesulfonamide.

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