A fluorosulfonamide reagent, its preparation method and application

Abstract

This invention discloses a fluorosulfonamide reagent, its preparation method, and its application. The fluorosulfonamide reagent has the structural formula [formula omitted], wherein [value omitted] represents a cation; and X1 [value omitted] represents a cation. ‑ It is an anion. This invention provides a novel fluorosulfonamide reagent, which is a depyridine-desubstituted N-center free radical with sulfonyl fluoride substitution. This compound exhibits strong substrate adaptability, capable of C-H activation reactions of aromatics and free radical addition reactions of alkenes, efficiently synthesizing fluorosulfonated products, thus providing a new synthetic method for the synthesis of sulfonyl fluoride-containing compounds. The fluorosulfonamide reagent of this invention utilizes a free radical reaction in the preparation of sulfonyl fluoride-containing compounds, requiring only simple heating or light irradiation to initiate the reaction. The reaction conditions are mild, the equipment requirements are low, and the operation is simple. Furthermore, the fluorosulfonamide reagent of this invention is a stable solid, making it easy to use and store.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a fluorosulfonamide reagent, its preparation method, and its application. Background Technology

[0002] Due to the unique properties of their SF bonds, sulfonyl fluoride compounds have shown great application value in organic synthesis methodology, medicinal chemistry, materials chemistry, and chemical biology. Therefore, expanding the synthetic methods for these compounds has gradually become a topic of interest for scientists. Common fluorosulfonyl compounds include sulfonyl fluoride (R-SO2F), fluorosulfonates (RO-SO2F), and fluorosulfonamides (R-SO2F). 1 R 2 Fluorosulfonyl fluoride (N-SO2F2) and other fluorosulfonyl compounds are widely used in various fields; however, current methods for obtaining these fluorosulfonyl compounds are very limited, thus necessitating the development of new fluorosulfonyl reagents. Using fluorosulfonyl reagents is a simple and efficient route for synthesizing fluorosulfonamides, but the existing reagents are quite limited. Currently, the main method for obtaining fluorosulfonamides is the N-fluorosulfonation of amino groups using sulfuryl fluoride gas (SO2F2) and its solid substitutes (FDIT, AISF), resulting in a relatively simple bonding mode. Furthermore, in multi-step synthesis, functional group protection / deprotection operations of the reactive amino group are required, involving additional synthetic steps and cumbersome classification and purification, which brings certain inconveniences to the synthesis. Summary of the Invention

[0003] To overcome the problems existing in the prior art, one objective of this invention is to provide a novel fluorosulfonamide reagent. A second objective is to provide a method for preparing this fluorosulfonamide reagent. A third objective is to provide applications of this fluorosulfonamide reagent. A fourth objective is to provide a method for preparing fluorosulfonamide compounds. Based on the above problems, this invention designs and synthesizes a fluorosulfonamide reagent, which is a nitrogen-centered free radical (FSO2(R)N·) with a sulfonyl fluoride substituent and extremely high electrophilicity. It can attack the π bonds of substrates such as alkenes and aromatics, thereby achieving a direct fluorosulfonamide reaction and synthesizing various sulfonyl fluoride-containing compounds. Furthermore, this reagent also features a simple synthesis method, stable properties, and high yield.

[0004] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0005] The first aspect of this invention provides a fluorosulfonamide reagent, the structural formula of which is shown in Formula I-1:

[0006]

[0007] in, R represents a cation. 1 It is hydrogen, alkyl, aromatic ring or substituted aromatic ring;

[0008] The R 1 R 2 and R 6 Independently hydrogen, alkyl, aromatic ring, or substituted aromatic ring; the R 4 The R group is hydrogen, alkyl, alkoxy, aromatic, substituted aromatic, or electron-deficient. 3 and R 5 Independently hydrogen or alkyl; the X1 - X1 is an anion. - for - F, - Cl、 - Br、 - I, - OTf, - OSO2F, - OSO3H, - OTs - BF4 - BF6 - PF6 - PF4, - SbF6 - NTf2 or - ClO4.

[0009] Preferably, the parent ring of the aromatic ring or substituted aromatic ring is independently a benzene ring, a naphthalene ring, an anthracene ring, or a phenanthrene ring.

[0010] Preferably, the substituents in the substituted aromatic ring are independently alkoxy, alkyl, phenyl, cyano, halogen, trifluoromethyl, nitro, ester, aldehyde, acetyl, fluorosulfonyl, benzenesulfonyl, or alkylsulfonyl, wherein the halogen group is... - F, - Cl、 - Br, -I.

[0011] Preferably, the electron-deficient group is selected from halogen group, trifluoromethyl group, nitrile group, nitro group, ester group, aldehyde group, acetyl group, fluorosulfonyl group, benzenesulfonyl group or alkylsulfonyl group.

[0012] Preferably, the alkyl group has 1 to 8 carbon atoms. More preferably, the alkyl group has 1 to 3 carbon atoms.

[0013] More preferably, the structural formula of the cation is shown in Formula I-2:

[0014]

[0015] The second aspect of this invention provides a method for preparing the fluorosulfonamide reagent described in the first aspect of this invention, comprising the following steps:

[0016] S1. A pyran salt compound as shown in Formula II-1, hydrazine monohydrate, and an organic solvent are mixed and reacted to obtain an aminopyridine salt compound as shown in Formula III-1; wherein, the reaction formula of S1 is shown below:

[0017]

[0018] S2. The aminopyridine salt compound (Formula III-1), thioyl fluoride, a basic reagent, and an organic solvent are mixed and subjected to a nucleophilic substitution reaction to obtain the fluorosulfonamide ylide compound shown in Formula IV-1; wherein, the reaction formula of S2 is as follows:

[0019]

[0020] S3. The fluorosulfonamide ylide compound, the anion source material, and an organic solvent are mixed and subjected to an electrophilic reaction to obtain a cation and anion X1 as shown in Formula I-1. - The fluorosulfonamide reagent; wherein the anion source is selected from iodonium salts or oxonium salts, and the chemical formula of the iodonium salt is R1R1I. + X1 - The chemical formula of the oxonium salt is R1R1O. + X1 - Among them, anion X1 - Can be - F, - Cl、 - Br、 - I, - OTf, - OSO2F, - OSO3H, - OTs - BF4 - BF6 - PF6 - PF4, - SbF6 - One of NTf2 or -ClO4; the reaction formula for S3 is shown below:

[0021]

[0022] Wherein, the R 1 R 2 R 3 R 4 R 5 R 6 X1- As described in the first aspect, the X2 - It is an anion.

[0023] Preferably, in step S1, the reaction temperature is 70-90°C.

[0024] Preferably, in step S1, the reaction time is 8-12 hours.

[0025] Preferably, in step S1, the molar ratio of the pyran salt compound to hydrazine monohydrate is 1:(1-5).

[0026] Preferably, in step S1, the organic solvent is an alcohol solvent. More preferably, the alcohol solvent is ethanol.

[0027] Preferably, in step S1, the volume molar ratio of the organic solvent to the pyran salt compound is 0.2-5 L / mol. More preferably, the volume molar ratio is 1-3 L / mol.

[0028] Preferably, in step S2, the reaction temperature is 15-40°C. More preferably, the reaction temperature is 20-30°C.

[0029] Preferably, in step S2, the reaction time is 6-12 hours. More preferably, the reaction time is 6-9 hours.

[0030] Preferably, in step S2, the mixture is evacuated to a negative pressure and then sulfuryl fluoride gas is introduced.

[0031] Preferably, in step S2, the organic solvent is selected from one of dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, acetone, acetonitrile, ethylene glycol dimethyl ether, toluene, xylene, N,N-dimethylformamide, or N,N-dimethylacetamide.

[0032] Preferably, in step S2, the volume molar ratio of the organic solvent to the aminopyridine salt compound is 1-5 L / mol. More preferably, the volume molar ratio is 1-3 L / mol.

[0033] Preferably, in step S2, the alkaline reagent includes organic bases and inorganic bases.

[0034] More preferably, the organic base is selected from triethylamine, 4-dimethylaminopyridine, or diisopropylethylamine; the inorganic base is selected from one or more of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, and calcium hydroxide.

[0035] More preferably, the molar ratio of the aminopyridine salt compound to the organic base is 1:(0.05-0.2).

[0036] More preferably, the molar ratio of the aminopyridine salt compound to the inorganic base is 1:(1-4).

[0037] Preferably, in step S3, the reaction temperature is 15-40°C.

[0038] Preferably, in step S3, the reaction time is 1-12 hours.

[0039] Preferably, in step S3, the molar ratio of the fluorosulfonamide yllide compound to the anion source raw material is 1:(1-2).

[0040] Preferably, the X2 - for - F, - Cl、 - Br、 - I, - ODNP, - ClO4, - BF4 - BF6 - PF6 - PF4, - SbF6 - NTf2 or - OTf.

[0041] Preferably, in each step, the reaction may further include a post-treatment, which includes the following steps: after the reaction is completed, the reaction mixture is cooled to 23°C, then cooled to -20°C, the resulting solid is recrystallized from CH2Cl2 and Et2O, and the residue is vacuum dried at 70°C to obtain the product.

[0042] The third aspect of the present invention also provides the application of the fluorosulfonating agent described in the first aspect of the present invention in the fluorosulfonation reaction.

[0043] The fourth aspect of the present invention also provides a method for preparing fluorosulfonamide compounds, comprising the following steps: mixing a reaction substrate, the fluorosulfonating reagent described in the first aspect, a photosensitizer, and an organic solvent, and carrying out a fluorosulfonation reaction under ultraviolet light, blue light, or visible light irradiation to obtain a fluorosulfonated product; wherein the reaction substrate includes an aromatic compound or an olefin compound;

[0044] Preferably, the aromatic compound is selected from structures shown in formula V-1, V-2, V-3 or V-4:

[0045]

[0046] In formula V-1, R1 is hydrogen, alkyl, alkoxy, aromatic ring, substituted aromatic ring, cyano, halogen, trifluoromethyl, nitro, ester, aldehyde, acetyl, fluorosulfonyl, benzenesulfonyl, or alkylsulfonyl; R2, R3, R4, R5, and R6 are independently selected from hydrogen, alkyl, alkoxy, halogen, ester, aromatic ring, or substituted aromatic ring.

[0047] In equation V-2, R 13 For hydrogen, hydroxyl, alkoxy; R7, R8, R9, R 10 R 11 R 12 R 14 It is independently selected from hydrogen, alkyl, alkoxy, halogen, or ester groups;

[0048] In equation V-3, X 1 For nitrogen, oxygen, or sulfur; R 15 R 16 R 17 R 18 It is independently selected from hydrogen, alkyl, alkoxy, halogen, or ester groups;

[0049] In equation V-4, X 2 For nitrogen, oxygen, or sulfur; R 19 R 20 It is independently selected from hydrogen, alkyl, aromatic ring, substituted aromatic ring, cyano, halogen, trifluoromethyl, nitro, ester, aldehyde, acetyl, fluorosulfonyl, benzenesulfonyl or alkylsulfonyl.

[0050] More preferably, the aromatic ring is a benzene ring, a naphthalene ring, an anthracene ring, or a phenanthrene ring;

[0051] The substituents of the substituted aromatic ring are independently alkoxy, alkyl, phenyl, halogen, trifluoromethyl, nitrile, nitro, ester, aldehyde, acetyl, fluorosulfonyl, benzenesulfonyl, or alkylsulfonyl; wherein the halogen group is... - F, - Cl、 - Br、 - I.

[0052] The alkyl group has 1 to 8 carbon atoms.

[0053] Preferably, the molar ratio of the aromatic compound to the fluorosulfonating agent is 1:(1-3). More preferably, it is 1:(1-1.5).

[0054] Preferably, when the reaction substrate is an olefin compound, it is selected from the structure shown in Formula VII:

[0055]

[0056] In the olefin compound, R1 and R2 are independently selected from hydrogen, alkyl, aromatic ring and substituted aromatic ring, and the substituent of the substituted aromatic ring is alkyl, electron-rich group or electron-deficient group; in the olefin compound, R3 and R4 are independently selected from hydrogen, alkyl and phenyl, and the alkyl has 1 to 8 carbon atoms.

[0057] More preferably, the electron-rich group is methoxy, ethoxy, propoxy, butoxy, dimethylamino, diethylamino, methylthio, or ethylthio, and the alkyl group has 1 to 8 carbon atoms; the electron-deficient group includes - F, - Cl、 - Br、 - I. Trifluoromethyl, nitrile, nitro, ester, aldehyde, acetyl, fluorosulfonyl, benzenesulfonyl, or alkylsulfonyl.

[0058] The olefin compounds R3 and R4 are preferably hydrogen, alkyl, and phenyl, and the alkyl group has 1 to 8 carbon atoms.

[0059] Preferably, when the reaction substrate is an olefin compound, the reaction further includes a nucleophile (NuH); the nucleophile is selected from water, alkyl alcohols, alkenyl alcohols, TMSN3, and TMSCN.

[0060] More preferably, the molar ratio of the nucleophile to the fluorosulfonating agent is (1-30):1. More preferably, it is (3-25):1.

[0061] Preferably, the molar ratio of the olefin compound to the fluorosulfonating agent is (1-3):1. More preferably, it is (1-1.5):1.

[0062] Preferably, the photosensitizer is selected from one or more of thioxanone, benzophenone, Ru(bpy)3(PF6)2, Ru(bpy)3Cl2, Ir[dF(CF3)ppy]2(bpy)PF6 or Ir[dF(CF3)ppy]2(dtbbpy)PF6.

[0063] Preferably, the molar ratio of the photosensitizer to the fluorosulfonamide reagent is (0.01-0.02):1.

[0064] Preferably, the reaction temperature of the fluorosulfonation reaction is 15-40°C. More preferably, it is 20-30°C.

[0065] Preferably, the reaction time for the fluorosulfonation reaction is 1 to 12 hours. More preferably, it is 3 to 9 hours.

[0066] Preferably, after the reaction is completed, the solvent in the resulting reaction solution is removed, and the crude product is separated by silica gel column chromatography to obtain the fluorosulfonamide product; the developing solvent used for the silica gel column chromatography is preferably petroleum ether and ethyl acetate.

[0067] More preferably, the volume ratio of petroleum ether to ethyl acetate is 50:1; and the silica gel used for silica gel column chromatography has a particle size of 200-300 mesh.

[0068] Preferably, the organic solvent is selected from any one of dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, dioxane, acetone, acetonitrile, ethylene glycol dimethyl ether, toluene, xylene, N,N-dimethylformamide, and N,N-dimethylacetamide. More preferably, it is acetonitrile.

[0069] Preferably, the volume molar ratio of the organic solvent to the fluorosulfonamide reagent is 1 L / mol to 5 L / mol.

[0070] The beneficial effects of this invention are:

[0071] 1. This invention provides a novel fluorosulfonamide reagent, wherein the N-aminopyridinium salt combines the nucleophilicity of the N-center with potential electrophilicity or free radical reactivity, possesses a reducible N-N bond, and ultimately generates a depyridine-substituted N-center free radical with sulfonyl fluoride substitution; this compound has strong substrate adaptability and can carry out CH activation reactions of aromatics and free radical addition reactions of alkenes, efficiently synthesizing fluorosulfonated products, thus providing a new synthetic method for the synthesis of sulfonyl fluoride-containing compounds.

[0072] 2. The fluorosulfonamide reagent of the present invention uses a free radical reaction in the preparation of sulfonyl fluoride compounds. The reaction can be initiated by simple heating or light irradiation. The reaction conditions are mild, the equipment requirements are low, and the operation is simple.

[0073] 3. The fluorosulfonamide reagent of the present invention is a stable solid state, which is easy to use and store. Attached Figure Description

[0074] Figure 1 The 1-((fluorosulfonyl)(methyl)amino)pyridine-1-onium prepared in Example 1 1 H NMR spectrum;

[0075] Figure 2 The 1-((fluorosulfonyl)(methyl)amino)pyridine-1-onium prepared in Example 1 13 C NMR spectrum;

[0076] Figure 3 1-((fluorosulfonyl)(methyl)amino)pyridine-1-onium prepared in Example 119 F NMR spectrum;

[0077] Figure 4 For the methyl(naphth-1-yl)aminosulfonyl fluoride prepared in Example 4 1 H NMR spectrum;

[0078] Figure 5 For the methyl(naphth-1-yl)aminosulfonyl fluoride prepared in Example 4 13 C NMR spectrum;

[0079] Figure 6 For the methyl(naphth-1-yl)aminosulfonyl fluoride prepared in Example 4 19 F NMR spectrum;

[0080] Figure 7 For the (2-methoxy-2,2-diphenylethyl)(methyl)aminosulfonyl fluoride prepared in Example 5 1 H NMR spectrum;

[0081] Figure 8 For the (2-methoxy-2,2-diphenylethyl)(methyl)aminosulfonyl fluoride prepared in Example 5 13 C NMR spectrum;

[0082] Figure 9 For the (2-methoxy-2,2-diphenylethyl)(methyl)aminosulfonyl fluoride prepared in Example 5 19 F NMR spectrum. Detailed Implementation

[0083] The present invention will be further described in detail below through specific embodiments. Unless otherwise specified, the raw materials used in the following embodiments can be obtained from conventional commercial channels or prepared and isolated through simple synthesis; unless otherwise specified, the processes employed are conventional processes in the art.

[0084] Example 1

[0085] This embodiment provides a fluorosulfonamide reagent as 1-((fluorosulfonyl)(methyl)amino)pyridine-1-onium, and its preparation steps are as follows:

[0086] The reaction formula for S1 is as follows:

[0087]

[0088] The specific steps of S1 are as follows:

[0089] At room temperature, 10 mmol of 1-aminopyridine iodonium salt, 36 mmol of potassium carbonate, 1 mmol of 4-dimethylaminopyridine, and 30 mL of acetonitrile were added to a 100 mL dry flask and mixed. The resulting mixture was then evacuated to negative pressure using a water pump and purged with sulfuryl fluoride gas (1 atm) using a balloon. The mixture was stirred at room temperature for 6 hours. After the reaction was complete, the mixture was extracted with dichloromethane and water and washed with brine. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under vacuum. The mixture was purified by rapid column chromatography on silica gel (CH2Cl2:MeOH = 20:1) to give N-fluorosulfonyl-1-aminopyridine ylide.

[0090] The reaction formula for S2 is as follows:

[0091]

[0092] The specific steps of S2 are as follows:

[0093] N-fluorosulfonyl-1-aminopyridinium (5 mmol) and dichloromethane (30 mL) were added to a 50 mL flask and reacted at room temperature for 2 h. After the reaction was complete, trimethyloxonium tetrafluoroborate (5.5 mmol) was added to the solution at room temperature. The reaction mixture was rotary evaporated, and then the resulting mixture was recrystallized from CH2Cl2 and Et2O to give a white solid product, 1-((fluorosulfonyl)(methyl)amino)pyridin-1-onium fluoroborate, in 90% yield. The NMR spectra of 1-((fluorosulfonyl)(methyl)amino)pyridin-1-onium fluoroborate are shown below. Figure 1 , Figure 2 , Figure 3 The specific NMR information is as follows: 1 H NMR (400MHz, Deuterium Oxide) δ9.35(d,J=6.3Hz,2H),8.84(t,J=7.8Hz,1H),8.31(t,J=7.1Hz,2H),3.87(s,3H). 13 CNMR(101MHz,Deuterium Oxide)δ150.75,146.35,130.51,42.02. 19 F NMR (376MHz, Deuterium Oxide) δ41.76.

[0094] Application Example 1

[0095] Application Example 1 involves the fluorosulfonation of benzene using the fluorosulfonating reagent from Example 1. The specific reaction formula and reaction steps are as follows:

[0096]

[0097] 1-((fluorosulfonyl)(methyl)amino)pyridine-1-onium (0.1 mmol), Ru(bpy)3(PF6)2 (0.002 mmol), benzene (0.3 mmol), and MeCN (2 mL) were added to a 10 mL test tube. The mixture was reacted under blue LED light at room temperature for 6 h. After the reaction was complete, the mixture was purified by rapid column chromatography on silica gel (PE:EA = 10:1) to obtain a colorless oily substance, N-methyl-N-phenylaminosulfonyl fluoride (CAS RN: 2070-62-4), in 58% yield. The specific NMR information of the product is as follows: 1 H NMR (400MHz, Chloroform-d) δ7.42–7.20 (m, 5H), 3.29 (d, J = 2.3Hz, 3H). 13 C NMR (101MHz, Chloroform-d) δ139.88, 129.88, 129.07, 126.67, 126.65, 40.69 (d, J = 1.4Hz). 19 F NMR (376MHz, Chloroform-d) δ42.36.

[0098] Application Example 2

[0099] Application Example 2 involves the fluorosulfonation of 2-bromothiophene using the fluorosulfonating reagent from Example 1. The specific reaction formula and reaction steps are as follows:

[0100]

[0101] 1-((fluorosulfonyl)(methyl)amino)pyridin-1-onium (0.12 mmol), Ru(bpy)3(PF6)2 (0.002 mmol), 2-bromothiophene (0.1 mmol), and MeCN (2 mL) were added to a 10 mL test tube. The mixture was reacted under blue LED light at room temperature for 6 h. After the reaction was complete, the mixture was purified by rapid column chromatography on silica gel (PE:EA = 10:1) to give a pale yellow oily product of (5-bromothiophene-2-yl)(methyl)aminosulfonyl fluoride in a yield of 64%. The specific NMR information of the product is as follows: 1 H NMR (400MHz, Chloroform-d) δ6.95 (d, J = 4.0Hz, 1H), 6.85 (d, J = 4.0Hz, 1H), 3.44 (d, J = 2.0Hz, 3H). 13 C NMR (101MHz, Chloroform-d) δ128.59, 126.60, 126.59, 112.37, 42.50 (d, J = 1.5Hz). 19FNMR (377MHz, Chloroform-d) δ 40.60.

[0102] Application Example 3

[0103] Application Example 3 involves the fluorosulfonating of 3-methylindole using the fluorosulfonating reagent from Example 1. The specific reaction formula and reaction steps are as follows:

[0104]

[0105] 1-((fluorosulfonyl)(methyl)amino)pyridin-1-onium (0.12 mmol), Ru(bpy)3(PF6)2 (0.002 mmol), 3-methylindole (0.1 mmol), and MeCN (2 mL) were added to a 10 mL test tube. The mixture was reacted under blue LED light at room temperature for 6 h. After the reaction was complete, the mixture was purified by rapid column chromatography on silica gel (PE:EA = 10:1) to give a yellow oily methyl(3-methyl-1H-indole-2-yl)aminosulfonyl fluoride in 52% yield. The specific NMR information of the product is as follows: 1 HNMR(400MHz,Chloroform-d)δ7.95(s,1H),7.57(d,J=7.9Hz,1H),7.34–7.26(m,2H),7.16(t,J=7.3Hz,1H),3.49(d,J=2.1Hz,3H),2.32(d,J=1.1Hz,3H). 13 C NMR (101MHz, Chloroform-d) δ 133.68, 127.61, 127.41, 124.04, 120.20, 119.65, 111.25, 109.34, 40.69 (d, J = 1.8Hz), 7.93. 19 FNMR (376MHz, Chloroform-d) δ45.36.

[0106] Application Example 4

[0107]

[0108] 1-((fluorosulfonyl)(methyl)amino)pyridin-1-onium (0.12 mmol), Ru(bpy)3(PF6)2 (0.002 mmol), naphthalene ring (0.1 mmol), and MeCN (0.05 M) were added to a 10 mL test tube. The mixture was reacted under blue LED light at room temperature for 6 h. After the reaction was complete, the mixture was purified by rapid column chromatography on silica gel (PE:EA = 10:1) to obtain a white solid methyl(naphthyl-1-yl)aminosulfonyl fluoride, with a yield of 78%. The NMR spectra of the product (H, C, and fluorine) are shown below. Figure 4, Figure 5 , Figure 6 The specific NMR information is as follows: 1 H NMR (400MHz, Chloroform-d) δ8.12–8.04(m,1H),7.97–7.88(m,2H),7.70–7.47(m,4H),3.52(d,J=2.3Hz,3H). 13 C NMR (101MHz, Chloroform-d) δ 136.03 (d, J = 2.9Hz), 134.81, 130.18, 128.61, 127.84, 127.04, 125.54, 125.28, 122.21, 41.20 (d, J = 1.7Hz). 19 F NMR (377MHz, Chloroform-d) δ 44.36.

[0109] Application Example 5

[0110]

[0111] 1-((fluorosulfonyl)(methyl)amino)pyridine-1-onium (0.1 mmol), Ru(bpy)3(PF6)2 (0.001 mmol), 1,1-stilbene (0.15 mmol), methanol (2.5 mmol), and MeCN (2 mL) were added to a 10 mL test tube. The mixture was reacted under blue LED light irradiation at room temperature for 6 h. After the reaction was complete, the mixture was purified by rapid column chromatography on silica gel (PE:EA = 50:1) to give a white oily product of (2-methoxy-2,2-diphenylethyl)(methyl)aminosulfonyl fluoride, with a yield of 77%. The NMR spectra of the product (H, C, and fluorine) are shown below. Figure 7 , Figure 8 , Figure 9 The specific NMR information is as follows: 1 H NMR (400MHz, Chloroform-d) δ7.39–7.25 (m, 10H), 4.21 (d, J = 1.6Hz, 2H), 3.06 (s, 3H), 2.68 (d, J = 1.8Hz, 3H). 13 C NMR (101MHz, Chloroform-d) δ141.51,128.26,127.83,127.64,82.83,82.81,56.32,56.30,51.60,37.76. 19 F NMR (377MHz, CDCl3) δ 43.79.

[0112] Application Example 6

[0113]

[0114] 1-((fluorosulfonyl)(methyl)amino)pyridin-1-onium (0.1 mmol), Ru(bpy)3(PF6)2 (0.001 mmol), 1-methyl-4-(1-phenylvinyl)benzene (0.15 mmol), methanol (2.5 mmol), and MeCN (2 mL) were added to a 10 mL test tube. The mixture was reacted under blue LED light irradiation at room temperature for 6 h. After the reaction was completed, the mixture was purified by rapid column chromatography on silica gel (PE:EA = 50:1) to give a white oily product of (2-methoxy-2-phenyl-2-(p-tolyl)ethyl)(methyl)aminosulfonyl fluoride, with a yield of 78%. The specific NMR information of the product is as follows: 1 H NMR (400MHz, Chloroform-d) δ7.32–7.00(m,10H),4.16–4.06(m,2H),2.97(s,3H),2.61(d,J=1.8Hz,3H),2.27(s,3H). 13 C NMR(101MHz,Chloroform-d)δ141.74,138.35,137.60,128.96,128.18,127.69 ,127.58,82.71(d,J=2.3Hz),56.41(d,J=1.9Hz),51.53,37.75,29.72,21.08. 19 F NMR (376MHz, Chloroform-d) δ 43.76.

[0115] Application Example 7

[0116]

[0117] 1-((fluorosulfonyl)(methyl)amino)pyridine-1-onium (0.1 mmol), Ru(bpy)3(PF6)2 (0.001 mmol), 1,1-stilbene (0.15 mmol), water (2.5 mmol), and MeCN (2 mL) were added to a 10 mL test tube. The mixture was reacted under blue LED light at room temperature for 6 h. After the reaction was complete, the mixture was purified by rapid column chromatography on silica gel (PE:EA = 10:1) to give a white oily product of (2-hydroxy-2,2-diphenylethyl)(methyl)aminosulfonyl fluoride, with a yield of 51%. The specific NMR information of the product is as follows: 1 H NMR (400MHz, Chloroform-d) δ7.37–7.20 (m, 10H), 4.10 (s, 2H), 2.63 (d, J = 1.8Hz, 3H), 2.59 (s, 1H). 13C NMR (126MHz, Chloroform-d) δ143.82,128.53,127.90,126.19,61.15,38.33. 19 F NMR (376MHz, Chloroform-d) δ42.22.

[0118] Application Example 8

[0119]

[0120] 1-((fluorosulfonyl)(methyl)amino)pyridine-1-onium (0.1 mmol), Ru(bpy)3(PF6)2 (0.001 mmol), 1,1-stilbene (0.15 mmol), TMSN3 (0.3 mmol), and MeCN (2 mL) were added to a 10 mL test tube. The mixture was reacted under blue LED light at room temperature for 6 h. After the reaction was complete, the mixture was purified by rapid column chromatography on silica gel (PE:EA = 10:1) to give a yellow oily product of (2-azido-2,2-diphenylethyl)(methyl)aminosulfonyl fluoride, with a yield of 49%. The specific NMR information of the product is as follows: 1 H NMR (400MHz, Chloroform-d) δ7.35–7.23 (m, 10H), 4.19 (d, J = 1.4Hz, 2H), 2.56 (d, J = 1.6Hz, 3H). 13 C NMR (126MHz, Chloroform-d) δ 138.84, 127.72, 127.55, 126.33, 70.71 (d, J = 2.3Hz), 58.24 (d, J = 1.8Hz), 37.03. 19 F NMR (376MHz, Chloroform-d) δ 43.50.

[0121] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A fluorosulfonamide reagent, characterized in that, Its structural formula is shown in Equation I-1: Formula I-1; in, R represents a cation; 1 R is an alkyl group having 1 to 8 carbon atoms. 3 and R 5 Independently selected from hydrogen; R 2 R 4 R 6 Independently selected from hydrogen or alkyl groups having 1 to 8 carbon atoms; The X1 - X1 is an anion. - Selected from - F, - Cl、 - Br、 - I, - OTf, - OSO2F, - OTs - BF4 - BF6 - PF6 - PF4, - SbF6 or - One of NTf2.

2. The fluorosulfonamide reagent according to claim 1, characterized in that, The structural formula of the cation is shown in Formula I-2: Formula I-2.

3. The method for preparing the fluorosulfonamide reagent according to claim 1, characterized in that, Includes the following steps: S1. A pyran salt compound as shown in Formula II-1, hydrazine monohydrate, and an organic solvent are mixed and reacted to obtain an aminopyridine salt compound as shown in Formula III-1; wherein, the reaction formula of S1 is shown below: ； S2. The aminopyridine salt compound, sulfuryl fluoride gas, basic reagent, and organic solvent are mixed and subjected to a nucleophilic substitution reaction to obtain the fluorosulfonamide ylide compound shown in Formula IV-1; wherein, the reaction formula of S2 is shown below: ； S3. The fluorosulfonamide ylide compound, the anion source material, and an organic solvent are mixed and subjected to an electrophilic reaction to obtain a fluorosulfonamide reagent as shown in Formula I-1; wherein the anion source material is selected from iodonium salts or oxonium salts, and the chemical formula of the iodonium salt is R1R1I. + X1 - The chemical formula of the oxonium salt is R1R1O. + X1 - The reaction formula for S3 is shown below: ； Wherein, the R 1 R 2 R 3 R 4 R 5 R 6 X1 - As described in claim 1, the X2 - It is an anion.

4. The method for preparing the fluorosulfonamide reagent according to claim 3, characterized in that, The reaction conditions for the preparation method are selected from one or more of the following: A) In step S1, the reaction temperature is 70-90 ℃; B) In step S1, the reaction time is 8-12 h; C) In step S1, the molar ratio of the pyran salt compound to hydrazine monohydrate is 1:(1-5); D) In ​​step S2, the reaction temperature is 15-40 ℃; E) In step S2, the reaction time is 6-12 h; F) In step S3, the reaction temperature is 15-40 °C; G) In step S3, the reaction time is 1-12 h; H) In step S3, the molar ratio of the fluorosulfonamide yllide compound to the anion source raw material is 1:(1-2).

5. The method for preparing the fluorosulfonamide reagent according to claim 3, characterized in that, The X2 - for - F, - Cl、 - Br、 - I, - ODNP, - ClO4, - BF4 - BF6 - PF6 - PF4, - SbF6 - NTf2 or - OTf; And / or, the base reagent includes organic bases and inorganic bases.

6. The use of the fluorosulfonating agent according to claim 1 or 2 in the fluorosulfonation reaction.

7. A method for preparing a fluorosulfonamide compound, characterized in that, The process includes the following steps: mixing the fluorosulfonating reagent, reaction substrate, photosensitizer, and organic solvent according to any one of claims 1 or 2, and carrying out a fluorosulfonation reaction under ultraviolet light, blue light, or visible light irradiation to obtain a fluorosulfonated product; wherein the reaction substrate is an aromatic compound or an olefin compound; The aromatic compound is selected from the structure shown in formula V-1, formula V-2, formula V-3 or formula V-4: Formula V-1 Formula V-2 Formula V-3 Formula V-4; In formula V-1, R1 is hydrogen; R2, R3, R4, R5, and R6 are independently selected from hydrogen. In equation V-2, R 13 It is hydrogen; R7, R8, R9, R 10 R 11 R 12 R 14 Independently selected from hydrogen; In equation V-3, X 1 For sulfur; R 15 R 16 R 17 R 18 Independently selected from halogen groups; In equation V-4, X 2 For nitrogen; R 19 For hydrogen, R 20 It is an alkyl group with 1 carbon atom; The olefin compound is selected from the structure shown in Formula VII: ； In the olefin compound, R1 and R2 are independently selected from hydrogen; and R3 and R4 are independently selected from benzene. When the reaction substrate is an olefin compound, the reaction further includes a nucleophile; the nucleophile is selected from water, alkyl alcohols, alkenyl alcohols, TMSN3, and TMSCN.

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