A method for preparing cyanosulfonyl fluoride compounds

Abstract

The invention relates to the technical fields of chemical synthesis and medicinal chemistry, and in particular to a method for preparing a cyanosulfonyl fluoride compound. The invention adopts an oxime ether compound as a free radical precursor, and can realize cyano / fluorine sulfonylation of the oxime ether under the condition of photocatalyst regulation, in combination with a free radical sulfur dioxide insertion strategy, through photoredox catalysis, C-C bond homolytic ring opening, free radical SO2 insertion, and fluorination processes, to obtain a cyanosulfonyl fluoride product, and can realize the preparation of a series of cyanosulfonyl fluoride compounds. The invention provides a new synthesis method for the synthesis of cyanosulfonyl fluoride compounds, and the cyanosulfonyl fluoride group is a part of the molecular structure of various drugs, and is expected to be widely used in the fields of organic synthesis, drug development, polymer materials, etc.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis and medicinal chemistry, and in particular to a method for preparing cyanosulfonyl fluoride compounds. Background Art

[0002] Sulfonyl fluoride is the core group of the new generation of click chemistry reactions. It is widely used in many fields such as organic synthesis, materials and pharmaceutical research and development, and has become one of the hot spots in chemical research in recent years. Therefore, the development of simple and efficient synthesis methods for multifunctional sulfonyl fluoride compounds has certain research and application value. Cyano groups can be used to synthesize various functional groups such as carboxylic acids, amines, amides and ketones, and are also commonly found in biologically active molecules such as medicines and natural products.

[0003] At present, there are three main strategies for the synthesis of sulfonyl fluoride compounds: 1. In situ construction of sulfonyl fluoride groups; 2. Modular synthesis based on sulfonyl fluoride building blocks; 3. Direct fluorosulfonylation. In 2024, Liao Saihu's research group reported a photosensitizer and copper synergistically catalyzed addition of fluorosulfonyl radicals to alkyl olefins, followed by further cyanation. This reaction belongs to the direct fluorosulfonylation type. Existing synthetic methods cannot synthesize remote cyanosulfonyl fluoride compounds in one step. Summary of the invention

[0004] In view of the deficiencies of the above-mentioned prior art, the purpose of the present invention is to provide a method for preparing cyanosulfonyl fluoride compounds, and to construct remote cyanosulfonyl fluoride compounds in one step through a free radical SO2 insertion strategy. The present invention uses oxime ether compounds as free radical precursors, and under the conditions of a sulfur dioxide source, an organic base free radical initiator, a fluorine source, and a photocatalyst, the oxime ether substrate is subjected to photocatalytic oxidation-reduction to generate nitrogen radicals, CC bond homolytic ring cleavage, free radical SO2 insertion, and fluorination process, thereby realizing the cyano / fluorine sulfonylation reaction of the oxime ether to obtain a cyanosulfonyl fluoride product.

[0005] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0006] A method for preparing a cyanosulfonyl fluoride compound comprises the following steps:

[0007] In an organic solvent, an oxime ether compound is used as a free radical precursor, a photocatalyst, a sulfur dioxide source and an organic base free radical initiator are added thereto under a protective atmosphere, and the mixture is mixed and stirred under light conditions, so that the oxime ether compound undergoes photocatalytic oxidation and reduction to generate nitrogen free radicals, and CC bond homolytic ring cleavage and free radical SO2 insertion occur;

[0008] Then, a fluorine source is added, and a fluorination process is performed to realize the cyano / fluorosulfonylation reaction of the oxime ether to obtain a cyanosulfonyl fluoride compound;

[0009] The general reaction formula is as follows:

[0010] ;

[0011] Wherein, R is selected from one of hydrogen, alkyl, substituted alkyl, aryl, ester, substituted aryl, heterocycle, heterocycle derivative, cyclic ring, and spirocycle; X is selected from one of carbon, nitrogen, oxygen, sulfur, etc.; n is selected from one of 1, 2, and 3; and the sulfur dioxide source is 1,4-diazabicyclo[2.2.2]octane-1,4-diamine-1,4-disulfinic acid, abbreviated as DABSO.

[0012] The present invention uses oxime ether compounds as free radical precursors, adds a photocatalyst, a sulfur dioxide source, and an organic base free radical initiator thereto under a protective atmosphere, mixes and stirs under light conditions, and then adds a fluorine source. The present invention combines the free radical sulfur dioxide insertion fluorination strategy, selects oxime ether compounds as free radical precursors, and generates nitrogen free radicals, CC bond homolysis ring opening, free radical SO2 insertion and fluorination processes through photocatalytic oxidation and reduction, realizes the cyano / fluorosulfonylation reaction of oxime ether, and constructs remote cyanosulfonyl fluoride compounds in one step through the free radical SO2 insertion strategy. So far, the in-situ construction of fluorosulfonyl / cyano bifunctionalization reaction has not been reported.

[0013] In a preferred embodiment of the present invention, the oxime ether compound is selected from one or more of four-membered ring oxime ether, five-membered ring oxime ether, six-membered ring oxime ether, thiocyclic oxime ether and oxygen-cyclic oxime ether.

[0014] In a preferred embodiment of the present invention, the organic base free radical initiator is selected from one or more of tetramethylguanidine, triethylenediamine, 2,6-lutidine, triethylamine, isopropylamine, and di-tert-butyl peroxide, wherein tetramethylguanidine is abbreviated as TMG.

[0015] In a preferred embodiment of the present invention, the fluorine source is selected from potassium hydrogen difluoride, N - one or more of fluorobisbenzenesulfonamide and selective fluorine reagent, wherein the selective fluorine reagent is abbreviated as Selectfluor.

[0016] In a preferred embodiment of the present invention, the photocatalyst is selected from acid red 87, 2,4,5,6-tetrakis (9-carbazolyl) -isophthalonitrile, 2,4,6-triphenylpyran tetrafluoroborate, rhodamine B, terpyridine ruthenium chloride hexahydrate, fac-Ir(ppy)3, Ir(ppy)2bpyPF6, Ir[ppy]2(dtbbpy)PF6, Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10-methyl-9-mesityl acridine perchlorate, 3,6,-di-tert-butyl-9-mesityl-10-phenyl acridine-10-tetrafluoroborate, 9-m-methyl-10-methyl acridine-10-hydroiodide, 9-trimethyl-10-methyl acridine-10-hexafluorophosphate, 9-m-dimethyl-10-phenyl acridine-10-hydrochloride, 9-m-dimethyl-2,7-dimethyl-10-phenyl acridine-10-tetrafluoroborate; wherein Acid Red 87 is abbreviated as Eosin Y, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile is abbreviated as 4CzIPN, 2,4,6-triphenylpyran tetrafluoroborate is abbreviated as TPT, 10-methyl-9-mesityl acridine perchlorate is abbreviated as Mes-Acr-Me-ClO4, 3,6-di-tert-butyl-9-mesityl-10-phenylacridine-10-tetrafluoroborate is abbreviated as Mes-( t -Bu)2Acr-Ph-BF4.

[0017] In a preferred embodiment of the present invention, the molar ratio of the oxime ether compound to the photocatalyst is 1:0.02-0.1, and the molar ratio of the oxime ether compound to the sulfur dioxide source is 1:2-4.

[0018] In a preferred embodiment of the present invention, the molar ratio of the oxime ether compound to the organic base free radical initiator is 1:1-4.

[0019] In a preferred embodiment of the present invention, the molar ratio of the oxime ether compound to the fluorine source is 1:1.5-4.

[0020] In a preferred embodiment of the present invention, the illumination conditions are: irradiation with LED lamp, the irradiation wavelength is 460 nm~465 nm, the illumination time is 0.8 hour~1.2 hours, the reaction temperature is room temperature, and the reaction time is 2 hours~2.5 hours.

[0021] In a preferred embodiment of the present invention, the organic solvent is dichloroethane, acetonitrile, tetrahydrofuran, N , N -dimethylformamide, dimethyl sulfoxide, 1,4-dioxane or isopropanol, wherein dichloroethane is abbreviated as DCE.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. The present invention uses oxime ether compounds as free radical precursors, adds a photocatalyst, a sulfur dioxide source, and an organic base free radical initiator thereto under a protective atmosphere, mixes and stirs under light conditions, and then adds a fluorine source. The present invention combines the free radical sulfur dioxide insertion fluorination strategy, selects oxime ether compounds as free radical precursors, and undergoes photocatalytic oxidation-reduction to generate nitrogen radicals, CC bond homolytic ring opening, free radical SO2 insertion and fluorination processes to achieve the cyano / fluorosulfonylation reaction of oxime ethers, and constructs remote cyanosulfonyl fluoride compounds in one step through the free radical SO2 insertion strategy.

[0024] 2. The reaction yield of the present invention is good, the synthesis efficiency is high, and the cyano group and fluorosulfonyl group in the structure of the obtained product can be transformed in various ways, which shows that the method of the present invention has certain synthetic application value.

[0025] 3. The present invention provides a new method for the synthesis of cyanosulfonyl fluoride compounds, and cyanosulfonyl fluoride is a part of the molecular structure of many drugs, and is expected to be widely used in the fields of organic synthesis, drug development, polymer materials, etc.

[0026] 4. The present invention adopts a free radical reaction, which can be initiated by simple illumination, with mild reaction conditions, high yield, low instrument and equipment requirements, and simple operation. In addition, the sulfur dioxide source used in the present invention is easy to prepare and inexpensive. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is the H NMR spectrum of the product prepared in Example 4 of the present invention.

[0028] Figure 2 This is the NMR carbon spectrum of the product prepared in Example 4 of the present invention.

[0029] Figure 3 NMR fluorine spectrum of the product prepared in Example 4 of the present invention.

[0030] Figure 4 Mass spectrum of the product prepared in Example 4 of the present invention. DETAILED DESCRIPTION

[0031] The following is a detailed description of the technical solutions in the embodiments of the present invention in combination with preferred embodiments and data. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. 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.

[0032] It should be noted that all professional terms used in the present invention are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention. Unless otherwise specifically stated, various raw materials, reagents, instruments and equipment used in the following embodiments of the present invention can be purchased from the market or prepared by existing methods.

[0033] Example 1

[0034] The synthetic route is:

[0035] .

[0036] 0.1 mmol of 1a was added to a dry Schlenk reaction tube, followed by 0.005 mmol of 4CzIPN, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine and 4.0 mL of dichloroethane under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a 460 nm wavelength blue LED light.

[0037] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated, and further purified by column chromatography or preparative thin layer chromatography on silica gel, the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 63%.

[0038] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0039] 1 H NMR, 400 MHz, chloroform: d 7.44–7.36 (m, 3H), 7.29–7.27 (m, 2H), 3.93–3.86 (m, 1H), 3.81–3.75 (m, 1H), 3.72–3.65 (m, 1H), 2.97–2.86 (m, 2H);

[0040] 13 C NMR, 101 MHz, chloroform: d 137.2, 129.5, 129.0, 126.8, 116.5, 54.4 (d, J =16.0 Hz), 37.3, 23.9 (d, J = 1.8 Hz);

[0041] 19 F NMR, 377 MHz, chloroform: d 58.8;

[0042] HRMS (ESI) m / z calcd. for C 10 H 11 FNO2S [M + H] + 228.0490, found 228.0491.

[0043] Example 2

[0044] The synthetic route is:

[0045] .

[0046] 0.1 mmol of 1a was added to a dry Schlenk reaction tube, followed by 0.005 mmol of Eosin Y, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine and 4.0 mL of dichloroethane under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a 460 nm wavelength blue LED light.

[0047] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another 1 h, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product with a yield of 39%.

[0048] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0049] 1 H NMR, 400 MHz, chloroform: d 7.44–7.36 (m, 3H), 7.29–7.27 (m, 2H), 3.93–3.86 (m, 1H), 3.81–3.75 (m, 1H), 3.72–3.65 (m, 1H), 2.97–2.86 (m, 2H);

[0050] 13 C NMR, 101 MHz, chloroform: d 137.2, 129.5, 129.0, 126.8, 116.5, 54.4 (d, J =16.0 Hz), 37.3, 23.9 (d, J = 1.8 Hz);

[0051] 19 F NMR, 377 MHz, chloroform: d 58.8;

[0052] HRMS (ESI) m / z calcd. for C 10 H 11 FNO2S [M + H] + 228.0490, found 228.0491.

[0053] Example 3

[0054] The synthetic route is:

[0055] .

[0056] 0.1 mmol of 1a was added to a dry Schlenk reaction tube, followed by 0.005 mmol of TPT, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, and 4.0 mL of dichloroethane under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a 460 nm wavelength blue LED light.

[0057] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 67%.

[0058] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0059] 1 H NMR, 400 MHz, chloroform: d 7.44–7.36 (m, 3H), 7.29–7.27 (m, 2H), 3.93–3.86 (m, 1H), 3.81–3.75 (m, 1H), 3.72–3.65 (m, 1H), 2.97–2.86 (m, 2H);

[0060] 13 C NMR, 101 MHz, chloroform: d 137.2, 129.5, 129.0, 126.8, 116.5, 54.4 (d, J=16.0 Hz), 37.3, 23.9 (d, J = 1.8 Hz);

[0061] 19 F NMR, 377 MHz, chloroform: d 58.8;

[0062] HRMS (ESI) m / z calcd. for C 10 H 11 FNO2S [M + H] + 228.0490, found 228.0491.

[0063] Example 4

[0064] The synthetic route is:

[0065] .

[0066] 0.1 mmol of 1a was added to a dry Schlenk reaction tube, followed by 0.005 mmol of Mes-Acr-Me-ClO4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, and 4.0 mL of dichloroethane under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a 460 nm wavelength blue LED light.

[0067] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 74%.

[0068] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0069] 1 H NMR, 400 MHz, chloroform: d 7.44–7.36 (m, 3H), 7.29–7.27 (m, 2H), 3.93–3.86 (m, 1H), 3.81–3.75 (m, 1H), 3.72–3.65 (m, 1H), 2.97–2.86 (m, 2H);

[0070] 13 C NMR, 101 MHz, chloroform: d137.2, 129.5, 129.0, 126.8, 116.5, 54.4 (d, J =16.0 Hz), 37.3, 23.9 (d, J = 1.8 Hz);

[0071] 19 F NMR, 377 MHz, chloroform: d 58.8;

[0072] HRMS (ESI) m / z calcd. for C 10 H 11 FNO2S [M + H] + 228.0490, found 228.0491.

[0073] Example 5

[0074] The synthetic route is:

[0075] .

[0076] 0.1 mmol of 1a was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0077] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 93%.

[0078] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0079] 1 H NMR, 400 MHz, chloroform: d 7.44–7.36 (m, 3H), 7.29–7.27 (m, 2H), 3.93–3.86 (m, 1H), 3.81–3.75 (m, 1H), 3.72–3.65 (m, 1H), 2.97–2.86 (m, 2H);

[0080] 13 C NMR, 101 MHz, chloroform: d 137.2, 129.5, 129.0, 126.8, 116.5, 54.4 (d, J =16.0 Hz), 37.3, 23.9 (d, J = 1.8 Hz);

[0081] 19 F NMR, 377 MHz, chloroform: d 58.8;

[0082] HRMS (ESI) m / z calcd. for C 10 H 11 FNO2S [M + H] + 228.0490, found 228.0491.

[0083] Example 6

[0084] The synthetic route is:

[0085] .

[0086] 0.1 mmol of 1b was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0087] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 69%.

[0088] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0089] 1 H NMR, 400 MHz, chloroform: d7.30–7.26 (m, 2H), 7.15–7.09 (m, 2H), 3.92–3.85 (m, 1H), 3.80–3.74 (m, 1H), 3.73–3.67 (m, 1H), 2.96–2.85 (m, 2H);

[0090] 13 C NMR, 101 MHz, chloroform: d 162.8 (d, J = 248.9 Hz), 132.9 (d, J = 3.3 Hz),128.7 (d, J = 8.3 Hz), 116.6 (d, J = 21.9 Hz), 116.3, 54.4 (d, J = 16.1 Hz), 36.7,24.1;

[0091] 19 F NMR, 377 MHz, chloroform: d 59.1, -112.0;

[0092] HRMS (ESI) m / z calcd. for C 10 H 10 F2NO2S [M + H] + 246.0395, found 246.0393.

[0093] Example 7

[0094] The synthetic route is:

[0095] .

[0096] 0.1 mmol of 1c was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine and 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm wavelength.

[0097] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 95%.

[0098] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0099] 1 H NMR, 400 MHz, chloroform: d 7.42–7.39 (m, 2H), 7.26–7.23 (m, 2H), 3.92–3.85 (m, 1H), 3.80–3.74 (m, 1H), 3.72–3.65 (m, 1H), 2.96–2.85 (m, 2H);

[0100] 13 C NMR, 101 MHz, chloroform: d 135.5, 135.0, 129.8, 128.3, 116.2, 54.2 (d, J =16.3 Hz), 36.8, 23.9 (d, J = 1.8 Hz);

[0101] 19 F NMR, 377 MHz, chloroform: d 59.2;

[0102] HRMS (ESI) m / z calcd. for C 10 H 10 ClFNO2S [M + H] + 262.0100, found 262.0092.

[0103] Example 8

[0104] The synthetic route is:

[0105] .

[0106] 0.1 mmol of 1d was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t-Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0107] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 82%.

[0108] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0109] 1 H NMR, 400 MHz, chloroform: d 6.31 (d, J = 8.2 Hz, 2H), 5.93 (d, J = 8.2 Hz,2H), 2.66–2.59 (m, 1H), 2.54–2.48 (m, 1H), 2.45–2.38 (m, 1H), 1.72–1.59 (m,2H);

[0110] 13 C NMR, 101 MHz, chloroform: d 136.1, 132.8, 128.5, 123.2, 116.1, 54.2 (d, J =16.5 Hz), 36.9, 23.9 (d, J = 1.8 Hz);

[0111] 19 F NMR, 377 MHz, chloroform: d 59.2;

[0112] HRMS (ESI) m / z calcd. for C 10 H 10 BrFNO2S [M + H] + 305.9595, found 305.9592.

[0113] Example 9

[0114] The synthetic route is:

[0115] .

[0116] 0.1 mmol of 1e was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine and 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm wavelength.

[0117] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a light yellow oily product with a yield of 83%.

[0118] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0119] 1 H NMR, 400 MHz, chloroform: d 7.22–7.19 (m, 2H), 6.95–6.91 (m, 2H), 3.91–3.83 (m, 1H), 3.81 (s, 3H), 3.78–3.73 (m, 1H), 3.68–3.62 (m, 1H), 2.94–2.83(m, 2H);

[0120] 13 C NMR, 101 MHz, chloroform: d 159.8, 129.0, 128.0, 116.6, 114.8, 55.3, 54.6(d, J = 15.5 Hz), 36.6, 24.1 (d, J = 1.9 Hz);

[0121] 19 F NMR, 377 MHz, chloroform: d 58.9;

[0122] HRMS (ESI) m / z calcd. for C 11 H 13 FNO3S [M + H] +258.0595, found 258.0596.

[0123] Example 10

[0124] The synthetic route is:

[0125] .

[0126] 0.1 mmol of 1f was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0127] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, and a colorless oily product was obtained with a yield of 80%.

[0128] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0129] 1 H NMR, 400 MHz, chloroform: d 7.70 (d, J = 8.1 Hz, 2H), 7.44 (d, J = 8.1 Hz,2H), 3.96–3.89 (m,1H), 3.85–3.79 (m,1H), 3.77–3.74 (m,1H), 2.99–2.88 (m, 2H);

[0130] 13 C NMR, 101 MHz, chloroform: d 140.9, 131.2 (q, J = 32.8 Hz), 127.5, 126.5 (q, J = 3.8 Hz), 123.6 (q, J = 273.3 Hz), 53.9 (d, J = 16.7 Hz), 37.1, 23.7 (d, J = 1.8Hz);

[0131] 19 F NMR, 377 MHz, chloroform: d 59.1, -62.8;

[0132] HRMS (ESI) m / z calcd. for C 11 H 10 F4NO2S [M + H] + 296.0303, found 296.0365.

[0133] Embodiment 11

[0134] The synthetic route is:

[0135] .

[0136] 0.1 mmol of 1h was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0137] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 64%.

[0138] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0139] 1 H NMR, 400 MHz, chloroform: d 8.31 (d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.5 Hz,2H), 4.00–3.92 (m, 1H), 3.89–3.82 (m, 2H), 3.05–2.92 (m, 2H);

[0140] 13 C NMR, 101 MHz, chloroform: d148.3, 143.8, 128.3, 124.8, 115.7, 53.9 (d, J =17.4 Hz), 37.2, 23.8 (d, J = 1.6 Hz);

[0141] 19 F NMR, 377 MHz, chloroform: d 59.6;

[0142] HRMS (ESI) m / z calcd. for C 11 H 10 F4NO2S [M + H] + 296.0303, found 296.0365.

[0143] Example 12

[0144] The synthetic route is:

[0145] .

[0146] 0.1 mmol of 1 g of 2-nitropropene was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0147] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed on silica gel by column chromatography or preparative thin layer chromatography, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 20:1, to obtain a colorless oily product in a yield of 68%.

[0148] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0149] 1 H NMR, 400 MHz, chloroform: d 4.12–4.05 (m, 1H), 3.86 (s, 3H), 3.83–3.76 (m,1H), 3.43–3.37 (m, 1H), 3.04–2.94 (m, 2H);

[0150] 13 C NMR, 101 MHz, chloroform: d 168.4, 115.7, 53.7, 50.1 (d, J = 19.0 Hz), 37.1,18.6 (d, J = 1.4 Hz);

[0151] 19 F NMR, 377 MHz, chloroform: d 59.0;

[0152] HRMS (ESI) m / z calcd. for C6H9FNO4S [M + H] + 210.0231, found 210.0227.

[0153] Example 13

[0154] The synthetic route is:

[0155] .

[0156] 0.1 mmol of 1i was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0157] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 76%.

[0158] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0159] 1 H NMR, 400 MHz, chloroform: d7.42–7.34 (m, 5H), 4.74–4.67 (m, 2H), 4.33–4.27 (m, 1H), 3.80–3.74 (m, 1H), 3.67–3.61 (m, 1H), 2.81–2.69 (m, 2H);

[0160] 13 C NMR, 101 MHz, chloroform: d 135.6, 128.9, 128.8, 128.3, 115.5, 73.2, 69.4,54.1 (d, J = 16.2 Hz), 23.0 (d, J = 2.1 Hz);

[0161] 19 F NMR, 377 MHz, chloroform: d 61.5;

[0162] HRMS (ESI) m / z calcd. for C 11 H 13 FNO3S [M + H] + 258.0595, found 258.0655.

[0163] Embodiment 14

[0164] The synthetic route is:

[0165] .

[0166] 0.1 mmol of 1j was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine and 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm wavelength.

[0167] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 69%.

[0168] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0169] 1 H NMR, 400 MHz, dimethyl sulfoxide: d 7.51 (d, J = 8.7 Hz, 1H), 4.34–4.25 (m,1H), 4.19–4.13 (m, 1H), 4.02–3.95 (m, 1H), 2.90–2.74 (m, 2H), 1.47 (s, 9H);

[0170] 13 C NMR, 101 MHz, dimethyl sulfoxide: d 155.0, 118.0, 79.4, 53.3 (d, J = 13.0 Hz),44.0, 28.5, 23.3 (d, J = 2.7 Hz);

[0171] 19 F NMR, 377 MHz, dimethyl sulfoxide: d 61.0;

[0172] HRMS (ESI) m / z calcd. for C9H 16 FN2O4S [M + H] + 267.0810, found 267.0943.

[0173] Embodiment 15

[0174] The synthetic route is:

[0175] .

[0176] 0.1 mmol of 1k was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0177] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed on silica gel by column chromatography or preparative thin layer chromatography, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 10:1, to obtain a colorless oily product in a yield of 75%.

[0178] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0179] 1 H NMR, 400 MHz, chloroform: d 3.60–3.55 (m, 2H), 2.66 (t, J = 7.0 Hz, 2H),2.37–2.30 (m, 2H);

[0180] 13 C NMR, 101 MHz, chloroform: d 117.3, 48.9 (d, J = 18.4 Hz), 19.9, 15.7;

[0181] 19 F NMR, 377 MHz, chloroform: d 55.1;

[0182] HRMS (EI) m / z calcd. for C4H7FNO2S [M + H] + 152.0177, found 152.0178.

[0183] Example 16

[0184] The synthetic route is:

[0185] .

[0186] 0.1 mmol of 1L was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0187] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified on silica gel by column chromatography or preparative thin layer chromatography, and the eluent was petroleum ether and ethyl acetate in a volume ratio of 50:1 to obtain a colorless oily product in a yield of 62%.

[0188] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0189] 1 H NMR, 400 MHz, chloroform: d 4.49 (d, J = 3.0 Hz, 2H), 3.72 (d, J = 0.8 Hz,2H);

[0190] 13 C NMR, 101 MHz, chloroform: d 114.3, 49.8 (d, J = 21.7 Hz), 17.8;

[0191] 19 F NMR, 377 MHz, chloroform: d 52.7;

[0192] HRMS (EI) m / z calcd. for C3H4FNO2S2[M] + 168.9662, found 168.9662.

[0193] Embodiment 17

[0194] The synthetic route is:

[0195] .

[0196] 0.1 mmol of 1m was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine and 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm wavelength.

[0197] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 94%.

[0198] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0199] 1 H NMR, 400 MHz, chloroform: d 7.46–7.42 (m, 2H), 7.39–7.35 (m, 3H), 3.91–3.82 (m, 2H), 3.11 (q, J = 21.7 Hz, 2H), 1.86 (s, 3H);

[0200] 13 C NMR, 101 MHz, chloroform: d 140.0, 129.3, 128.5, 125.2, 116.5, 60.5(d, J =13.2 Hz), 39.3, 29.4, 25.2 (d, J = 1.8 Hz);

[0201] 19 F NMR, 377 MHz, chloroform: d 66.1;

[0202] HRMS (ESI) m / z calcd. for C 11 H 13 FNO2S [M + H] + 242.0646, found 242.0643.

[0203] Embodiment 18

[0204] The synthetic route is:

[0205] .

[0206] 0.1 mmol of 1n was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t-Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0207] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed on silica gel by column chromatography or preparative thin layer chromatography, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 10:1, to obtain a colorless oily product in 82% yield.

[0208] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0209] 1 H NMR, 400 MHz, chloroform: d 2.44 (t, J = 6.9 Hz, 2H), 2.05–2.00 (m, 2H), 1.91–1.83 (m, 2H), 1.58 (d, J = 1.0 Hz, 6H);

[0210] 13 C NMR, 101 MHz, chloroform: d 118.6, 63.7 (d, J = 10.7 Hz), 36.1, 22.4, 20.2(d, J = 0.9 Hz), 17.3;

[0211] 19 F NMR, 377 MHz, chloroform: d 34.6;

[0212] HRMS (ESI) m / z calcd. for C7H 12 FNNaO2S [M + Na] + 216.0465, found 216.0466.

[0213] Embodiment 19

[0214] The synthetic route is:

[0215] .

[0216] 0.1 mmol of 1o was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0217] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 60%.

[0218] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0219] 1 H NMR, 400 MHz, chloroform: d 7.47–7.40 (m, 5H), 4.44 (dd, J = 10.8, 4.5 Hz,1H), 2.49–2.40 (m, 1H), 2.36–2.24 (m, 3H), 1.78–1.63 (m, 2H), 1.53–1.38 (m,2H);

[0220] 13 C NMR, 101 MHz, chloroform: d 130.2, 129.6, 129.4, 129.2, 118.9, 67.8 (d, J =12.8 Hz), 29.3, 25.6, 24.8, 16.9;

[0221] 19 F NMR, 377 MHz, chloroform: d 45.6;

[0222] HRMS (ESI) m / z calcd. for C 14 H 24 FN2O4S [M + H] + 256.0803, found 256.0658.

[0223] Embodiment 20

[0224] The synthetic route is:

[0225] .

[0226] 0.1 mmol of 1p was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0227] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 92%.

[0228] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0229] 1 H NMR, 400 MHz, chloroform: d 4.02 (d, J = 9.4 Hz, 2H), 3.92–3.88 (m, 4H), 3.04 (s, 2H), 1.45 (s, 9H);

[0230] 13 C NMR, 101 MHz, chloroform: d 155.6, 115.5 81.0, 57.6, 55.5 (d, J = 16.1 Hz),33.1, 28.2, 25.2 (d, J = 1.5 Hz);

[0231] 19 F NMR, 377 MHz, chloroform: d 64.5;

[0232] HRMS (ESI) m / z calcd. for C 11 H 18 FN2O4S [M + H] + 293.0966, found 293.0920.

[0233] Embodiment 21

[0234] The synthetic route is:

[0235] .

[0236] 0.1 mmol of 1q was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0237] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 3:1, to obtain a colorless oily product in a yield of 71%.

[0238] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0239] 1 H NMR, 400 MHz, chloroform: d 3.95 (s, 2H), 3.19 (t, J = 12.2 Hz, 2H), 2.46(t, J = 6.7 Hz, 2H), 2.29–2.21 (m, 2H), 2.17–2.12 (m, 2H), 1.97–1.89 (m, 4H), 1.47 (s, 9H);

[0240] 13 C NMR, 101 MHz, chloroform: d 154.2, 118.5, 80.6, 65.5 (d, J = 9.4 Hz), 31.3,29.6, 28.3, 19.7 (d, J = 0.93 Hz), 17.4.

[0241] 19 F NMR, 377 MHz, chloroform: d 39.3;

[0242] HRMS (ESI) m / z calcd. for C 14 H 24 FN2O4S [M + H] + 335.1436, found 335.1361.

[0243] Embodiment 22

[0244] The synthetic route is:

[0245] .

[0246] 0.1 mmol of 1r was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0247] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 90%.

[0248] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0249] 1 H NMR, 400 MHz, chloroform: d 5.96–5.94 (m, 1H), 5.74–5.71 (m, 1H), 3.90–3.84 (m, 1H), 3.67–3.58 (m, 1H), 3.16–2.99 (m, 2H), 2.83–2.66 (m, 2H);

[0250] 13 C NMR, 101 MHz, chloroform: d 130.8, 129.1, 116.5, 62.5 (d, J = 15.6 Hz),44.8, 34.9, 22.4;

[0251] 19 F NMR, 377 MHz, chloroform: d 46.2;

[0252] HRMS (ESI) m / z calcd. for C7H9FNO2S [M + H] + 190.0333, found 190.0336.

[0253] Embodiment 23

[0254] The synthetic route is:

[0255] .

[0256] 0.1 mmol of 1s was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine, 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0257] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, and then extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over Na2SO4, filtered and concentrated. It was further purified by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 90%.

[0258] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0259] 1 H NMR, 400 MHz, chloroform: d 7.36–7.28 (m, 4H), 4.14–4.05 (m, 2H), 3.64–3.51 (m, 2H), 3.08–2.94 (m, 2H);

[0260] 13 C NMR, 101 MHz, chloroform: d 138.1 (d, J = 1.5 Hz), 137.8, 129.2, 128.3,124.9, 123.4, 116.5, 63.6 (d, J = 15.3 Hz), 43.2, 33.5, 21.9;

[0261] 19 F NMR, 377 MHz, chloroform: d 47.7;

[0262] HRMS (ESI) m / z calcd. for C 11 H 11 FNO2S [M + H] + 240.0490, found 240.0490.

[0263] Embodiment 24

[0264] The synthetic route is:

[0265] .

[0266] 0.1 mmol of 1t was added to a dry Schlenk reaction tube, and then 0.005 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.2 mmol of DABSO, 0.2 mmol of tetramethylguanidine and 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm wavelength.

[0267] Then, 0.3 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour and then extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume fraction of 2:1, to obtain a white solid product with a yield of 64%, mp 168–170 °C.

[0268] The hydrogen spectrum, carbon spectrum, fluorine spectrum and high-resolution mass spectrum data of the product are as follows:

[0269] 1 H NMR, 400 MHz, dichloromethane: d 7.12–7.09 (m, 1H), 6.65–6.62 (m, 1H), 6.57–6.55 (m, 1H), 4.98 (s, 1H), 2.93–2.80 (m, 2H), 2.56–2.08 (m, 8H), 1.85–1.71 (m, 2H), 1.56 (s, 3H), 1.51–1.37 (m, 3H);

[0270] 13 C NMR, 101 MHz, dichloromethane: d 154.4, 137.9, 130.7, 126.9, 115.3, 115.2,113.5, 70.6 (d, J = 6.4 Hz), 45.2, 42.7, 42.5 (d, J = 1.2 Hz), 34.2, 30.2, 27.2,26.1, 25.6, 18.1, 14.9;

[0271] 19 F NMR, 377 MHz, dichloromethane: d 51.7, 36.9;

[0272] HRMS (ESI) m / z calcd. for C 18 H 23 FNNaO3S [M + Na] + 374.1197, found374.1198.

[0273] Embodiment 25

[0274] The synthetic route is:

[0275] .

[0276] 0.1 mmol of 1c was added to a dry Schlenk reaction tube, and then 0.002 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.3 mmol of DABSO, 0.1 mmol of tetramethylguanidine and 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0277] Then, 0.15 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in 81% yield.

[0278] Embodiment 26

[0279] The synthetic route is:

[0280] .

[0281] 0.1 mmol of 1c was added to a dry Schlenk reaction tube, and then 0.01 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.4 mmol of DABSO, 0.4 mmol of tetramethylguanidine and 4.0 mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 hour under irradiation with a blue LED light of 460 nm.

[0282] Then, 0.4 mmol of the selective fluorine reagent was added, and the reaction mixture was stirred for another hour, then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was performed by column chromatography or preparative thin layer chromatography on silica gel, with the eluent being petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a colorless oily product in a yield of 93%.

[0283] The method of the present invention is used to synthesize remote cyanosulfonyl fluorides substituted with various functional groups, and their typical structures and reaction yields are shown above. The disclosed molecular structural formula of the multi-substituted cyanosulfonyl fluoride compound is not intended to limit the protection scope of the present invention.

[0284] It should be noted that when the present invention relates to a numerical range, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. Since the steps and methods used are the same as those in the embodiments, in order to avoid redundant description, the present invention describes a preferred embodiment. Although the preferred embodiments of the present invention have been described, once those skilled in the art know the basic creative concept, they can make other changes and modifications to these embodiments. Therefore, the attached protection scope is intended to be interpreted as including the preferred embodiment and all changes and modifications that fall within the scope of the present invention.

[0285] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the protection scope of the present invention and its equivalent technology, the present invention is also intended to include these modifications and variations.

Claims

1. A method for preparing a cyanosulfonyl fluoride compound, characterized in that: The following steps are involved: In an organic solvent, an oxime ether compound is used as a free radical precursor, a photocatalyst, a sulfur dioxide source and an organic base free radical initiator are added thereto under a protective atmosphere, and the mixture is mixed and stirred under light conditions, so that the oxime ether compound undergoes photocatalytic oxidation and reduction to generate nitrogen free radicals, and CC bond homolytic ring cleavage and free radical SO2 insertion occur; Then, a fluorine source is added, and after a fluorination process, a cyano / fluorosulfonylation reaction of the oxime ether is achieved to obtain a cyanosulfonyl fluoride compound; The general reaction formula is as follows: ； Wherein, R is one of hydrogen, alkyl, aryl, ester and heterocyclic ring, X is one of carbon, oxygen and sulfur, n is one of 1, 2 and 3, and the sulfur dioxide source is 1,4-diazabicyclo[2.2.2]octane-1,4-diamine-1,4-disulfinic acid; The fluorine source is a selective fluorine reagent, the sulfur dioxide source is DABSO, the organic base free radical initiator is tetramethylguanidine, the organic solvent is dichloroethane, and the photocatalyst is 4CzIPN, Eosin Y, TPT, Mes-Acr-Me-ClO4 or Mes-( t -Bu)2Acr-Ph-BF4, the photocatalytic irradiation wavelength is 460nm.

2. The method for preparing cyanosulfonyl fluoride compounds according to claim 1, characterized in that: The molar ratio of the oxime ether compound to the photocatalyst is 1:0.02-0.1, and the molar ratio of the oxime ether compound to the sulfur dioxide source is 1:2-4.

3. The method for preparing cyanosulfonyl fluoride compounds according to claim 1, characterized in that: The molar ratio of the oxime ether compound to the organic base free radical initiator is 1:1-4.

4. The method for preparing cyanosulfonyl fluoride compounds according to claim 1, characterized in that: The molar ratio of the oxime ether compound to the fluorine source is 1:1.5-4.

5. The method for preparing cyanosulfonyl fluoride compounds according to claim 1, characterized in that: The illumination conditions are: irradiation with LED light, the illumination time is 0.8 hours to 1.2 hours, the reaction temperature is room temperature, and the reaction time is 2 hours to 2.5 hours.

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