Dibenzoazepine / dioxodibenzothiazine functionalized allyl sulfonyl fluoride compounds, methods of making and uses thereof

Abstract

This invention discloses a dibenzozazepine / dioxodibenzothiazine-functionalized allyl sulfonyl fluoride compound. This allyl sulfonyl fluoride compound can serve as a highly efficient fluorosulfonylation reagent, reacting with various nucleophiles such as alcohols, phenols, and amines via SuFEx click chemistry to construct structurally diverse sulfonate esters and sulfonamide derivatives, showing significant application potential in medicinal chemistry and functional materials. This invention also discloses a method for preparing the allyl sulfonyl fluoride compound. Using readily available terminal aryl alkynes and bromomethylsulfonyl fluoride as raw materials, the target product is synthesized in one step through a tandem reaction of free radical addition / cyclization / oxidation / deprotonation under alkaline conditions, inert gas protection, and blue light irradiation. This method has the advantages of mild conditions, simple steps, and high atom economy, and can specifically generate Z-configured allyl sulfonyl fluoride products.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology, specifically relating to a dibenzozazepine / dioxodibenzothiazine functionalized allyl sulfonyl fluoride compound, its preparation method, and its application. Background Technology

[0002] Sulfonyl fluoride compounds, especially allyl sulfonyl fluorides, are key building blocks for next-generation click chemistry (SuFEx) and have significant applications in medicinal chemistry, chemical biology, and materials science. However, existing methods for synthesizing allyl sulfonyl fluorides have limitations, mainly relying on multi-step transformations of pre-constructed allyl skeletons (such as allyl bromide and allyl sulfone) or further derivatization of simple allyl sulfonyl fluorides. These methods are not cost-effective, have limited structural diversity, and the starting materials are not readily available.

[0003] Alkynes, as readily available sp-hybridized carbon precursors, have been used in addition reactions with fluorosulfonyl radicals (·SO2F) to construct vinylsulfonyl fluorides. However, a method for directly constructing allylsulfonyl fluoride skeletons from alkynes in one step has not been reported, which limits the efficient acquisition of structurally diverse allylsulfonyl fluorides from more basic raw materials. Summary of the Invention

[0004] The purpose of this invention is to provide a method for synthesizing dibenzodiazepine / dioxodibenzothiodiazepine functionalized allyl / vinylsulfonyl fluoride compounds that is mild, simple, uses readily available raw materials, has a wide range of applicable substrates, and exhibits high stereoselectivity.

[0005] The present invention adopts the following technical solution:

[0006] An allyl sulfonyl fluoride compound, the structure of which is shown in general formula I:

[0007] (I)

[0008] Among them, R 1 It is one of trifluoroacetyl, methyl, or isopropyl; X is one of CH2 or SO2; Ar 1 It is one of the following: methyl-substituted aryl, isopropyl-substituted aryl, methoxy-substituted aryl, trifluoromethyl-substituted aryl, ester-substituted aryl, halogen-substituted aryl, cyano-substituted aryl, phenyl-substituted aryl, pyridyl, naphthyl, and tert-butyl-substituted aryl; Ar 2 It is one of the following: halogen-substituted aryl, ester-substituted aryl, or methyl-substituted aryl.

[0009] A method for preparing the above-mentioned allyl sulfonyl fluoride compounds includes the following steps: reacting alkynes, bromomethyl sulfonyl fluoride (BMSF), and a base under solvent, inert gas, base, and photocatalytic reaction conditions.

[0010] Furthermore, the alkyne is a terminal aryl alkyne.

[0011] Preferably, the alkyne has a structure such as general formula II:

[0012] (II)

[0013] Among them, R 1 It is one of trifluoroacetyl, methyl, or isopropyl; X is one of CH2 or SO2; Ar 1 It is one of the following: methyl-substituted aryl, isopropyl-substituted aryl, methoxy-substituted aryl, trifluoromethyl-substituted aryl, ester-substituted aryl, halogen-substituted aryl, cyano-substituted aryl, phenyl-substituted aryl, pyridyl, naphthyl, and tert-butyl-substituted aryl; Ar 2 It is one of the following: halogen-substituted aryl, ester-substituted aryl, or methyl-substituted aryl.

[0014] Furthermore, the molar ratio between the compound of formula II, bromomethylsulfonyl fluoride, and the base is 1:2:2.5; the reaction temperature is 40℃, and the reaction time is 12 h.

[0015] Furthermore, the bromomethylsulfonyl fluoride (BMSF) has the structural formula BrCH2SO2F.

[0016] Furthermore, the solvent is dichloromethane; the amount of solvent used is in the volume ratio of the molar amount of compound II to the solvent as 1 mmol: 10 mL.

[0017] Furthermore, the light source used for the photocatalytic reaction was 30 W of 465 nm blue light, and the photocatalyst was fac-Ir(ppy)3; the amount of photocatalyst used was 1.0 mol of the compound of formula II.

[0018] Furthermore, the above reaction process can be represented as:

[0019] .

[0020] Application of the above-mentioned allyl sulfonyl fluoride compound in fluorosulfonation.

[0021] In the aforementioned application, the specific method is as follows: reacting the substrate with an allyl sulfonyl fluoride compound in an organic solvent; the substrate is a hydroxyl alcohol, phenol, ammonia, or a secondary amine; the reaction temperature is 25~80℃, and the reaction time is 1~24 h.

[0022] The beneficial effects of this invention are as follows:

[0023] (1) The raw materials used in this invention are simple and readily available. Commercially available or easily prepared terminal aryl alkynes and inexpensive BMSF are used as raw materials, without the need for a pre-prepared allyl skeleton.

[0024] (2) The reaction conditions of the present invention are mild. Visible light catalysis is used, the reaction conditions are mild, and the operation is simple.

[0025] (3) This invention has high efficiency and high selectivity. The reaction has excellent regioselectivity and stereoselectivity, specifically generating Z-configuration allyl sulfonyl fluoride products.

[0026] (4) The substrates of the present invention have a wide range of applications: the reaction has good compatibility with various electron-donating and electron-withdrawing substituents on the aromatic ring as well as nitrogen protecting groups of different sizes, and can be applied to the synthesis of two important heterocyclic skeletons: dibenzodiazepines and dioxodibenzothiodiazepines.

[0027] (5) The synthesis of the present invention is highly practical: the synthesized sulfonyl fluoride products can be successfully reacted with a variety of nucleophiles (alcohols, phenols, amines, etc.) through SuFEx click chemistry, and can efficiently construct a variety of sulfonate esters and sulfonamide derivatives, which have great application potential in drug molecule modification and functional material preparation. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of the reaction principle of the present invention.

[0029] Figure 2 This is the hydrogen spectrum of the compound obtained in Example 1 of the present invention.

[0030] Figure 3 This is the hydrogen spectrum of the compound obtained in Example 11 of this invention.

[0031] Figure 4 This is the carbon spectrum of the compound obtained in Example 11 of the present invention.

[0032] Figure 5 This is the fluorine spectrum of the compound obtained in Example 11 of the present invention.

[0033] Figure 6 This is the hydrogen spectrum of the compound obtained in Example 13 of this invention.

[0034] Figure 7 This is the hydrogen spectrum of the compound obtained in Example 15 of this invention.

[0035] Figure 8 This is the carbon spectrum of the compound obtained in Example 15 of the present invention.

[0036] Figure 9 This is the fluorine spectrum of the compound obtained in Example 15 of the present invention.

[0037] Figure 10This is the hydrogen spectrum of the compound obtained in Example 20 of the present invention. Detailed Implementation

[0038] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0039] This invention is the first to apply the fluorosulfonylmethyl radical (·CH₂SO₂F) to the functionalization of alkynes, achieving a one-step, highly efficient construction of an allyl sulfonyl fluoride skeleton with a Z-configuration, fused seven-membered nitrogen heterocycle (dibenzozazepine / dioxodibenzothiazine), starting from readily available terminal aryl alkynes and BMSF, via a photocatalytic tandem radical addition / cyclization / oxidation / deprotonation reaction. This method avoids the use of pre-prepared allyl frameworks and exhibits excellent atom economy and step economy. The reaction principle of this invention is as follows: Figure 1 As shown.

[0040] Example 1

[0041] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (66.2 mg, 83%).

[0042] The reaction process is as follows:

[0043]

[0044] The structural characterization data of the product are as follows:

[0045] 1 H NMR (400 MHz, CDCl3) δ 7.53-7.49 (m, 3H), 7.45-7.41 (m, 2H), 7.44-7.42 (m, 2H), 7.14 (d, J = 8.9 Hz, 1H), 6.11 (dd, J = 10.2, 5.6 Hz, 1H), 5.90 (d, J = 17.0 Hz, 1H), 4.35 (d, J = 17.0 Hz, 1H), 4.16-4.04 (m, 2H). like Figure 2 As shown.

[0046] 13C NMR (150 MHz, CDCl3) δ 156.1 (q, J C-F = 35.9 Hz), 148.7, 136.9,136.8, 135.3, 133.1, 130.4, 130.3, 129.6, 129.5, 128.8, 128.2, 127.9, 127.7,116.4 (q, J C-F = 289.0 Hz), 116.3, 51.9 (d, J C-F = 17.3 Hz), 50.9.

[0047] 19 F NMR (564 MHz, CDCl3) δ 54.5, -67.9, -69.5.

[0048] HRMS (ESI-TLQ) m / z: [M + NH4] + calcd for C 18 H 17 F4N2O3S, 417.0890; found, 417.0887.

[0049] Example 2

[0050] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (61.8 mg, 70%).

[0051] The reaction process is as follows:

[0052]

[0053] The structural characterization data of the product are as follows:

[0054] 1H NMR (400 MHz, CDCl3) δ 7.52-7.48 (m, 3H), 7.42 (d, J = 6.2 Hz,1H), 7.21 (d, J = 8.1 Hz, 2H), 7.07 (d, J = 7.5 Hz, 1H), 6.10 (dd, J = 10.1,5.6 Hz, 1H), 5.87 (d, J = 16.7 Hz, 1H), 4.31 (d, J = 16.7 Hz, 1H), 4.15-4.01(m, 2H), 2.97-2.90 (m, 1H), 1.27-1.24 (m, 6H).

[0055] 13 C NMR (150 MHz, CDCl3) δ 156.1 (q, J C-F = 35.9 Hz),149.1, 149.0,136.9, 135.1, 130.4, 130.3, 130.2, 128.8, 128.0, 127.7, 127.6, 127.5, 116.4(q, J C-F = 289.0 Hz), 116.3, 116.0, 52.0 (d, J C-F = 17.5 Hz), 50.8, 33.9, 24.124.0.

[0056] 19 F NMR (564 MHz, CDCl3) δ 54.4, -67.9, -69.5.

[0057] HRMS (ESI-TLQ) m / z: [M + NH4] + calcd for C 21 H 23 F4N2O3S, 459.1360; found,459.1357.

[0058] Example 3

[0059] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (64.7 mg, 78%).

[0060] The reaction process is as follows:

[0061]

[0062] The structural characterization data of the product are as follows:

[0063] 1 H NMR (400 MHz, CDCl3) δ 7.53-7.47 (m, 3H), 7.42 (d, J = 7.3 Hz, 1H), 7.21 (s, 1H), 7.14 (d, J = 7.8 Hz, 1H), 7.02 (d, J = 7.9 Hz, 1H), 6.09 (dd, J = 10.4, 5.5 Hz, 1H), 5.86 (d, J = 16.9 Hz, 1H), 4.31 (d, J = 16.9 Hz, 1H), 4.14-4.01 (m, 2H), 2.36 (s, 3H).

[0064] 13 C NMR (150 MHz, CDCl3) δ 156.1 (q, J C-F = 35.9 Hz), 149.9, 138.0,136.9, 135.0, 130.3, 130.3, 130.2, 130.0, 129.9, 128.7, 127.8, 127.7, 126.8,116.4 (q, J C-F = 289.0 Hz), 115.9. 51.9 (d, J C-F = 17.5 Hz), 50.7, 21.0.

[0065] 19 F NMR (564 MHz, CDCl3) δ 54.4, -67.9, -69.5.

[0066] HRMS (ESI-TLQ) m / z: [M + NH4]+ calcd for C 19 H 19 F4N2O3S, 436.0601; found, 436.0592.

[0067] Example 4

[0068] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (58.3 mg, 68%).

[0069] The reaction process is as follows:

[0070]

[0071] The structural characterization data of the product are as follows:

[0072] 1 H NMR (400 MHz, CDCl3) δ 7.53-7.47 (m, 3H), 7.43 (d, J = 7.3 Hz, 1H), 7.05 (d, J = 8.6 Hz, 1Hz), 6.93 (d, J = 2.7 Hz, 1H), 6.94-6.86 (m, 1H), 6.12(dd, J = 10.1, 5.6 Hz, 1H), 5.83 (d, J = 16.6 Hz, 1H), 4.28 (d, J = 16.6 Hz, 1H), 4.14-4.00 (m, 2H), 3.84 (s, 3H).

[0073] 13 C NMR (150 MHz, CDCl3) δ 159.1, 156.0 (q, J C-F = 35.1 Hz), 148.7,136.9, 136.6, 136.2, 130.3, 129.1, 128.7, 127.7, 126.8, 125.0, 116.4, 116.4(q, J C-F = 289.0 Hz), 115.2, 114.6, 55.7, 51.9 (d, J C-F= 17.5 Hz), 50.5.

[0074] 19 F NMR (564 MHz, CDCl3) δ 54.5, -67.9, -69.6.

[0075] HRMS (ESI-TLQ) m / z: [M + NH4] + calcd for C 19 H 19 F4N2O4S, 447.0996; found, 447.0995.

[0076] Example 5

[0077] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (70.7 mg, 77%).

[0078] The reaction process is as follows:

[0079]

[0080] The structural characterization data of the product are as follows:

[0081] 1 H NMR (400 MHz, CDCl3) δ 7.66 (s, 1H), 7.61-7.55 (m, 3H), 7.54-7.50(m, 1H), 7.49-7.45 (m, 1H), 7.29 (d, J = 8.2 Hz, 1H), 6.18 (dd, J = 9.7, 6.0Hz, 1H), 5.97 (d, J = 17.2 Hz, 1H), 4.40 (d, J = 17.4 Hz, 1H), 4.18-4.02 (m,2H).

[0082] 13 C NMR (150 MHz, CDCl3) δ 156.2 (q, J C-F = 37.0 Hz),147.4, 137.2,136.8, 136.1, 136.0, 130.8, 130.7 (q, JC-F = 32.8 Hz), 130.6, 128.9, 128.7,127.8, 126.3 (q, J C-F = 3.2 Hz), 126.1 (q, J C-F = 3.2 Hz), 124.6, 122.8,118.0,116.3 (q, J C-F = 288.0 Hz), 51.8 (d, J C-F = 16.3 Hz), 50.7.

[0083] 19 F NMR (564 MHz, CDCl3) δ 54.9, -62.6, -67.0, -68.0, -68.3, -69.5.

[0084] HRMS (ESI-TLQ) m / z: [M + NH4] + calcd for C 19 H 16 F7N2O3S, 485.0764; found, 485.0760.

[0085] Example 6

[0086] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (56.8 mg, 67%).

[0087] The reaction process is as follows:

[0088]

[0089] The structural characterization data of the product are as follows:

[0090] 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.56-7.48 (m, 3H), 7.47-7.44 (m, 1H), 7.27-7.21 (m, 2H), 6.19 (dd, J = 9.7,5.9 Hz, 1H), 5.96 (d, J = 17.5 Hz, 1H), 4.39 (d, J = 17.4 Hz, 1H), 4.15-4.03(m, 2H), 3.96 (s, 3H).

[0091] 13 C NMR (100 MHz, CDCl3) δ 166.22, 156.2 (q, J C-F = 36.4 Hz),147.8,138.1, 136.8, 136.4, 135.5, 130.6, 130.5, 130.4, 130.2, 130.1, 128.9, 128.3,127.8, 117.8, 116.3 (q, J C-F = 289.8 Hz), 52.6, 51.8 (d, J C-F = 18.0 Hz), 50.9.

[0092] 19 F NMR (564 MHz, CDCl3) δ 54.8, -66.9, -67.9, -69.5.

[0093] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 20 H 15 F4NO5SNa, 480.0499; found, 480.0494.

[0094] Example 7

[0095] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (71.7 mg, 75%).

[0096] The reaction process is as follows:

[0097]

[0098] The structural characterization data of the product are as follows:

[0099] 1 H NMR (400 MHz, CDCl3) δ 7.59-7.51 (m, 3H), 7.51-7.48 (m, 1H), 7.47-7.42 (m, 2H), 7.02 (d, J = 8.3 Hz, 1H), 6.13 (dd, J = 9.8, 6.0 Hz, 1H), 5.85(d, J = 17.1 Hz, 1H), 4.28 (d, J = 17.0 Hz, 1H), 4.13-4.02 (m, 2H).

[0100] 13 C NMR (150 MHz, CDCl3) δ 156.1 (q, J C-F = 37.1 Hz), 147.4, 137.0,136.8, 136.2, 132.4, 132.1, 132.0, 130.6, 130.6, 129.5, 128.8, 127.8, 121.6,117.5, 116.3 (q, J C-F = 288.9 Hz), 51.8 (d, J C-F = 18.6 Hz), 50.5.

[0101] 19 F NMR (564 MHz, CDCl3) δ 54.9, -68.0, -69.6.

[0102] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 18 H 12 BrF4NO3SNa, 496.9976; found, 496.9978.

[0103] Example 8

[0104] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (39 mg, 46%).

[0105] The reaction process is as follows:

[0106]

[0107] The structural characterization data of the product are as follows:

[0108] 1 H NMR (400 MHz, CDCl3) δ 7.74 (s, 1H), 7.62 (d, J = 7.9 Hz, 1H), 7.59-7.55 (m, 2H), 7.53-7.45 (m, 2H), 7.28 (d, J = 7.5 Hz, 1H), 6.17 (dd, J =9.5, 6.2 Hz, 1H), 5.96 (d, J = 17.5 Hz, 1H), 4.39 (d, J = 17.7 Hz, 1H), 4.15-4.02 (m, 2H).

[0109] 13 C NMR (150 MHz, CDCl3) δ 156.1 (q, J C-F = 36.4 Hz), 146.5, 138.4,136.5, 136.5, 135.6, 133.1, 132.3, 130.8, 130.7, 128.9, 128.8, 127.8, 118.6,117.7, 116.1 (q, J C-F = 288.0 Hz), 112.3, 51.5 (d, J C-F = 18.6 Hz), 50.7.

[0110] 19 F NMR (564 MHz, CDCl3) δ 55.2, -62.5, -68.0, -69.5.

[0111] HRMS (ESI-TLQ) m / z: [M + Na] +calcd for C 19 H 12 F4N2O3SNa, 447.0396; found, 447.0395.

[0112] Example 9

[0113] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (61.6 mg, 65%).

[0114] The reaction process is as follows:

[0115]

[0116] The structural characterization data of the product are as follows:

[0117] 1 H NMR (400 MHz, CDCl3) δ 7.61-7.58 (m, 2H), 7.57 (s, 1H), 7.56-7.51(m, 4H), 7.49-7.44 (m, 3H), 7.41-7.37 (m, 1H), 7.21 (d, J = 7.9 Hz, 1H), 6.18 (dd, J = 10.1, 5.6 Hz, 1H), 5.94 (d, J = 17.1 Hz, 1H), 4.38 (d, J = 17.0 Hz, 1H), 4.17-4.02 (m, 2H).

[0118] 13 C NMR (100 MHz, CDCl3) δ 156.1 (q, J C-F = 36.2 Hz), 148.7, 141.4,139.9, 136.9, 136.8, 135.7, 132.0, 130.8, 130.4, 129.1, 128.8, 128.5, 128.2,128.0, 127.8, 127.2, 116.5, 116.4 (q, J C-F = 289.8 Hz), 51.9 (d, J C-F = 17.1Hz), 50.8.

[0119] 19 F NMR (564 MHz, CDCl3) δ 54.6, -67.9, -69.4.

[0120] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 24 H 17 F4NO3SNa, 498.0757; found, 498.0754.

[0121] Example 10

[0122] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (17 mg, 21%).

[0123] The reaction process is as follows:

[0124]

[0125] The structural characterization data of the product are as follows:

[0126] 1 H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 3.1 Hz, 1H), 7.75 (d, J = 7.9Hz, 1H), 7.58-7.53 (m, 2H), 7.53-7.48 (m, 2H), 7.30-7.26 (m, 1H), 6.12 (dd, J = 10.3, 5.5 Hz, 1H), 6.03 (d, J = 17.7 Hz, 1H), 4.42 (d, J = 17.7 Hz, 1H), 4.19-4.04 (m, 2H).

[0127] 13 C NMR (150 MHz, CDCl3) δ 156.3 (q, J C-F= 35.9 Hz), 152.9, 150.1,146.4, 137.3, 136.8, 136.2, 131.7, 130.8, 130.6, 128.7, 128.2, 123.0, 117.5,116.4 (q, J C-F = 288.9 Hz), 53.4, 51.8 (d, J C-F = 18.6 Hz).

[0128] 19 F NMR (564 MHz, CDCl3) δ 54.9, -68.0, -69.6.

[0129] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 17 H 12 F4N2O3SNa, 423.0396; found, 423.0392.

[0130] Example 11

[0131] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (9.5 mg, 11%).

[0132] The reaction process is as follows:

[0133]

[0134] The structural characterization data of the product are as follows:

[0135] 1 H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.1 Hz, 1H), 7.87-7.80 (m, 2H), 7.60-7.54 (m, 2H), 7.53-7.48 (m, 5H), 6.53 (d, J = 17.2 Hz, 1H), 6.24 (dd, J= 10.5, 4.9 Hz, 1H), 4.70 (d, J= 17.1 Hz, 1H), 4.23-4.07 (m, 2H). like Figure 3 As shown.

[0136] 13 C NMR (150 MHz, CDCl3) δ 156.3 (q, J C-F = 36.1 Hz), 149.4, 137.9,136.5, 133.6, 132.7, 130.7, 130.4, 130.3, 129.1, 128.8, 128.2, 128.1, 127.6,127.5, 126.9, 122.3, 116.7, 116.5 (q, J C-F = 289.0 Hz), 52.1 (d, J C-F = 18.6Hz), 49.3. For example... Figure 4 As shown.

[0137] 19 F NMR (564 MHz, CDCl3) δ 54.5, -67.8, -69.5. (e.g.) Figure 5 As shown.

[0138] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 22 H 15 F4NO3SNa, 472.0600; found, 472.0599.

[0139] Example 12

[0140] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (53.3 mg, 62%).

[0141] The reaction process is as follows:

[0142]

[0143] The structural characterization data of the product are as follows:

[0144] 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 10.0 Hz, 2H), 7.42-7.37 (m,2H), 7.36-7.29 (m, 2H), 7.14 (d, J = 7.3 Hz, 1H), 6.15-6.09 (m, 1H), 5.90 (d,J = 17.0 Hz, 1H), 4.33 (d,J = 17.0 Hz, 1H), 4.16-4.05 (m, 2H).

[0145] 13 C NMR (100 MHz, CDCl3) δ 156.0 (q, J C-F = 36.0 Hz), 147.4, 138.5,136.3, 135.3, 134.7, 132.8, 130.4, 129.8, 129.7, 129.1, 128.8, 128.3, 127.9,117.0, 116.3 (q, J C-F = 290.2 Hz), 52.1 (d, J C-F = 19.5 Hz), 50.7.

[0146] 19 F NMR (564 MHz, CDCl3) δ 54.6, -67.9, -69.5.

[0147] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 18 H 12 ClF4NO3SNa, 456.0054; found, 456.0048.

[0148] Example 13

[0149] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (37.7 mg, 41%).

[0150] The reaction process is as follows:

[0151]

[0152] The structural characterization data of the product are as follows:

[0153] 1 H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.2 Hz, 1H), 8.14 (s, 1H), 7.52 (d, J = 8.2 Hz, 1H), 7.44 (d, J = 9.3 Hz, 1H), 7.37-7.30 (m, 2H), 7.14 (d, J = 6.5 Hz, 1H), 6.21-6.12 (m, 1H), 5.93 (d, J = 17.8 Hz, 1H), 4.35 (d, J =16.4 Hz, 1H), 4.14-4.03 (m, 2H), 3.95 (s, 3H). like Figure 6 As shown.

[0154] 13 C NMR (150 MHz, CDCl3) δ 165.44, 155.8 (q, J C-F = 35.9 Hz), 147.6,140.7, 137.2, 134.8, 132.7, 132.2, 131.7, 129.9, 129.7, 129.6, 128.4, 128.0,127.9, 117.2, 116.3 (q, J C-F = 289.0 Hz), 52.9, 51.7 (d, J C-F = 18.6 Hz), 50.7.

[0155] 19 F NMR (564 MHz, CDCl3) δ 54.6, -67.9, -69.6.

[0156] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 20 H 15 F4NO5SNa, 480.0499; found, 480.0495.

[0157] Example 14

[0158] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (60 mg, 71%).

[0159] The reaction process is as follows:

[0160]

[0161] The structural characterization data of the product are as follows:

[0162] 1 H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 1H), 7.59-7.52 (m, 2H), 7.52-7.46 (m, 1H), 7.45-7.38 (m, 2H), 7.28 (s, 1H), 6.18 (t, J = 7.7 Hz, 1H), 4.22 (d, J = 7.8 Hz, 2H), 3.34 (s, 3H), 1.36 (s, 9H).

[0163] 13 C NMR (100 MHz, CDCl3) δ 156.4, 149.2, 138.0, 137.1, 136.5, 135.4,131.1, 130.5, 129.4, 129.3, 127.7, 127.6, 126.0, 118.6, 51.7 (d,J C-F = 18.4Hz), 38.7, 35.3, 31.1.

[0164] 19 F NMR (564 MHz, CDCl3) δ 55.0.

[0165] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 20 H 22 FNO4S2Na, 446.0866; found, 446.0858.

[0166] Example 15

[0167] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (60.2 mg, 68%).

[0168] The reaction process is as follows:

[0169]

[0170] The structural characterization data of the product are as follows:

[0171] 1 H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 1H), 7.59-7.54 (m, 2H), 7.37 (d, J = 2.1 Hz, 1H), 7.21-7.15 (m, 1H), 7.01-6.97 (m, 1H), 6.20 (t, J =7.7 Hz, 1H), 4.27-4.21 (m, 2H), 3.33 (s, 3H), 1.36 (s, 9H). like Figure 7 As shown.

[0172] 13 C NMR (100 MHz, CDCl3) δ 163.4, 160.9, 156.6, 148.1, 138.8 (d, J C-F =8.4 Hz), 137.2, 134.8, 134.1 (d, J C-F = 3.6 Hz), 132.8 (d, J C-F = 9.6 Hz),127.9, 126.1, 119.2, 118.1, 117.9, 116.4, 116.2, 51.6 (d, J C-F = 18.7 Hz), 38.8, 35.3, 31.2. For example... Figure 8 As shown.

[0173] 19 F NMR (564 MHz, CDCl3) δ 55.2, -109.9. (e.g.) Figure 9 As shown.

[0174] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 20 H 21 F2NO4S2Na, 464.0772; found, 464.0776.

[0175] Example 16

[0176] At 40 °C, a 10 mL reaction tube was filled with alkyne substrate (0.2 mmol), BMSF (0.4 mmol), NaHCO3 (0.5 mmol), fac-Ir(ppy)3 (0.002 mmol), and dichloromethane (2.0 mL). The mixture was reacted under 30 W blue light for 12 hours. The resulting mixture was then concentrated under vacuum, and the residue was purified by column chromatography to give the product, an allyl sulfonyl fluoride compound (59.5 mg, 66%).

[0177] The reaction process is as follows:

[0178]

[0179] The structural characterization data of the product are as follows:

[0180] 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.6 Hz, 1H), 7.60-7.43 (m, 4H), 7.38 (d, J = 7.7 Hz, 2H), 6.16 (t, J = 7.6 Hz, 1H), 4.63-4.52 (m, 1H), 4.27-4.05 (m, 2H), 1.50 (d, J = 6.2 Hz, 3H), 1.35 (s, 9H), 1.04 (d, J = 6.8 Hz, 3H).

[0181] 13 C NMR (100 MHz, CDCl3) δ 156.1, 149.9, 139.0, 138.2, 135.5, 133.9,132.7, 130.7, 129.7, 129.5, 127.6, 127.2, 126.1, 117.7, 53.7, 52.2 (d, J C-F =18.3 Hz), 35.2, 31.2, 24.7, 21.5.

[0182] 19F NMR (564 MHz, CDCl3) δ 55.2.

[0183] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 22 H 26 FNO4S2Na, 474.1179; found, 474.1175.

[0184] Example 17

[0185] The application of allyl sulfonyl fluoride compounds as fluorosulfonylating agents involves mixing allyl sulfonyl fluoride compounds with primary secondary amines or compounds containing phenolic hydroxyl groups to undergo hexavalent hexafluoro exchange to obtain various compounds.

[0186] The following experiment was conducted in this embodiment:

[0187] A mixture of (Z)-9-methyl-5-trifluoroacetyl-5,6-dihydrodibenzo[b,e]aza-11-ethylsulfonyl fluoride (41.7 mg, 0.1 mmol), methyl maltol (15.2 mg, 0.12 mmol), and cesium carbonate (39.0 mg, 0.12 mmol) was dissolved in acetonitrile (2.0 mL). The reaction mixture was stirred in an oil bath at 50 °C for 8 hours to ensure complete conversion. The crude product was concentrated under reduced pressure and purified by rapid column chromatography to give the derivatized product (33.6 mg, 65% yield).

[0188]

[0189] The structural characterization data of the product are as follows:

[0190] 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 5.7 Hz, 1H), 7.63 (d, J = 8.6Hz, 1H), 7.50-7.43 (m, 2H), 7.38 (d, J = 7.8 Hz, 1H), 7.29 (s, 1H), 7.10 (d,J = 7.8 Hz, 1H), 7.00 (d, J = 7.9 Hz, 1H), 6.42 (d, J = 5.7 Hz, 1H), 6.34 (dd, J = 10.2, 5.9 Hz, 1H), 5.87 (d, J = 17.0 Hz, 1H), 4.50 (d, J = 8.8 Hz,1H), 4.38-4.27 (m, 2H), 2.50 (s, 3H), 2.34 (s, 3H).

[0191] 13 C NMR (100 MHz, CDCl3) δ 172.5, 163.2, 156.3 (q, J C-F = 35.4 Hz),154.4, 146.9, 138.9, 137.6, 137.5, 136.9, 135.8, 130.2, 130.0, 129.9, 129.8,129.7, 129.4, 127.6, 127.3, 118.7, 117.6, 116.4 (q, J C-F = 288.5 Hz), 54.7, 50.8, 21.0, 16.0.

[0192] 19 F NMR (564 MHz, CDCl3) δ -72.6, -74.1.

[0193] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 25 H 20 F3NO6SNa 542.0856; found,542.0852.

[0194] Example 18

[0195] The application of allyl sulfonyl fluoride compounds as fluorosulfonylating agents involves mixing allyl sulfonyl fluoride compounds with primary secondary amines or compounds containing phenolic hydroxyl groups to undergo hexavalent hexafluoro exchange to obtain various compounds.

[0196] The following experiment was conducted in this embodiment:

[0197] A mixture of (Z)-9-methyl-5-trifluoroacetyl-5,6-dihydrodibenzo[b,e]aza-11-ethylsulfonyl fluoride (41.7 mg, 0.1 mmol), ammonia (71.5 μL, 1.0 mmol), and pyridine (16 μL, 0.2 mmol) was added to acetonitrile (2 mL), and the reaction was stirred at 60 °C for 12 hours. The resulting mixture was concentrated, and the residue was purified by column chromatography to give the derivatized product (30.9 mg, 81%).

[0198] The reaction process is as follows:

[0199]

[0200] The structural characterization data of the product are as follows:

[0201] 1 H NMR (400 MHz, DMSO) δ 7.60 (d, J = 5.3 Hz, 1H), 7.58-7.52 (m, 3H), 7.34 (s, 1H), 7.18 (s, 2H), 7.15-7.11 (m, 2H), 6.13 (t, J = 7.7 Hz, 1H), 5.68(d, J = 17.6 Hz, 1H), 4.40 (d, J = 16.7 Hz, 1H), 3.64 (d, J = 8.2 Hz, 2H), 2.32 (s, 3H).

[0202] 13 C NMR (100 MHz, DMSO) δ 155.0 (q, J C-F = 35.0 Hz), 143.3, 137.2,136.9, 136.5, 135.6, 129.8, 129.7, 129.7, 129.6, 129.3, 128.9, 127.8, 127.5,121.8, 116.1 (q, J C-F = 288.9 Hz), 55.3, 50.4, 20.5.

[0203] 19 F NMR (564 MHz, DMSO) δ -67.1, -68.7.

[0204] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C19 H 17 F3N2O3SNa 433.0804; found, 433.0801.

[0205] Example 19

[0206] The application of allyl sulfonyl fluoride compounds as fluorosulfonylating agents involves mixing allyl sulfonyl fluoride compounds with primary secondary amines or compounds containing phenolic hydroxyl groups to undergo hexavalent hexafluoro exchange to obtain various compounds.

[0207] The following experiment was conducted in this embodiment:

[0208] A mixture of (Z)-9-methyl-5-trifluoroacetyl-5,6-dihydrodibenzo[b,e]aza-11-ethylsulfonyl fluoride (41.7 mg, 0.1 mmol), estrone (54 mg, 0.2 mmol), and potassium hydroxide (11 mg, 0.2 mmol) was added to acetonitrile (2 mL), and the reaction was stirred at room temperature for 12 hours. The resulting mixture was concentrated, and the residue was purified by column chromatography to give the derivatized product (45.6 mg, 69%).

[0209] The reaction process is as follows:

[0210]

[0211] The structural characterization data of the product are as follows:

[0212] 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 3.3 Hz, 1H), 7.48-7.43 (m, 2H),7.42-7.38 (m, 1H), 7.33 (d, J = 8.6 Hz, 1H), 7.24 (s, 1H), 7.14-7.06 (m, 2H),7.04-6.99 (m, 2H), 6.15 (dd, J = 10.1, 5.7 Hz, 1H), 5.85 (d, J = 16.6 Hz,1H), 4.31 (d, J = 17.0 Hz, 1H), 4.02-3.89 (m, 2H), 2.95-2.90 (m, 2H), 2.56-2.48 (m, 1H), 2.41 (d, J = 12.0 Hz, 1H), 2.35 (s, 3H), 2.29 (d, J = 16.0 Hz,1H), 2.21-2.13 (m, 1H), 2.12-1.95 (m, 4H), 1.69-1.60 (m, 2H), 1.53-1.45 (m,3H), 0.92 (s, 3H)。

[0213] 13 C NMR (150 MHz, CDCl3) δ 156.1 (q, J C-F = 35.4 Hz), 147.4, 147.3,139.4, 139.1, 137.8, 137.4, 136.9, 135.6, 130.1, 130.1, 130.0, 129.9, 129.8,129.2, 127.7, 127.5, 127.2, 122.1, 119.2, 118.1, 116.4 (q, J C-F = 288.8 Hz),113.0, 51.4, 50.8, 50.6, 48.0, 44.3, 38.0, 36.0, 31.7, 29.5, 26.3, 25.9,21.7, 21.1, 14.0。

[0214] 19 F NMR (564 MHz, CDCl3) δ -67.9, -69.4。

[0215] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 37 H36 F3NO5SNa 686.2158; found, 686.2161.

[0216] Example 20

[0217] The application of allyl sulfonyl fluoride compounds as fluorosulfonylating agents involves mixing allyl sulfonyl fluoride compounds with primary secondary amines or compounds containing phenolic hydroxyl groups to undergo hexavalent hexafluoro exchange to obtain various compounds.

[0218] The following experiment was conducted in this embodiment:

[0219] A mixture of (Z)-9-methyl-5-trifluoroacetyl-5,6-dihydrodibenzo[b,e]aza-11-ethylenesulfonyl fluoride (41.7 mg, 0.1 mmol), 1-(2-pyrimidinyl)piperazine (18 mg, 0.11 mmol) and cesium carbonate (65.0 mg, 0.2 mmol) was added to acetonitrile (2 mL), and the reaction was stirred at room temperature for 10 hours. The resulting mixture was concentrated, and the residue was purified by column chromatography to give the derivatized product (40.6 mg, 73%).

[0220] The reaction process is as follows:

[0221]

[0222] 1 H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 4.8 Hz, 2H), 7.72-7.66 (m, 1H), 7.49-7.42 (m, 2H), 7.40-7.35 (m, 1H), 7.25 (s, 1H), 7.10 (d, J = 6.1 Hz, 1H), 6.99 (d, J = 7.8 Hz, 1H), 6.55 (t, J = 4.7 Hz, 1H), 6.11 (dd, J = 10.5, 5.5Hz, 1H), 5.83 (d, J = 16.7 Hz, 1H), 4.29 (d, J = 16.9 Hz, 1H), 4.00-3.94 (m, 4H), 3.64-3.51 (m, 2H), 3.39-3.29 (m, 4H), 2.35 (s, 3H). For example... Figure 10 As shown.

[0223] 13 C NMR (150 MHz, CDCl3) δ 161.4, 158.0, 156.1 (q, J C-F= 36.0 Hz),146.3, 137.8, 137.7, 137.0, 135.8, 130.3, 130.1, 129.8, 129.8, 129.7, 129.7,129.4, 127.6, 127.4, 118.9, 116.4 (q, J C-F = 288.8 Hz), 110.9, 50.8, 49.8, 45.9, 43.70 21.1.

[0224] 19 F NMR (564 MHz, CDCl3) δ -67.9, -69.5.

[0225] HRMS (ESI-TLQ) m / z: [M + Na] + calcd for C 27 H 26 F3N5O3SNa 580.1601; found,580.1595.

[0226] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. An allyl sulfonyl fluoride compound, characterized in that, Its structure is shown in general formula I: （I） Among them, R 1 It is one of trifluoroacetyl, methyl, or isopropyl; X is one of CH2 or SO2; Ar 1 It is one of the following: methyl-substituted aryl, isopropyl-substituted aryl, methoxy-substituted aryl, trifluoromethyl-substituted aryl, ester-substituted aryl, halogen-substituted aryl, cyano-substituted aryl, phenyl-substituted aryl, pyridyl, naphthyl, and tert-butyl-substituted aryl; Ar 2 It is one of the following: halogen-substituted aryl, ester-substituted aryl, or methyl-substituted aryl.

2. A method for preparing an allyl sulfonyl fluoride compound as described in claim 1, characterized in that, The alkyne, bromomethylsulfonyl fluoride, and alkali are reacted under solvent, inert gas, alkali, and photocatalytic reaction conditions to obtain the product.

3. The preparation method according to claim 2, characterized in that, The alkyne has a structure such as general formula II: (II) Among them, R 1 It is one of trifluoroacetyl, methyl, or isopropyl; X is one of CH2 or SO2; Ar 1 It is one of the following: methyl-substituted aryl, isopropyl-substituted aryl, methoxy-substituted aryl, trifluoromethyl-substituted aryl, ester-substituted aryl, halogen-substituted aryl, cyano-substituted aryl, phenyl-substituted aryl, pyridyl, naphthyl, and tert-butyl-substituted aryl; Ar 2 It is one of the following: halogen-substituted aryl, ester-substituted aryl, or methyl-substituted aryl.

4. The preparation method according to claim 3, characterized in that, The molar ratio of the compound of formula II, bromomethylsulfonyl fluoride, and base is 1:2:2.5; the reaction temperature is 40℃, and the reaction time is 12 h.

5. The preparation method according to claim 4, characterized in that, The solvent is dichloromethane; the amount of solvent used is in the volume ratio of the molar amount of compound II to the solvent as 1 mmol: 10 mL.

6. The preparation method according to claim 5, characterized in that, The light source used for the photocatalytic reaction was 30 W of 465 nm blue light, and the photocatalyst was fac-Ir(ppy)3; the amount of photocatalyst used was 1.0 mol of the compound of formula II.

7. The use of an allyl sulfonyl fluoride compound as described in claim 1 in fluorosulfonylation.

8. The application according to claim 7, characterized in that, The substrate is reacted with an allyl sulfonyl fluoride compound in an organic solvent; the substrate is a hydroxyl alcohol, phenol, ammonia, or a secondary amine; the reaction temperature is 25-80℃, and the reaction time is 1-24h.

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