A method for preparing a beta-fluorosulfonyl ketone compound

Abstract

The application discloses a preparation method of a beta-fluorosulfonyl ketone compound and relates to the technical field of chemical synthesis and medicinal chemistry. In the application, aldehyde compounds are selected as radical precursors, acyl radicals are generated through photocatalytic oxidation and reduction, addition is performed on the acyl radicals and ESF, and single electron transfer is performed, so that a sulfonyl fluoride group is introduced at the beta position of a carbonyl group, and a beta-fluorosulfonyl ketone compound is obtained. The application can realize preparation of a series of beta-fluorosulfonyl ketone compounds, and provides a new synthesis method for synthesis of the beta-fluorosulfonyl ketone compound. Moreover, the carbonyl group and the sulfonyl fluoride group are part of the structure of various drug molecules, and the beta-fluorosulfonyl ketone compound prepared by the application is expected to be widely applied in the fields of organic synthesis, drug development, polymer materials and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical synthesis and medicinal chemistry, and particularly relates to a preparation method of a beta-fluorosulfonyl ketone compound. BACKGROUND

[0002] Sulfonyl fluoride is a core group of a new generation of click chemistry reactions, and is widely used in organic synthesis, material and pharmaceutical research and development and many other fields, and has become one of the hotspots of chemical research in recent years. Therefore, developing a simple and efficient synthesis method of multifunctional sulfonyl fluoride compounds has certain research and application value. On the other hand, carbonyl groups are widely present in a large number of natural products, biologically active molecules, drugs, agricultural chemicals and functional materials, which makes multifunctional ketone compounds important intermediates in basic organic synthesis and production of various chemical and life science products, and has important research and application value.

[0003] At present, there are mainly three strategies for the synthesis of sulfonyl fluoride compounds: 1, in-situ construction of sulfonyl fluoride group; 2, modular synthesis based on sulfonyl fluoride building blocks; 3, direct fluorosulfonylation. In 2021, Liao Saihu and Huang Shenlin's research group reported a strategy for introducing sulfonyl fluoride at the alpha position of the carbonyl group through electrochemistry. However, the strategy for introducing sulfonyl fluoride at the beta position of the carbonyl group has not been reported yet. SUMMARY

[0004] The present application aims to provide a preparation method of a beta-fluorosulfonyl ketone compound to solve the problems existing in the prior art. The present application constructs a beta-fluorosulfonyl ketone compound by acyl radical and ESF addition in one step. Specifically, the present application uses an aldehyde compound as a radical precursor, and under the conditions of ESF, HAT reagent and photocatalyst, the aldehyde compound is oxidized and reduced by photocatalysis to generate an acyl radical, which undergoes an addition reaction with ESF, and then undergoes single electron transfer to introduce sulfonyl fluoride at the beta position of the carbonyl group, thereby obtaining a beta-fluorosulfonyl ketone compound.

[0005] To achieve the above-mentioned purpose, the present application provides the following scheme:

[0006] The technical scheme of the present application is a preparation method of a beta-fluorosulfonyl ketone compound, comprising the following steps:

[0007] An aldehyde compound, an organic solvent, a photocatalyst, a hydrogen atom transfer reagent (HAT reagent for short) and ethylenesulfonyl fluoride (ESF for short, structural formula ) are mixed, and then stirred and reacted under light irradiation to obtain a beta-fluorosulfonyl ketone compound;

[0008] The structural formula of the aldehyde compound is , and the structural formula of the beta-fluorosulfonyl ketone compound is ;

[0009] wherein R is one of alkyl, substituted alkyl, aryl, substituted aryl, heterocycle, and heterocycle-derived groups.

[0010] The reaction formula of the preparation method of the beta-fluorosulfonyl ketone compound of the present application is as follows:

[0011] .

[0012] The present application uses aldehyde compounds as radical precursors in organic solvents, adds a photocatalyst, a hydrogen atom transfer reagent (abbreviated as HAT reagent) and ethylenesulfonyl fluoride (abbreviated as ESF) thereto, and mixes and stirs under light irradiation conditions, so that the aldehyde compounds generate acyl radicals through photocatalytic oxidation-reduction, addition reaction occurs between the acyl radicals and the ESF, and then a single electron transfer process is carried out to introduce sulfonyl fluoride at the beta position of the carbonyl group, thereby obtaining a beta-fluorosulfonyl ketone compound. The present application can realize the preparation of a series of beta-fluorosulfonyl ketone compounds, and provides a new synthesis method for the synthesis of beta-fluorosulfonyl ketone compounds.

[0013] Preferably, the aldehyde compound comprises 、 、 、 、 、 、 、 、 、 or .

[0014] Further, the hydrogen atom transfer reagent comprises one or more of 1-octanethiol, quinuclidine, tert-butyl mercaptan and 2-mercapto propionic acid ethyl ester.

[0015] Further, the photocatalyst comprises acid red 87, 2,4,5,6-tetra(9-carbazolyl)-1,3-benzenedicarbonitrile (abbreviated as 4CzIPN), rhodamine B, tris(2,2'-bipyridine) ruthenium (II) bis(hexafluorophosphate) salt, fac Ir(ppy)3, Ir[ppy]2(dtbbpy)PF6, Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10-methyl-9-mesityl acridinium perchlorate, 3,6,-di-tert-butyl-9-mesityl-10-phenylacridine-10-tetrafluoroborate, 9-m- methyl-10-methylacridinium-10-hydroiodide, 9-trimethyl-10-methylacridinium-10- hexafluorophosphate, 9-m-dimethyl-10-phenylacridinium-10-hydrochloride and 9-m- dimethyl-2,7-dimethyl-10-phenylacridinium-10-tetrafluoroborate (abbreviated as Mes-( tOne or more of (-Bu)2Acr-Ph-BF4).

[0016] Furthermore, the organic solvent includes one or more of dichloroethane, dichloromethane (DCM), acetonitrile (MeCN), tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, and methanol.

[0017] Furthermore, the molar ratio of the aldehyde compound to the photocatalyst is 5:0.01~0.05.

[0018] Furthermore, the molar ratio of the aldehyde compound to the ethylene sulfonyl fluoride is 5:1~2.

[0019] Furthermore, the molar ratio of the aldehyde compound to the hydrogen atom transfer reagent is 5:0.1~0.4.

[0020] Furthermore, the ratio of the aldehyde compound to the organic solvent is 1 mmol: 0.5~5 mL.

[0021] Furthermore, the stirring reaction under light irradiation includes: an irradiation wavelength of 460~465 nm, an irradiation time (i.e., reaction time) of 12~16 h, and a reaction temperature of 0~50 ℃.

[0022] Furthermore, the illumination specifically uses LED lights as the light source.

[0023] Furthermore, the mixing of the aldehyde compound, organic solvent, photocatalyst, hydrogen atom transfer reagent, and ethylene sulfonyl fluoride, as well as the stirring reaction under light irradiation, are all carried out under a protective atmosphere.

[0024] The present invention discloses the following technical effects:

[0025] (1) In this invention, aldehydes are selected as free radical precursors. Acyl free radicals are generated through photocatalytic oxidation-reduction, followed by addition with ESF and single electron transfer. This process introduces sulfonyl fluoride at the β-position of the carbonyl group and constructs β-fluorosulfonyl ketones in one step through addition with alkenes.

[0026] (2) The preparation method of the present invention has good reaction yield and high synthesis efficiency, and the 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.

[0027] (3) This invention provides a new method for the synthesis of β-fluorosulfonyl ketones, and carbonyl and sulfonyl fluoride groups are part of the structure of many drug molecules, and are expected to be widely used in organic synthesis, drug development, polymer materials and other fields.

[0028] (4) The present application adopts free radical reaction, which can be initiated by simple light irradiation, and has the advantages of mild reaction conditions, high yield, low requirement for instruments and equipment, simple operation and low cost of raw materials. BRIEF DESCRIPTION OF DRAWINGS

[0029] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed in the embodiments will be briefly introduced as follows. Obviously, the drawings in the following description only constitute some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained without creative effort based on these drawings.

[0030] Figure 1 NMR hydrogen spectrum of the product prepared in Example 4 of the present application.

[0031] Figure 2 NMR carbon spectrum of the product prepared in Example 4 of the present application.

[0032] Figure 3 NMR fluorine spectrum of the product prepared in Example 4 of the present application.

[0033] Figure 4 Mass spectrum of the product prepared in Example 4 of the present application. DETAILED DESCRIPTION

[0034] The various exemplary embodiments of the present application will now be described in detail, which should not be considered as limiting the present application, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present application.

[0035] It should be understood that the terms described in the present application are only for describing the specific embodiments, and are not used to limit the present application. In addition, for the numerical range in the present application, it should be understood that each intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. Each smaller range between any stated value or intermediate value in the stated range, and any other stated value or intermediate value in the stated range, is also included in the present application. The upper limit and the lower limit of these smaller ranges can be independently included or excluded from the range.

[0036] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, preferred methods and materials are described. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials in connection with which the documents are cited. In case of conflict between the content of the specification and that of any document incorporated by reference, the content of the specification prevails.

[0037] Many modifications and variations to the illustrative embodiments described herein will be apparent to those of ordinary skill in the art from context. Such modifications and variations are intended to fall within the scope of the present application. The illustrative embodiments should not be construed as limiting the present application, but rather as giving specific context to the disclosure.

[0038] As used herein, the terms "comprise", "comprising", "include", "including", "have", "having" or the like are open-ended and do not exclude additional, unrecited elements or method steps.

[0039] It should be noted that the present application does not describe in detail the conventional operation means in the art, and is not the focus of the present application.

[0040] In the specific embodiments of the present application, if the room temperature is mentioned, it specifically refers to 25±5℃.

[0041] In the specific embodiments of the present application, each raw material used is the ordinary commercially available product, wherein the structural formula of Ir[dF(CF3)ppy]2(dtbbpy)PF6 is , the structural formula of Mes-(t-Bu)2Acr-Ph-BF4 is t , the structural formula of Ir[ppy]2(dtbbpy)PF6 is , and the structural formula of 4CzIPN is . .

[0042] In the synthesis route in the following examples, the meaning of 1 mol% in the bracket behind the photocatalyst (Ir[dF(CF3)ppy]2(dtbbpy)PF6, etc.) is that the molar amount of the photocatalyst is 1 mol% of the ESF, and the meaning of 10 mol% in the bracket behind the HAT reagent (quinuclidine) is that the molar amount of quinuclidine is 10 mol% of the ESF.

[0043] Example 1

[0044] A kind of preparation of β-fluorosulfonyl ketone compound, the synthesis route is as follows:

[0045] ;

[0046] The specific preparation steps are as follows:

[0047] To a dry Schlenk reaction tube was added 0.5 mmol of 1a, followed by 0.001 mmol of Ir[dF(CF3)ppy]2(dtbbpy)PF6, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under nitrogen atmosphere. The reaction mixture was stirred under irradiation with a 30 W blue LED lamp of 460 nm wavelength at room temperature for 16 h.

[0048] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2S04, filtered and concentrated, further purified by column chromatography on silica gel with eluent of petroleum ether and ethyl acetate in volume ratio of 20:1 to give the product as a colorless oil (yield 93%).

[0049] The product's NMR,13C,19F and HRMS data are as follows:

[0050] 1 H NMR, 400 MHz, chloroform: δ 3.63-3.58 (m, 2H), 3.00 (t, J = 7.40 Hz, 2H), 2.38-2.31 (m, 1H), 1.83-1.79 (m, 2H), 1.76-1.72 (m, 2H), 1.65-1.60 (m, 1H), 1.33-1.16 (m, 5H).

[0051] 13 C NMR, 101 MHz, chloroform: δ 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3, 25.6, 25.4.

[0052] 19 F NMR, 377 MHz, chloroform: δ 53.9.

[0053] HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621.

[0054] Example 2

[0055] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0056] ;

[0057] The specific preparation steps are as follows:

[0058] Into a dry Schlenk reaction tube was added 0.5 mmol of 1a, followed by 0.001 mmol of Mes-(Bu)2Acr-Ph-BF4, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under a nitrogen atmosphere. The reaction mixture was stirred under irradiation with a 30 W blue LED lamp of 460 nm wavelength at room temperature for 16 h. t

[0059] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2S04, filtered and concentrated. Further purification was carried out by column chromatography on silica gel with eluent petroleum ether and ethyl acetate in a volume ratio of 20:1 to give the product as a colorless oil (25% yield).

[0060] The product's NMR, C NMR, F NMR and high resolution mass spectrometry data are as follows:

[0061] 1 H NMR, 400 MHz, chloroform: δ 3.63-3.58 (m, 2H), 3.00 (t, J = 7. 40 Hz, 2H),2.38–2.31 (m, 1H), 1.83–1.79 (m, 2H), 1.76–1.72(m, 2H), 1.65–1.60 (m, 1H),1.33–1.16(m, 5H).

[0062] 13 C NMR, 101 MHz, chloroform: δ 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3,25.6, 25.4.

[0063] 19 F NMR, 377 MHz, chloroform: δ 53.9.

[0064] HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621.

[0065] Example 3 ​

[0066] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0067] ;

[0068] The specific preparation steps are as follows:

[0069] Into a dry Schlenk tube was added 0.5 mmol of 1a, followed by 0.001 mmol of Ir[ppy]2(dtbbpy)PF6, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under nitrogen atmosphere. The reaction mixture was irradiated with a 30 W blue LED lamp of 460 nm wavelength at room temperature for 16 h with stirring.

[0070] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was carried out by column chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to obtain the product as colorless oil (yield 47%).

[0071] The product's NMR, C NMR, F NMR and high resolution mass spectrometry data are as follows:

[0072] 1 H NMR, 400 MHz, chloroform: δ 3.63-3.58 (m, 2H), 3.00 (t, J = 7. 40 Hz, 2H),2.38–2.31 (m, 1H), 1.83–1.79 (m, 2H), 1.76–1.72(m, 2H), 1.65–1.60 (m, 1H),1.33–1.16(m, 5H).

[0073] 13 C NMR, 101 MHz, chloroform: δ 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3,25.6, 25.4.

[0074] 19 F NMR, 377 MHz, chloroform: δ 53.9.

[0075] HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] +245.0624, found 245.0621.

[0076] Example 4

[0077] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0078] ;

[0079] The specific preparation steps are as follows:

[0080] Into a dry Schlenk tube, 0.5 mmol of 1a was added, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under nitrogen atmosphere. The reaction mixture was irradiated with a 30 W blue LED lamp with a wavelength of 460 nm under stirring at room temperature for 16 h.

[0081] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2S04, filtered and concentrated. Further purification was performed by column chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to obtain the product as colorless oil (yield 96%).

[0082] The product's NMR, C NMR, F NMR and HRMS data are as follows (the corresponding NMR hydrogen spectrum, NMR carbon spectrum, NMR fluorine spectrum and mass spectrum are shown in δ :

[0083] 1 H NMR, 400 MHz, chloroform: δ 3.63-3.58 (m, 2H), 3.00 (t, J = 7.40 Hz, 2H), 2.38-2.31 (m, 1H), 1.83-1.79 (m, 2H), 1.76-1.72 (m, 2H), 1.65-1.60 (m, 1H), 1.33-1.16 (m, 5H).

[0084] 13 C NMR, 101 MHz, chloroform: δ 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3, 25.6, 25.4.

[0085] 19 F NMR, 377 MHz, chloroform: m / z 53.9.

[0086] HRMS (ESI) Figure 1 - Figure 4 calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621.

[0087] Example 5

[0088] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0089] ;

[0090] The specific preparation steps are as follows:

[0091] Into a dry Schlenk tube, 0.5 mmol of 1a was added, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of dichloromethane under nitrogen atmosphere. The reaction mixture was irradiated with a 30 W blue LED lamp with a wavelength of 460 nm at room temperature for 16 h with stirring.

[0092] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2S04, filtered and concentrated. Further purification was carried out by column chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to obtain the product as colorless oil (yield 65%).

[0093] The product's NMR, C NMR, F NMR and high resolution mass spectrum data are as follows:

[0094] 1 H NMR, 400 MHz, chloroform: δ 3.63–3.58 (m, 2H), 3.00 (t, J = 7. 40 Hz, 2H),2.38–2.31 (m, 1H), 1.83–1.79 (m, 2H), 1.76–1.72(m, 2H), 1.65–1.60 (m, 1H),1.33–1.16(m, 5H).

[0095] 13 C NMR, 101 MHz, chloroform: δ 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3,25.6, 25.4.

[0096] 19F NMR, 377 MHz, chloroform: δ 53.9.

[0097] HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621.

[0098] Example 6

[0099] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0100] ;

[0101] The specific preparation steps are as follows:

[0102] Into a dry Schlenk tube, 0.5 mmol of 1a was added, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of 1,4-dioxane under nitrogen atmosphere. The reaction mixture was irradiated with a 30 W blue LED lamp with a wavelength of 460 nm under stirring at room temperature for 16 h.

[0103] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2S04, filtered and concentrated. Further purification was performed by column chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to give the product as colorless oil (yield 54%).

[0104] The product's NMR, C NMR, F NMR and high resolution mass spectrum data are as follows:

[0105] 1 H NMR, 400 MHz, chloroform: δ 3.63–3.58 (m, 2H), 3.00 (t, J = 7. 40Hz, 2H),2.38–2.31 (m, 1H), 1.83–1.79 (m, 2H), 1.76–1.72(m, 2H), 1.65–1.60 (m, 1H),1.33–1.16(m, 5H).

[0106] 13 C NMR, 101 MHz, chloroform: δ 207.6, 50.7, 45.4 (d, J= 18.8 Hz), 33.8, 28.3,25.6, 25.4.

[0107] 19 F NMR, 377 MHz, chloroform: δ 53.9.

[0108] HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621.

[0109] Example 7

[0110] The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows:

[0111] ;

[0112] The specific preparation steps are as follows:

[0113] 0.5 mmol of 1b was added to a dry Schrank reaction tube, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinine ring, and 0.5 mL of acetonitrile under a nitrogen atmosphere. The reaction mixture was stirred and irradiated with a 30 W blue LED lamp at a wavelength of 460 nm at room temperature for 16 h.

[0114] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered, and concentrated. Further purification was achieved by column chromatography on silica gel, using petroleum ether and ethyl acetate in a 50:1 volume ratio as eluent, yielding a colorless oily product (85% yield).

[0115] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows:

[0116] 1 H NMR, 400 MHz, chloroform: δ 3.72–3.67 (m, 2H), 3.23 (t, J = 7.4 Hz, 2H), 2.01–1.95 (m, 1H), 1.15–1.11 (m, 2H), 1.04–0.99 (m, 2H).

[0117] 13 C NMR, 101 MHz, chloroform: δ 204.4, 45.3 (d, J= 18.8 Hz), 36.3, 20.7, 11.8.

[0118] 19 F NMR, 377 MHz, chloroform: δ 53.8.

[0119] HRMS (EI) m / z calcd. for C6H9FO3S [M-H] - 179.0184, found 179.0176.

[0120] Example 8

[0121] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0122] ;

[0123] The specific preparation steps are as follows:

[0124] Into a dry Schlenk tube, 0.5 mmol of 1c was added, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under nitrogen atmosphere. The reaction mixture was irradiated with a 30 W blue LED lamp with a wavelength of 460 nm under stirring at room temperature for 16 h.

[0125] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2S04, filtered and concentrated. Further purification was performed by column chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 50:1 to give the product as colorless oil (yield 96%).

[0126] The product's NMR, C NMR, F NMR and high resolution mass spectrum data are as follows:

[0127] 1 H NMR, 400 MHz, chloroform: δ 3.65-3.60 (m, 2H), 3.30-3.21 (m, 1H), 2.92 (t, J = 7.4 Hz, 2H), 2.25-2.10 (m, 4H), 1.99-1.92 (m, 1H), 1.85-1.75 (m, 1H).

[0128] 13 C NMR, 101 MHz, chloroform: δ 205.4, 45.2 (d, J= 18.7 Hz), 45.1, 33.1, 24.3,17.8.

[0129] 19 F NMR, 377 MHz, chloroform: δ 53.8.

[0130] HRMS (CI) m / z calcd. for C7H 11 FO3S [M + H] + 195.0491, found 195.0484.

[0131] Example 9

[0132] The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows:

[0133] ;

[0134] The specific preparation steps are as follows:

[0135] 0.5 mmol of 1d was added to a dry Schrank reaction tube, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinine ring, and 0.5 mL of acetonitrile under a nitrogen atmosphere. The reaction mixture was stirred and irradiated with a 30 W blue LED lamp at a wavelength of 460 nm at room temperature for 16 h.

[0136] The reaction product was 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 on silica gel, using petroleum ether and ethyl acetate in a 20:1 volume ratio as eluent, to give a white solid product (94% yield).

[0137] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows:

[0138] 1 H NMR, 400 MHz, chloroform: δ 3.72–3.67 (m, 2H), 3.09 (t, J = 7.4 Hz, 2H), 2.97–2.89 (m, 1H), 1.92-1.84 (m, 2H), 1.77–1.61 (m, 6H).

[0139] 13 C NMR, 101 MHz, chloroform: δ 206.9, 51.3, 45.3 (d,J = 18.7 Hz), 34.8, 28.9, 25.9.

[0140] 19 F NMR, 377 MHz, chloroform: δ 53.9.

[0141] HRMS (EI) m / z calcd. for C8H 13 FO3S [M] + 208.0569, found 208.0565.

[0142] Example 10

[0143] The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows:

[0144] ;

[0145] The specific preparation steps are as follows:

[0146] 0.5 mmol of 1e was added to a dry Schrank reaction tube, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinine ring, and 0.5 mL of acetonitrile under a nitrogen atmosphere. The reaction mixture was stirred and irradiated with a 30 W blue LED lamp at a wavelength of 460 nm at room temperature for 16 h.

[0147] The reaction product was 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 preparative thin-layer chromatography using petroleum ether and ethyl acetate in a 10:1 volume ratio as eluent, yielding a white solid product (43% yield).

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

[0149] 1 H NMR, 400 MHz, chloroform: δ 7.98 (d, J = 7.7 Hz, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H), 3.91–3.86 (m, 2H), 3.64 (t, J = 7.5Hz, 2H).

[0150] 13C NMR, 101 MHz, chloroform: δ 193.8, 135.3, 134.2, 129.0, 128.1, 45.7 (d, J = 19.0 Hz), 32.4.

[0151] 19 F NMR, 377 MHz, chloroform: δ 54.0.

[0152] HRMS (ESI) m / z calcd. for C9H9FO3S [M + Na] + 239.0154, found 239.0149.

[0153] Example 11

[0154] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0155] ;

[0156] The specific preparation steps are as follows:

[0157] Into a dry Schlenk tube, 0.5 mmol of 1f was added, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under nitrogen atmosphere. The reaction mixture was irradiated with a 30 W blue LED lamp with a wavelength of 460 nm under stirring at room temperature for 16 h.

[0158] The reaction product was 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 preparative thin layer chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to give the product as a white solid (47% yield).

[0159] The product's NMR, C NMR, F NMR and high resolution mass spectrum data are as follows:

[0160] 1 H NMR, 600 MHz, chloroform: δ 7.87 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz,2H), 3.88–3.85 (m, 2H), 3.62–3.59 (m, 2H), 2.44 (s, 3H).

[0161] 13 C NMR, 151 MHz, chloroform: δ 194.1, 146.0, 133.5, 130.3, 128.9, 46.4(d, J = 18.8 Hz), 33.0, 22.4.

[0162] 19 F NMR, 565 MHz, chloroform: δ 53.8.

[0163] HRMS (ESI) m / z calcd. for C 10 H 11 FO3S [M + H] + 231.0491, found 231.0480.

[0164] Example 12

[0165] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0166] ;

[0167] The specific preparation steps are as follows:

[0168] Into a dry Schlenk tube, 0.5 mmol of 1g was added, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under nitrogen atmosphere. The reaction mixture was irradiated with a 30 W blue LED lamp with a wavelength of 460 nm at room temperature for 16 h with stirring.

[0169] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2S04, filtered and concentrated. Further purification was carried out by preparative thin layer chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain the product as a yellow oil (yield 75%).

[0170] The product's NMR, C NMR, F NMR and high resolution mass spectrum data are as follows:

[0171] 1 H NMR, 600 MHz, chloroform: δ 7.96-7.94 (m, 2H), 6.97-6.95 (m, 2H), 3.89 (s, 3H), 3.59-3.56 (m, 2H), 2.98-2.94 (m, 2H).

[0172] 13 C NMR, 151 MHz, chloroform: δ 187.8, 139.8, 131.0, 128.6, 114.0, 55.5, 49.5(d, J = 16.3 Hz), 26.6.

[0173] 19 F NMR, 565 MHz, chloroform: δ 54.3.

[0174] HRMS (ESI) m / z calcd. for C 10 H 11 FO4S [M + H] + 247.0440, found 247.0448.

[0175] Example 13

[0176] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0177] ;

[0178] The specific preparation steps are as follows:

[0179] Into a dry Schlenk tube, 0.5 mmol of 1h was added, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under nitrogen atmosphere. The reaction mixture was irradiated with a 30 W blue LED lamp with a wavelength of 460 nm at room temperature for 16 h with stirring.

[0180] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2S04, filtered and concentrated. Further purification was carried out by preparative thin layer chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain the product as a yellow oil (yield 96%).

[0181] The product's NMR, C NMR, F NMR and high resolution mass spectrum data are as follows:

[0182] 1 H NMR, 400 MHz, chloroform: δ 4.05–4.00 (m, 2H), 3.73–3.68 (m, 2H), 3.47–3.41 (m, 2H), 3.09 (t, J= 7.3 Hz, 2H), 2.68–2.61 (m, 1H), 1.83–1.68 (m, 4H).

[0183] 13 C NMR, 101 MHz, chloroform: δ 205.7, 66.9, 47.4, 45.2 (d, J = 18.9 Hz), 33.6,27.9.

[0184] 19 F NMR, 377 MHz, chloroform: δ 54.1.

[0185] HRMS (ESI) m / z calcd. for C8H 13 FO4S [M + Na] + 247.0416, found 247.0412.

[0186] Example 14

[0187] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0188] ;

[0189] The specific preparation steps are as follows:

[0190] Into a dry Schlenk tube, 0.5 mmol of 1i was added, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under nitrogen atmosphere. The reaction mixture was irradiated with a 30 W blue LED lamp with a wavelength of 460 nm at room temperature for 16 h with stirring.

[0191] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered and concentrated. Further purification was carried out by column chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 50:1 to obtain the product as colorless oil (yield 87%).

[0192] The product's NMR, C NMR, F NMR and high resolution mass spectrum data are as follows:

[0193] 1 H NMR, 400 MHz, chloroform: δ 3.65– 3.60 (m, 2H), 2.97 (t, J= 7.4 Hz, 2H),2.38– 2.31 (m, 1H), 1.65–1.54 (m, 2H), 1.46–1.41 (m, 2H), 0.81 (t, J = 7.5 Hz, 6H).

[0194] 13 C NMR, 101 MHz, chloroform: δ 208.3, 55.3, 45.2 (d, J = 18.9 Hz), 35.4, 24.0, 11.7.

[0195] 19 F NMR, 377 MHz, chloroform: δ 54.0.

[0196] HRMS (ESI) m / z calcd. for C8H 15 FO3S [M + Na] + 233.0624, found 233.0616.

[0197] Example 15

[0198] The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows:

[0199] ;

[0200] The specific preparation steps are as follows:

[0201] 0.5 mmol of 1j was added to a dry Schrank reaction tube, followed by 0.001 mmol of 4CzIPN, 0.1 mmol of ESF, 0.01 mmol of quinine ring, and 0.5 mL of acetonitrile under a nitrogen atmosphere. The reaction mixture was stirred and irradiated with a 30 W blue LED lamp at a wavelength of 460 nm at room temperature for 16 h.

[0202] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2SO4, filtered, and concentrated. Further purification was achieved by column chromatography on silica gel, using petroleum ether and ethyl acetate in a 50:1 volume ratio as eluent, yielding a colorless oily product (94% yield).

[0203] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows:

[0204] 1 H NMR, 400 MHz, chloroform: δ3.71 - 3.66 (m, 2H), 3.02 (t, J = 7.4 Hz, 2H), 2.39 (d, J = 7.0 Hz, 2H), 2.22 - 2.12 (m, 1H), 0.95 (d, J = 6.6 Hz, 6H).

[0205] 13 C NMR, 101 MHz, chloroform: δ 204.2, 51.6, 45.1 (d, J = 19.1 Hz), 36.2, 24.7, 22.4.

[0206] 19 F NMR, 377 MHz, chloroform: δ 53.9.

[0207] HRMS (EI) m / z calcd. for C7H 13 FO3S [M] + 196.0569, found 196.0562.

[0208] Example 16

[0209] A β-fluorosulfonyl ketone compound was prepared according to the following synthetic route:

[0210] ;

[0211] The specific preparation steps are as follows:

[0212] Into a dry Schlenk tube was added 0.5 mmol of 1k, followed by 0.001 mmol of Ir[dF(CF3)ppy]2(dtbbpy)PF6, 0.1 mmol of ESF, 0.01 mmol of quinuclidine and 0.5 mL of acetonitrile under nitrogen atmosphere. The reaction mixture was stirred under irradiation with a 30 W blue LED lamp of 460 nm wavelength at room temperature for 16 h.

[0213] The reaction product was then extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over Na2S04, filtered and concentrated. Further purification was carried out by column chromatography on silica gel with eluent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to give the product as a yellow oil (yield 87%).

[0214] The product's NMR, C NMR, F NMR and high resolution mass spectrum data are as follows:

[0215] The product's NMR, C NMR, F NMR and high resolution mass spectrum data are as follows:1 H NMR, 400 MHz, chloroform: δ 3.64–3.59 (m, 2H), 2.97 (t, J = 7.4 Hz, 2H), 1.58–1.49 (m, 2H), 1.25–1.19 (m, 8H), 0.81(t, J = 6.4Hz, 3H). J

[0216] 13 C NMR, 101 MHz, chloroform: δ 204.7, 45.2 (d, J = 18.8 Hz), 42.7, 35.7,31.6, 29.0, 28.9, 23.6, 22.6, 14.0.

[0217] 19 F NMR, 377 MHz, chloroform: δ 53.9.

[0218] HRMS (ESI) m / z δ δ δ m / z δ δ δ m / z calcd. for C 10 H 19 FO3S [M + Na] + 261.0937, found 261.0929.

[0219] A variety of functional group-substituted β-fluorosulfonyl ketone compounds are synthesized by the method of the present application, and the typical structures and reaction yields thereof are shown in the above examples. The molecular structural formulas of the polysubstituted β-fluorosulfonyl ketone compounds disclosed in the above examples are not intended to limit the scope of protection of the present application.

[0220] The above examples only describe the preferred modes of the present application, and are not intended to limit the scope of the present application. Any modifications and improvements to the technical solutions of the present application made by those of ordinary skill in the art without departing from the design spirit of the present application shall fall within the scope of protection of the present application as defined by the claims.​

Claims

1. A method for producing a β-fluorosulfonyl ketone compound, characterized by, The method comprises the following steps: Mixing an aldehyde compound, an organic solvent, a photocatalyst, a hydrogen atom transfer reagent and ethylenesulfonyl fluoride, and then stirring and reacting under light irradiation to obtain a β-fluorosulfonyl ketone compound; The aldehyde compound has a structural formula R is one of an alkyl group, an aryl group and a heterocycle; The hydrogen atom transfer reagent is quinuclidine; The photocatalyst is 2,4,5,6-tetrakis(9-carbazolyl)-1,3-benzenedicarbonitrile; The organic solvent is acetonitrile; The molar ratio of the aldehyde compound to the photocatalyst is 5:0.01; The molar ratio of the aldehyde compound to the ethylenesulfonyl fluoride is 5:1; The molar ratio of the aldehyde compound to the hydrogen atom transfer reagent is 5:0.1; The stirring and reaction under light irradiation comprises the following: the wavelength of the irradiation is 460-465 nm, the light irradiation time is 12-16 h, and the reaction temperature is 0-50 ℃.

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