Preparation method of beta-fluorosulfonyl ketone compound

Abstract

The invention discloses a preparation method of a beta-fluorosulfonyl ketone compound, and relates to the technical field of chemical synthesis and medicinal chemistry. The preparation method comprises the following steps: selecting an aldehyde compound as a free radical precursor, carrying out photocatalytic oxidation reduction to generate an acyl free radical, carrying out addition with ESF, and carrying out single electron transfer to introduce a sulfonyl fluoride group into the beta position of carbonyl so as to obtain the beta-fluorosulfonyl ketone compound. The preparation of a series of beta-fluorosulfonyl ketone compounds can be realized, and a novel synthesis method is provided for the synthesis of the beta-fluorosulfonyl ketone compounds. And carbonyl and sulfonyl fluoride are parts of molecular structures of various drugs, so that the beta-fluorosulfonyl ketone compound prepared by the method is expected to be widely applied to the fields of organic synthesis, drug development, high polymer materials and the like.

Description

Technical Field

[0001] This invention relates to the fields of chemical synthesis and medicinal chemistry, and in particular to a method for preparing β-fluorosulfonyl ketone compounds. Background Technology

[0002] Sulfonyl fluorides are core groups in next-generation click chemistry reactions and are widely used in organic synthesis, materials science, and pharmaceutical research, becoming a hot topic in chemical research in recent years. Therefore, developing simple and efficient synthetic methods for multifunctional sulfonyl fluorides has significant research and application value. On the other hand, carbonyl groups are widely found in numerous natural products, bioactive molecules, pharmaceuticals, agrochemicals, and functional materials, making multifunctional ketones important intermediates in basic organic synthesis and the production of various chemical and life science products, thus possessing significant research and application value.

[0003] Currently, there are three main strategies for synthesizing sulfonyl fluoride compounds: 1. in-situ construction of sulfonyl fluoride groups; 2. modular synthesis based on sulfonyl fluoride building blocks; and 3. direct fluorosulfonation. In 2021, Liao Saihu and Huang Shenlin's research group reported a strategy for introducing sulfonyl fluoride at the α-position of the carbonyl group via electrochemical methods. However, a strategy for introducing sulfonyl fluoride at the β-position of the carbonyl group has not yet been reported. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing β-fluorosulfonyl ketones to solve the problems existing in the prior art. This invention constructs β-fluorosulfonyl ketones in one step via the addition of an acyl radical to ESF. Specifically, this invention uses an aldehyde compound as a radical precursor. Under the conditions of ESF, HAT reagent, and a photocatalyst, the aldehyde compound undergoes photocatalytic oxidation-reduction to generate an acyl radical, which then undergoes an addition reaction with ESF. Following a single-electron transfer, a sulfonyl fluoride is introduced at the β-position of the carbonyl group to obtain the β-fluorosulfonyl ketone compound.

[0005] To achieve the above objectives, the present invention provides the following solution: The technical solution of the present invention: a method for preparing β-fluorosulfonyl ketone compounds, comprising the following steps: An aldehyde compound, an organic solvent, a photocatalyst, a hydrogen atom transfer reagent (HAT reagent), and vinyl sulfonyl fluoride (ESF, structural formula: [insert structural formula here]) are used. The mixture was stirred under light to obtain β-fluorosulfonyl ketone compounds; The structural formula of the aldehyde compound is as follows: The structural formula of the β-fluorosulfonyl ketone compound is as follows: ; Wherein, R is one of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclic and heterocyclic derivative groups.

[0006] The general reaction formula for the preparation method of the β-fluorosulfonyl ketone compounds of the present invention is as follows: .

[0007] This invention involves using aldehydes as free radical precursors in an organic solvent, adding a photocatalyst, a hydrogen atom transfer reagent (HAT reagent), and vinyl sulfonyl fluoride (ESF), and mixing and stirring under light irradiation. This allows the aldehydes to undergo photocatalytic oxidation-reduction to generate acyl radicals, which then undergo an addition reaction with ESF. Following a single-electron transfer process, sulfonyl fluoride is introduced at the β-position of the carbonyl group, yielding β-fluorosulfonyl ketones. This invention enables the preparation of a series of β-fluorosulfonyl ketones, providing a novel synthetic method for their synthesis.

[0008] Preferably, the aldehyde compound includes , , , , , , , , , or .

[0009] Furthermore, the hydrogen atom transfer reagent includes one or more of 1-octylthiol, quinine ring, tert-butylthiol, and ethyl 2-mercaptopropionate.

[0010] Furthermore, the photocatalyst comprises Acid Red 87, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (abbreviated as 4CzIPN), Rhodamine B, tris(2,2'-bipyridine)ruthenium di(hexafluorophosphate), fac -Ir(ppy)3, Ir[ppy]2(dtbbpy)PF6, Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10-methyl-9-trimethylacrylidine perchlorate, 3,6,-di-tert-butyl-9-trimethylacryl-10-phenylacryl-10-tetrafluoroborate, 9-m-methyl-10-methylacryl-10-hydroiodate, 9-trimethyl-10-methylacryl-10-hexafluorophosphate, 9-m-dimethyl-10-phenylacryl-10-hydrochloride, and 9-m-dimethyl-2,7-dimethyl-10-phenylacryl-10-tetrafluoroborate (abbreviated as Mes-( t One or more of (-Bu)2Acr-Ph-BF4).

[0011] 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.

[0012] Furthermore, the molar ratio of the aldehyde compound to the photocatalyst is 5:0.01~0.05.

[0013] Furthermore, the molar ratio of the aldehyde compound to the ethylene sulfonyl fluoride is 5:1~2.

[0014] Furthermore, the molar ratio of the aldehyde compound to the hydrogen atom transfer reagent is 5:0.1~0.4.

[0015] Furthermore, the ratio of the aldehyde compound to the organic solvent is 1 mmol: 0.5~5 mL.

[0016] 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 ℃.

[0017] Furthermore, the illumination specifically uses LED lights as the light source.

[0018] 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.

[0019] The present invention discloses the following technical effects: (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.

[0020] (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.

[0021] (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.

[0022] (4) The present invention uses a free radical reaction, which can be initiated by simple light irradiation. The reaction conditions are mild, the yield is high, the requirements for instruments and equipment are low, the operation is simple, and the raw materials used in the present invention are inexpensive. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 The image shows the hydrogen NMR spectrum of the product prepared in Example 4 of this invention.

[0025] Figure 2 The image shows the carbon NMR spectrum of the product prepared in Example 4 of this invention.

[0026] Figure 3 The NMR fluorine spectrum of the product prepared in Example 4 of this invention.

[0027] Figure 4 This is the mass spectrum of the product prepared in Example 4 of the present invention. Detailed Implementation

[0028] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0029] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0030] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0031] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0032] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0033] It should be noted that any aspects not described in detail in this invention are conventional practices in the field and are not the focus of this invention.

[0034] In specific embodiments of the present invention, room temperature refers to 25±5℃.

[0035] Unless otherwise specified, all raw materials used in the specific embodiments of this invention are commercially available products. Among them, the structural formula of Ir[dF(CF3)ppy]2(dtbbpy)PF6 is... Mes-( t The structural formula of -Bu)2Acr-Ph-BF4 is: The structural formula of Ir[ppy]2(dtbbpy)PF6 is The structural formula of 4CzIPN is .

[0036] In the synthesis routes of the following examples, the 1 mol% in parentheses after the photocatalyst (Ir[dF(CF3)ppy]2(dtbbpy)PF6, etc.) means that the molar amount of the photocatalyst is 1 mol of ESF, and the 10 mol% in parentheses after the HAT reagent (quinine ring) means that the molar amount of the quinine ring is 10 mol of ESF.

[0037] Example 1 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1a was added to a dry Schrank reaction tube, followed by 0.001 mmol of Ir[dF(CF3)ppy]2(dtbbpy)PF6, 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.

[0038] The reaction product was 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 on silica gel with petroleum ether and ethyl acetate in a volume ratio of 20:1 to obtain a colorless oily product (yield of 93%).

[0039] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3,25.6, 25.4. 19 F NMR, 377 MHz, chloroform: d 53.9. HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621. Example 2 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: Add 0.5 mmol of 1a to a dry Schrank reaction tube, then add 0.001 mmol of Mes-( t -Bu)2Acr-Ph-BF4, 0.1 mmol of ESF, 0.01 mmol of quinine ring, and 0.5 mL of acetonitrile. 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.

[0040] 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 20:1 volume ratio as eluent, yielding a colorless oily product (25% yield).

[0041] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3,25.6, 25.4. 19 F NMR, 377 MHz, chloroform: d 53.9. HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621. Example 3 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1a was added to a dry Schrank reaction tube, followed by 0.001 mmol of Ir[ppy]2(dtbbpy)PF6, 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.

[0042] 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 20:1 volume ratio as eluent, yielding a colorless oily product (47% yield).

[0043] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3,25.6, 25.4. 19 F NMR, 377 MHz, chloroform: d 53.9. HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621. Example 4 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1a 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.

[0044] 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 20:1 volume ratio as eluent, yielding a colorless oily product (96% yield).

[0045] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows (the corresponding proton, carbon, fluorine, and mass spectra are shown below). Figure 1-Figure 4 (as shown) 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3,25.6, 25.4. 19 F NMR, 377 MHz, chloroform: d 53.9. HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621. Example 5 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1a 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 dichloromethane 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.

[0046] 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 volume ratio of 20:1, to give a colorless oily product (yield 65%).

[0047] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3,25.6, 25.4. 19 F NMR, 377 MHz, chloroform: d 53.9. HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621. Example 6 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1a 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 1,4-dioxane 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.

[0048] 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 20:1 volume ratio as eluent, yielding a colorless oily product (54% yield).

[0049] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 207.6, 50.7, 45.4 (d, J = 18.8 Hz), 33.8, 28.3,25.6, 25.4. 19 F NMR, 377 MHz, chloroform: d 53.9. HRMS (ESI) m / z calcd. for C9H 15 FO3S [M + Na] + 245.0624, found 245.0621. Example 7 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 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.

[0050] 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).

[0051] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 204.4, 45.3 (d, J = 18.8 Hz), 36.3, 20.7, 11.8. 19 F NMR, 377 MHz, chloroform: d 53.8. HRMS (EI) m / z calcd. for C6H9FO3S [MH] - 179.0184, found 179.0176. Example 8 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1c 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.

[0052] 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 (96% yield).

[0053] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 205.4, 45.2 (d, J = 18.7 Hz), 45.1, 33.1, 24.3,17.8. 19 F NMR, 377 MHz, chloroform: d 53.8. HRMS (CI) m / z calcd. for C7H 11 FO3S [M + H] + 195.0491, found 195.0484. Example 9 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 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.

[0054] 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).

[0055] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d3.72–3.67 (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). 13 C NMR, 101 MHz, chloroform: d 206.9, 51.3, 45.3 (d, J = 18.7 Hz), 34.8, 28.9, 25.9. 19 F NMR, 377 MHz, chloroform: d 53.9. HRMS (EI) m / z calcd. for C8H 13 FO3S [M] + 208.0569, found 208.0565. Example 10 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 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.

[0056] 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).

[0057] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 193.8, 135.3, 134.2, 129.0, 128.1, 45.7 (d, J =19.0 Hz), 32.4. 19 F NMR, 377 MHz, chloroform: d 54.0. HRMS (ESI) m / z calcd. for C9H9FO3S [M + Na] + 239.0154, found 239.0149. Example 11 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1f 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.

[0058] 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 (yield 47%).

[0059] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 600 MHz, chloroform: d 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). 13C NMR, 151 MHz, chloroform: d 194.1, 146.0, 133.5, 130.3, 128.9, 46.4(d, J =18.8 Hz), 33.0, 22.4. 19 F NMR, 565 MHz, chloroform: d 53.8. HRMS (ESI) m / z calcd. for C 10 H 11 FO3S [M + H] + 231.0491, found 231.0480. Example 12 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1 g of acetonitrile 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.

[0060] 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 preparative thin-layer chromatography on silica gel, using petroleum ether and ethyl acetate in a 10:1 volume ratio as eluent, yielding a yellow oily product (75% yield).

[0061] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 600 MHz, chloroform: d 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). 13 C NMR, 151 MHz, chloroform: d 187.8, 139.8, 131.0, 128.6, 114.0, 55.5, 49.5(d, J= 16.3 Hz), 26.6. 19 F NMR, 565 MHz, chloroform: d 54.3. HRMS (ESI) m / z calcd. for C 10 H 11 FO4S [M + H] + 247.0440, found 247.0448. Example 13 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1 h 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.

[0062] 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 preparative thin-layer chromatography on silica gel, using petroleum ether and ethyl acetate in a 10:1 volume ratio as eluent, yielding a yellow oily product (96% yield).

[0063] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 205.7, 66.9, 47.4, 45.2 (d, J = 18.9 Hz), 33.6, 27.9. 19 F NMR, 377 MHz, chloroform: d54.1. HRMS (ESI) m / z calcd. for C8H 13 FO4S [M + Na] + 247.0416, found 247.0412. Example 14 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1i 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.

[0064] 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 (87% yield).

[0065] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 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). 13 C NMR, 101 MHz, chloroform: d 208.3, 55.3, 45.2 (d, J = 18.9 Hz), 35.4, 24.0, 11.7. 19 F NMR, 377 MHz, chloroform: d 54.0. HRMS (ESI) m / z calcd. for C8H 15FO3S [M + Na] + 233.0624, found 233.0616. Example 15 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 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.

[0066] 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).

[0067] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 3.71–3.66 (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). 13 C NMR, 101 MHz, chloroform: d 204.2, 51.6, 45.1 (d, J = 19.1 Hz), 36.2, 24.7, 22.4. 19 F NMR, 377 MHz, chloroform: d 53.9. HRMS (EI) m / z calcd. for C7H 13 FO3S [M] + 196.0569, found 196.0562. Example 16 The synthetic route for the preparation of a β-fluorosulfonyl ketone compound is as follows: ; The specific preparation steps are as follows: 0.5 mmol of 1kJ was added to a dry Schrank reaction tube, followed by 0.001 mmol of Ir[dF(CF3)ppy]2(dtbbpy)PF6, 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.

[0068] 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 20:1 v / v ratio, yielding a yellow oily product (87% yield).

[0069] The proton, carbon, fluorine, and high-resolution mass spectrometry data of the product are as follows: 1 H NMR, 400 MHz, chloroform: d 3.64–3.59 (m, 2H), 2.97 (t, J = 7.4 Hz, 2H), 2.43 (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). 13 C NMR, 101 MHz, chloroform: d 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. 19 F NMR, 377 MHz, chloroform: d 53.9. HRMS (ESI) m / z calcd. for C 10 H 19 FO3S [M + Na] + 261.0937, found 261.0929. The method of the present invention is used to synthesize β-fluorosulfonyl ketones with various functional groups substituted. Their typical structures and reaction yields are shown in the above examples. The molecular structures of the polysubstituted β-fluorosulfonyl ketones disclosed in the above examples are not intended to limit the scope of protection of the present invention.

[0070] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for preparing a β-fluorosulfonyl ketone compound, characterized in that, Includes the following steps: An aldehyde compound, an organic solvent, a photocatalyst, a hydrogen atom transfer reagent, and ethylene sulfonyl fluoride are mixed and then reacted under light irradiation to obtain β-fluorosulfonyl ketone compounds. The structural formula of the aldehyde compound is as follows: The structural formula of the β-fluorosulfonyl ketone compound is as follows: ; Wherein, R is one of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclic and heterocyclic derivative groups.

2. The method for preparing β-fluorosulfonyl ketone compounds as described in claim 1, characterized in that, The hydrogen atom transfer reagent includes one or more of 1-octylthiol, quinine ring, tert-butylthiol, and ethyl 2-mercaptopropionate.

3. The method for preparing β-fluorosulfonyl ketone compounds as described in claim 1, characterized in that, The photocatalyst includes Acid Red 87, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, Rhodamine B, tris(2,2'-bipyridine)ruthenium di(hexafluorophosphate), fac-Ir(ppy)3, Ir[ppy]2(dtbbpy)PF6, Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10-methyl-9-trimethylylacrimidine perchlorate, One or more of the following: 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridine-10-tetrafluoroborate, 9-m-methyl-10-methylacridine-10-hydroiodate, 9-trimethyl-10-methylacridine-10-hexafluorophosphate, 9-m-dimethyl-10-phenylacridine-10-hydrochloride, and 9-m-dimethyl-2,7-dimethyl-10-phenylacridine-10-tetrafluoroborate.

4. The method for preparing β-fluorosulfonyl ketone compounds as described in claim 1, characterized in that, The organic solvent includes one or more of dichloroethane, dichloromethane, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, and methanol.

5. The method for preparing β-fluorosulfonyl ketone compounds as described in claim 1, characterized in that, The molar ratio of the aldehyde compound to the photocatalyst is 5:0.01~0.

05.

6. The method for preparing β-fluorosulfonyl ketone compounds according to claim 1, characterized in that, The molar ratio of the aldehyde compound to the ethylene sulfonyl fluoride is 5:1~2.

7. The method for preparing β-fluorosulfonyl ketone compounds according to claim 1, characterized in that, The molar ratio of the aldehyde compound to the hydrogen atom transfer reagent is 5:0.1~0.

4.

8. The method for preparing β-fluorosulfonyl ketone compounds as described in claim 1, characterized in that, The stirring reaction under light irradiation includes: an irradiation wavelength of 460~465 nm, an irradiation time of 12~16 h, and a reaction temperature of 0~50℃.

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