Preparation of γ,δ-unsaturated ketones by visible light-induced radical reaction

Abstract

The present invention discloses the preparation of γ,δ-unsaturated ketone compounds by visible light-induced radical reaction, belonging to the technical field of organic synthesis. A method for preparing γ,δ-unsaturated ketone compounds by visible light-induced radical reaction comprises the following steps: mixing compound A, a sulfonyl chloride compound, a base, a photosensitizing catalyst and a solvent uniformly, and carrying out a visible light irradiation reaction under a nitrogen atmosphere, and obtaining the γ,δ-unsaturated ketone compound after the reaction ends. Under the action of light, the photosensitizing catalyst of the present invention undergoes single electron transfer with the sulfonyl chloride compound to obtain a sulfonyl radical, and the radical selectively adds to the double bond on the exocyclic alkenyl-substituted cyclobutanol compound, and then through carbon-carbon bond homolysis / radical transfer to obtain a new and more stable radical, and the radical is further oxidized to obtain the γ,δ-unsaturated ketone compound.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly to the preparation of γ,δ-unsaturated ketone compounds by visible light-induced radical reactions. Background Art

[0002] γ,δ-unsaturated ketone compounds are a class of important functional group-dense organic compounds, with extremely strong derivatization properties, and they are also commonly found in some natural product molecules or drug molecules. The structural formulas of representative compounds are shown below:

[0003]

[0004] For the construction of double bonds in γ,δ-unsaturated ketone compounds, the Wittig reaction is currently mostly used. This transformation itself has the disadvantages of poor functional group tolerance and low atom utilization. Therefore, there is an urgent need to find a method that can efficiently form double bonds and achieve the synthesis of γ,δ-unsaturated ketones. Summary of the Invention

[0005] The purpose of the present invention is to provide a method for preparing γ,δ-unsaturated ketone compounds by visible light-induced radical reactions to solve the problems existing in the above-mentioned prior art.

[0006] To achieve the above purpose, the present invention provides the following solutions:

[0007] One of the technical solutions of the present invention: A γ,δ-unsaturated ketone compound, the structural formula is shown in formula (1):

[0008]

[0009] In formula (1), R 1 , R 2 and R 3 are independently selected from any one of aryl or alkyl.

[0010] Further, the aryl is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole or thiophene.

[0011] Further, the substituents in the substituted phenyl, naphthalene, furan, pyrrole or thiophene are selected from any one of hydrogen, alkyl, halogen atom, ester group, nitro group, cyano group, phenyl or alkoxy group.

[0012] Another technical solution of the present invention: A method for preparing the above γ,δ-unsaturated ketone compound by visible light-induced radical reaction, comprising the following steps:

[0013] Mix compound A, sulfonyl chloride compound, base, photosensitizing catalyst and solvent evenly, and carry out visible light irradiation reaction under nitrogen atmosphere. After the reaction, the γ,δ-unsaturated ketone compound is obtained;

[0014] The structural formula of the said compound A is shown in formula (2):

[0015]

[0016] R 1 and R 2 are each independently selected from any one of aryl or alkyl; the aryl is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole or thiophene; the substituent in the substituted phenyl, naphthalene, furan, pyrrole or thiophene is selected from any one of hydrogen, alkyl, halogen atom, ester group, nitro group, cyano group, phenyl or alkoxy group.

[0017] The structural formula of the said sulfonyl chloride compound is shown in formula (3):

[0018]

[0019] R 3 is selected from any one of aryl or alkyl; the aryl is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole or thiophene; the substituent in the substituted phenyl, naphthalene, furan, pyrrole or thiophene is selected from any one of hydrogen, alkyl, halogen atom, ester group, nitro group, cyano group, phenyl or alkoxy group.

[0020] Furthermore, the molar ratio of the compound A (cyclic olefinyl-substituted cyclobutanol compound), sulfonyl chloride compound and base is 1:1.1:1.

[0021] Even further, the base includes Na2CO3, K2CO3, NaOAc or Et3N.

[0022] Furthermore, the photosensitizing catalyst includes [Ru(bpy)3]Cl2, Ir[dF(CF3)ppy]2(dtbbpy)PF6, Ir(ppy)2(dtbbpy)PF6, fac-Ir(ppy)3 or Eosin Y.

[0023] Even further, the molar percentage of the photosensitizing catalyst and compound A is 0.1 - 3% mol.

[0024] Even further, the photosensitizing catalyst is fac-Ir(ppy)3.

[0025] Further, the solvent includes at least one of acetonitrile (MeCN), water, dichloroethane, methanol, isopropanol, hexafluoroisopropanol, ethyl acetate, N,N-dimethylformamide (DMF), and tetrahydrofuran (THF).

[0026] Furthermore, the solvent is acetonitrile.

[0027] Further, the visible light is blue light (the light source is blue light of 15 - 30 W); the temperature of the photoreaction is 20 - 70 °C, and the time is 0.5 - 10 h.

[0028] Furthermore, the temperature of the photoreaction is 30 °C, and the time is 1.5 h.

[0029] If the photoreaction time is less than 1 h and there are remaining reactants, the yield of the target product will be reduced.

[0030] Under the irradiation of a blue light lamp, an electron transfer occurs between the sulfonyl chloride in the sulfonyl chloride compound used in the present invention and the photosensitizing catalyst to form a sulfonyl radical; this radical preferentially attacks the alkenyl part of the cycloalkanol compound substituted with an exocyclic alkenyl group of the reactant to obtain an alkyl radical. At the same time, due to the combined driving force of the strain of the four-membered ring and the energy level difference of the radicals, a carbon-carbon bond on the cyclobutyl group breaks, and after the radical transfer, a new radical with greater thermodynamic stability is generated. Finally, this radical is further oxidized to form a ketone carbonyl group, obtaining a γ,δ-unsaturated ketone compound (a γ,δ-unsaturated ketone compound of one configuration).

[0031] For example, by using a cycloalkanol compound substituted with an exocyclic alkenyl group to react with a sulfonyl chloride compound (such as methylbenzenesulfonyl chloride), which is a sulfonyl radical precursor, in acetonitrile under blue light irradiation, a γ,δ-unsaturated ketone compound is obtained through radical addition / ring-opening of the cyclobutanol.

[0032] When methylbenzenesulfonyl chloride is the sulfonyl chloride compound, the reaction equation for preparing the γ,δ-unsaturated ketone compound is as follows:

[0033]

[0034] The reaction mechanism is as follows:

[0035]

[0036] Methylbenzenesulfonyl chloride (sulfonyl chloride compound) reacts with an excited photosensitizing catalyst to obtain electrons and decompose to form methylbenzenesulfonyl radical and chloride ion; this radical attacks the alkenyl moiety of the alkenyl-substituted cyclobutanol (compound of exocyclic alkenyl-substituted cyclobutanol), and then the newly formed alkyl radical A undergoes ring opening of the four-membered ring / radical transfer to obtain radical B, and B is further oxidized to form a carbocation intermediate C, and C deprotonates to form a sulfonyl-substituted γ,δ-unsaturated ketone (3).

[0037] The third technical solution of the present invention: An application of the above γ,δ-unsaturated ketone compound as an intermediate for synthesizing natural product molecules or drug molecules.

[0038] The present invention discloses the following technical effects:

[0039] (1) The γ,δ-unsaturated ketone compound of the present invention has extremely strong derivatization properties and can be used as an intermediate for synthesizing natural product molecules or drug molecules.

[0040] (2) By carrying out a photocatalytic reaction in the presence of a small amount of photosensitizing catalyst, the present invention can realize the preparation of γ,δ-unsaturated ketone compounds under mild and green reaction conditions. Moreover, the catalyst used in the present invention has a small amount, the reaction system is simple, and the reaction time is short.

[0041] (3) Under the action of light, the photosensitizing catalyst of the present invention undergoes single-electron transfer with the sulfonyl chloride compound to obtain a sulfonyl radical, and the radical selectively adds to the double bond on the exocyclic alkenyl-substituted cyclobutanol compound, and then undergoes homolytic cleavage / radical transfer of the carbon-carbon bond to obtain a new and more stable radical, and this radical is further oxidized to obtain a γ,δ-unsaturated ketone compound. Description of the Drawings

[0042] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required to be used in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0043] Figure 1 1H NMR spectrum of the product 3a prepared in Example 1 of the present invention 1 1H NMR spectrum;

[0044] Figure 2 13C NMR spectrum of the product 3a prepared in Example 1 of the present invention 13 13C NMR spectrum;

[0045] Figure 3 1H NMR spectrum of the product 3b prepared in Example 2 of the present invention 11H NMR spectrum;

[0046] Figure 4 for the product 3b prepared in Example 2 of the present invention 13 13C NMR spectrum;

[0047] Figure 5 for the product 3c prepared in Example 3 of the present invention 1 1H NMR spectrum;

[0048] Figure 6 for the product 3c prepared in Example 3 of the present invention 13 13C NMR spectrum;

[0049] Figure 7 for the product 3d prepared in Example 4 of the present invention 1 1H NMR spectrum;

[0050] Figure 8 for the product 3d prepared in Example 4 of the present invention 13 13C NMR spectrum;

[0051] Figure 9 for the product 3e prepared in Example 5 of the present invention 1 1H NMR spectrum;

[0052] Figure 10 for the product 3e prepared in Example 5 of the present invention 13 13C NMR spectrum;

[0053] Figure 11 for the product 3f prepared in Example 6 of the present invention 1 1H NMR spectrum;

[0054] Figure 12 for the product 3f prepared in Example 6 of the present invention 13 13C NMR spectrum;

[0055] Figure 13 for the product 3g prepared in Example 7 of the present invention 1 1H NMR spectrum;

[0056] Figure 14 for the product 3g prepared in Example 7 of the present invention 13 13C NMR spectrum. Detailed Description of the Invention

[0057] Now, various exemplary embodiments of the present invention will be described in detail. This detailed description should not be construed as a limitation on the present invention, but rather as a more detailed description of certain aspects, characteristics, and embodiments of the present invention.

[0058] It should be understood that the terms used in the present invention are only for describing specific embodiments and are not intended to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0059] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0060] Without departing from the scope or spirit of the present invention, various improvements and changes can be made to the specific embodiments of the present invention specification, which are obvious to those skilled in the art. Other embodiments obtained from the specification of the present invention are obvious to those skilled in the art. The specification and examples of this application are merely exemplary.

[0061] Regarding the use of "comprising", "including", "having", "containing", etc. herein, they are all open-ended terms, meaning including but not limited to.

[0062] In the first aspect of the present invention, there is provided a γ,δ-unsaturated ketone compound, the structural formula of which is shown in formula (1):

[0063]

[0064] In formula (1), R 1 , R 2 and R 3 are independently selected from any one of aryl or alkyl.

[0065] In the present invention, the aryl is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole or thiophene.

[0066] In the present invention, the substituents in the substituted phenyl, naphthalene, furan, pyrrole or thiophene are selected from any one of hydrogen, alkyl, halogen atom, ester group, nitro, cyano, phenyl or alkoxy.

[0067] In the second aspect of the present invention, there is provided a method for preparing the above-mentioned γ,δ-unsaturated ketone compound by visible light-initiated radical reaction, comprising the following steps:

[0068] Compound A, a sulfonyl chloride compound, a base, a photosensitizing catalyst, and a solvent are mixed evenly, and a visible light irradiation reaction is carried out under a nitrogen atmosphere. After the reaction, a γ,δ-unsaturated ketone compound is obtained.

[0069] The structural formula of compound A in the present invention is shown in formula (2):

[0070]

[0071] R 1 and R 2 are each independently selected from any one of aryl or alkyl; the aryl is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole, or thiophene; the substituent in the substituted phenyl, naphthalene, furan, pyrrole, or thiophene is selected from any one of hydrogen, alkyl, halogen atom, ester group, nitro group, cyano group, phenyl, or alkoxy group.

[0072] The structural formula of the sulfonyl chloride compound in the present invention is shown in formula (3):

[0073]

[0074] R 3 is selected from any one of aryl or alkyl; the aryl is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole, or thiophene; the substituent in the substituted phenyl, naphthalene, furan, pyrrole, or thiophene is selected from any one of hydrogen, alkyl, halogen atom, ester group, nitro group, cyano group, phenyl, or alkoxy group.

[0075] The molar ratio of compound A (a cycloalkenyl-substituted cyclobutanol compound), the sulfonyl chloride compound, and the base in the present invention is 1:1.1:1.

[0076] The photosensitizing catalyst in the present invention includes [Ru(bpy)3]Cl2, Ir[dF(CF3)ppy]2(dtbbpy)PF6, Ir(ppy)2(dtbbpy)PF6, fac-Ir(ppy)3, or Eosin Y.

[0077] The molar percentage of the photosensitizing catalyst and compound A in the present invention is 0.5 - 3% mol.

[0078] The photosensitizing catalyst in the present invention is preferably fac-Ir(ppy)3.

[0079] The solvent in the present invention includes at least one of acetonitrile (MeCN), water, dichloroethane, methanol, isopropanol, hexafluoroisopropanol, ethyl acetate, N,N-dimethylformamide (DMF), and tetrahydrofuran (THF).

[0080] The solvent in the present invention is preferably acetonitrile.

[0081] The visible light in the present invention is blue light (the light source is blue light of 15 - 30 W); the temperature of the photoreaction is 20 - 70 °C, and the time is 0.5 - 10 h.

[0082] Preferably, the temperature of the photoreaction in the present invention is 30 °C, and the time is preferably 1.5 h.

[0083] If the photoreaction time is less than 1 h, there will be remaining reactants, which will reduce the yield of the target product.

[0084] Both the compound with the structure shown in formula (2) and the compound with the structure shown in formula (3) in the present invention can be used to prepare γ,δ-unsaturated ketone compounds under the irradiation of a blue light lamp. Because the compounds with the structure shown in formula (2) can break the carbon-carbon bond on the cyclobutane under the action of the sulfonyl radical generated by the compounds with the structure shown in formula (3), and generate a new radical that is thermodynamically more stable. Finally, this radical is further oxidized to form a ketone carbonyl group, obtaining γ,δ-unsaturated ketone compounds.

[0085] In the third aspect of the present invention, there is provided an application of the above-mentioned γ,δ-unsaturated ketone compound as an intermediate for synthesizing natural product molecules or drug molecules.

[0086] Example 1

[0087] A method for preparing γ,δ-unsaturated ketone compounds by visible light-induced radical reaction:

[0088] In a reaction tube, cyclobutanol analogue 1a (35.0 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (42 mg, 0.22 mmol, 1.1 equiv.), sodium carbonate (22 mg, 0.2 mmol, 1.0 equiv.), photosensitizer catalyst fac-Ir(ppy)3 (1.0 mg, 0.001 mmol, 0.5% mol), and solvent MeCN (acetonitrile, 3 mL) were added. After mixing evenly, under a nitrogen atmosphere, it was irradiated with a 30 W blue light lamp for 1.5 h (the temperature of the photoreaction was 30 °C). After the reaction was completed, the reaction product was transferred to a round-bottom flask, and silica was added to the round-bottom flask, and the solvent was evaporated under vacuum. Using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent, purification was carried out by silica gel column chromatography to obtain γ,δ-unsaturated ketone compounds, that is, product 3a, with a yield of 89%.

[0089] The reaction formula for preparing product 3a is as follows:

[0090]

[0091] For the product 3a prepared in this example1 The \(^1H\) NMR spectrum is shown in Figure 1 , 13 The \(^{13}C\) NMR spectrum is shown in Figure 2 ; The nuclear magnetic resonance data of product 3a: 1 \(^1H\) NMR (400 MHz, \(CDCl_3\)) \(\delta\) 7.83 (s, 1H), 7.80 (d, \(J\) = 1.7 Hz, 1H), 7.79 (d, \(J\) = 1.8 Hz, 1H), 7.42 - 7.38 (m, 4H), 7.38 - 7.33 (m, 3H), 2.84 - 2.80 (m, 2H), 2.73 - 2.69 (m, 2H), 2.45 (s, 3H), 2.13 (s, 3H). 13 \(^{13}C\) NMR (151 MHz, \(CDCl_3\)) \(\delta\) 207.0, 144.6, 140.5, 138.5, 136.1, 133.4, 130.1, 129.8, 129.4, 129.1, 128.3, 42.1, 29.9, 21.7, 21.1.

[0092] Example 2

[0093] A method for preparing γ,δ-unsaturated ketone compounds by visible light-induced radical reaction:

[0094] In a reaction tube, cyclobutanol analogue 1b (50.0 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (42 mg, 0.22 mmol, 1.1 equiv.), sodium carbonate (22 mg, 0.2 mmol, 1.0 equiv.), photosensitizer catalyst fac-Ir(ppy)\(_3\) (1.0 mg, 0.001 mmol, 0.5% mol), and solvent MeCN (acetonitrile, 3 mL) were added. After mixing evenly, under a nitrogen atmosphere, the mixture was irradiated with a 30 W blue light lamp for 1.5 h (the temperature of the photoirradiation reaction was 30 °C). After the reaction was completed, the reaction product was transferred to a round-bottom flask, and silica was added to the round-bottom flask, and the solvent was evaporated under vacuum. Using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent, purification was carried out by silica gel column chromatography to obtain γ,δ-unsaturated ketone compounds, namely product 3b, with a yield of 55%.

[0095] The reaction formula for preparing product 3b is as follows:

[0096]

[0097] For the product 3b prepared in this example 1 The \(^1H\) NMR spectrum is shown in Figure 3 , 13 The \(^{13}C\) NMR spectrum is shown in Figure 4; NMR data of product 3b: 1 H NMR(600MHz,CDCl3)δ7.96 - 7.93(d,J=5.2Hz,2H),7.92(s,1H),7.83(d,J=5.2Hz,2H),7.60 - 7.58(m,1H),7.49 - 7.46(m,3H),7.45 - 7.43(m,3H),7.41 - 7.40(m,1H),7.36(d,J=5.6Hz,2H),3.40 - 3.37(m,2H),2.92 - 2.90(m,2H),2.45(s,3H). 13 C NMR(151MHz,CDCl3)δ198.5,144.6,140.6,138.7,136.3,133.5,130.1,129.9,129.5,129.5,129.2,128.7,128.3,128.2,37.4,21.8,21.7。

[0098] Example 3

[0099] Method for preparing γ,δ-unsaturated ketone compounds by visible light-induced radical reaction:

[0100] In a reaction tube, cyclobutanol analogue 1c (40.0 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (42 mg, 0.22 mmol, 1.1 equiv.), sodium carbonate (22 mg, 0.2 mmol, 1.0 equiv.), photosensitizer catalyst fac-Ir(ppy)3 (1.0 mg, 0.001 mmol, 0.5% mol), and solvent MeCN (acetonitrile, 3 mL) were added. After mixing evenly, under a nitrogen atmosphere, it was irradiated with a 30W blue light lamp for 1.5 h (the temperature of the photochemical reaction was 30 °C). After the reaction, the reaction product was transferred to a round-bottom flask, and silica was added to the round-bottom flask, and the solvent was evaporated under vacuum. Using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent, purification was carried out by silica gel column chromatography to obtain γ,δ-unsaturated ketone compounds, namely product 3c, with a yield of 45%.

[0101] The reaction formula for preparing product 3c is as follows:

[0102]

[0103] The product 3c prepared in this example 1 The H NMR spectrum is shown in Figure 5 , 13 The C NMR spectrum is shown in Figure 6 ; NMR data of product 3c:1 1H NMR (600 MHz, CDCl3) δ 7.84 (s, 1H), 7.80 (d, J = 10.8 Hz, 2H), 7.43 - 7.38 (m, 5H), 7.36 (s, 1H), 7.35 (s, 1H), 5.92 - 5.86 (m, 1H), 5.21 - 5.12 (m, 2H), 3.16 (dt, J = 6.6, 2.4 Hz, 2H), 2.85 - 2.82 (m, 2H), 2.74 - 2.71 (m, 2H), 2.45 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 207.0, 144.6, 140.5, 138.5, 136.1, 133.4, 130.2, 130.1, 129.8, 129.4, 129.1, 128.3, 119.3, 47.7, 40.7, 21.7, 21.1.

[0104] Example 4

[0105] Method for preparing γ,δ-unsaturated ketone compounds by visible light-induced radical reaction:

[0106] In a reaction tube, accurately add cyclobutanol analogue 1d (47.2 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (42 mg, 0.22 mmol, 1.1 equiv.), sodium carbonate (22 mg, 0.2 mmol, 1.0 equiv.), photosensitizer catalyst fac-Ir(ppy)3 (1.0 mg, 0.001 mmol, 0.5% mol), solvent MeCN (acetonitrile, 3 mL). After mixing evenly, under a nitrogen atmosphere, irradiate with a 30 W blue light lamp for 4 h (the temperature of the photoirradiation reaction is 30 °C). After the reaction is completed, transfer the reaction product to a round-bottom flask, add silica in the round-bottom flask, and evaporate the solvent under vacuum. Using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent, purify by silica column chromatography to obtain the γ,δ-unsaturated ketone compound, namely product 3d, with a yield of 51%.

[0107] The reaction formula for preparing product 3d is as follows:

[0108]

[0109] For the product 3d prepared in this example 1 The 1H NMR spectrum is shown in Figure 7 , 13 The 13C NMR spectrum is shown in Figure 8 ; The nuclear magnetic resonance data of product 3d: 11H NMR (600 MHz, CDCl3) δ 7.41 (d, J = 7.8 Hz, 3H), 7.35 (d, J = 8.4 Hz, 3H), 7.16 - 7.14 (m, 2H), 7.05 - 7.03 (m, 2H), 7.00 (t, J = 1.2 Hz, 1H), 2.95 (t, J = 7.2 Hz, 2H), 2.79 (t, J = 7.2 Hz, 2H), 2.38 (s, 3H), 2.21 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 206.9, 144.4, 143.8, 138.3, 137.3, 132.8, 130.8, 130.7, 129.4, 127.7, 122.6, 43.0, 30.3, 28.5, 21.7。

[0110] Example 5

[0111] Method for preparing γ,δ-unsaturated ketone compounds by visible light-induced radical reaction:

[0112] In a reaction tube, add cyclobutanol analogue 1e (47.2 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (42 mg, 0.22 mmol, 1.1 equiv.), sodium carbonate (22 mg, 0.2 mmol, 1.0 equiv.), photosensitizer catalyst fac-Ir(ppy)3 (1.0 mg, 0.001 mmol, 0.5% mol), solvent MeCN (acetonitrile, 3 mL). After mixing evenly, under a nitrogen atmosphere, irradiate with a 30 W blue light lamp for 1.5 h (the temperature of the photochemical reaction is 30 °C). After the reaction is completed, transfer the reaction product to a round-bottom flask, add silica in the round-bottom flask, and evaporate the solvent under vacuum. Using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent, purify by silica column chromatography to obtain γ,δ-unsaturated ketone compounds, namely product 3e, with a yield of 75%.

[0113] The reaction formula for preparing product 3e is as follows:

[0114]

[0115] The product 3e prepared in this example 1 The 1H NMR spectrum is shown in Figure 9 , 13 The 13C NMR spectrum is shown in Figure 10 ; The nuclear magnetic resonance data of product 3e: 11H NMR (600 MHz, CDCl3) δ 7.79 (d, J = 2.4 Hz, 2H), 7.77 (d, J = 2.0 Hz, 1H), 7.56 (dd, J = 2.8, 1.2 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.22 (dd, J = 5.2, 1.2 Hz, 1H), 7.17 - 7.15 (m, 1H), 2.83 - 2.79 (m, 2H), 2.75 - 2.70 (m, 2H), 2.45 (s, 3H), 2.16 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 207.2, 144.4, 140.3, 139.2, 138.4, 136.3, 130.5, 130.0, 129.9, 129.5, 128.3, 42.1, 30.0, 21.7, 21.5, 21.1。

[0116] Example 6

[0117] Method for preparing γ,δ-unsaturated ketone compounds by visible light-induced radical reaction:

[0118] In a reaction tube, cyclobutanol analogue 1f (36.0 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (42 mg, 0.22 mmol, 1.1 equiv.), sodium carbonate (22 mg, 0.2 mmol, 1.0 equiv.), photosensitizer catalyst fac-Ir(ppy)3 (1.0 mg, 0.001 mmol, 0.5% mol), and solvent MeCN (acetonitrile, 3 mL) were added. After mixing evenly, under a nitrogen atmosphere, the mixture was irradiated with a 30 W blue light lamp for 4 h (the temperature of the photoirradiation reaction was 30 °C). After the reaction was completed, the reaction product was transferred to a round-bottom flask, and silica was added to the round-bottom flask, and the solvent was evaporated under vacuum. Using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent, purification was carried out by silica column chromatography to obtain γ,δ-unsaturated ketone compounds, namely product 3f, with a yield of 65%.

[0119] The reaction formula for preparing product 3f is as follows:

[0120]

[0121] The product 3f prepared in this example 1 The 1H NMR spectrum is shown in Figure 11 , 13 The 13C NMR spectrum is shown in Figure 12 ; The nuclear magnetic resonance data of product 3f: 11H NMR (400 MHz, CDCl3) δ δ 7.79 (d, J = 2.4 Hz, 2H), 7.77 (d, J = 2.0 Hz, 1H), 7.56 (dd, J = 2.8, 1.2 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.22 (dd, J = 5.2, 1.2 Hz, 1H), 7.17 - 7.15 (m, 1H), 2.83 - 2.79 (m, 2H), 2.75 - 2.70 (m, 2H), 2.45 (s, 3H), 2.16 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 206.4, 150.4, 149.5, 145.4, 145.2, 141.3, 135.5, 135.3, 130.3, 129.9, 128.5, 123.2, 42.0, 29.9, 21.8, 21.0。

[0122] Example 7

[0123] Method for preparing γ,δ-unsaturated ketone compounds by visible light-induced free radical reaction:

[0124] In a reaction tube, accurately add cyclobutanol analogue 1a (35.0 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2b (42.0 mg, 0.22 mmol, 1.0 equiv.), sodium carbonate (22 mg, 0.2 mmol, 1.0 equiv.), photosensitizer catalyst fac-Ir(ppy)3 (1.0 mg, 0.001 mmol, 0.5% mol), solvent MeCN (acetonitrile, 3 mL). After mixing evenly, under a nitrogen atmosphere, irradiate with a 30 W blue light lamp for 4 h (the temperature of the photoirradiation reaction is 30 °C). After the reaction is completed, transfer the reaction product to a round-bottom flask, add silica in the round-bottom flask, and evaporate the solvent under vacuum. Using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent, purify by silica column chromatography to obtain γ,δ-unsaturated ketone compounds, namely product 3g, with a yield of 70%.

[0125] The reaction formula is as follows:

[0126]

[0127] For the product 3g prepared in this example 1 The 1H NMR spectrum is shown in Figure 13 , 13 The 13C NMR spectrum is shown in Figure 14 ; The nuclear magnetic resonance data of product 3g: 11H NMR (600 MHz, CDCl3) δ 7.88 (d, J = 1.8 Hz, 1H), 7.85 (s, 1H), 7.70 (dd, J = 7.8, 1.8 Hz, 1H), 7.45 - 7.40 (m, 6H), 2.88 - 2.85 (m, 2H), 2.73 - 2.71 (m, 2H), 2.48 (s, 3H), 2.16 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 206.9, 142.7, 139.9, 139.4, 138.1, 135.7, 133.2, 131.8, 130.1, 129.5, 129.2, 128.7, 126.4, 42.1, 30.0, 21.1, 20.5。

[0128] Example 8

[0129] Method for removing sulfonyl radicals from the γ,δ-unsaturated ketone compounds prepared in Examples 1 - 7 (reference: Photocatalytic C-C Cleavage of Methylenecyclobutanes for γ,δ-Unsaturated Aldehydes by Strain Release, Angew. Chem. Int. Ed. 2023, 62, e202300166) is as follows:

[0130]

[0131] The substance obtained after removing the sulfonyl radicals in this example can be used as an intermediate for synthesizing natural product molecules or drug molecules.

[0132] Example 9

[0133] Yields of γ,δ-unsaturated ketone compounds prepared by visible light-induced radical reaction under different reaction conditions:

[0134]

[0135] Table 1 Reaction conditions

[0136]

[0137]

[0138] Reaction parameter conditions:

[0139] Reaction parameter conditions [a] for groups 1 to 18: 1a (0.20 mmol), 2a (0.20 mmol, 1.0 equiv), solvent (2 mL), N2, the amount of photosensitizing catalyst is 0.5% mol of the amount of 1a, photoirradiation reaction (30 W blue light) for 1.5 h, room temperature.

[0140] [b] is to change the amount of the photosensitizing catalyst on the basis of [a], and the amount of the photosensitizing catalyst is 1% mol of the amount of 1a;

[0141] [c] is not to perform photoirradiation on the basis of [a];

[0142] [d] is to change the 30 W blue light to 15 W blue light on the basis of [a];

[0143] [e] is to replace N2 with air on the basis of [a].

[0144] The above-described embodiments are only descriptions of the preferred embodiments of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. A method for preparing γ,δ-unsaturated ketone compounds by visible light-induced free radical reaction, characterized in that, It includes the following steps: Mix compound A, sulfonyl chloride compound, base, photosensitive catalyst and solvent evenly, and carry out visible light irradiation reaction under nitrogen atmosphere. After the reaction, the γ,δ-unsaturated ketone compound is obtained; The structural formula of the γ,δ-unsaturated ketone compound is shown in formula (1): Formula (1) The structural formula of compound A is shown in formula (2): Formula (2) The structural formula of the sulfonyl chloride compound is shown in formula (3): Formula (3) wherein, R 1 , R 2 and R 3 are independently selected from any one of aryl or alkyl; The aryl group is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole or thiophene; The substituents in the substituted phenyl, naphthalene, furan, pyrrole or thiophene are selected from any one of alkyl, halogen atom, ester group, nitro group, cyano group, phenyl or alkoxy group; The visible light is blue light; the temperature of the irradiation reaction is 20~70°C and the time is 1.5~4h; The photosensitive catalyst is fac-Ir(ppy)3; the solvent is acetonitrile.

2. The method according to claim 1, characterized in that, The molar ratio of compound A, sulfonyl chloride compound and base is 1:1.1:1.

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