Preparation of 1, 4-sulfonylated chlorinated compound through free radical reaction initiated by visible light

Abstract

The invention discloses a method for preparing a 1, 4-sulfonylated chlorinated compound through a free radical reaction initiated by visible light, and belongs to the technical field of organic synthesis. The invention relates to a method for preparing a 1, 4-sulfonylated chlorinated compound through a free radical reaction initiated by visible light, which comprises the following steps: uniformly mixing a cyclobutyl olefin derivative, a sulfonyl chloride compound, alkali, a photosensitive catalyst and a solvent, and carrying out a visible light illumination reaction in a nitrogen atmosphere to obtain the 1, 4-sulfonylated chlorinated compound. According to the invention, the photocatalytic reaction is carried out in the presence of a small amount of the photosensitive catalyst, the preparation of the 1, 4-sulfonylated chlorinated compound can be realized under mild and green reaction conditions, and the method has the advantages of small catalyst dosage, simple reaction system and short reaction time.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, in particular to the preparation of 1,4-sulfonylated chlorinated compounds by free radical reaction initiated by visible light. Background Art

[0002] The difunctionalization of olefins is a basic unit for increasing the complexity of molecules, and two different functional groups can be introduced into the same molecule. Chlorosulfonylation of olefins is an extremely economical method to achieve difunctionalization of olefins, because both functional groups are derived from sulfonyl chloride, the atomic utilization rate can reach 100%, and the generation of waste can be minimized. In recent years, the transition metal-catalyzed chlorosulfonylation of olefins has developed relatively maturely. Fig.13 As shown, transition metal-mediated visible light photocatalysis under mild reaction conditions has become an effective strategy to achieve chlorosulfonylation of olefins (references: A. Hossain, O. Reiser, ACS Catal. 2019, 9, 1103-1109; b) S. Engl, O. Reiser, Eur. J. Org. Chem. 2020, 2020, 1523-1533), and this strategy has been used by various scientific groups for the difunctionalization of unsaturated bonds.

[0003] Compared with transition metal catalysis, electrochemistry provides a safe, green and sustainable synthetic method that can achieve chemical reactions without additional oxidants or reductants. Fig.14 A method for chlorosulfonylation of olefins by electrolysis under manganese-based catalyst or organoboron reagent conditions is reported (references: M. Yu, A. Lei, Cell Rep. Phys. Sci. 2021, 2, No. 100476; b) X. Peng, X. Zheng, Org. Lett. 2024, 26, 4018-4023.).

[0004] However, the methods in the prior art are basically about the 1,2-difunctionalization of unsaturated bonds, and there are fewer reports on the 1,4-difunctionalization of olefins. Although the chlorosulfonylation of olefins has also developed rapidly in recent years, there has been no report on 1,4-chlorosulfonylation. Summary of the invention

[0005] The purpose of the present invention is to provide a method for preparing 1,4-sulfonylated chlorinated compounds by using visible light to initiate free radical reactions, so as to solve the problems existing in the above-mentioned prior art.

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

[0007] One of the technical solutions of the present invention is a method for preparing 1,4-sulfonylated chlorinated compounds by free radical reaction induced by visible light, comprising the following steps:

[0008] The cyclobutyl olefin derivative, the sulfonyl chloride compound, the base, the photosensitive catalyst and the solvent are uniformly mixed, and the mixture is subjected to visible light illumination reaction under a nitrogen atmosphere to obtain the 1,4-sulfonylated chlorinated compound;

[0009] The structural formula of the cyclobutyl olefin derivative is shown in formula (1):

[0010]

[0011] The structural formula of the sulfonyl chloride compound is shown in formula (2):

[0012]

[0013] The structural formula of the 1,4-sulfonylated chlorinated compound is shown in formula (3):

[0014]

[0015] Among them, R 1 and R 2 Each is independently selected from any one of an aryl group and an alkyl group.

[0016] In the technical solution of the present invention, the aryl group is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole or thiophene.

[0017] In the technical solution of the present invention, the substituent in the substituted phenyl, naphthalene, furan, pyrrole or thiophene is selected from one or more of hydrogen, alkyl, halogen atom, ester group, nitro group, cyano group, phenyl, trifluoromethyl and alkoxy group.

[0018] In the technical solution of the present invention, the molar ratio of the cyclobutyl olefin derivative (cyclobutanol compound substituted with an exocyclic alkenyl group), the sulfonyl chloride compound and the base is 1:(1.5-2):(1.5-2).

[0019] In the technical solution of the present invention, the molar percentage of the photosensitive catalyst and the cyclobutyl olefin derivative is 2-3 mol%.

[0020] In the technical solution of the present invention, the photosensitive catalyst comprises Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 、Ir(ppy) 2 (dtbbpy)PF 6 or fac-Ir(ppy) 3, preferably fac-Ir(ppy) 3 .

[0021] In the technical solution of the present invention, the visible light is blue light (the light source is 15 to 30W blue light);

[0022] The temperature of the light irradiation reaction is 20-70° C., and the time is 0.5-10 hours.

[0023] Preferably, the temperature of the light irradiation reaction is 30° C. and the time is 7 hours.

[0024] In the technical solution of the present invention, the solvent includes at least one of acetonitrile (MeCN), water, dichloroethane, 1,2-dichloroethane (DCE), 1,4-dioxane, ethyl acetate, N,N-dimethylformamide (DMF) and tetrahydrofuran (THF), preferably acetonitrile.

[0025] In the technical solution of the present invention, the base includes Na 2 CO 3 , K 2 CO 3 , NaOAc or Et 3 N.

[0026] Under the condition of blue light irradiation, electron transfer occurs between the sulfonyl chloride in the sulfonyl chloride compound used in the present invention and the photosensitive catalyst to form a sulfonyl free radical; the free radical preferentially attacks the alkenyl site of the cyclobutanol compound substituted with an exocyclic alkenyl group as a reactant to obtain an alkyl free radical, and at the same time, due to the tension effect of the four-membered ring and the energy level difference of the free radical, a carbon-carbon bond on the cyclobutyl group is broken, and a new free radical with higher thermodynamic stability is generated after the free radical transfer, and finally the free radical is further oxidized to generate a carbon cation, which combines with a chloride ion to obtain a 1,4-sulfonylated chlorinated compound (a configuration of a 1,4-sulfonylated chlorinated compound).

[0027] For example, cyclobutanol compounds substituted with an exocyclic alkenyl group are reacted with sulfonyl radical precursor sulfonyl chloride compounds (such as methylbenzenesulfonyl chloride) in acetonitrile, and 1,4-sulfonylated chlorinated compounds are obtained through free radical addition / cyclobutanol ring opening under blue light irradiation.

[0028] The reaction mechanism for preparing 1,4-sulfonylated chlorinated compounds is as follows (R 1 =R):

[0029]

[0030] Toluenesulfonyl chloride (sulfonyl chloride compound) reacts with an excited photosensitive catalyst to obtain electrons and decompose to generate toluenesulfonyl radicals and chloride ions; the radical attacks the alkenyl site of the cyclobutane compound substituted with an exocyclic alkenyl group, and then the newly generated alkyl radical A undergoes four-membered ring opening / radical transfer to obtain radical B, which is then oxidized to obtain carbon cation intermediate C, and carbon cation intermediate C reacts with chloride ions to form sulfonyl-substituted 1,4-sulfonylated chlorinated compound 3.

[0031] The second technical solution of the present invention: a 1,4-sulfonylated chlorinated compound prepared by the above method.

[0032] The third technical solution of the present invention: an application of the above-mentioned 1,4-sulfonylated chlorinated compound as an intermediate for synthesizing natural product molecules or drug molecules.

[0033] The present invention discloses the following technical effects:

[0034] (1) The 1,4-sulfonylated chlorinated compound synthesized by the present invention has a strong derivatization property and can be used as an intermediate for synthesizing natural product molecules or drug molecules.

[0035] (2) The present invention can prepare 1,4-sulfonylated chlorinated compounds under mild and green reaction conditions by carrying out a photocatalytic reaction in the presence of a small amount of photosensitive catalyst. In addition, the present invention uses a small amount of catalyst, has a simple reaction system, and has a short reaction time.

[0036] (3) Under the action of light, the photosensitive catalyst of the present invention undergoes single electron transfer with sulfonyl chloride compounds to obtain sulfonyl radicals, which selectively add to the double bonds of cyclobutanol compounds substituted with exocyclic alkenyl groups, and then undergo carbon-carbon bond homolysis / radical transfer to obtain a new, more stable free radical, which is further oxidized and captured by chloride ions to obtain 1,4-sulfonylated chlorinated compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0038] Figure 1 The product 3a prepared in Example 1 of the present invention 1 H NMR spectrum;

[0039] Figure 2 The product 3a prepared in Example 1 of the present invention 13C NMR spectrum;

[0040] Figure 3 The product 3b prepared in Example 2 of the present invention 1 H NMR spectrum;

[0041] Figure 4 The product 3b prepared in Example 2 of the present invention 13 C NMR spectrum;

[0042] Figure 5 The product 3c prepared in Example 3 of the present invention is 1 H NMR spectrum;

[0043] Figure 6 The product 3c prepared in Example 3 of the present invention is 13 C NMR spectrum;

[0044] Figure 7 The product 3d prepared in Example 4 of the present invention 1 H NMR spectrum;

[0045] Figure 8 The product 3d prepared in Example 4 of the present invention 13 C NMR spectrum;

[0046] Fig. 9 The product 3e prepared in Example 5 of the present invention 1 H NMR spectrum;

[0047] Fig.10 The product 3e prepared in Example 5 of the present invention 13 C NMR spectrum;

[0048] Fig.11 The product 3f prepared in Example 6 of the present invention 1 H NMR spectrum;

[0049] Fig.12 The product 3f prepared in Example 6 of the present invention 13 C NMR spectrum;

[0050] Fig.13 The present invention is a reaction flow chart of the visible light photocatalysis mediated by transition metals to realize chlorosulfonylation of olefins in the prior art;

[0051] Fig.14 The present invention is a reaction flow chart of realizing chlorosulfonylation of olefins by electrochemical method under the condition of manganese-based catalyst or organic boron reagent in the prior art. DETAILED DESCRIPTION

[0052] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0053] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0054] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation 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 associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0055] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to the skilled artisan. The present invention description and examples are exemplary only.

[0056] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0057] In a first aspect of the present invention, a method for preparing a 1,4-sulfonylated chlorinated compound by a free radical reaction initiated by visible light is provided, comprising the following steps:

[0058] The cyclobutyl olefin derivative, the sulfonyl chloride compound, the base, the photosensitive catalyst and the solvent are uniformly mixed, and the mixture is subjected to visible light irradiation reaction under a nitrogen atmosphere to obtain a 1,4-sulfonylated chlorinated compound;

[0059] The structural formula of the cyclobutyl olefin derivative is shown in formula (1):

[0060]

[0061] The structural formula of sulfonyl chloride compounds is shown in formula (2):

[0062]

[0063] The structural formula of the 1,4-sulfonylated chlorinated compound is shown in formula (3):

[0064]

[0065] Among them, R 1 and R 2 Each is independently selected from any one of an aryl group and an alkyl group.

[0066] In the technical solution of the present invention, the aryl group is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole or thiophene.

[0067] In the technical solution of the present invention, 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 group or alkoxy group.

[0068] In the technical solution of the present invention, the molar ratio of the cyclobutyl olefin derivative (cyclobutanol compound substituted with an exocyclic alkenyl group), the sulfonyl chloride compound and the base is 1:1.5:1.5.

[0069] In the technical solution of the present invention, the molar percentage of the photosensitive catalyst and the cyclobutyl olefin derivative is 2-3 mol%.

[0070] In the technical solution of the present invention, the photosensitive catalyst comprises Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 、Ir(ppy) 2 (dtbbpy)PF 6 or fac-Ir(ppy) 3 , preferably fac-Ir(ppy) 3 .

[0071] In the technical solution of the present invention, the visible light is blue light (the light source is 15 to 30W blue light);

[0072] And / or, the temperature of the light irradiation reaction is 20-70° C., and the time is 0.5-10 h.

[0073] Preferably, the temperature of the light irradiation reaction is 30° C. and the time is 7 hours.

[0074] In the technical solution of the present invention, the solvent includes at least one of acetonitrile (MeCN), water, dichloroethane, 1,2-dichloroethane (DCE), 1,4-dioxane, ethyl acetate, N,N-dimethylformamide (DMF) and tetrahydrofuran (THF), preferably acetonitrile.

[0075] In the technical solution of the present invention, the base includes Na 2 CO 3 , K 2 CO 3 , NaOAc or Et 3 N.

[0076] The compounds of the structures shown in formula (1) and (2) of the present invention can be prepared into 1,4-sulfonylated chlorinated compounds under the condition of irradiation with a blue light lamp, because the compounds of the structures shown in formula (1) can break the carbon-carbon bond on the cyclobutane under the action of the sulfonyl free radical generated by the compounds of the structures shown in formula (2), and generate a new free radical that is more thermodynamically stable. Finally, the free radical is further oxidized to generate a carbon cation, which combines with a chloride ion to obtain a 1,4-sulfonylated chlorinated compound.

[0077] In a second aspect, the present invention provides a 1,4-sulfonylated chlorinated compound prepared by the above preparation method.

[0078] The third aspect of the present invention provides a use of the above-mentioned 1,4-sulfonylated chlorinated compound as an intermediate for synthesizing natural product molecules or drug molecules.

[0079] Example 1

[0080] Method for preparing 1,4-sulfonylated chlorinated compounds by free radical reaction induced by visible light:

[0081] In a reaction tube, cyclobutyl olefin derivative 1a (50.0 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (57.0 mg, 0.3 mmol, 1.5 equiv.), sodium carbonate (33.0 mg, 0.3 mmol, 1.5 equiv.), sodium chloride (24.0 mg, 0.4 mmol, 2.0 equiv.), and photosensitive catalyst fac-Ir(ppy) were added. 3 (3.0 mg, 0.004 mmol, 2.0% mmol), solvent MeCN (acetonitrile, 3 mL), H 2 O (72 mg, 4.0 mmol, 20.0 equiv), mixed evenly, and then irradiated with a 30 W blue light lamp in a nitrogen atmosphere for 9 h (the temperature of the irradiation reaction was 30 ° C). After the reaction, the reaction product was transferred to a round-bottom flask, silica was added to the round-bottom flask, and the solvent was evaporated in vacuo. The product was purified by silica gel column chromatography using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent to obtain a 1,4-sulfonylated chloro compound, i.e., product 3a, with a yield of 77%.

[0082] The reaction formula for preparing product 3a is as follows:

[0083]

[0084] The product 3a prepared in this example 1 H NMR spectrum is shown in Figure 1 , 13 C NMR spectrum is shown in Figure 2 ; NMR data of product 3a: 1 H NMR (600 MHz, CDCl 3 )δ7.80(s,1H),7.75(d,J=7.8Hz,2H),7.37(s,5H),7.32(d,J=8.4Hz,2H),7.19(d,J=9.0Hz,2H),6.87(d,J=8.4Hz ,2H),4.63(t,J=6.0Hz,1H),3.82(s,3H),2.64-2.59(m,1H),2.51-2.2.46(m,1H),2.45(s,3H),1.98-1.95(m,1H). 13 C NMR (101 MHz, CDCl 3 )δ159.2,144.4,141.2,138.1,136.5,135.9,133.5,73.2,55.4,37.1,23.3,21.7.HR-MS(ESI)m / z calc.for C 25 H 25 O 3 S[M] + :405.1509,found:405.1496.

[0085] Example 2

[0086] Method for preparing 1,4-sulfonylated chlorinated compounds by free radical reaction induced by visible light:

[0087] In a reaction tube, cyclobutyl olefin derivative 1b (65.5 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (57.0 mg, 0.3 mmol, 1.5 equiv.), sodium carbonate (33.0 mg, 0.3 mmol, 1.5 equiv.), sodium chloride (24.0 mg, 0.4 mmol, 2.0 equiv.), and photosensitive catalyst fac-Ir(ppy) were added. 3 (3.0 mg, 0.004 mmol, 2.0% mmol), solvent MeCN (acetonitrile, 3 mL), H 2O (72 mg, 4.0 mmol, 20.0 equiv), mixed evenly, and then irradiated with a 30 W blue light lamp under a nitrogen atmosphere for 9 h (the temperature of the irradiation reaction was 30 ° C). After the reaction, the reaction product was transferred to a round-bottom flask, silica was added to the round-bottom flask, and the solvent was evaporated in vacuo. The 1,4-sulfonylated chloro compound, i.e., product 3b, was purified by silica gel column chromatography using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent to obtain a 1,4-sulfonylated chloro compound, i.e., product 3b, with a yield of 36%.

[0088] The reaction formula for preparing product 3b is as follows:

[0089]

[0090] The product 3b prepared in this example 1 H NMR spectrum is shown in Figure 3 , 13 C NMR spectrum is shown in Figure 4 ; NMR data of product 3b: 1 H NMR (600 MHz, CDCl 3 )δ7.74(d,J=8.4Hz,2H),7.71(s,1H),7.60(s,H),7.50(d,J=7.8Hz,1H),7 .33(d,J=7.8Hz,2H),7.29(dd,J=8.7,1.5Hz,1H),7.23(d,J=7.8Hz,1H),7. 19(d,J=9.0Hz,2H),6.87(d,J=8.4Hz,2H),4.63(t,J=6.6Hz,1H),3.82(s, 3H),2.62-2.57(m,1H),2.46(s,3H),2.42-2.35(m,1H),1.96-1.91(m,2H). 13 C NMR (151 MHz, CDCl 3 )δ159.2,144.6,143.2,136.3,136.2,135.8,135.6,132.5,132.4,130.4,130.1, 128.5,128.0,127.1,123.0,114.0,73.2,55.4,37.2,23.4,21.8.HR-MS(ESI)m / z calc.forC 25 H 24 B O 3 S[M] + :483.0624,found:485.0619.

[0091] Example 3

[0092] Method for preparing 1,4-sulfonylated chlorinated compounds by free radical reaction induced by visible light:

[0093] In a reaction tube, cyclobutyl olefin derivative 1c (51.2 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (57.0 mg, 0.3 mmol, 1.5 equiv.), sodium carbonate (33.0 mg, 0.3 mmol, 1.5 equiv.), sodium chloride (24.0 mg, 0.4 mmol, 2.0 equiv.), and photosensitive catalyst fac-Ir(ppy) were added. 3 (3.0 mg, 0.004 mmol, 2.0% mmol), solvent MeCN (acetonitrile, 3 mL), H 2 O (72 mg, 4.0 mmol, 20.0 equiv), mixed evenly, and then irradiated with a 30 W blue light lamp under a nitrogen atmosphere for 9 h (the temperature of the irradiation reaction was 30 ° C). After the reaction, the reaction product was transferred to a round-bottom flask, silica was added to the round-bottom flask, and the solvent was evaporated in vacuo. The 1,4-sulfonylated chloro compound, i.e., product 3c, was purified by silica gel column chromatography using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent to obtain a 1,4-sulfonylated chloro compound, i.e., product 3c, with a yield of 31%.

[0094] The reaction formula for preparing product 3c is as follows:

[0095]

[0096] The product 3c prepared in this example 1 H NMR spectrum is shown in Figure 5 , 13 C NMR spectrum is shown in Figure 6 ; NMR data of product 3c: 1 H NMR (600 MHz, CDCl 3 )δ7.77(s,1H),7.75(d,J=8.4Hz,2H),7.50(dd,J=3.0,1.3Hz,1H),7.34-7.33(m,1H),7.32(s,1H),7.31(s,1H),7.23(d,J=9.0Hz,2H),7.20(d, J=6.0Hz,1H),6.89(d,J=8.4Hz,2H),4.70(t,J=6.6Hz,1H),3.84(s,3H) ,2.69-2.64(m,1H),2.54-2.48(m,1H),2.45(s,3H),1.96-1.93(m,2H). 13 C NMR (151 MHz, CDCl 3)δ159.3,144.3,139.0,136.7,136.0,134.8,131.5,129.9,129.2,128.5, 128.3,127.2,126.6,114.0,73.2,55.5,36.9,23.7,21.7.HR-MS(ESI)m / z calc.for C 23 H 23 O 3 S 2 [M] + :411.1083,found:411.1080.

[0097] Example 4

[0098] Method for preparing 1,4-sulfonylated chlorinated compounds by free radical reaction induced by visible light:

[0099] In a reaction tube, cyclobutyl olefin derivative 1d (64.0 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (57.0 mg, 0.3 mmol, 1.5 equiv.), sodium carbonate (33.0 mg, 0.3 mmol, 1.5 equiv.), sodium chloride (24.0 mg, 0.4 mmol, 2.0 equiv.), and photosensitive catalyst fac-Ir(ppy) were added. 3 (3.0 mg, 0.004 mmol, 2.0% mmol), solvent MeCN (acetonitrile, 3 mL), H 2 O (72 mg, 4.0 mmol, 20.0 equiv), mixed evenly, and then irradiated with a 30W blue light lamp in a nitrogen atmosphere for 9 h (the temperature of the irradiation reaction was 30°C). After the reaction, the reaction product was transferred to a round-bottom flask, silica was added to the round-bottom flask, and the solvent was evaporated in vacuo. The product was purified by silica gel column chromatography using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent to obtain a 1,4-sulfonylated chloro compound, i.e., product 3d, with a yield of 40%.

[0100] The reaction formula for preparing product 3d is as follows:

[0101]

[0102] The product 3d prepared in this example 1 H NMR spectrum is shown in Figure 7 , 13 C NMR spectrum is shown in Figure 8 ; NMR data of product 3d: 1 H NMR (600 MHz, CDCl 3)δ7.80(s,1H),7.76(d,J=8.4Hz,2H),7.60(d,J=7.8Hz,2H),7.45(d,J=8.4Hz,2H),7.35(s,1H),7.34(s,1H),7.18(d,J=8.4Hz,2H ),6.88(d,J=8.4Hz,2H),4.63(t,J=6.6Hz,1H),3.83(s,3H),2.62-2.57(m,1H),2.49-2.47(m,1H),2.47(s,1H),1.96-1.92(m,2H). 13 CNMR (151MHz, CDCl 3 )δ159.4,144.8,144.1,137.1,136.3,135.7,130.1,129.7,128.5,127.2,12 5.8(d,J=4.5),114.0,73.2,55.4,37.3,23.3,21.8.HR-MS(ESI)m / zcalc.for C 26 H 24 F 3 O 3 S[M] + :473.1393,found:473.1391.

[0103] Example 5

[0104] Method for preparing 1,4-sulfonylated chlorinated compounds by free radical reaction induced by visible light:

[0105] In a reaction tube, cyclobutyl olefin derivative 1e (54.0 mg, 0.2 mmol, 1.0 equiv.), p-toluenesulfonyl chloride 2a (57.0 mg, 0.3 mmol, 1.5 equiv.), sodium carbonate (33.0 mg, 0.3 mmol, 1.5 equiv.), sodium chloride (24.0 mg, 0.4 mmol, 2.0 equiv.), and photosensitive catalyst fac-Ir(ppy) were added. 3 (3.0 mg, 0.004 mmol, 2.0% mmol), solvent MeCN (acetonitrile, 3 mL), H 2O (72 mg, 4.0 mmol, 20.0 equiv), mixed evenly, and then irradiated with a 30 W blue light lamp under a nitrogen atmosphere for 9 h (the temperature of the irradiation reaction was 30 ° C). After the reaction, the reaction product was transferred to a round-bottom flask, silica was added to the round-bottom flask, and the solvent was evaporated in vacuo. The 1,4-sulfonylated chloro compound, i.e., product 3e, was purified by silica gel column chromatography using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent to obtain a 1,4-sulfonylated chloro compound, i.e., product 3e, with a yield of 68%.

[0106] The reaction formula for preparing product 3e is as follows:

[0107]

[0108] The product 3e prepared in this example 1 H NMR spectrum is shown in Fig. 9 , 13 C NMR spectrum is shown in Fig.10 ; NMR data of product 3e: 1 H NMR (400 MHz, CDCl 3 )δ7.76(s,1H),7.75(s,1H),7.74(s,1H),7.38-7.35(m,2H),7.34(s,1H),7.32(s,1H),7.20(s,1H),7.18(s,1H),7.04(t,J=8.6Hz,2H ),6.89(s,1H),6.87(s,1H),4.64(t,J=6.2Hz,1H),3.83(s,3H),2.63-2.56(m,1H),2.50-2.48(m,1H),2.45(s,3H),1.96-1.91(m,2H). 13 CNMR (101MHz, CDCl 3 )δ163.3(d,J=251.5),159.3,144.5,141.0(d,J=2.0),136.7,136.4,135.9,131.8(d,J=8.1),130.0,129.7 (d,J=4.0),128.4,127.2,116.2(d,J=22.2),114.0,73.2,55.5,37.0,23.2,21.8.HR-MS(ESI)m / zcalc.for C 25 H 24 FO 3 S[M] + :423.1425,found:423.1423.

[0109] Example 6

[0110] Method for preparing 1,4-sulfonylated chlorinated compounds by free radical reaction induced by visible light:

[0111] In a reaction tube, cyclobutyl olefin derivative 1a (50.0 mg, 0.2 mmol, 1.0 equiv.), 2-chloro-3-methylbenzenesulfonyl chloride 2b (67.5 mg, 0.3 mmol, 1.5 equiv.), sodium carbonate (33.0 mg, 0.3 mmol, 1.5 equiv.), sodium chloride (24.0 mg, 0.4 mmol, 2.0 equiv.), and photosensitive catalyst fac-Ir(ppy) were added. 3 (3.0 mg, 0.004 mmol, 2.0% mmol), solvent MeCN (acetonitrile, 3 mL), H 2 O (72 mg, 4.0 mmol, 20.0 equiv), mixed evenly, and then irradiated with a 30W blue light lamp in a nitrogen atmosphere for 9 h (the temperature of the irradiation reaction was 30°C). After the reaction, the reaction product was transferred to a round-bottom flask, silica was added to the round-bottom flask, and the solvent was evaporated in vacuo. The product was purified by silica gel column chromatography using n-hexane / EtOA (n-hexane / ethyl acetate, v / v, 5:1) as the eluent to obtain a 1,4-sulfonylated chloro compound, i.e., product 3f, with a yield of 53%.

[0112] The reaction formula for preparing product 3f is as follows:

[0113]

[0114] The product 3f prepared in this example 1 H NMR spectrum is shown in Fig.11 , 13 C NMR spectrum is shown in Fig.12 ; NMR data of product 3f: 1 H NMR (600 MHz, CDCl 3 )δ7.85(d,J=1.8Hz,1H),7.81(s,1H),7.64(d,J=9.6Hz,1H),7.40-7.38(m,6H),7.21(d,J=8.4Hz,2H),6.89(d,J=8. 4Hz,2H),4.66(t,J=6.6Hz,1H),3.83(s,3H),2.65-2.60(m,1H),2.51-2.49(m,1H),2.47(s,3H),2.02-1.99(m,2H). 13 CNMR (151MHz, CDCl 3)δ159.2,142.3,140.5,138.8,138.5,135.7,135.4,133.2,131.6,129.8,129.7, 128.9,128.7,127.1,126.4,113.9,73.1,55.3,37.0,23.3,20.4.HR-MS(ESI)m / z calc.for C 25 H 24 O 3 S[M] + :439.1134,found:439.1123.

[0115] Example 7

[0116] The same as Example 1, the only difference is that the reaction conditions (Table 1) are changed, and the yield of 1,4-sulfonylated chlorinated compound prepared by visible light induced free radical reaction under different reaction conditions is statistically analyzed.

[0117] Table 1 Reaction conditions

[0118] Reaction parameters:

[0119] Reaction parameters of groups 1 to 25 [a]: 1a (0.20 mmol), 2a (0.30 mmol, 1.0 equiv), solvent (3 mL), N 2 The amount of photosensitive catalyst used was 2% mmol of that used in 1a, and the reaction was irradiated with light (30 W blue light) for 9 h at room temperature.

[0120] [b] is based on [a] without adding NaCl;

[0121] [c] changes the amount of NaCl based on [a], and the amount of NaCl is twice that of 1a;

[0122] [d] is to change the dosage of the photosensitive catalyst based on [a], and the dosage of the photosensitive catalyst is 0.5 times the dosage in 1a;

[0123] [e] is to change the 30W blue light to 15W blue light based on [a];

[0124] [f] is based on [a] and N 2 Change to air.

[0125] [g] is based on [a], the photosensitizer fac-Ir(ppy) 3 Changed to EosinY.

[0126] [h] is based on [a], the photosensitizer fac-Ir(ppy)3 Change to [Ru(bpy) 3 ]Cl 2 .

[0127] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A method for preparing 1,4-sulfonylated chlorinated compounds by free radical reaction induced by visible light, characterized in that: The following steps are involved: The cyclobutyl olefin derivative, the sulfonyl chloride compound, the base, the photosensitive catalyst and the solvent are uniformly mixed, and the mixture is subjected to visible light illumination reaction under a nitrogen atmosphere to obtain the 1,4-sulfonylated chlorinated compound; The structural formula of the cyclobutyl olefin derivative is shown in formula (1): The structural formula of the sulfonyl chloride compound is shown in formula (2): The structural formula of the 1,4-sulfonylated chlorinated compound is shown in formula (3): Among them, R 1 and R 2 Each is independently selected from any one of an aryl group and an alkyl group.

2. The method according to claim 1, characterized in that: The aryl group is selected from any one of substituted or unsubstituted phenyl, naphthalene, furan, pyrrole or thiophene.

3. The method according to claim 2, characterized in that The substituents in the substituted phenyl, naphthalene, furan, pyrrole or thiophene are selected from one or more of hydrogen, alkyl, halogen atom, ester group, nitro group, cyano group, phenyl group, trifluoromethyl group and alkoxy group.

4. The method according to claim 1, characterized in that: The molar ratio of the cyclobutyl olefin derivative, the sulfonyl chloride compound and the base is 1:(1.5-2):(1.5-2).

5. The method according to claim 1, characterized in that The photosensitive catalyst includes Ir[dF(CF3)ppy]2(dtbbpy)PF6, Ir(ppy)2(dtbbpy)PF6 or fac-Ir(ppy)3.

6. The method according to claim 1, characterized in that The visible light is blue light; And / or, the temperature of the light irradiation reaction is 20-70° C., and the time is 0.5-10 h.

7. A 1,4-sulfonylated chlorinated compound prepared by the method according to any one of claims 1 to 6.

8. Use of the 1,4-sulfonylated chlorinated compound according to claim 7 as an intermediate for synthesizing natural product molecules or drug molecules.

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