Preparation method of (Z)-beta-sulfonamido-alpha, beta-unsaturated carbonyl series compounds

Abstract

The invention relates to a preparation method of a (Z)-beta-sulfonamide-alpha, beta-unsaturated carbonyl series compound, which comprises the following steps of: carrying out high-selectivity C (sp2)-H bond direct amination reaction on a compound containing alpha, beta-unsaturated carbonyl and N-fluoro diaryl sulfonamide serving as reaction substrates under the combined action of a cheap and easily available copper catalyst and alkali, thereby obtaining the (Z)-beta-sulfonamide-alpha, beta-unsaturated carbonyl series compound. (Z)-beta-sulfamido-alpha, beta-unsaturated carbonyl series compounds are prepared with high efficiency and high stereoselectivity. According to the method, the (Z)-type olefin derivative can be directionally obtained. The method has the advantages of high reaction chemical, regional and stereoselectivity, wide substrate applicability, simple reaction operation, mild reaction conditions, short reaction time, extremely low cost, simple operation and low requirements on equipment, and is suitable for large-scale preparation.

Description

Technical Field

[0001] The invention relates to a derivative of an olefin drug skeleton containing imine, and in particular to a preparation method of a (Z)-β-sulfonamide-α,β-unsaturated carbonyl series compound. Background Art

[0002] Olefins are one of the most common and abundant raw materials in industrial production. Olefins are a class of compounds containing unsaturated carbon-carbon double bonds, whose double bonds consist of a σ bond and a π bond. Because the "shoulder-to-shoulder" overlapping mode of π bonds is unstable and easy to break, olefins are prone to various chemical reactions such as addition. Based on such characteristics, olefins have a very important position in organic chemical reactions and have many and important application transformations. For example, polyolefins are polymer compounds formed by addition polymerization of olefins. Due to their good chemical corrosion resistance, small mass and excellent physical properties, people have applied them to the manufacture of special chemicals such as biomedicine, bulletproof vests, load-bearing fields and high-performance rubbers [ZakariaM, Bhuiyan MAR, Hossain M S. Discover Nano., 2024, 19: 24-60; Higman CS, Lummiss JAM, Fogg D E, Angew. Chem. Int. Ed., 2016, 55: 3552-3565.].

[0003] Olefin functionalization is an important reaction in organic chemistry, and its core lies in the introduction of functional groups on olefin molecules. The advantage of this reaction strategy is that it can be used to convert the C(sp) of olefins into functional groups in a single reaction step. 2) to form chemical bonds, thereby increasing the structural complexity and functionality of the molecule. This property provides a powerful method for organic synthesis and helps to synthesize compounds with specific functions and properties. In 2006, the Doris research group reported a reaction to achieve efficient conversion of alcohol to dibenzenesulfonamide [Emerson G, Eric D, Bernard R. Tetrahedron Letters., 2006, 47: 8457-8458.]. In this process, the synergistic effect of triphenylphosphine and N-fluorodibenzenesulfonamide played a key role. This conversion strategy demonstrates the potential and application value in the conversion of alcohol to dibenzenesulfonamide. However, this strategy requires a long time, so the requirements for equipment are strict during large-scale preparation, and the production cost is high. Subsequently, in 2015, the Studer group reported the free radical amination oxidation of olefins with N-fluorodiphenylsulfonamide (N-fluorodiphenylsulfonamide) and TEMPONa [LiY, HartmannM, DaniliucCG, StuderA.Chem.Commun, 2015, 51: 5706-5709.]. The reaction uses trifluorotoluene as a solvent, and the ortho-amino oxidation product can be obtained in moderate to good yields at room temperature for 6 hours, which greatly shortens the reaction time. However, trifluorotoluene, which is highly toxic, is used as a solvent, which poses a great safety hazard. In 2021, the Zhang group reported an efficient and versatile free radical hydrogenation reaction, which is catalyzed by CoII-Sharon complex and initiated by the HAT (hydrogen atom transfer) process [Qin T, Lv G, Meng Q, Zhang G, Xiong T, Zhang Q.Angew.Chem.Int.Ed., 2021, 60: 25949-25957.]. The reaction shows good compatibility with a variety of olefins. This conversion not only proceeds at room temperature, but also shows a wide range of functional group tolerance and high chemical and regional selectivity. The only drawback is that the reaction requires the use of a special Co II-Sharon complex as a catalyst, which is difficult to synthesize and expensive to mass produce.

[0004] In pharmacology, sulfonamide structures have attracted much attention due to their wide application and importance. They are commonly found in drugs for the treatment and prevention of various diseases [Paramita M, Cristian PW, Leah C, Mark R, Ryan WF, Matthew R R, Joseph WT, John MH, Sarah ME, Sabrina CK, Christopher W E, Nicholas DB. Org. Lett., 2018, 20(13): 3943-3947.]. For example, Crestor (rosuvastatin), as a statin, is mainly used to treat cardiovascular diseases such as hypercholesterolemia and coronary heart disease [Ren Y, Zhu H, Fan Z, Gao Y and Tian N. Exp Ther Med., 2017, 14: 4942-4950.]. It inhibits HMG-CoA reductase and reduces the synthesis of cholesterol in the liver, thereby effectively reducing the cholesterol level in the blood. On the other hand, Imitrex Oral (sumatriptan) is a serotonin receptor agonist, particularly used to treat acute symptoms of migraine with or without aura in adults [Blaise A, Amanda LY, Jehan ZB, Harold L, Michael RR. Kidney Int Rep., 2018, 3: 1233-1236.]. It significantly reduces the pain and other related symptoms of migraine by constricting blood vessels and inhibiting the release of specific neurotransmitters. In addition, Hydrochlorothiazide is a chemical and drug belonging to the hydrochlorothiazide class of diuretics [Moran AE, Whelton PK, Frieden T R. Jama Intern Med., 2020, 180: 1132-1133.]. Its working principle is mainly to inhibit the reabsorption of sodium and chloride by the renal tubules, thereby increasing urine volume, reducing blood volume and lowering blood pressure. Hydrochlorothiazide is often used to treat hypertension and edema, and is also used to prevent and treat certain kidney diseases and cardiovascular diseases. These drugs have significant importance in the field of pharmacology due to their unique structure and function, and provide effective means for the treatment of various diseases. Therefore, the synthesis of compounds containing sulfonamide structures is particularly important and has great practical value.

[0005] The above method provides an alternative route for synthesizing α,β-unsaturated carbonyl compounds containing sulfonamide structures. However, the current method requires multi-step synthesis reactions, raw materials are not easy to obtain, and expensive precious metal catalysts are required. The obtained product cannot control the stereostructure of olefins, the synthesis conditions are harsh, and it cannot be prepared on a large scale. Summary of the invention

[0006] The object of the present invention is to provide a method for preparing a series of (Z)-β-sulfonyl-α,β-unsaturated carbonyl compounds. The method has high chemical, regional and stereoselectivity, wide substrate applicability, mild reaction conditions and simple operation. The method can react under simple heating conditions, has a short reaction time and low requirements on equipment, and is suitable for large-scale preparation.

[0007] The present invention uses carbonyl-containing olefins and N-fluorodiarylsulfonamide as reaction substrates in an organic solvent, and reacts for a period of time under the catalytic effect of a copper catalyst and a base at 70-90°C to obtain a product (Z)-β-sulfonamide-α,β-unsaturated carbonyl series compound. The general reaction formula is as follows:

[0008]

[0009] Among them, R 1 is H or various electron-donating groups such as alkyl and alkoxy, or various electron-withdrawing groups such as fluorine and chlorine, or alkenyl, aryl, naphthyl, benzoaryl, etc., R 2 , R 3 , R 4 It is phenyl, naphthyl or aryl or benzoaryl having a substituent.

[0010] Preferably, the copper catalyst is CuCN, cuprous thiophene-2-carboxylate, CuI, Cu2O, CuTc or CuBr2.

[0011] Preferably, the base is K3PO4, K2CO3, Na2CO3, Li2CO3, Cs2CO3, or NaOH.

[0012] Preferably, the organic mixed solvent is 1,4-dichloroethane, acetonitrile, toluene, or 1,4-dioxane.

[0013] Preferably, the reaction temperature is 70-90° C., the reaction time is 1 to 4.0 h by oil bath heating or 0.5 to 1 h by microwave heating.

[0014] On the molecular skeleton of the (Z)-β-sulfonamide-α,β-unsaturated carbonyl series compounds, the structure containing N element, aromatic group and ester group at the end of olefin, while introducing imine, the product of Z configuration is selectively obtained;

[0015]

[0016] Among them, R 1 is H or various electron-donating groups such as alkyl and alkoxy, or various electron-withdrawing groups such as fluorine and chlorine, or alkenyl, aryl, naphthyl, benzoaryl, etc., R 2, R 3 , R 4 It is phenyl, naphthyl or aryl or benzoaryl having a substituent.

[0017] The present invention aims to develop a class of catalysts that utilize cheap and readily available copper salts as catalysts to react with a base to produce C(sp 2 )-H bond direct amination reaction, under simple reaction conditions, a series of compounds containing (Z)-β-sulfonamide-α,β-unsaturated carbonyl groups are synthesized with high efficiency and high chemical selectivity. The method of the present invention has good compatibility with various groups with good reaction activity, such as fluorine, chlorine (halogen), trifluoromethyl (electron-withdrawing group) and other sensitive groups. Therefore, the obtained product can be further transformed, thereby introducing more functional groups on the molecular skeleton of acrylate or α,β-unsaturated ketone containing sulfonamide structure, and at the same time, some other new structure compounds can be constructed.

[0018] The invention has the following beneficial effects: the stereoselectivity of the reaction is perfect, and (Z)-type olefin derivatives can be obtained in a directional manner. The reaction operation is simple, the conditions are mild, the reaction time is short, the cost is extremely low, and it can be applied to large-scale preparation; the chemical selectivity of the reaction is high, and the substrate applicability is wide; the reaction product has good compatibility with various groups that have good reaction activity, such as halogens, unsaturated groups and other sensitive groups. After further conversion, more functional groups can be introduced into the product to construct other novel compounds containing sulfonamide structures, which has very good application prospects in the fields of biomedicine, pesticides and materials science. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a schematic diagram of the single crystal structure of Example 6 of the present invention, (Z)-2-(4-methoxyphenyl)-3-(N-(phenylsulfonyl)benzenesulfonamido)methyl acrylate 3f.

[0020] Figure 2 It is the chemical structural formula of Example 6 of the present invention, methyl (Z)-2-(4-methoxyphenyl)-3-(N-(phenylsulfonyl)benzenesulfonamido)acrylate 3f. DETAILED DESCRIPTION

[0021] The following examples are provided to further illustrate the present invention, but are not intended to limit the scope of the present invention.

[0022] Embodiment 1:

[0023]

[0024] N-fluorodiphenylsulfonamide (631 mg), cuprous cyanide (36 mg), K2CO3 (120 mg), and methyl 2-phenylacrylate (390 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, solvent MeCN (10 mL) was added, and the reaction was carried out at 70°C in an oil bath for 3 hours, or under microwave heating for 0.5 hours, and then detected by TLC. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel, and the obtained filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-phenyl-3-(N-(phenylsulfonyl)phenylsulfonamido)methyl acrylate 3a. Yield: 70%. The following is the NMR experimental data of product 3a:

[0025] 1 H NMR (400MHz, CDCl3) δ: 8.13-8.08 (m, 4H), 7.75 (t, J = 7.4Hz, 2H), 7.64 (t, J = 8.0Hz, 4H), 7.47-7.41 (m, 5H), 6.54 (s, 1H), 3.51 (s, 3H).

[0026] 13 C NMR (100MHz, CDCl3) δ: 165.4, 141.5, 139.5, 134.4, 134.2, 129.6, 129.0, 129.0, 128.8, 128.6, 128.2, 123.8, 52.0.

[0027] Embodiment 2:

[0028]

[0029] N-fluorodiphenylsulfonamide (63.1 mg), cuprous thiophene-2-carboxylate (3.8 mg), K3PO4 (14.0 mg), and methyl 2-(4-fluorophenyl)acrylate (43.3 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, solvent MeCN (2.0 mL) was added and the reaction was continued at 70°C for 2.5 hours. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-(4-fluorophenyl)-3-(N-(phenylsulfonyl)phenylsulfonamido)methyl acrylate 3b. Yield: 82%. The following is the NMR experimental data of product 3b:

[0030] 1H NMR (400MHz, CDCl3) δ: 8.07 (d, J=7.6Hz, 4H), 7.71 (t, J=7.5Hz, 2H), 7.60 (t, J= 7.9Hz,4H),7.42-7.36(m,2H),7.09(t,J=8.6Hz,2H),6.49(s,1H),3.46(s,3H).

[0031] 13 C NMR (100MHz, CDCl3) δ: 165.2, 163.6 (d, J = 48.8Hz), 140.3, 139.4, 134.3, 13 0.5,130.5,130.3,130.2,129.1,129.0,128.6,124.0,115.9,115.6,52.1.

[0032] 19 F NMR(376MHz, CDCl3)δ:-111.1,-111.1,-111.1.

[0033] Embodiment three:

[0034]

[0035] N-fluorodiphenylsulfonamide (63.1 mg, 0.2 mmol), CuI (4.6 mg, 10 mol%), Na2CO3 (11.0 mg, 0.6 mmol), and methyl 2-(4-chlorophenyl)acrylate (43.3 mg, 0.24 mmol) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent 1,4-dioxane (2.0 mL) was added and the reaction was continued at 70°C for 2 hours. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-(4-chlorophenyl)-3-(N-(phenylsulfonyl)phenylsulfonamido)methyl acrylate 3c. Yield: 70%. The following is the NMR experimental data of product 3c:

[0036] 1 H NMR (400MHz, CDCl3) δ: 8.07 (d, J = 7.5Hz, 4H), 7.73 (t, J = 7.5Hz, 2H), 7.62 (t, J = 8.0Hz, 4H), 7.37 (q, J = 8.6Hz, 4H), 6.54 (s, 1H), 3.47 (s, 3H).

[0037] 13C NMR (100MHz, CDCl3) δ: 165.1, 140.1, 139.3, 135.8, 134.3, 134.0, 132.8, 129.6, 129.2, 129.1, 128.9, 128.6, 128.0, 124.4, 52.1.

[0038] Embodiment 4:

[0039]

[0040] N-fluorodiphenylsulfonamide (63.1 mg), Cu2O (5.0 mg), Li2CO3 (9.0 mg, 0.6 mmol), and 2-(p-tolyl) methyl acrylate (42.3 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent toluene (1.5 mL) was added and the reaction was continued at 70°C for 2 hours. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-3-(N-(phenylsulfonyl)benzenesulfonamido)-2-(p-tolyl) methyl acrylate 3d. Yield: 68%. The following is the NMR experimental data of product 3d:

[0041] 1 H NMR (400MHz, CDCl3) δ: 8.13-8.06 (m, 4H), 7.73 (t, J = 7.5Hz, 2H), 7.62 (t, J = 8. 0Hz, 4H), 7.27 (dd, J = 31.1, 7.9Hz, 4H), 6.49 (s, 1H), 3.50 (s, 3H), 2.42 (s, 3H).

[0042] 13 C NMR (100MHz, CDCl3) δ: 165.5, 141.5, 139.8, 139.5, 134.1, 129.4, 129.0, 128.6, 128.07, 122.9, 52.0, 21.3.

[0043] Embodiment five:

[0044]

[0045] N-fluorodiphenylsulfonamide (63.1 mg), CuTc (3.8 mg), NaOH (12.0 mg), and methyl 2-(4-(tert-butyl)phenyl)acrylate (52.4 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent 1,4-dichloroethane (1.0 mL) was added and the reaction was continued at 70°C for 1 hour. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-(4-(tert-butyl)phenyl)-3-(N-(phenylsulfonyl)phenylsulfonamido)methyl acrylate 3e. Yield: 66%. The following is the NMR experimental data of product 3e:

[0046] 1 H NMR (400MHz, CDCl3) δ: 8.10 (d, J = 8.0Hz, 4H), 7.73 (t, J = 7.4Hz, 2H), 7.63 (t, J = 7 .4Hz,4H),7.41(dd,J=36.5,7.8Hz,4H),6.52(s,1H),3.50(s,3H),1.37(s,9H).

[0047] 13 C NMR (100MHz, CDCl3) δ: 165.6, 153.0, 141.3, 139.5, 134.2, 131.5, 129.0, 128.6, 127.9, 125.7, 123.0, 52.0, 34.8, 31.2.

[0049] Embodiment six:

[0050]

[0051] N-fluorodiphenylsulfonamide (631 mg), CuCN (35 mg), Na2CO3 (120 mg), and methyl 2-(4-methoxyphenyl)acrylate (462 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent MeCN (10 mL) was added and the reaction was continued at 80°C for 1 hour. The reaction was completely detected by TLC. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-(4-methoxyphenyl)-3-(N-(phenylsulfonyl)phenylsulfonamido)methyl acrylate 3f. Yield: 73%. The following is the NMR experimental data of the product 3f:

[0052] 1H NMR(400MHz, CDCl3)δ:8.08(d,J=7.6Hz,4H),7.72(t,J=7.6Hz,2H),7.61(t,J=7.6Hz,4 H),7.35(d,J=8.5Hz,2H),6.94(d,J=8.5Hz,2H),6.45(s,1H),3.86(s,3H),3.49(s,3H).

[0053] 13 C NMR (100MHz, CDCl3) δ: 165.8, 160.9, 141.2, 139.6, 134.3, 129.7, 129.2, 129.1, 129.0, 126.8, 122.0, 114.2, 55.56, 52.1.

[0054] Embodiment seven:

[0055]

[0056] N-fluorodiphenylsulfonamide (63.1 mg), cuprous thiophene-2-carboxylate (3.8 mg), Na2CO3 (15 mg), and methyl 2-(3-methoxyphenyl)acrylate (46.2 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent 1,4-dioxane (2.0 mL) was added and the reaction was continued at 70°C for 1 to 4 hours. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain a pure product (Z)-2-(3-methoxyphenyl)-3-(N-(phenylsulfonyl)phenylsulfonamido)methyl acrylate 3g. Yield: 80%. The following is the nuclear magnetic resonance experimental data of the product 3g:

[0057] 1 H NMR (400MHz, CDCl3) δ8.09(d,J=7.9Hz,4H),7.73(t,J=7.4Hz,2H),7.62(t,J=7.8Hz, 4H),7.34(t,J=7.9Hz,1H),7.01-6.95(m,3H),6.52(s,1H),3.86(s,3H),3.50(s,3H).

[0058] 13 C NMR (100MHz, CDCl3) δ: 165.2, 159.6, 141.3, 139.4, 135.6, 134.1, 129.6, 129.2, 123.9, 120.6, 115.0, 114.0, 55.4, 52.0.

[0059] Embodiment eight:

[0060]

[0061] N-fluorodiphenylsulfonamide (63.1 mg), CuBr2 (5.8 mg), Cs2CO3 (15.0 mg), and ethyl 2-(4-methoxyphenyl)acrylate (49.5 mg) were added to a test tube under air atmosphere. Solvent 1,4-dioxane (3.0 mL) was added and the reaction was continued at 90°C for 2 hours. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-(4-methoxyphenyl)-3-(N-(phenylsulfonyl)phenylsulfonamido)ethyl acrylate 3h. Yield: 72%. The following is the NMR experimental data of product 3h:

[0062] 1 H NMR (400MHz, CDCl3) δ8.09-8.06(m,4H),7.72(t,J=7.5Hz,2H),7.61(t,J=8.0Hz,4H),7.37(d,J=8.8H z,2H),6.94(d,J=8.8Hz,2H),6.42(s,1H),4.04(q,J=7.1Hz,2H),3.86(s,3H),1.11(t,J=7.1Hz,3H).

[0063] 13 C NMR (100MHz, CDCl3) δ: 165.3, 160.8, 141.6, 139.5, 134.1, 129.5, 129.0, 128.9, 128.8, 128.7, 126.9, 126.8, 121.4, 114.1, 61.6, 55.4, 13.9.

[0064] Embodiment nine:

[0065]

[0066] N-fluorodiphenylsulfonamide (63.1 mg), cuprous thiophene-2-carboxylate (3.8 mg), K3PO4 (15.0 mg), and methyl 2-(naphthalene-2-yl)acrylate (50.9 mg, 0.24 mmol) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent MeCN (1.0 mL) was added and the reaction was continued at 70°C for 3-4 hours. TLC detection showed that the reaction was complete. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-(naphthalene-2-yl)-3-(N-(phenylsulfonyl)phenylsulfonamido)methyl acrylate 3i. Yield: 40%. The following is the NMR experimental data of product 3i:

[0067] 1 H NMR(400MHz, CDCl3)δ8.14(d,J=7.7Hz,4H),7.93-7.87(m,4H),7.75(t,J=7.5Hz,2H),7.64 (t,J=7.9Hz,4H),7.58-7.55(m,2H),7.51(dd,J=8.6,1.5Hz,1H),6.67(s,1H),3.55(s,3H).

[0068] 13 C NMR(100MHz, CDCl3)δ:165.5,141.5,139.5,134.3,133.6,133.0,131.7,129.1,12 8.8,128.7,128.5,128.5,128.4,128.1,127.7,127.2,126.8,125.2,124.0,52.1.

[0069] Embodiment ten:

[0070]

[0071] N-fluorodiphenylsulfonamide (631 mg), cuprous thiophene-2-carboxylate (38 mg), Li2CO3 (90 mg), and ethyl 2-(4-phenoxyphenyl)acrylate (611 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent 1,4-dichloroethane (20 mL) was added and the reaction was continued at 90°C for 2 hours. The reaction was completely detected by TLC. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-(4-phenoxyphenyl)-3-(N-(phenylsulfonyl)phenylsulfonamido)ethyl acrylate 3j. Yield: 80%. The following is the NMR experimental data of product 3j:

[0072] 1 H NMR (400MHz, CDCl3) δ8.10(d,J=7.8Hz,4H),7.74(t,J=7.4Hz,2H),7.63(t,J=7.8Hz,4H),7.45-7.40(m,4H),7.21(t, J=7.4Hz,1H),7.11(d,J=8.0Hz,2H),7.05(d,J=8.6Hz,2H),6.50(s,1H),4.07(q,J=7.2Hz,2H),1.13(t,J=7.2Hz,3H).

[0073] 13 C NMR(100MHz, CDCl3)δ:165.2,158.8,156.3,141.2,139.4,134.2,130.0,129.8,1 29.2,129.1,129.0,128.9,128.7,128.7,124.0,122.4,119.6,118.4,61.7,13.9.

[0074] Embodiment eleven:

[0075]

[0076] N-fluorodiphenylsulfonamide (63.1 mg), CuI (3.8 mg), Li2CO3 (9.0 mg), and 3-(4-methoxyphenyl)but-3-ene-2-one (42.3 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent toluene (1.0 mL) was added and the reaction was continued at 70°C for 1 hour. The reaction was complete when detected by TLC. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-N-(2-(4-methoxyphenyl)-3-oxobut-1-ene-1-yl)-N-(phenylsulfonyl)benzenesulfonamide 3k. Yield: 62%. The following is the nuclear magnetic resonance experimental data of the product 3k:

[0077] 1 H NMR (400MHz, CDCl3) δ8.09(d,J=7.5Hz,4H),7.74(t,J=7.4Hz,2H),7.63(t,J=7.9Hz,4H ),7.20(d,J=8.7Hz,2H),6.95(d,J=8.7Hz,2H),6.08(s,1H),3.85(s,3H),2.27(s,3H).

[0078] 13C NMR (100MHz, CDCl3) δ: 200.7, 160.9, 150.8, 138.7, 134.4, 129.1, 129.0, 128.9, 126.4, 117.3, 114.5, 55.4, 30.4.

[0079] Embodiment 12:

[0080]

[0081] N-fluorodiphenylsulfonamide (63.1 mg), cuprous thiophene-2-carboxylate (3.8 mg), Li2CO3 (9.0 mg), and 1,2-bis(4-methoxyphenyl)prop-2-en-1-one (64.4 mg) were added to the test tube under air atmosphere. After N2 replacement 3-4 times, the solvent 1,4-dioxane (1.0 mL) was added and the reaction was continued at 70°C for 3-4 hours. The reaction was completely detected by TLC. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel, and the filtrate was separated by rapid column chromatography to obtain the pure product (Z)-N-(2,3-bis(4-methoxyphenyl)-3-oxoprop-1-en-1-yl)-N-(phenylsulfonyl)benzenesulfonamide 3l.

[0082] Yield: 68%. The following is the NMR experimental data of product 3l:

[0083] 1 H NMR (400MHz, CDCl3) δ7.95(d,J=8.1Hz,4H),7.86(d,J=8.6Hz,2H),7.68(t,J=7.4Hz,2H),7.54(t ,J=7.6Hz,4H),7.29(d,J=8.7Hz,2H),6.92-6.85(m,4H),6.28(s,1H),3.86(s,3H),3.83(s,3H).

[0084] 13 C NMR (100MHz, CDCl3) δ: 191.7, 163.9, 160.8, 149.8, 138.7, 134.1, 132.8, 129.3, 129.0, 128.8, 128.5, 127.5, 117.5, 114.5, 113.6, 55.5, 55.4.

[0085] Embodiment 13:

[0086]

[0087] N-fluoro-4-methyl-N-(phenylsulfonyl)benzenesulfonamide (65.9 mg), cuprous thiophene-2-carboxylate (3.8 mg), Li2CO3 (9.0 mg), and methyl 2-(4-methoxyphenyl)acrylate (46.2 mg) were added to the test tube under air atmosphere. After N2 replacement 3-4 times, the solvent 1,4-dichloroethane (1.8 mL) was added, and the reaction was continued at 90°C for 1 hour. TLC detection showed that the reaction was complete. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel, and the filtrate was separated by rapid column chromatography to obtain the pure product ((Z)-2-(4-methoxyphenyl)-3-((4-methyl-N-(phenylsulfonyl)phenyl)sulfonamido) methyl acrylate 3m. Yield: 37%. The following is the nuclear magnetic resonance experimental data of the product 3m:

[0088] 1 H NMR (400MHz, CDCl3) δ8.09(d,J=7.4Hz,2H),7.96(d,J=8.3Hz,2H),7.72(t,J=7.4Hz ,1H),7.61(t,J=8.0Hz,2H),7.40(d,J=8.2Hz,2H),7.35(d,J=8.8Hz,2H),6.94(d,J

[0089] =8.8Hz,2H),6.44(s,1H),3.86(s,3H),3.51(s,3H),2.51(s,3H).

[0090] 13 C NMR(100MHz, CDCl3)δ:165.7,160.8,145.3,141.0,139.5,136.5,134.1,1 29.6,129.6,129.0,128.7,128.7,126.8,122.0,114.1,55.4,52.0,21.8.

[0091] Embodiment 14:

[0092]

[0093] 4-(tert-butyl)-N-fluoro-N-(phenylsulfonyl)benzenesulfonamide (74.3 mg), cuprous thiophene-2-carboxylate (3.8 mg), Na2CO3 (18 mg), and methyl 2-(4-methoxyphenyl)acrylate (46.2 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent MeCN (1.0 mL) was added and the reaction was continued at 80°C for 1.5 hours. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-3-((4-(tert-butyl)-N-(phenylsulfonyl)phenyl)sulfonamido)-2-(4-methoxyphenyl)acrylate 3n. Yield: 72%. The following is the nuclear magnetic resonance experimental data of the product 3n:

[0094] 1 H NMR (400MHz, CDCl3) δ8.08(d,J=7.5Hz,2H),7.99(d,J=8.6Hz,2H),7.72(t,J=7.4Hz,1H),7.64-7.58(m ,4H),7.36(d,J=8.7Hz,2H),6.94(d,J=8.8Hz,2H),6.45(s,1H),3.87(s,3H),3.47(s,3H),1.41(s,9H).

[0095] 13 C NMR(100MHz, CDCl3)δ:165.7,160.8,158.2,140.9,139.6,136.4,134.0,129 .6,129.0,128.6,128.5,126.8,126.0,122.2,114.1,55.4,51.9,35.4,31.1.

[0096] Embodiment 15:

[0097]

[0098] N-fluoro-N-(phenylsulfonyl)naphthalene-2-sulfonamide (73.2 mg), cuprous thiophene-2-carboxylate (3.8 mg), K2CO3 (14 mg), and methyl 2-(4-methoxyphenyl)acrylate (46.2 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent toluene (3.0 mL) was added and the reaction was continued at 70°C for 3-4 hours. The reaction was complete after TLC detection. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-(4-methoxyphenyl)-3-(N-(phenylsulfonyl)naphthalene-2-sulfonamido) methyl acrylate 3o. Yield: 72%. The following is the nuclear magnetic resonance experimental data of the product 3o:

[0099] 1 H NMR (400MHz, CDCl3) δ8.64(s,1H),8.13(d,J=8.1Hz,2H),8.10-8.04(m,3H),8.00(d,J=8.1Hz,1H),7. 77-7.61(m,5H),7.38(d,J=8.6Hz,2H),6.95(d,J=8.6Hz,2H),6.51(s,1H),3.88(s,3H),3.44(s,3H).

[0100] 13 C NMR(100MHz, CDCl3)δ:165.7,160.8141.2,139.4,136.2,135.5,134.2,132.0,130.6 ,129.7,129.7,129.6,128.7,128.0,127.8,126.7,123.1,121.9,114.1,55.4,52.0.

[0101] Embodiment 16:

[0102]

[0103] N-fluoro-N-(benzenesulfonyl)-4-(trifluoromethyl)benzenesulfonamide (76.7 mg), cuprous thiophene-2-carboxylate (3.8 mg), Cs2CO3 (12.0 mg), and methyl 2-(4-methoxyphenyl)acrylate (46.2 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent MeCN (1.0 mL) was added and the reaction was continued at 90°C for 0.5 hours. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-2-(4-methoxyphenyl)-3-((N-(benzenesulfonyl)-4-(trifluoromethyl)phenyl)sulfonamido)methyl acrylate 3p. Yield: 72%. The following is the NMR experimental data of the product 3p:

[0104] 1 H NMR (400MHz, CDCl3) δ8.26(d,J=8.2Hz,2H),8.09(d,J=8.0Hz,2H),7.90(d,J=8.2Hz,2H),7.75(t,J=7.3Hz,1H ),7.64(t,J=7.7Hz,2H),7.37(d,J=8.5Hz,2H),6.95(d,J=8.6Hz,2H),6.47(s,1H),3.87(s,3H),3.49(s,3H).

[0105] 13 C NMR (100MHz, CDCl3) δ: 165.4, 161.0, 142.9, 141.7, 139.0, 135.5 (q, J = 33.0Hz), 134.4, 129. 6,129.3,129.1,128.7,128.8,126.4,126.2,126.1,124.5,121.8,121.3,114.1,55.4,52.0.

[0106] 19 FNMR (376MHz,CDCl3)δ:-63.2.

[0107] Embodiment 17:

[0108]

[0109] N-fluorodiphenylsulfonamide (63.1 mg), CuCN (4.6 mg), Li2CO3 (9.0 mg), and methyl cinnamate (39.0 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent MeCN (1.8 mL) was added and the reaction was continued at 70°C for 3-4 hours. The reaction was complete when detected by TLC. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-3-phenyl-3-(N-(phenylsulfonyl)benzenesulfonamido) methyl acrylate 3q. Yield: 50%. The following is the NMR experimental data of the product 3q:

[0110] 1 H NMR (400MHz, CDCl3) δ8.07-7.99(m,5H),7.63-1.58(m,4H),7.46(t,J=7.9Hz,4H),7.32-7.27(m,1H),7.16(t,J=7.8Hz,2H),3.52(s,3H).

[0111] 13 C NMR (100MHz, CDCl3) δ: 165.1, 146.1139.6, 134.1, 131.4, 131.3, 131.2, 129.5, 128.5, 122.3, 52.4.

[0112] Embodiment 18:

[0113]

[0114] N-fluorodiphenylsulfonamide (63.1 mg), cuprous thiophene-2-carboxylate (3.8 mg), K3PO4 (15 mg), and (E)-3-(p-tolyl) methyl acrylate (42.3 mg) were added to a test tube under air atmosphere. After N2 replacement 3-4 times, the solvent toluene (2.0 mL) was added and the reaction was continued at 80°C for 2.5 hours. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-3-(N-(phenylsulfonyl)benzenesulfonamido)-3-(p-tolyl) methyl acrylate 3r. Yield: 77%. The following is the NMR experimental data of product 3r:

[0115] 1H NMR (400MHz, CDCl3) δ8.02(d,J=6.8Hz,5H),7.61(t,J=7.5Hz,2H),7.47(dd,J=17.4,9.0Hz,6H),6.95(d,J=8.0Hz,2H),3.50(s,3H),2.32(s,3H).

[0116] 13 C NMR (100MHz, CDCl3) δ: 165.3, 146.2, 142.2, 139.7, 133.9, 131.4, 129.5, 129.3, 128.5, 121.3, 52.2, 21.5.

[0117] Embodiment 19:

[0118]

[0119] N-fluorodiphenylsulfonamide (631 mg), cuprous thiophene-2-carboxylate (38 mg), Cs2CO3 (90 mg), and (E)-3-(4-chlorophenyl)methyl acrylate (423 mg) were added to the test tube under air atmosphere. After N2 replacement 3-4 times, the solvent 1,4-dichloroethane (8.0 mL) was added and the reaction was continued at 70°C for 3 hours. TLC detected the complete reaction. During post-treatment, other impurities were first removed by suction filtration through a sand core funnel filled with silica gel. The filtrate was separated by rapid column chromatography to obtain the pure product (Z)-3-(4-chlorophenyl)-3-(N-(phenylsulfonyl)phenylsulfonamido)methyl acrylate 3s. Yield: 61%. The following is the NMR experimental data of the product 3s:

[0120] 1 H NMR (400MHz, CDCl3) δ8.04-7.98(m,5H),7.65(t,J=7.4Hz,2H),7.54-7.45(m,6H),7.11(d,J=8.6Hz,2H),4.03(q,J=7.1Hz,2H),1.08(t,J=7.1Hz,3H).

[0121] 13 C NMR (100MHz, CDCl3) δ: 164.4, 144.1, 139.7, 137.4, 134.0, 132.3, 129.8, 129.5, 128.8, 128.6, 123.4, 61.9, 13.8.

Claims

1. A method for preparing a (Z)-β-sulfonamide-α,β-unsaturated carbonyl series compound, characterized in that: The method comprises the following steps: in an organic mixed solvent, using a carbonyl-containing olefin of a structure such as formula I and an N-fluorodiarylsulfonamide of a structure such as formula II as reaction substrates, reacting under the combined action of a copper catalyst and a base to obtain a product (Z)-β-sulfonamide-α,β-unsaturated carbonyl series compound of a structure such as formula III; Among them, R 1 is H or various electron-donating groups such as alkyl and alkoxy, or various electron-withdrawing groups such as fluorine and chlorine, or alkenyl, aryl, naphthyl, or benzoaryl, R 2 , R 3 , R 4 It is phenyl, naphthyl or aryl or benzoaryl having a substituent.

2. The method for preparing the (Z)-β-sulfonylamide-α,β-unsaturated carbonyl series compound according to claim 1, characterized in that: The copper catalyst is CuCN, cuprous thiophene-2-carboxylate, CuI, Cu2O, CuTc or CuBr2.

3. The method for preparing the (Z)-β-sulfonamide-α,β-unsaturated carbonyl series compound according to claim 1, characterized in that: The base is K3PO4, K2CO3, Na2CO3, Li2CO3, Cs2CO3, and NaOH.

4. The method for preparing the (Z)-β-sulfonylamide-α,β-unsaturated carbonyl series compound according to claim 1, characterized in that: The organic solvent is 1,4-dioxane, acetonitrile, toluene or 1,4-dichloroethane.

5. The method for preparing the (Z)-β-sulfonylamide-α,β-unsaturated carbonyl series compound according to claim 1, characterized in that: The reaction temperature is 70-90° C., the reaction time is 1-4.0 h by oil bath heating or 0.5-1 h by microwave heating.

6. A (Z)-β-sulfonylamide-α,β-unsaturated carbonyl series compound having a structure of formula III prepared according to the method of claims 1 to 5, characterized in that: The molecular skeleton of the compound contains a structure of N element, aromatic group and ester group at the end of olefin, and a product of Z configuration is selectively obtained while introducing imine; Among them, R 1 , R 2 , R 3 , R 4 The various substituents described in claim 1.

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