(Z)-butyl-1, 3-diene derivative containing alkenyl amide skeleton and preparation method of (Z)-butyl-1, 3-diene derivative

Abstract

The invention relates to the technical field of organic synthesis, in particular to (Z)-butyl-1, 3-diene derivatives containing an alkenyl amide framework and a preparation method of the (Z)-butyl-1, 3-diene derivatives. The invention provides an alkenyl amide skeleton-containing (Z)-butyl-1, 3-diene derivative and a preparation method thereof.The preparation method comprises the steps that alkenyl amide, vinyltriethoxysilane, a catalyst, a cocatalyst, an oxidizing agent, a fluorine source, an additive and a solvent are mixed and then subjected to an alkenylation reaction in an oil bath pan, and the alkenyl amide skeleton-containing (Z)-butyl-1, 3-diene derivative is prepared. The (Z)-butyl-1, 3-diene derivative containing the alkenyl amide skeleton has the advantages of good selectivity, wide substrate range, good functional group tolerance and the like, and meanwhile, the important core skeleton containing diene has important value for research and development of natural products, drug molecules and functional materials.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, in particular to a method for preparing an enamide skeleton ( Z )-buta-1,3-diene derivatives and preparation methods thereof. Background Art

[0002] Enamide skeletons and butadiene skeletons are widely present in natural products and bioactive molecules. In addition, 1,3-butadiene compounds are precursors for the synthesis of retinoids and are also raw materials for the manufacture of synthetic rubber, synthetic resins, synthetic fibers, plasticizers, and latex paints. Therefore, 1,3-butadiene compounds play a key role in modern synthetic chemistry and biochemistry. Therefore, it is necessary to develop an effective and practical method to synthesize 1,3-butadiene-containing compounds with enamide skeletons ( Z )-buta-1,3-diene derivatives are of great interest.

[0003] In summary, the present application now proposes a rhodium-catalyzed β-C (sp 2 )-H olefination reaction to synthesize olefin amide skeleton ( Z )-buta-1,3-diene derivatives are used to solve the above problems. Summary of the invention

[0004] The present invention aims to solve the problems raised in the background technology. The purpose of this specification is to provide a method containing an olefin amide skeleton ( Z )-buta-1,3-diene derivatives and preparation methods thereof are provided to solve the problems raised in the background technology.

[0005] Based on the above purpose, the present invention provides a kind of olefin amide skeleton ( Z )-buta-1,3-diene derivatives, wherein the structural formula of the (Z)-buta-1,3-diene derivatives containing an eneamide skeleton is: ; Among them, R 1 is phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, alkyl or aromatic heterocycle; R 2 is hydrogen or aryl.

[0006] According to the present invention, the olefin amide skeleton ( Z )-buta-1,3-diene derivatives of enamide derivatives, wherein R 1 wherein the alkyl-substituted phenyl group is an alkyl-substituted phenyl group having 1 to 3 carbon atoms, the alkoxy-substituted phenyl group is an alkoxy-substituted phenyl group having 1 to 3 carbon atoms, and the halogen-substituted phenyl group is a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, a bromine-substituted phenyl group or an iodine-substituted phenyl group; wherein R 2In the above, the aryl group is an alkyl-substituted phenyl group or a halogen-substituted phenyl group.

[0007] According to the present invention, the olefin amide skeleton ( Z )-buta-1,3-diene derivatives of enamide derivatives, wherein R 1 wherein the alkyl-substituted phenyl group is p-methylphenyl, m-methylphenyl or o-methylphenyl, the alkoxy-substituted phenyl group is p-methoxyphenyl, m-methoxyphenyl or o-methoxyphenyl, and the halogen-substituted phenyl group is p-fluorophenyl, p-chlorophenyl, p-bromophenyl, m-chlorophenyl, m-bromophenyl, m-iodophenyl, o-chlorophenyl or o-bromophenyl; wherein R 2 In the above, the alkyl-substituted phenyl group is p-methylphenyl group, and the halogen-substituted phenyl group is p-fluorophenyl group.

[0008] The present invention also provides the above-mentioned olefin amide skeleton ( Z The preparation method of )-buta-1,3-diene derivatives comprises the following steps: The enamide, vinyl triethoxysilane, catalyst, co-catalyst, oxidant, fluorine source, additive and solvent are mixed to obtain a mixed solution, and the mixed solution is subjected to an olefination reaction in an oil bath to obtain the enamide skeleton ( Z )-Butane-1,3-diene derivatives; Wherein, the structural formula of the enamide is: ; The structural formula of the vinyl triethoxysilane is: .

[0009] According to the present invention, the olefin amide skeleton ( Z The invention discloses a method for preparing a 1,3-butadiene derivative, wherein the olefination reaction is carried out in an oil bath; the temperature of the oil bath is 90 to 130° C.; and the olefination reaction time is 12 to 24 hours.

[0010] According to the present invention, the olefin amide skeleton ( Z )-buta-1,3-diene derivatives, wherein the catalyst is [Rh(COD)Cl]2, or ; The co-catalyst is AgSbF6, AgBF4 or AgNTf2; the oxidant is Cu(OTf)2, Cu(acac)2, Cu(SO4)2, CuF2, Cu(OAc)2, AgF, Ag2CO3, AgOAc, Ag2O, AgTFA.

[0011] According to the preparation method of the (Z)-buta-1,3-diene derivatives containing an eneamide skeleton provided by the present invention, the fluorine source is KF, NaF, LiF, TBAF (tetrabutylammonium fluoride), CuF2, and AgF; the additive is Ac2O, HFAA (heptafluorobutyric anhydride), Tf2O (trifluoromethanesulfonic anhydride), HOAc, and PivOH.

[0012] According to the present invention, the olefin amide skeleton ( Z )-buta-1,3-diene derivatives, wherein the solvent is DMF, DMSO, THF, DCE, Dioxane, TFE, n -hexane, CH3OH, t BuOH, CH3CN or NMP, one or more of the mixture, the volume of the solvent is 1.0-3.0 mL, and the ratio of the solvent volume is 1.0:(0.5-2.0).

[0013] According to the present invention, the olefin amide skeleton ( Z )-buta-1,3-diene derivatives, wherein the molar ratio of the enamide, vinyltriethoxysilane, catalyst, co-catalyst, oxidant, fluorine source and additive is 1.0: (1.0-3.0): (0.01-0.05): (0.1-0.2): (2.0-4.0): (2.0-4.0): (0.5-1.5).

[0014] According to the present invention, the olefin amide skeleton ( Z )-buta-1,3-diene derivatives, wherein the reaction equation of the olefination reaction is: ;

[0015] The product structure is as follows:

[0016] Compared with the prior art, the present invention has the following advantages: The present invention provides a kind of olefin amide skeleton ( Z )-buta-1,3-diene derivatives and preparation methods thereof, wherein enamide, vinyl triethoxysilane, a catalyst, a co-catalyst, an oxidant, a fluorine source, an additive and a solvent are mixed and then subjected to an olefination reaction in an oil bath to prepare an enamide skeleton ( Z )-buta-1,3-diene derivatives, the olefin amide skeleton ( Z )-Butane-1,3-diene derivatives have the advantages of good selectivity, wide substrate range, and good functional group tolerance. At the same time, the important core skeleton containing diene is of great value for the research and development of natural products, drug molecules and functional materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 is the H NMR spectrum of the product prepared in Example 1; Figure 2 is the carbon spectrum of the product prepared in Example 1; Figure 3 is the H NMR spectrum of the product prepared in Example 2; Figure 4 is the carbon spectrum of the product prepared in Example 2; Figure 5 is the H NMR spectrum of the product prepared in Example 3; Figure 6 is the carbon spectrum of the product prepared in Example 3; Figure 7 is the H NMR spectrum of the product prepared in Example 4; Figure 8 is the carbon spectrum of the product prepared in Example 4; Fig. 9 is the H NMR spectrum of the product prepared in Example 5; Fig.10 is the carbon spectrum of the product prepared in Example 5; Fig.11 is the H NMR spectrum of the product prepared in Example 6; Fig.12 is the carbon spectrum of the product prepared in Example 6; Fig.13 is the H NMR spectrum of the product prepared in Example 7; Fig.14 is the carbon spectrum of the product prepared in Example 7; Fig.15 is the H NMR spectrum of the product prepared in Example 8; Fig.16 is the carbon spectrum of the product prepared in Example 8; Fig.17 is the H NMR spectrum of the product prepared in Example 9; Fig.18 is the carbon spectrum of the product prepared in Example 9; Fig.19 is the H NMR spectrum of the product prepared in Example 10; Fig. 20 is the carbon spectrum of the product prepared in Example 10; Fig.21 is the H NMR spectrum of the product prepared in Example 11; Fig. 22 is the carbon spectrum of the product prepared in Example 11; Fig.23 is the H NMR spectrum of the product prepared in Example 12; Fig.24 This is the carbon spectrum of the product prepared in Example 12. DETAILED DESCRIPTION

[0018] In order to make the objectives, technical solutions and advantages of the present disclosure more clearly understood, the present disclosure is further described in detail below in conjunction with specific embodiments.

[0019] See also Figure 1-Figure 24 , according to the enamide skeleton ( Z )-butane-1,3-diene derivatives, the structural formula is as follows: ; In the above structural formula, R 1 is phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, ring-substituted phenyl, alkyl or aromatic heterocycle; R 2 is hydrogen or aryl.

[0020] Among them, R 1 The alkyl-substituted phenyl group is an alkyl-substituted phenyl group having 1 to 3 carbon atoms, and is further preferably p-methylphenyl, m-methylphenyl or o-methylphenyl, and is more preferably o-methylphenyl; the alkoxy-substituted phenyl group is an alkoxy-substituted phenyl group having 1 to 3 carbon atoms, and is further preferably p-methoxyphenyl, m-methoxyphenyl or o-methoxyphenyl, and is more preferably m-methoxyphenyl; the halogen-substituted phenyl group is fluorine-substituted phenyl, chlorine-substituted phenyl, bromine-substituted phenyl or iodine-substituted phenyl, and is further preferably p-fluorophenyl, m-chlorophenyl, p-bromophenyl or m-iodophenyl.

[0021] In the present invention, R 2 is hydrogen or aryl; the aryl group is preferably alkyl-substituted phenyl or halogen-substituted phenyl; the alkyl-substituted phenyl is more preferably p-methylphenyl; the halogen-substituted phenyl is more preferably p-fluorophenyl.

[0022] In a specific embodiment of the present invention, the olefin amide skeleton ( Z The specific structure of the )-buta-1,3-diene derivatives is as follows: .

[0023] The present invention provides the above-mentioned olefin amide skeleton ( Z The preparation method of )-buta-1,3-diene derivatives comprises the following steps: The enamide, vinyl triethoxysilane, catalyst, co-catalyst, oxidant, fluorine source, additive and solvent are mixed to obtain a mixed solution; the mixed solution is subjected to an olefination reaction in an oil bath to obtain an enamide skeleton ( Z )-Butane-1,3-diene derivatives; Wherein, the structural formula of the above enamide is: ; The structural formula of the above-mentioned vinyl triethoxysilane is: .

[0024] In the preparation method, the olefination reaction is carried out under oil bath conditions, the temperature of the oil bath is 90 to 130°C, more preferably 100 to 120°C, and more preferably 110°C; the olefination reaction time is 12 to 24 h, more preferably 12 to 20 h, and more preferably 16 h.

[0025] In the preparation method, the catalyst is [Rh(COD)Cl]2, or , further preferably .

[0026] In the preparation method, the co-catalyst is AgSbF6, AgBF4 or AgNTf2, and AgSbF6 is more preferred.

[0027] In the preparation method, the oxidant is Cu(OTf)2, Cu(acac)2, Cu(SO4)2, CuF2, Cu(OAc)2, AgF, Ag2CO3, AgOAc, Ag2O, AgTFA, and CuF2 is more preferred.

[0028] In the preparation method, the fluorine source is KF, NaF, LiF, TBAF (tetrabutylammonium fluoride), CuF2 or AgF, and CuF2 is more preferably used.

[0029] In the preparation method, the additive is Ac2O, HFAA (heptafluorobutyric anhydride), Tf2O (trifluoromethanesulfonic anhydride), HOAc or PivOH, more preferably Ac2O or Tf2O, and more preferably Tf2O.

[0030] In the preparation method, the solvent is DMF, DMSO, THF, DCE, Dioxane, TFE, n -hexane, CH3OH, t BuOH, CH3CN or NMP, one or more mixtures thereof, more preferably n -hexane, DMF, more preferably n -hexane, DMF mixed solvent; the volume of the solvent is 1.0 to 3.0 mL, more preferably 2.0 mL; the volume ratio of the mixed solvent is 1.0: (0.5 to 2.0), more preferably 1.0: 1.0.

[0031] In the preparation method, the molar ratio of olefin amide, vinyltriethoxysilane, catalyst, co-catalyst, oxidant, fluorine source and acid additive is 1.0:(1.0-3.0):(0.01-0.05):(0.1-0.2):(2.0-4.0):(2.0-4.0):(0.5-1.5), and is further preferably 1.0:(1.5-2.5):(0.01-0.05):(0.1-0.2):(2.0-3.0):(2.0-3.0):(0.5-1.5), and is more preferably 1.0:2.0:0.05:0.2:2.0:2.0:1.0.

[0032] As the above preferred embodiment, the olefin amide skeleton ( Z The preparation process of )-buta-1,3-diene derivatives is as follows: .

[0033] The present invention is to contain ene amide skeleton ( Z The conditions for the preparation of the 1,3-diene derivatives are not particularly limited. In the embodiments of the present invention, enamide, vinyl triethoxysilane, 、AgSbF6、CuF2、Tf2O n -hexane and DMF were mixed to obtain a mixed solution, and then the mixed solution was placed in an oil bath at 110 °C for 16 h to obtain an amide skeleton containing an olefin ( Z )-buta-1,3-diene derivatives.

[0034] The olefin amide skeleton prepared by the present invention ( Z )-Butane-1,3-diene derivatives have the advantages of good selectivity, wide substrate range, and good functional group tolerance. At the same time, the important core skeleton containing diene is of great value for the research and development of natural products, drug molecules and functional materials.

[0035] The following is a description of the olefin amide skeleton ( Z )-buta-1,3-diene derivatives are described in detail, but it should not be understood as limiting the scope of protection of the present invention.

[0036] Example 1 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -BenZyl- N The preparation method of -(1-phenylbuta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N -(1-phenylvinyl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 44.3 mg of the target product with a yield of 79%.

[0037] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Figure 1 and Figure 2 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.53 – 7.37 (m, 5H), 7.27 (m, 5H), 6.62 (dd, J = 10.9, 3.1 HZ, 1H), 5.87 (dt, J = 16.5, 10.5 HZ, 1H), 5.44 (dd, J = 13.7,2.9 HZ, 1H), 5.32 (d, J = 16.8 Hz, 1H), 5.06 (d, J = 10.4 HZ, 1H), 3.82 (dd, J = 13.7, 3.0HZ, 1H), 2.04 (s, 3H).

[0038] 13 C NMR (101 MHZ, CDCl3) δ 170.9, 138.6, 136.6, 135.5, 131.5, 129.90,128.97, 128.8, 128.5, 128.1, 127.5, 125.7, 121.1, 49.5, 21.6.

[0039] HRMS (ESI) m / Z: [M+Na] + Calcd for C 19 H 19 NONa 300.1359; found 300.1366.

[0040] This example prepares the product ( Z )- N -BenZyl- N The structural formula of -(1-phenylbuta-1,3-dien-1-yl)acetamide is: .

[0041] Example 2

[0042] This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -BenZyl- N The preparation method of -(1-(p-tolyl)buta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N -(1-( p -tolyl)vinyl)acetamide , 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, then add 2.0 mL of a 1:1 volume ratio of ultra-dry DMF and n-hexane mixed solvent, and react in an oil bath at 110°C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 44.7 mg of the target product with a yield of 76%.

[0043] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Figure 3 and Figure 4 The structural characterization data are shown below: 1H NMR (400 MHZ, CDCl3) δ 7.51 – 7.21 (m, 9H), 6.56 (d, J = 10.8 HZ,1H), 5.83 (dt, J = 17.0, 10.5 HZ, 1H), 5.42 (d, J = 13.8 Hz, 1H), 5.26 (d, J = 16.9 HZ, 1H), 5.00 (dd, J = 10.2, 1.7 HZ, 1H), 3.78 (d, J = 13.8 Hz, 1H), 2.39 (s, 3H), 2.01 (s, 3H).

[0044] 13 C NMR (101 MHZ, CDCl3) δ 170.8, 138.9, 138.6, 136.7, 132.6, 131.6,129.9, 129.7, 128.1, 127.6, 127.4, 125.6, 120.5, 49.5, 21.6, 21.1.

[0045] HRMS (ESI) m / Z: [M+Na] + Calcd for C 20 H 21 NONa 314.1515; found 314.1523.

[0046] This example prepares the product ( Z )- N -BenZyl- N The structural formula of -(1-(p-tolyl)buta-1,3-dien-1-yl)acetamide is: .

[0047] Example 3 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -(1-([1,1'-Biphenyl]-4-yl)buta-1,3-dien-1-yl)- N The preparation method of -benZylacetamide comprises the following steps: Add 0.2 mmol of N -(1-([1,1'-biphenyl]-4-yl)vinyl)- N -benZylacetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 55.2 mg of the target product with a yield of 78%.

[0048] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Figure 5 and Figure 6 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.64 (dt, J = 8.0, 2.5 HZ, 4H), 7.52 – 7.45(m, 4H), 7.42 – 7.38 (m, 1H), 7.35 – 7.20 (m, 5H), 6.66 (d, J = 10.8 HZ, 1H),5.88 (dt, J = 16.9, 10.4 HZ, 1H), 5.45 (d, J = 13.8 Hz, 1H), 5.33 (d, J =16.9 HZ, 1H), 5.07 (d, J = 10.1 HZ, 1H), 3.88 (d, J = 13.7 HZ, 1H), 2.05 (s, 3H).

[0049] 13C NMR (101 MHZ, CDCl3) δ 170.9, 141.5, 140.0, 138.3, 136.6, 134.4,131.5, 129.9, 128.8, 128.4, 128.1, 127.6, 127.6, 127.5, 126.9, 126.1, 121.1,49.7, 21.6.

[0050] HRMS (ESI) m / Z: [M+Na] + Calcd for C 25 H 23 NONa 376.1672; found 376.1681.

[0051] This example prepares the product ( Z )- N -(1-([1,1'-Biphenyl]-4-yl)buta-1,3-dien-1-yl)- N The structural formula of -benZylacetamide is: .

[0052] Example 4 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -benZyl- N The preparation method of -(1-(3-methoxyphenyl)buta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N -(1-(3-methoxyphenyl)vinyl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and separated by column chromatography using an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 40.5 mg of the target product with a yield of 65%.

[0053] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Figure 7 and Figure 8 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.26 (ddd, J = 24.2, 11.8, 5.6 HZ, 6H), 7.01(d, J = 7.8 Hz, 1H), 6.89 (d, J = 5.4 HZ, 2H), 6.58 (d, J = 10.8 HZ, 1H),5.84 (dt, J = 17.1, 10.5 HZ, 1H), 5.32 (dd, J = 23.5, 15.3 HZ, 2H), 5.04 (d, J = 10.2HZ, 1H), 3.83 (t, 4H), 2.00 (s, 3H).

[0054] 13 C NMR (101 MHZ, CDCl3) δ 170.8, 160.0, 138.6, 137.1, 136.6, 131.4,129.93, 129.88, 128.6, 128.1, 127.4, 121.2, 118.2, 114.1, 111.3, 55.2, 49.7,21.6.

[0055] HRMS (ESI) m / Z: [M+Na] + Calcd for C 20 H 21 NO2Na 330.1464; found 330.1474.

[0056] This example prepares the product ( Z )- N -benZyl- NThe structural formula of -(1-(3-methoxyphenyl)buta-1,3-dien-1-yl)acetamide is: .

[0057] Example 5 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -BenZyl- N The preparation method of -(1-(3,4,5-trimethoxyphenyl)buta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N -(1-(3,4,5-trimethoxyphenyl)vinyl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 4:1 to obtain 38.1 mg of the target product with a yield of 51%.

[0058] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Fig. 9 and Fig.10 The structural characterization data are shown below: 1H NMR (400 MHZ, CDCl3) δ 7.39 – 7.23 (m, 5H), 6.56 (d, J = 8.2 HZ, 3H), 5.96 (dt, J = 17.0, 10.5 HZ, 1H), 5.38 (d, J = 16.9 HZ, 1H), 5.13 (d, J = 12.9 HZ, 2H), 4.20 (d, J = 13.7 HZ, 1H), 3.86 (d, J = 23.6 HZ, 9H), 2.02 (s, 3H).

[0059] 13 C NMR (101 MHZ, CDCl3) δ 171.0, 153.5, 139.3, 138.7, 136.8, 131.53,131.48, 130.0, 128.2, 127.6, 127.4, 121.1, 102.9, 60.9, 56.1, 50.4, 21.8.

[0060] HRMS (ESI) m / Z: [M+Na] + Calcd for C 22 H 25 NO4Na 390.1676; found 390.1692.

[0061] This example prepares the product ( Z )- N -BenZyl- N The structural formula of -(1-(3,4,5-trimethoxyphenyl)buta-1,3-dien-1-yl)acetamide is: .

[0062] Example 6 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -BenZyl- N The preparation method of -(1-(4-fluorophenyl)buta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N-(1-(4-fluorophenyl)vinyl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 42.4 mg of the target product with a yield of 71%.

[0063] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Fig.11 and Fig.12 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.40 – 7.30 (m, 2H), 7.21 (h, J = 1.5 HZ,5H), 7.12 – 7.01 (m, 2H), 6.51 (d, J = 10.9 HZ, 1H), 5.84 (dt, J = 17.0, 10.3HZ, 1H), 5.38 – 5.25 (m, 2H), 5.04 (d, J = 10.2 HZ, 1H), 3.83 (d, J = 13.8HZ, 1H), 1.99 (s, 3H).

[0064] 13 C NMR (101 MHZ, CDCl3) δ 170.7, 162.9 (d, 1 J C-F = 249.4 HZ), 137.8,136.4, 131.7 (d, 3 J C-F = 3.2 HZ), 131.3, 129.8, 128.3 (d, 4 J C-F= 1.8 HZ),128.1, 127.5, 127.4, 121.2, 115.9 (d, 2 J C-F = 21.8 HZ), 49.6, 21.6.

[0065] HRMS (ESI) m / Z: [M+Na] + Calcd for C 19 H 18 NOFNa 318.1265; found 318.1277.

[0066] This example prepares the product ( Z )- N -BenZyl- N The structural formula of -(1-(4-fluorophenyl)buta-1,3-dien-1-yl)acetamide is: .

[0067] Example 7 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -BenZyl- N The preparation method of -(1-(3-chlorophenyl)buta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N -(1-(3-chlorophenyl)vinyl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 48.4 mg of the target product with a yield of 77%.

[0068] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Fig.13 and Fig.14 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.44 – 7.28 (m, 4H), 7.23 (q, J = 5.2, 3.2HZ, 5H), 6.59 (d, J = 10.8 Hz, 1H), 5.84 (dt, J = 17.0, 10.5 HZ, 1H), 5.33(d, J = 14.3 HZ, 2H), 5.08 (d, J = 9.4 HZ, 1H), 3.83 (d, J = 13.8 Hz, 1H), 1.98 (s, 3H).

[0069] 13 C NMR (101 MHZ, CDCl3) δ 170.6, 137.6, 137.4, 136.3, 135.0, 131.1,130.1, 129.8, 129.5, 128.7, 128.2, 127.6, 125.7, 123.7, 122.1, 49.6, 21.6.

[0070] HRMS (ESI) m / Z: [M+Na] + Calcd for C 19 H 18 NOClNa 334.0969; found 334.0981.

[0071] This example prepares the product ( Z )- N -BenZyl- N The structural formula of -(1-(3-chlorophenyl)buta-1,3-dien-1-yl)acetamide is: .

[0072] Example 8 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -BenZyl-N The preparation method of -(1-(4-bromophenyl)buta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N -(1-(4-bromophenyl)vinyl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 44.1 mg of the target product with a yield of 61%.

[0073] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Fig.15 and Fig.16 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.50 (d, J = 8.4 HZ, 2H), 7.24 (d, J = 12.9HZ, 7H), 6.58 (d, J = 10.8 Hz, 1H), 5.86 (dt, J = 16.9, 10.5 HZ, 1H), 5.48 –5.27 (m, 2H), 5.08 (d, J = 10.2 HZ, 1H), 3.84 (d, J = 13.7 HZ, 1H), 1.99 (s, 3H).

[0074] 13C NMR (101 MHZ, CDCl3) δ 170.6, 137.6, 136.3, 134.5, 132.0, 131.2,129.8, 128.8, 128.1, 127.5, 127.1, 122.8, 121.7, 49.6, 21.5.

[0075] HRMS (ESI) m / Z: [M+Na] + Calcd for C 19 H 18 NOBrNa 378.0464; found 378.0479.

[0076] This example prepares the product ( Z )- N -BenZyl- N The structural formula of -(1-(4-bromophenyl)buta-1,3-dien-1-yl)acetamide is: .

[0077] Example 9 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -BenZyl- N The preparation method of -(1-(3-iodophenyl)buta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N -(1-(3-iodophenyl)vinyl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and separated by column chromatography using an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 36.2 mg of the target product with a yield of 44%.

[0078] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Fig.17 and Fig.18 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.74 (td, J = 16.6, 16.1, 8.0 HZ, 1H), 7.59– 7.16 (m, 8H), 6.63 (dq, J = 16.0, 8.7, 8.1 HZ, 1H), 5.90 (dd, J = 16.9,11.0 HZ, 1H), 5.59 – 5.28 (m, 2H), 5.12 (dd, J = 16.3, 8.5 HZ, 1H), 3.90 (td, J = 22.7, 18.6, 11.3HZ, 1H), 2.06 (s, 3H).

[0079] 13 C NMR (101 MHZ, CDCl3) δ 170.8, 137.7, 137.5, 136.5, 135.2, 131.3,130.3, 130.0, 129.7, 128.8, 128.3, 127.7, 125.8, 123.9, 122.3, 49.8, 21.7.

[0080] HRMS (ESI) m / Z: [M+Na] + Calcd for C 19 H 18 NOINa 426.0325; found 426.0342.

[0081] This example prepares the product ( Z )- N -BenZyl- N The structural formula of -(1-(3-iodophenyl)buta-1,3-dien-1-yl)acetamide is: .

[0082] Example 10 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )-N -Methyl- N The preparation method of -(1-phenylbuta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -methyl- N -(1-phenylvinyl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 4:1 to obtain 37.0 mg of the target product with a yield of 91%.

[0083] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Fig.19 and Fig. 20 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.35 (dt, J = 20.4, 7.1 HZ, 5H), 6.66 (d, J = 10.8 Hz, 1H), 6.45 (dt, J = 16.7, 10.5 HZ, 1H), 5.51 (d, J = 16.8 HZ, 1H),5.34 (d, J = 10.2 Hz, 1H), 3.05 (s, 3H), 1.92 (s, 3H).

[0084] 13 C NMR (101 MHZ, CDCl3) δ 171.3, 140.9, 135.3, 131.2, 129.0, 128.8,126.3, 125.2, 121.7, 34.8, 21.3.

[0085] HRMS (ESI) m / Z: [M+Na]+ Calcd for C 13 H 15 NONa 224.1046; found 224.1053.

[0086] This example prepares the product ( Z )- N -Methyl- N The structural formula of -(1-phenylbuta-1,3-dien-1-yl)acetamide is: .

[0087] Embodiment 11 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -BenZyl- N The preparation method of -(1-(thiophen-2-yl)buta-1,3-dien-1-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N -(1-(thiophen-2-yl)vinyl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 9.7 mg of the target product with a yield of 17%.

[0088] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Fig.21 and Fig. 22 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.29 (ddt, J= 23.4, 6.7, 3.3 HZ, 6H), 7.09– 6.93 (m, 2H), 6.53 (d, J = 10.9 HZ, 1H), 5.79 (dt, J = 17.0, 10.5 HZ, 1H),5.31 (dd, J = 17.9, 15.3 HZ, 2H), 5.02 (d, J = 10.2 HZ, 1H), 4.12 (d, J =13.7 HZ, 1H), 2.01 (s, 3H).

[0089] 13 C NMR (101 MHZ, CDCl3) δ 170.6, 141.3, 136.8, 133.9, 130.8, 130.1,128.2, 128.0, 127.6, 127.6, 126.1, 125.1, 121.0, 50.2, 21.5.

[0090] HRMS (ESI) m / Z: [M+Na] + Calcd for C 17 H 17 NOSNa 306.0923; found 306.0935.

[0091] This example prepares the product ( Z )- N -BenZyl- N The structural formula of -(1-(thiophen-2-yl)buta-1,3-dien-1-yl)acetamide is: .

[0092] Example 12 This embodiment provides a specific olefin amide skeleton ( Z )-Butadiene-1,3-diene derivatives( Z )- N -BenZyl- N The preparation method of -(penta-2,4-dien-2-yl)acetamide comprises the following steps: Add 0.2 mmol of N -benZyl- N-(prop-1-en-2-yl)acetamide, 0.4 mmol of vinyltriethoxysilane, 0.01 mmol of , 0.04 mmol of AgSbF6, 0.4 mmol of CuF2 and 0.2 mmol of Tf2O, and then add 2.0 mL of ultra-dry DMF and n -hexane mixed solvent, react in an oil bath at 110 °C for 16 h; After the reaction was completed, it was extracted with 20.0 mL×3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and column chromatography was performed with an eluent of petroleum ether and ethyl acetate in a ratio of 6:1 to obtain 8.3 mg of the target product with a yield of 19%.

[0093] The product prepared in this example was characterized, and the hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum were as follows: Fig.23 and Fig.24 The structural characterization data are shown below: 1 H NMR (400 MHZ, CDCl3) δ 7.27 (dt, J = 14.0, 6.1 HZ, 5H), 6.17 – 5.75(m, 2H), 5.13 (dd, J = 15.7, 6.0 HZ, 1H), 4.96 (d, J = 7.5 Hz, 1H), 4.73 (t, J = 9.5 HZ, 1H), 4.65 – 4.49 (m, 1H), 2.00 (s, 3H), 1.81 (s, 3H).

[0094] 13 C NMR (101 MHZ, CDCl3) δ 169.6, 137.2, 136.9, 130.8, 129.3, 129.1,128.2, 127.4, 118.6, 49.1, 21.5, 21.4.

[0095] HRMS (ESI) m / Z: [M+Na] + Calcd for C 14 H 17 NONa 238.1202; found 238.1213.

[0096] This example prepares the product ( Z )- N-BenZyl- N The structural formula of -(penta-2,4-dien-2-yl)acetamide is: .

[0097] The above is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent change made to the above embodiment according to the technical essence of the invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. An amide-containing skeleton ( Z )-buta-1,3-diene derivatives, characterized in that The olefin amide skeleton ( Z The structural formula of )-buta-1,3-diene derivatives is: ； Among them, R 1 is phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, alkyl or aromatic heterocycle; R 2 is hydrogen or aryl.

2. The olefin amide skeleton according to claim 1 ( Z )-buta-1,3-diene derivatives, characterized in that: The R 1 wherein the alkyl-substituted phenyl group is a phenyl group substituted by an alkyl group having 1 to 3 carbon atoms, the alkoxy-substituted phenyl group is a phenyl group substituted by an alkoxy group having 1 to 3 carbon atoms, and the halogen-substituted phenyl group is a phenyl group substituted by fluorine, chlorine, bromine or iodine; wherein R 2 In the above, the aryl group is an alkyl-substituted phenyl group or a halogen-substituted phenyl group.

3. The olefin amide skeleton according to claim 2 ( Z )-buta-1,3-diene derivatives, characterized in that The R 1 wherein the alkyl-substituted phenyl group is p-methylphenyl, m-methylphenyl or o-methylphenyl, the alkoxy-substituted phenyl group is p-methoxyphenyl, m-methoxyphenyl or o-methoxyphenyl, and the halogen-substituted phenyl group is p-fluorophenyl, p-chlorophenyl, p-bromophenyl, m-chlorophenyl, m-bromophenyl, m-iodophenyl, o-chlorophenyl or o-bromophenyl; wherein R 2 In the above, the alkyl-substituted phenyl group is p-methylphenyl group, and the halogen-substituted phenyl group is p-fluorophenyl group.

4. A polyamide-containing skeleton as described in any one of claims 1 to 3 ( Z )-buta-1,3-diene derivatives, characterized in that: The following steps are involved: The enamide, vinyl triethoxysilane, catalyst, co-catalyst, oxidant, fluorine source, additive and solvent are mixed to obtain a mixed solution, and the mixed solution is subjected to an olefination reaction in an oil bath to obtain the enamide skeleton ( Z )-Butane-1,3-diene derivatives; Wherein, the structural formula of the enamide is: ； The structural formula of the vinyl triethoxysilane is: 。 5. The olefin amide skeleton according to claim 4 ( Z )-buta-1,3-diene derivatives, characterized in that: The olefination reaction is carried out under the condition of an oil bath; the temperature of the oil bath is 90 to 130° C.; and the olefination reaction time is 12 to 24 hours.

6. The olefin amide skeleton according to claim 4 ( Z )-buta-1,3-diene derivatives, characterized in that: The catalyst is [Rh(COD)Cl]2, or ; The co-catalyst is AgSbF6, AgBF4 or AgNTf2; the oxidant is Cu(OTf)2, Cu(acac)2, Cu(SO4)2, CuF2, Cu(OAc)2, AgF, Ag2CO3, AgOAc, Ag2O, AgTFA.

7. The olefin amide skeleton according to claim 4 ( Z )-buta-1,3-diene derivatives, characterized in that: The fluorine source is KF, NaF, LiF, TBAF (tetrabutylammonium fluoride), CuF2, and AgF; the additive is Ac2O, HFAA (heptafluorobutyric anhydride), Tf2O (trifluoromethanesulfonic anhydride), HOAc, and PivOH.

8. The olefin amide skeleton according to claim 4 ( Z )-buta-1,3-diene derivatives, characterized in that: The solvent is DMF, DMSO, THF, DCE, Dioxane, TFE, n -hexane, CH3OH, t BuOH, CH3CN or NMP, one or more of which are mixed, the volume of the solvent is 1.0-3.0 mL, and when the solvent is a mixture of the above two solutions, the volume ratio is 1.0:(0.5-2.0).

9. The olefin amide skeleton according to claim 4 ( Z )-buta-1,3-diene derivatives, characterized in that: The molar ratio of the enamide, vinyl triethoxysilane, catalyst, co-catalyst, oxidant, fluorine source and additive is 1.0: (1.0-3.0): (0.01-0.05): (0.1-0.2): (2.0-4.0): (2.0-4.0): (0.5-1.5).

10. The olefin amide skeleton according to claim 4 ( Z )-buta-1,3-diene derivatives, characterized in that: The reaction equation of the olefination reaction is: ； The product structure is as follows: 。

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