Amide derivative containing N-(2Z, 4E) dienylsilyl skeleton and preparation method thereof

Abstract

The invention relates to the technical field of organic synthesis, in particular to an alkenyl amide derivative containing an N-(2Z, 4E) dienylsilyl skeleton and a preparation method of the alkenyl amide derivative. According to the present invention, the alkenyl amide, the alkenyl silane, the catalyst, the co-catalyst, the oxidizing agent, the additive and the solvent are mixed, the obtained mixed solution is subjected to the alkenylation reaction in the oil bath pan to prepare the alkenyl amide derivative containing the N-(2Z, 4E) dienylsilyl skeleton, and the alkenyl amide derivative containing the N-(2Z, 4E) dienylsilyl skeleton has characteristics of good selectivity, wide substrate range, high yield, high yield and the like, and can be used for the preparation of the alkenyl amide derivative containing the N-(2Z, 4E) dienylsilyl skeleton. The compound disclosed by the invention has the advantages of simple synthesis process, good functional group tolerance and the like, contains two important core frameworks of 1, 3-butadiene and alkenyl amide, and has important value for research and development of natural products and organic functional materials.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to an enamide derivative containing an N-(2Z, 4E) dienesilyl skeleton and a preparation method thereof. Background Art

[0002] Enamides and their derivatives are an important class of chemical substances with remarkable chemical stability. Functionalization of enamides is an important route to synthesize valuable chiral amines and natural products. Therefore, the functionalization reaction of enamides is an important chemical reaction. 2 )-H functionalization reaction has attracted wide attention in recent years, and the research on acyclic olefinamide β-C(sp 2 )-H olefination reactions are rarely reported, and most of them use activated alkenes as coupling substrates to react with non-cyclic olefinamides. There are currently no reports in the literature on the olefination of non-cyclic olefinamides using unactivated alkenylsilanes as coupling substrates.

[0003] In summary, the present application now proposes a rhodium-catalyzed β-C (sp 2 The invention relates to a method for preparing olefin amide derivatives containing an N-(2Z, 4E) diene silicon skeleton by a olefination reaction of olefins to solve the above problems. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to address the deficiencies of the above-mentioned prior art and provide an enamide derivative containing an N-(2Z,4E) dienesilyl skeleton and a preparation method thereof. Enamide, alkenylsilane, a catalyst, a co-catalyst, an oxidant, an additive and a solvent are mixed to obtain a mixed liquid, and the mixed liquid is then subjected to an alkenylation reaction under oil bath conditions to prepare the enamide derivative containing an N-(2Z,4E) dienesilyl skeleton.

[0005] In order to solve the above technical problems, the present invention provides an eneamide derivative containing an N-(2Z, 4E) dienesilyl skeleton, wherein the eneamide derivative containing an N-(2Z, 4E) dienesilyl skeleton is:

[0006]

[0007] 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; R 3 is a straight-chain alkyl group; R 4 It is a straight-chain alkyl or aryl group.

[0008] According to the enamide derivatives containing N-(2Z, 4E) dienesilyl skeleton provided by the present invention, the 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 2 In the embodiment, aryl is phenyl substituted by alkyl or phenyl substituted by halogen; 3 In the embodiment, the straight chain alkyl group is methyl or ethyl; 4 In the example, the straight-chain alkyl group is methyl or ethyl, and the aryl group is phenyl.

[0009] According to the enamide derivatives containing N-(2Z, 4E) dienesilyl skeleton provided by the present invention, 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 embodiment, the alkyl-substituted phenyl group is p-methylphenyl group, and the halogen-substituted phenyl group is p-fluorophenyl group.

[0010] The present invention also provides a method for preparing the above-mentioned enamide derivative containing an N-(2Z,4E) dienesilyl skeleton, comprising the following steps:

[0011] mixing enamide, alkenylsilane, a catalyst, a co-catalyst, an oxidant, an additive and a solvent to obtain a mixed solution; performing an alkenylation reaction on the mixed solution in an oil bath to obtain the enamide derivative containing an N-(2Z,4E) dienesilyl skeleton;

[0012] Wherein, the structural formula of the enamide is:

[0013]

[0014] The structural formula of the alkenylsilane is:

[0015]

[0016] According to the preparation method of olefinic amide derivatives containing an N-(2Z, 4E) dienesilyl skeleton provided by the present invention, the olefination reaction is carried out under oil bath conditions; the temperature of the oil bath is 70 to 110° C.; and the olefination reaction time is 12 to 36 hours.

[0017] According to the preparation method of olefin amide derivatives containing an N-(2Z,4E) diene silicon skeleton provided by the present invention, the catalyst is [Rh(COD)Cl]2, [Cp*Rh(MeCN)3](SbF6)2 or [Cp*RhCl2]2; the co-catalyst is AgSbF6, AgBF4 or AgNTf2.

[0018] According to the preparation method of olefin amide derivatives containing an N-(2Z,4E) dienesilyl skeleton provided by the present invention, the oxidant is Ag2CO3, Ag2O, Cu(OAc)2, Cu(acac)2, AgOAc or Cu(SO4)2; the additive is Zn(OTf)2, AgOTf, Cu(OTf)2 or In(OTf)3.

[0019] According to the preparation method of enamide derivatives containing an N-(2Z,4E) dienesilyl skeleton provided by the present invention, the solvent is one or a mixture of DMF, DMSO, THF, DCE, Dioxane, TFE, n-hexane, CH3OH, tBuOH, CH3CN or NMP, and the volume of the solvent is 0.5 to 1.5 mL. If two solvents are mixed, the volume ratio thereof is 1.0:(0.5 to 2.0).

[0020] According to the preparation method of enamide derivatives containing an N-(2Z, 4E) dienesilyl skeleton provided by the present invention, the molar ratio of the enamide, alkenylsilane, catalyst, co-catalyst, oxidant, and additive is 1.0:(4.0~8.0):(0.01~0.05):(0.1~0.2):(2.0~4.0):(0.2~1.0).

[0021] According to the method for preparing enamide derivatives containing an N-(2Z, 4E) dienesilyl skeleton provided by the present invention, the reaction equation of the alkenylation reaction is:

[0022]

[0023] The product structure is as follows:

[0024]

[0025] Compared with the prior art, the present invention has the following advantages:

[0026] The present invention provides an enamide derivative containing an N-(2Z,4E) diene silyl skeleton. The enamide derivative containing an N-(2Z,4E) diene silyl skeleton is prepared by mixing enamide, alkenyl silane, a catalyst, a co-catalyst, an oxidant, an additive and a solvent, and subjecting the obtained mixed solution to an alkenylation reaction in an oil bath. The enamide derivative containing an N-(2Z,4E) diene silyl skeleton has the advantages of good selectivity, a wide substrate range, good functional group tolerance, and the like. The compound contains two important core skeletons, 1,3-butadiene and enamide, and is of great value for the research and development of natural products and organic functional materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 is the H NMR spectrum of the product prepared in Example 1;

[0028] Figure 2 is the carbon spectrum of the product prepared in Example 1;

[0029] Figure 3 is the H NMR spectrum of the product prepared in Example 2;

[0030] Figure 4 is the carbon spectrum of the product prepared in Example 2;

[0031] Figure 5 is the H NMR spectrum of the product prepared in Example 3;

[0032] Figure 6 is the carbon spectrum of the product prepared in Example 3;

[0033] Figure 7 is the H NMR spectrum of the product prepared in Example 4;

[0034] Figure 8 is the carbon spectrum of the product prepared in Example 4;

[0035] Figure 9 is the H NMR spectrum of the product prepared in Example 5;

[0036] Figure 10 is the carbon spectrum of the product prepared in Example 5;

[0037] Figure 11 is the H NMR spectrum of the product prepared in Example 6;

[0038] Figure 12 is the carbon spectrum of the product prepared in Example 6;

[0039] Figure 13 is the H NMR spectrum of the product prepared in Example 7;

[0040] Figure 14 is the carbon spectrum of the product prepared in Example 7;

[0041] Figure 15 is the H NMR spectrum of the product prepared in Example 8;

[0042] Figure 16 is the carbon spectrum of the product prepared in Example 8;

[0043] Figure 17 is the H NMR spectrum of the product prepared in Example 9;

[0044] Figure 18 is the carbon spectrum of the product prepared in Example 9;

[0045] Figure 19 is the H NMR spectrum of the product prepared in Example 10;

[0046] Figure 20 is the carbon spectrum of the product prepared in Example 10;

[0047] Figure 21 is the H NMR spectrum of the product prepared in Example 11;

[0048] Figure 22 is the carbon spectrum of the product prepared in Example 11;

[0049] Figure 23 is the H NMR spectrum of the product prepared in Example 12;

[0050] Figure 24 This is the carbon spectrum of the product prepared in Example 12. DETAILED DESCRIPTION

[0051] In order to make the objectives, technical solutions and advantages of the present disclosure more clear, the present disclosure is further described in detail below with reference to specific embodiments.

[0052] See also Figure 1-Figure 24 According to an embodiment of the present invention, an olefinic amide derivative containing an N-(2Z,4E) diene silyl skeleton has the following structure:

[0053]

[0054] In the above structural formula, R 1 is phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, alkyl or aromatic heterocycle; R 2 is hydrogen or aryl; R 3 is a straight-chain alkyl group; R 4 It is a straight-chain alkyl or aryl group.

[0055] Among them, R 1 The alkyl-substituted phenyl group is an alkyl-substituted phenyl group having 1 to 3 carbon atoms, more preferably p-methylphenyl, m-methylphenyl or o-methylphenyl, more preferably o-methylphenyl; the alkoxy-substituted phenyl group is an alkoxy-substituted phenyl group having 1 to 3 carbon atoms, more preferably p-methoxyphenyl, m-methoxyphenyl or o-methoxyphenyl, more preferably m-methoxyphenyl; 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, more preferably p-fluorophenyl group, m-chlorophenyl group, p-bromophenyl group or m-iodophenyl group.

[0056] R 2 It is hydrogen or aryl, and the aryl group is preferably alkyl-substituted phenyl or halogen-substituted phenyl; the alkyl-substituted phenyl is more preferably p-methylphenyl; and the halogen-substituted phenyl is more preferably p-fluorophenyl.

[0057] R 3 It is a straight-chain alkyl group, more preferably a methyl group or an ethyl group.

[0058] R 4 It is a straight-chain alkyl group or an aryl group, the straight-chain alkyl group is more preferably a methyl group or an ethyl group, and the aryl group is more preferably a phenyl group.

[0059] In a specific embodiment of the present invention, the specific structure of the enamide derivative containing an N-(2Z, 4E) dienesilyl skeleton is as follows:

[0060]

[0061] The present invention provides the above-mentioned enamide derivative containing an N-(2Z, 4E) dienesilyl skeleton, comprising the following steps:

[0062] mixing enamide, alkenylsilane, a catalyst, a co-catalyst, an oxidant, an additive and a solvent to obtain a mixed solution; performing an alkenylation reaction on the mixed solution in an oil bath to obtain an enamide derivative containing an N-(2Z,4E)dienesilyl skeleton;

[0063] Wherein, the structural formula of the above enamide is:

[0064]

[0065] The structural formula of the above alkenylsilane is:

[0066]

[0067] In the preparation method, the olefination reaction is carried out in an oil bath at a temperature of 70 to 110° C., preferably 80 to 100° C., and more preferably 90° C.; the olefination reaction time is 12 to 36 h, preferably 18 to 30 h, and more preferably 24 h.

[0068] In the preparation method, the catalyst is [Rh(COD)Cl]2, [Cp*Rh(MeCN)3](SbF6)2 or [Cp*RhCl2]2, and more preferably [Cp*RhCl2]2.

[0069] In the preparation method, the co-catalyst is AgSbF6, AgBF4 or AgNTf2, and more preferably AgSbF6.

[0070] In the preparation method, the oxidant is Ag2CO3, Ag2O, Cu(OAc)2, Cu(acac)2, AgOAc or Cu(SO4)2, more preferably AgOAc.

[0071] In the preparation method, the additive is Zn(OTf)2, AgOTf, Cu(OTf)2 or In(OTf)3, more preferably AgOTf or Cu(OTf)2, and more preferably AgOTf.

[0072] In the preparation method, the solvent is one or a mixture of DMF, DMSO, THF, DCE, Dioxane, TFE, n-hexane, CH3OH, tBuOH, CH3CN or NMP, more preferably n-hexane, CH3OH, and more preferably a mixed solvent of n-hexane and CH3OH; the volume of the solvent is 0.5 to 1.5 mL, more preferably 1.0 mL; the ratio of the volumes of the mixed solvents is 1.0:(0.5 to 2.0), more preferably 1.0:1.0.

[0073] In the preparation method, the molar ratio of olefin amide, olefin silane, catalyst, co-catalyst, oxidant and acid additive is 1.0:(4.0~8.0):(0.01~0.05):(0.1~0.2):(2.0~4.0):(0.2~1.0), more preferably 1.0:(5.0~7.0):(0.03~0.05):(0.1~0.2):(2.5~3.5):(0.3~0.6), and more preferably 1.0:6.0:0.05:0.2:3.0:0.5.

[0074] As the preferred embodiment, the preparation process of the enamide derivatives containing N-(2Z, 4E) dienesilyl skeleton is as follows:

[0075]

[0076] The present invention does not particularly limit the conditions for the preparation process of enamide derivatives containing an N-(2Z, 4E) dienesilyl skeleton. In the embodiments of the present invention, enamide, alkenylsilane, [Cp*RhCl2]2, AgSbF6, AgOAc, AgOTf are mixed with n-hexane and CH3OH to obtain a mixed solution, and the mixed solution is then placed in a 90°C oil bath to react for 24 hours to obtain an enamide derivative containing an N-(2Z, 4E) dienesilyl skeleton.

[0077] This eneamide derivative containing an N-(2Z,4E) diene silicon-based skeleton has the advantages of good selectivity, a wide substrate range, and good functional group tolerance. This type of compound contains two important core skeletons, 1,3-butadiene and eneamide, and is of great value for the research and development of natural products and organic functional materials.

[0078] The following examples describe in detail the enamide derivatives of the N-(2Z,4E) diene skeleton provided by the present invention and their preparation methods, but they should not be construed as limiting the scope of protection of the present invention.

[0079] Example 1

[0080] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((1Z,3E)-1-phenyl-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0081] Add 0.2 mmol of N-benzyl-N-(1-phenylvinyl)acetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0082] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 8:1 to obtain the target product, a total of 46.1 mg, with a yield of 65%.

[0083] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 1 and Figure 2 As shown, the structural characterization data are as follows:

[0084] 1 H NMR (400MHz, CDCl3) δ7.47–7.36(m,5H),7.28(ddd,J=6.7,5.4,2.3Hz,2H),7.23(h,J=3.4,2.2Hz,3H),6.59(d ,J=9.5Hz,1H),6.03–5.84(m,2H),5.54(d,J=13.7Hz,1H),3.63(d,J=13.7Hz,1H),2.00(s,3H),-0.08(s,9H).

[0085] 13 C NMR (101MHz, CDCl3) δ170.8,139.6,138.2,137.8,136.7,135.5,130.5,129.9,129.0,128.8,128.2,127.5,125.7,49.4,21.5,-1.5.

[0086] HRMS (ESI) m / z: [M+H] + Calcd for C 22 H 28 NOSi 350.1935; found 350.1951.

[0087] The structural formula of the product N-Benzyl-N-((1Z,3E)-1-phenyl-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide prepared in this example is:

[0088]

[0089] Example 2

[0090] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((1Z,3E)-1-(o-tolyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0091] Add 0.2 mmol of N-benzyl-N-(1-(o-tolyl)vinyl)acetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0092] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using an eluent of petroleum ether and ethyl acetate in a ratio of 8:1 to obtain the target product, a total of 50.3 mg, with a yield of 69%.

[0093] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 3 and Figure 4 As shown, the structural characterization data are as follows:

[0094] 1 H NMR (400MHz, CDCl3) δ7.38–7.17(m,9H),6.18–6.01(m,2H),5.91(d,J=15.9Hz,1H),5. 47(d,J=13.7Hz,1H),3.44(d,J=12.2Hz,1H),2.35(s,3H),2.16(s,3H),-0.02(s,9H).

[0095] 13 C NMR (101MHz, CDCl3) δ170.7,138.6,138.3,137.3,136.9,136.7,135.3,133.5 ,131.7,129.4,128.55,128.51,128.2,127.3,126.2,48.7,21.9,21.0,-1.4.

[0096] HRMS (ESI) m / z: [M+H] + Calcd for C 23 H 30 NOSi 364.2091; found 364.2419.

[0097] The structural formula of the product N-Benzyl-N-((1Z,3E)-1-(o-tolyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide prepared in this example is:

[0098]

[0099] Example 3

[0100] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((1Z,3E)-1-(3-methoxyphenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0101] Add 0.2 mmol of N-benzyl-N-(1-(3-methoxyphenyl)vinyl)acetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0102] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using an eluent of petroleum ether and ethyl acetate in a ratio of 8:1 to obtain the target product, a total of 52.5 mg, with a yield of 69%.

[0103] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 5 and Figure 6 As shown, the structural characterization data are as follows:

[0104] 1 H NMR (400MHz, CDCl3) δ7.35–7.27(m,3H),7.22(dd,J=5.0,2.0Hz,3H),7.03(d,J=8.6Hz,1H),6.97–6.87(m,2H),6.57(d,J =9.6Hz,1H),6.07–5.85(m,2H),5.50(d,J=13.7Hz,1H),3.81(s,3H),3.68(d,J=13.7Hz,1H),1.99(s,3H),-0.08(s,9H).

[0105] 13C NMR (101MHz, CDCl3) δ170.7,160.1,139.8,138.2,137.7,137.1,136.7,130. 6,130.0,129.9,128.2,127.4,118.2,114.2,111.3,55.2,49.5,21.5,-1.5.

[0106] HRMS (ESI) m / z: [M+H] + Calcd for C23H30NO2Si 380.2040; found 380.2058.

[0107] The structural formula of the product N-Benzyl-N-((1Z,3E)-1-(3-methoxyphenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide prepared in this example is:

[0108]

[0109] Example 4

[0110] This embodiment provides a method for preparing an N-(2Z,4E) diene skeleton enamide derivative N-((1Z,3E)-1-([1,1'-Biphenyl]-4-yl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)-N-benzylacetamide, comprising the following steps:

[0111] Add 0.2 mmol of N-(1-([1,1'-biphenyl]-4-yl)vinyl)-N-benzylacetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0112] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 8:1 to obtain the target product, a total of 67.0 mg, with a yield of 76%.

[0113] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 7and Figure 8 As shown, the structural characterization data are as follows:

[0114] 1 H NMR (400MHz, CDCl3) δ7.72–7.61(m,4H),7.56–7.43(m,4H),7.43–7.31(m,3H),7.26(dd,J=5.0,2.1Hz,3H),6.66 (d,J=9.2Hz,1H),6.09–5.88(m,2H),5.58(d,J=13.7Hz,1H),3.73(d,J=13.7Hz,1H),2.04(s,3H),-0.04(s,9H).

[0115] 13 C NMR (101MHz, CDCl3) δ170.8,141.6,140.0,139.7,138.3,137.5,136.8,134.4,1 30.4,130.0,128.8,128.3,127.7,127.6,127.5,126.9,126.1,49.5,21.6,-1.5.

[0116] HRMS (ESI) m / z: [M+H] + Calcd for C 28 H 32 NOSi 426.2248; found 426.2268.

[0117] The structural formula of the product N-((1Z,3E)-1-([1,1'-Biphenyl]-4-yl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)-N-benzylacetamide prepared in this example is:

[0118]

[0119] Example 5

[0120] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((1Z,3E)-1-(3-chlorophenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0121] Add 0.2 mmol of N-benzyl-N-(1-(3-chlorophenyl)vinyl)acetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0122] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 8:1 to obtain the target product, a total of 46.1 mg, with a yield of 60%.

[0123] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 9 and Figure 10 As shown, the structural characterization data are as follows:

[0124] 1 H NMR(400MHz, CDCl3)δ7.40(q,J=1.5Hz,1H),7.35–7.19(m,8H),6.58(d,J=10.1Hz,1H),6.0 8–5.83(m,2H),5.49(d,J=13.7Hz,1H),3.65(d,J=13.7Hz,1H),1.98(s,3H),-0.07(s,9H).

[0125] 13 C NMR (101MHz, CDCl3) δ170.6,141.1,137.8,137.7,136.5,136.5,135.1,131.5,130.2,129.9,128.7,128.3,127.6,125.7,123.7,49.4,21.5,-1.6.

[0126] HRMS (ESI) m / z: [M+H] + Calcd for C 22 H 27 ClNOSi 384.1545; found 384.1563.

[0127] The structural formula of the product N-Benzyl-N-((1Z,3E)-1-(3-chlorophenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide prepared in this example is:

[0128]

[0129] Example 6

[0130] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((1Z,3E)-1-(4-bromophenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0131] Add 0.2 mmol of N-benzyl-N-(1-(4-bromophenyl)vinyl)acetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0132] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 8:1 to obtain the target product, a total of 54.9 mg, with a yield of 64%.

[0133] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 11 and Figure 12 As shown, the structural characterization data are as follows:

[0134] 1 H NMR(400MHz, CDCl3)δ7.51(d,J=8.6Hz,2H),7.34–7.16(m,7H),6.56(d,J=10.0Hz,1H),6.0 9–5.84(m,2H),5.48(d,J=13.7Hz,1H),3.64(d,J=13.7Hz,1H),1.96(s,3H),-0.08(s,9H).

[0135] 13C NMR (101MHz, CDCl3) δ170.6,140.6,137.9,136.8,136.5,134.5,132.1,130.8,129.9,128.2,127.5,127.1,122.8,49.4,21.5,-1.6.

[0136] HRMS (ESI) m / z: [M+H] + Calcd for C 22 H 27 BrNOSi 428.1040; found 428.1061.

[0137] The structural formula of the product N-Benzyl-N-((1Z,3E)-1-(4-bromophenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide prepared in this example is:

[0138]

[0139] Example 7

[0140] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((1Z,3E)-1-(3-iodophenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0141] Add 0.2 mmol of N-benzyl-N-(1-(3-iodophenyl)vinyl)acetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0142] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 8:1 to obtain the target product, a total of 44.3 mg, with a yield of 46%.

[0143] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 13 and Figure 14As shown, the structural characterization data are as follows:

[0144] 1 H NMR (400MHz, CDCl3) δ7.82–7.64(m,2H),7.43–7.19(m,6H),7.12(t,J=7.8Hz,1H),6.55(d,J=10.1Hz ,1H),6.13–5.82(m,2H),5.47(d,J=13.7Hz,1H),3.67(d,J=13.7Hz,1H),1.97(s,3H),-0.08(s,9H).

[0145] 13 C NMR (101MHz, CDCl3) δ170.7,141.1,137.9,137.8,137.7,136.5,136.3,134.5,131.5,130.6,129.9,128.3,127.6,124.8,95.1,49.5,21.6,-1.5.

[0146] HRMS (ESI) m / z: [M+H] + Calcd for C 22 H 27 INOSi 476.0901; found 476.0926.

[0147] The structural formula of the product N-Benzyl-N-((1Z,3E)-1-(3-iodophenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide prepared in this example is:

[0148]

[0149] Example 8

[0150] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((1Z,3E)-1-(4-nitrophenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0151] Add 0.2 mmol of N-benzyl-N-(1-(4-nitrophenyl)vinyl)acetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0152] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 8:1 to obtain the target product, a total of 44.1 mg, with a yield of 55%.

[0153] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 15 and Figure 16 As shown, the structural characterization data are as follows:

[0154] 1 H NMR (400MHz, CDCl3) δ8.37–8.15(m,2H),7.65–7.50(m,2H),7.24(q,J=3.4,3.0Hz,5H),6.75(d,J=10.2Hz,1H),6.18(d,J =18.3Hz, 1H), 5.97 (dd, J = 18.4, 10.2Hz, 1H), 5.46 (d, J = 13.7Hz, 1H), 3.71 (d, J = 13.8Hz, 1H), 1.97 (s, 3H), -0.05 (s, 9H).

[0155] 13 C NMR (101MHz, CDCl3) δ170.5,147.5,143.8,142.2,137.4,136.2,135.8,133.9,129.9,128.4,127.8,126.1,124.3,49.7,21.5,-1.7.

[0156] HRMS (ESI) m / z: [M+H] + Calcd for C 22 H 27 N2O3Si 395.1785; found 395.1805.

[0157] The structural formula of the product N-Benzyl-N-((1Z,3E)-1-(4-nitrophenyl)-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide prepared in this example is:

[0158]

[0159] Example 9

[0160] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Methyl-N-((1Z,3E)-1-phenyl-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0161] Add 0.2 mmol of N-methyl-N-(1-phenylvinyl)acetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0162] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 8:1 to obtain the target product, a total of 31.2 mg, with a yield of 57%.

[0163] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 17 and Figure 18 As shown, the structural characterization data are as follows:

[0164] 1 H NMR (400MHz, CDCl3) δ 7.46–7.28 (m, 5H), 6.76–6.54 (m, 2H), 6.24 (d, J = 17.0Hz, 1H), 3.08 (s, 3H), 1.93 (s, 3H), 0.11 (s, 9H).

[0165] 13C NMR (101MHz, CDCl3) δ171.3,140.6,140.3,137.5,135.5,129.0,128.8,128.3,125.2,34.9,21.4,-1.4.

[0166] HRMS (ESI) m / z: [M+H] + Calcd for C 16 H 24 NOSi 274.1622; found 274.1635.

[0167] The structural formula of the product N-Methyl-N-((1Z,3E)-1-phenyl-4-(trimethylsilyl)buta-1,3-dien-1-yl)acetamide prepared in this example is:

[0168]

[0169] Example 10

[0170] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((2Z,4E)-5-(trimethylsilyl)penta-2,4-dien-2-yl)acetamide, comprising the following steps:

[0171] Add 0.2 mmol of N-benzyl-N-(prop-1-en-2-yl)acetamide, 1.2 mmol of vinyltrimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0172] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using an eluent of petroleum ether and ethyl acetate in a ratio of 8:1 to obtain the target product, a total of 13.6 mg, with a yield of 23%.

[0173] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 19 and Figure 20 As shown, the structural characterization data are as follows:

[0174] 1H NMR (400MHz, CDCl3) δ7.44–7.18(m,5H),6.03–5.68(m,3H),5.04(d,J=14.0Hz,1H),4.21(d,J=14.1Hz,1H),1.98(s,3H),1.86(s,3H),-0.07(s,9H).

[0175] 13 C NMR (101MHz, CDCl3) δ169.5,137.6,137.2,136.3,135.9,131.8,129.4,128.3,127.4,48.6,21.5,21.1,-1.4.

[0176] HRMS (ESI) m / z: [M+H] + Calcd for C 17 H 26 NOSi 288.1778; found 288.1796.

[0177] The structural formula of the product N-Benzyl-N-((2Z,4E)-5-(trimethylsilyl)penta-2,4-dien-2-yl)acetamide prepared in this example is:

[0178]

[0179] Example 11

[0180] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((1Z,3E)-1-phenyl-4-(triethylsilyl)buta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0181] Add 0.2 mmol of N-benzyl-N-(1-phenylvinyl)acetamide, 1.2 mmol of vinyltriethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0182] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 8:1 to obtain the target product, a total of 41.9 mg, with a yield of 53%.

[0183] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 21 and Figure 22 As shown, the structural characterization data are as follows:

[0184] 1 H NMR(400MHz, CDCl3)δ7.69–7.20(m,10H),6.62(t,J=7.2Hz,1H),6.19–5.90(m,2H),5.55(d d, J=14.0, 5.4Hz, 1H), 3.71 (dd, J=14.0, 5.4Hz, 1H), 2.05 (s, 3H), 0.88 (t, 9H), 0.48 (q, 6H).

[0185] 13 C NMR (101MHz, CDCl3) δ170.8,139.6,137.7,136.7,136.4,135.6,130.7,129.8,129.0,128.8,128.2,127.5,125.8,49.4,21.5,7.3,3.2.

[0186] HRMS (ESI) m / z: [M+H] + Calcd for C 25 H 34 NOSi 392.2404; found 392.2427.

[0187] The structural formula of the product N-Benzyl-N-((1Z,3E)-1-phenyl-4-(triethylsilyl)buta-1,3-dien-1-yl)acetamide prepared in this example is:

[0188]

[0189] Example 12

[0190] This embodiment provides a method for preparing N-(2Z,4E) diene skeleton enamide derivative N-Benzyl-N-((1Z,3E)-4-(dimethyl(phenyl)silyl)-1-phenylbuta-1,3-dien-1-yl)acetamide, comprising the following steps:

[0191] Add 0.2 mmol of N-benzyl-N-(1-phenylvinyl)acetamide, 1.2 mmol of vinylphenyldimethylsilane, 0.01 mmol of [Cp*RhCl2]2, 0.04 mmol of AgSbF6, 0.6 mmol of AgOAc and 0.1 mmol of AgOTf to the reaction tube, and then add 1.0 mL of a mixed solvent of n-hexane and CH3OH with a volume ratio of 1:1, and react in an oil bath at 90°C for 24 hours.

[0192] After the reaction was completed, the product was extracted with 20.0 mL × 3 of ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate, and then separated by column chromatography using a 10:1 ratio of petroleum ether and ethyl acetate as the eluent to obtain the target product, a total of 48.1 mg, with a yield of 58%.

[0193] The product prepared in this example was characterized, and the H NMR spectrum and C NMR spectrum were as follows: Figure 23 and Figure 24 As shown, the structural characterization data are as follows:

[0194] 1 H NMR (400MHz, CDCl3) δ7.62–7.32(m,11H),7.25(ddd,J=18.1,6.7,3.2Hz,4H),6.63(d,J=8.5Hz,1H),6 .27–5.95(m,2H),5.56(d,J=13.7Hz,1H),3.64(d,J=13.7Hz,1H),2.01(s,3H),0.21(d,J=9.6Hz,6H).

[0195] 13 C NMR (101MHz, CDCl3) δ170.7,139.6,138.4,138.0,137.0,136.7,135.4,133.6,130 .3,129.9,129.0,128.9,128.2,127.7,127.5,125.8,99.9,49.4,21.5,-2.9,-3.1.

[0196] HRMS (ESI) m / z: [M+H] + Calcd for C 27 H 30 NOSi 412.2091; found 412.2113.

[0197] The structural formula of the product N-Benzyl-N-((1Z,3E)-4-(dimethyl(phenyl)silyl)-1-phenylbuta-1,3-dien-1-yl)acetamide prepared in this example is:

[0198]

[0199] The above description 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 variation made to the above embodiment based on the essence of the invention technology shall still fall within the scope of protection of the technical solution of the present invention.

Claims

1. An enamide derivative containing an N-(2Z, 4E) diene silyl skeleton, characterized in that: The structural formula of the enamide derivative containing N-(2Z, 4E) dienesilyl 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; R 3 is a straight chain alkyl group; R 4 It is a straight chain alkyl or aryl group.

2. The enamide derivative containing an N-(2Z, 4E) dienesilyl skeleton according to claim 1, characterized in that: The 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 2 In the embodiment, the aryl group is an alkyl-substituted phenyl group or a halogen-substituted phenyl group; 3 In the embodiment, the straight chain alkyl group is methyl or ethyl; 4 In the formula (A), the straight-chain alkyl group is methyl or ethyl, and the aryl group is phenyl.

3. The enamide derivative containing an N-(2Z, 4E) dienesilyl skeleton according to claim 1, 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 formula (A), the alkyl-substituted benzyl group is p-methylbenzyl, and the halogen-substituted benzyl group is p-fluorobenzyl.

4. A method for preparing an olefin amide derivative containing an N-(2Z,4E)diolefin silyl skeleton as claimed in any one of claims 1 to 3, characterized in that: The following steps are involved: The enamide, alkenyl silane, catalyst, co-catalyst, oxidant, additive and solvent are mixed to obtain a mixed solution; the mixed solution is subjected to an alkenylation reaction in an oil bath to obtain the enamide derivative containing the N-(2Z, 4E) diene silane skeleton; Wherein, the structural formula of the enamide is: The structural formula of the alkenyl silane is:

5. The method for preparing an olefin amide derivative containing an N-(2Z, 4E) diene silyl skeleton according to claim 4, characterized in that: The olefination reaction is carried out under the condition of an oil bath; the temperature of the oil bath is 70 to 110° C.; and the time of the olefination reaction is 12 to 36 hours.

6. The method for preparing an olefin amide derivative containing an N-(2Z, 4E) diene silyl skeleton according to claim 4, characterized in that: The catalyst is [Rh(COD)Cl]2, [Cp*Rh(MeCN)3](SbF6)2 or [Cp*RhCl2]2; the co-catalyst is AgSbF6, AgB F4 or AgNTf2.

7. The method for preparing an olefin amide derivative containing an N-(2Z, 4E) diene silyl skeleton according to claim 4, characterized in that: The oxidant is Ag2CO3, Ag2O, Cu(OAc)2, Cu(acac)2, AgOAc or Cu(SO4)2; the additive is Zn(OTf)2, AgOTf, Cu(OTf)2 or In(OTf)3.

8. The method for preparing an olefin amide derivative containing an N-(2Z, 4E) diene silyl skeleton according to claim 4, characterized in that: The solvent is one or a mixture of DMF, DMSO, THF, DCE, Dioxane, TFE, n-hexane, CH3OH, tBuOH, CH3CN or NMP, and the volume of the solvent is 0.5 to 1.5 mL. If two solvents are mixed, the volume ratio is 1.0:(0.5 to 2.0).

9. The method for preparing an olefin amide derivative containing an N-(2Z, 4E) diene silyl skeleton according to claim 4, characterized in that: The molar ratio of the enamide, the alkenyl silane, the catalyst, the co-catalyst, the oxidant and the additive is 1.0:(4.0-8.0):(0.01-0.05):(0.1-0.2):(2.0-4.0):(0.2-1.0).

10. The method for preparing an olefin amide derivative containing an N-(2Z, 4E) diene silyl skeleton according to claim 4, characterized in that: The reaction equation of the olefination reaction is: The product structure is as follows:

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