A synthesis method of a palladium-catalyzed synthesis of 1,4-diene-3-ketone compounds

Abstract

The application relates to a synthesis method of a palladium-catalyzed synthesis of a 1,4-diene-3-ketone compound. The synthesis method is characterized in that an alkenyl triflate and an alkyl acyl chloride are used as raw materials, a palladium salt is used as a catalyst, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene is used as a ligand, N,N-diisopropylethylamine is added, and the reaction is carried out in toluene at 40 DEG C for 16 hours; and the 1,4-diene-3-ketone compound is obtained after the reaction is completed. The synthesis method has the advantages that the substrate raw material is cheap and easy to obtain, the adaptability of functional groups is good, the reaction condition operation is simple, and the synthesis method has a good industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organometallic chemical synthesis, specifically relating to a method for synthesizing 1,4-dien-3-one compounds using palladium catalysis. Background Technology

[0002] 1,4-dien-3-one compounds are structural units found in many biologically active natural products, such as certain steroids, terpenes, and antibiotics. Furthermore, they serve as important intermediates in organic reactions and have wide applications in organic chemical synthesis.

[0003] 1,4-Dien-3-one compounds are widely used in the pharmaceutical and pesticide fields. They are extremely important building blocks in synthesis. Many complex natural products and drug molecules contain a core skeleton constructed from them via Nazarov cyclization or the Diels-Alder reaction. Therefore, chemists have been attracted to conduct synthetic research on compounds containing unsaturated ketones. Classical methods for generating 1,4-dien-3-one compounds include the Mannich reaction (Org. Lett. 2019, 21, 4039-4043); the reaction of alkynes with aryl halides or acyl chlorides under palladium catalysis can generate 1,4-dien-3-one compounds (J. Org. Chem. 2018, 83, 12887-12896); we have developed a transition metal-involved synthetic method with mild reaction conditions, simple operation, and readily available alkenyl trifluoromethanesulfonate as a starting material for the synthesis of 1,4-dien-3-one compounds. Summary of the Invention

[0004] The purpose of this invention is to provide a method for the synthesis of 1,4-dien-3-one compounds by palladium catalysis. This method uses readily available raw materials, has high reaction efficiency, mild reaction conditions, and is easy to operate, and has good prospects for industrial application.

[0005] A method for the palladium-catalyzed synthesis of 1,4-dien-3-one compounds, characterized in that the method comprises the following steps:

[0006] Using Pd2dba3 as a catalyst, 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene as a ligand, alkenyl trifluoromethanesulfonate and alkyl acyl chloride as raw materials, and N,N-diisopropylethylamine as a base, a 1,4-dien-3-one compound was prepared by reaction in toluene solvent.

[0007] The structural formula of the alkenyl trifluoromethanesulfonate is: The structural formula of the alkyl acyl chloride is: The structural formula of the 1,4-dien-3-one compound is as follows:

[0008] The alkenyl trifluoromethanesulfonate thereof is selected from any one or more of the following:

[0009]

[0010] The alkyl acyl chloride is selected from any one or more of the following:

[0011]

[0012] In one embodiment of the present invention, the reaction temperature is 40°C and the reaction time is 16 hours.

[0013] In one embodiment of the present invention, the ligand comprises any one or more of the following structures: 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (Xantphos) and triphenylphosphine (PPh3).

[0014] In one embodiment of the present invention, the amount of ligand relative to alkenyl trifluoromethanesulfonate is 15 mol.

[0015] In one embodiment of the present invention, the amount of palladium salt relative to alkenyl trifluoromethanesulfonate is 5 mol%.

[0016] In one embodiment of the present invention, the palladium salt is selected from any one or more of the following: Pd2dba3, PdCl2, and Pd(OAc)2.

[0017] In one embodiment of the present invention, the alkaline reagent is selected from any one or more of the following: N,N-diisopropylethylamine.

[0018] In one embodiment of the present invention, the organic solvent is selected from any one or more of the following: toluene, 1,4-dioxane, and tetrahydrofuran.

[0019] In one embodiment of the present invention, the molar ratio of the alkenyl trifluoromethanesulfonate to the alkyl acyl chloride is 1:2.

[0020] In one embodiment of the present invention, the molar ratio of alkenyl trifluoromethanesulfonate to alkaline reagent is 1:3.

[0021] In one embodiment of the present invention, the amount of organic solvent used is 1 mL / 0.2 mmol of alkenyl trifluoromethanesulfonate, i.e., 5 mL / mmol of alkenyl trifluoromethanesulfonate.

[0022] In one embodiment of the invention, the reaction is carried out under a nitrogen atmosphere.

[0023] In one embodiment of the present invention, the synthetic route of the reaction is as follows:

[0024]

[0025] In one embodiment of the present invention, the 1,4-dien-3-one compound specifically includes the following structure:

[0026]

[0027] In one embodiment of the present invention, the molar ratio of alkenyl trifluoromethanesulfonate, alkyl acyl chloride, and N,N-diisopropylethylamine may be specifically selected as 1:2:3.

[0028] In one embodiment of the present invention, the specific steps of the method are as follows:

[0029] In a reaction tube equipped with a stir bar, under a nitrogen atmosphere, Pd2dba3 catalyst, Xantphos ligand, alkenyl trifluoromethanesulfonate, alkyl acyl chloride, N,N-diisopropylethylamine, and solvent were added sequentially, and the mixture was stirred at 40°C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding the target compound, 1,4-dien-3-one.

[0030] Beneficial effects:

[0031] This invention uses Pd₂dba₃ as a catalyst and Xantphos as a ligand, adding alkenyl trifluoromethanesulfonate, alkyl acyl chloride, and N,N-diisopropylethylamine, reacting in toluene at 40°C for 16 hours to obtain a 1,4-dien-3-one compound. The synthetic method of this invention uses simple and readily available reactants, operates under mild conditions, and is convenient, showing great promise for industrial applications. Attached Figure Description

[0032] Figure 1 This is a schematic diagram of the synthesis method of the present invention. Detailed Implementation

[0033] To make the content of this invention easier to understand, the technical solutions of this invention will be further described below in conjunction with specific embodiments, but this does not limit the invention to the scope of the embodiments described.

[0034] Example 1

[0035] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 3,4-dihydronaphthyl-1-yltrifluoromethanesulfonate (0.2 mmol, 1 equiv), hexanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 1 (99% separation yield).

[0036]

[0037] 1 H NMR (600MHz, CDCl3) δ7.40-7.37 (m, 1H), 7.20-7.16 (m, 3H), 6.94 (dt, J=15.5, 7.0Hz, 1H), 6.66 (t, J=4.7Hz, 1H), 6.47 (dt, J=15.5, 1.5 Hz, 1H), 2.80 (t, J=8.0Hz, 2H), 2.44 (td, J=8.0, 4.7Hz, 2H), 2.24 (qd, J=7.2, 1.5Hz, 2H), 1.51 (p, J=7.4Hz, 2H), 0.95 (t, J=7.4Hz, 3H). 13 C NMR (151MHz, CDCl3) δ194.1, 149.7, 139.6, 136.1, 135.5, 131.5, 129.4, 127.7, 127.7, 126.6, 125.9, 34.7, 27.6, 23.3, 21.4, 13.8.HRMS m / z (ESI)calcd forC 16 H 19 O + (M+H) + 227.1430, found 227.1429.

[0038] Example 2

[0039] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 6-methoxy-3,4-dihydronaphthalene-1-trifluoromethanesulfonate (0.2 mmol, 1 equiv), hexanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 2 (96% separation yield).

[0040]

[0041] 1 H NMR (600MHz, CDCl3) δ7.39-7.35 (m, 1H), 6.93 (dt, J=15.6, 7.0Hz, 1H), 6.78-6.70 (m, 2H), 6.56 (t, J=4.8Hz, 1H), 6.47 (dt, J=15.6, 1.5Hz, 1H), 3 .80 (s, 3H), 2.77 (t, J=7.9Hz, 2H), 2.42 (ddd, J=8.8, 7.4, 4.8Hz, 2H), 2.23 (qd, J=7.1, 1.5Hz, 2H), 1.52 (q, J=7.4Hz, 2H), 0.95 (t, J=7.4Hz, 3H). 13 C NMR (151MHz, CDCl3) δ194.0, 159.0, 149.4, 139.1, 138.1, 133.5, 129.2, 127.2 ,124.6,113.8,111.1,55.3,34.6,28.1,23.3,21.4,13.8.HRMSm / z(ESI)calcd for C 17 H 21 O2 + (M+H) + 257.1536, found 257.1533.

[0042] Example 3

[0043] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 6-(benzyloxy)-3,4-dihydronaphthalene-1-trifluoromethanesulfonate (0.2 mmol, 1 equiv), hexanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 3 (85% separation yield).

[0044]

[0045] 1 H NMR (600MHz, CDCl3) δ7.43 (d, J=7.6Hz, 2H), 7.41-7.36 (m, 3H), 7.33 (t, J=7.3Hz, 1H), 6.94 (dt, J=15.4, 6.9Hz, 1H), 6.84-6.76 (m, 2H), 6.58 (t, J=4.8Hz, 1H), 6.48 (dt, J=15.6, 1.6Hz, 1H), 5.07 (s, 2H), 2.77 (t, J=8.0Hz, 2H), 2.42 (td, J=8.0, 4.8 Hz, 2H), 2.24 (qd, J=7.2, 1.5Hz, 2H), 1.52 (p, J=7.4Hz, 2H), 0.96 (t, J=7.4Hz, 3H). 13 C NMR (151MHz, CDCl3) δ194.0, 158.3, 149.4, 139.1, 138.2, 137.0, 133.7, 129.2, 128.6 ,128.0,127.5,127.2,124.8,114.8,112.1,70.0,34.7,28.1,23.3,21.4,13.8.HRMS m / z(ESI)calcd for C 23 H 25 O2 + (M+H) + 333.1849, found 333.1847.

[0046] Example 4

[0047] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 6-fluoro-3,4-dihydronaphthalene-1-trifluoromethanesulfonate (0.2 mmol, 1 equiv), hexanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 4 (98% separation yield).

[0048]

[0049] 1 H NMR (600MHz, CDCl3) δ7.24 (dd, J=10.5, 2.7Hz, 1H), 7.10 (dd, J=8.3, 5.8Hz, 1H) , 6.94 (dt, J=15.6, 6.9Hz, 1H), 6.87 (td, J=8.3, 2.7Hz, 1H), 6.77 (t, J=4.7Hz, 1 H), 6.49 (dt, J=15.6, 1.6Hz, 1H), 2.75 (t, J=8.0Hz, 2H), 2.44 (td, J=8.0, 4.8Hz , 2H), 2.25 (qd, J=7.2, 1.5Hz, 2H), 1.53 (q, J=7.4Hz, 2H), 0.96 (t, J=7.4Hz, 3H). 13 C NMR (151MHz, CDCl3) δ193.1, 161.5 (d, J=242.4Hz), 150.0, 138.6 (d, J=2.6Hz), 137.2, 132.9 (d, J=8.3Hz), 131.5 (d, J=3.0Hz), 128.8, 128.6 (d, J=8.1Hz), 114.1 (d, J=21.2Hz), 113.1 (d, J=23.7Hz), 34.7, 26.7, 23.5, 21.4, 13.8.HRMS m / z(ESI)calcd for C 16 H 18 F + (M+H) + 245.1336, found 245.1334

[0050] Example 5

[0051] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 6-chloro-3,4-dihydronaphthalene-1-trifluoromethanesulfonate (0.2 mmol, 1 equiv), hexanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 5 (65% yield).

[0052]

[0053] 11 H NMR (600MHz, CDCl3) δ7.41-7.36 (m, 1H), 7.20-7.13 (m, 2H), 6.93 (dt, J=15.5, 7.0Hz, 1H), 6.70 (t, J=4.8Hz, 1H), 6.47 (dt, J=15.5, 1.5 Hz, 1H), 2.77 (t, J=8.0Hz, 2H), 2.44 (td, J=8.1, 4.8Hz, 2H), 2.24 (qd, J=7.1, 1.5Hz, 2H), 1.51 (p, J=7.4Hz, 2H), 0.95 (t, J=7.4Hz, 3H). 13 C NMR (151MHz, CDCl3) δ193.3, 149.9, 138.7, 138.1, 136.1, 133.1, 129.9, 128.9, 127.7, 127.2, 126.6, 34.7, 27.4, 23.1, 21.4, 13.8.HRMS m / z (ESI)calcd forC 16 H 18 ClO + (M+H) + 261.1041, found 261.1038.

[0054] Example 6

[0055] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 4-(3,4-dichlorophenyl)3,4-dihydronaphthalene-1-trifluoromethanesulfonate (0.2 mmol, 1 equiv), hexanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 6 (65% yield).

[0056]

[0057] 1 H NMR (600MHz, CDCl3) δ7.41-7.36 (m, 1H), 7.20-7.13 (m, 2H), 6.93 (dt, J=15.5, 7.0Hz, 1H), 6.70 (t, J=4.8Hz, 1H), 6.47 (dt, J=15.5, 1.5 Hz, 1H), 2.77 (t, J=8.0Hz, 2H), 2.44 (td, J=8.1, 4.8Hz, 2H), 2.24 (qd, J=7.1, 1.5Hz, 2H), 1.51 (p, J=7.4Hz, 2H), 0.95 (t, J=7.4Hz, 3H). 13 C NMR (151MHz, CDCl3) δ193.3, 149.9, 138.7, 138.1, 136.1, 133.1, 129.9, 128.9, 127.7, 127.2, 126.6, 34.7, 27.4, 23.1, 21.4, 13.8.HRMS m / z (ESI)calcd forC 16 H 18 ClO + (M+H) + 261.1041, found 261.1038.

[0058] Example 7

[0059] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 7-bromo-3,4-dihydronaphthalene-1-trifluoromethanesulfonate (0.2 mmol, 1 equiv), hexanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 7 (58% yield).

[0060]

[0061] 1 H NMR (600MHz, CDCl3) δ7.61 (q, J=2.1Hz, 1H), 7.34-7.27 (m, 1H), 7.03 (dd, J= 8.5, 2.9Hz, 1H), 6.98-6.90 (m, 1H), 6.74 (td, J=4.7, 1.7Hz, 1H), 6.48 (dt, J =15.6, 2.0Hz, 1H), 2.74 (t, J = 7.9Hz, 2H), 2.44 (qd, J = 6.3, 5.5, 1.6Hz, 2H), 2.28-2.22 (m, 2H), 1.53 (qd, J=7.4, 1.6Hz, 2H), 0.97 (dd, J=7.4, 1.6Hz, 3H). 13 C NMR (151MHz, CDCl3) 1 δ193.0, 150.1, 138.4, 137.0, 134.9, 133.3, 130.5, 129.1, 128.9, 128.8, 120.0, 34.7, 27.0, 23.2, 21.4, 13.8.HRMS m / z(ESI)calcd for C 16 H 18 BrO + (M+H) + 305.0536, found 305.0535.

[0062] Example 8

[0063] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 2-thiophene-4-trifluoromethanesulfonate (0.2 mmol, 1 equiv), hexanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 8 (70% separation yield).

[0064]

[0065] 1 H NMR (600MHz, CDCl3) δ7.35 (dd, J=7.7, 1.4Hz, 1H), 7.31 (dd, J=7.7, 1.5Hz, 1H), 7.17 (td, J=7.5, 1.6Hz, 1H), 7.12 (td, J=7.5, 1.5Hz, 1H), 6.89 (dt, J=15.6, 6.9 Hz, 1H), 6.51 (t, J=5.8Hz, 1H), 6.34 (dt, J=15.6, 1.6Hz, 1H), 3.42 (d, J=5.8Hz, 2H), 2.20 (qd, J=7.1, 1.6Hz, 2H), 1.48 (p, J=7.4Hz, 2H), 0.92 (t, J=7.4Hz, 3H). 13 C NMR (151MHz, CDCl3) δ194.2, 151.0, 141.1, 133.2, 130.9, 129.4, 128.4, 127.8, 127.5, 127.4, 125.8, 34.6, 24.8, 21.3, 13.7.HRMS m / z (ESI)calcd for C 1s H 17 OS + (M+H) + 245.0995, found 245.0993.

[0066] Example 9

[0067] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 3,4-dihydronaphthyl-1-yltrifluoromethanesulfonate (0.2 mmol, 1 equiv), n-butyryl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 9 (95% separation yield).

[0068]

[0069] 1 H NMR (600MHz, CDCl3) δ7.41-7.36 (m, 1H), 7.22-7.14 (m, 3H), 6.95 (dq, J=15.4, 6.9Hz, 1H), 6.65 (t, J=4.7Hz, 1H), 6 .50 (dq, J=15.5, 1.7Hz, 1H), 2.80 (t, J=8.0Hz, 2H), 2.44 (ddd, J=8.6, 7.4, 4.8Hz, 2H), 1.94 (dd, J=6.8, 1.6Hz, 3H). 13 C NMR (151MHz, CDCl3) δ193.9, 145.0, 139.5, 136.1, 135.5, 131.5, 130.9, 127.7, 127.7, 126.6, 125.8, 27.6, 23.3, 18.4.HRMS m / z (ESI)calcd for C 14 H 15 O + [M+H] + 199.1117, found 199.1116.

[0070] Example 10

[0071] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 3,4-dihydronaphthyl-1-yltrifluoromethanesulfonate (0.2 mmol, 1 equiv), 3-cyclohexylpropionyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 10 (53% yield).

[0072]

[0073] 1 H NMR (600MHz, CDCl3) δ7.41-7.36 (m, 1H), 7.22-7.13 (m, 3H), 6.89 (dd, J=15.7, 6.8Hz, 1H), 6. 66 (t, J=4.7Hz, 1H), 6.42 (dd, J=15.7, 1.4Hz, 1H), 2.80 (t, J=8.0Hz, 2H), 2.44 (ddd, J=8.8, 7. 4, 4.8Hz, 2H), 2.18 (dttd, J=10.3, 7.0, 3.5, 1.7Hz, 1H), 1.84-1.72 (m, 4H), 1.68 (dddq, J=12 .1, 5.4, 3.5, 1.8Hz, 1H), 1.33 (dt, J=12.4, 3.7Hz, 1H), 1.28-1.24 (m, 1H), 1.23-1.12 (m, 3H). 13 C NMR (151MHz, CDCl3) δ194.4, 154.7, 139.7, 136.2, 135.6, 131.6, 127.7, 126.7, 126.5, 125.9, 40.8, 31.8, 27.6, 26.0, 25.7, 23.3.HRMS m / z (ESI)calcd for C 19 H 23 O + [M+H] + 267.1743, found 267.1741.

[0074] Example 11

[0075] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 3,4-dihydronaphthyl-1-yltrifluoromethanesulfonate (0.2 mmol, 1 equiv), isohexanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 11 (60% yield).

[0076]

[0077] 1 H NMR (600MHz, CDCl3) δ7.41-7.38 (m, 1H), 7.20-7.15 (m, 3H), 6.91 (dd, J=15.7, 6.7Hz, 1H), 6.67 (t, J=4. 8Hz, 1H), 6.43 (dd, J=15.6, 1.4Hz, 1H), 2.80 (t, J=8.0Hz, 2H), 2.57-2.38 (m, 3H), 1.09 (d, J=6.8Hz, 6H). 13 C NMR (151MHz, CDCl3) δ194.3, 155.8, 139.6, 136.2, 135.6, 131.5, 127.7, 127.7, 126.5, 126.3, 125.9, 31.3, 27.6, 23.3, 21.4.HRMS m / z (ESI)calcd for C 16 H 19 O + [M+H] + 227.1430, found 227.1429.

[0078] Example 12

[0079] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 3,4-dihydronaphthyl-1-yltrifluoromethanesulfonate (0.2 mmol, 1 equiv), hydrogenated cinnamyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 12 (52% yield).

[0080]

[0081] 1 H NMR (600MHz, CDCl3) δ7.70 (d, J=15.9Hz, 1H), 7.61-7.54 (m, 2H), 7.45 (tt, J=4.3, 2.4Hz, 1H), 7.40 (dp, J=5.1, 2.0Hz, 3H ), 7.24-7.18 (m, 3H), 7.13 (d, J=15.9Hz, 1H), 6.80 (t, J=4.7Hz, 1H), 2.84 (t, J=7.9Hz, 2H), 2.49 (td, J=8.0, 4.8Hz, 2H). 13 C NMR (151 MH) z , CDCl3) δ193.4, 144.4, 140.0, 136.3, 136.0, 134.8, 131.4, 130.5, 128.9, 128.4, 127.9, 127.8, 126.7, 125.9, 125.4, 27.6, 23.4.HRMS m / z(ESI)calcd for C 19 H 17 O + [M+H] + 261.1274, found 261.1272.

[0082] Example 13

[0083] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 3,4-dihydronaphthyl-1-yltrifluoromethanesulfonate (0.2 mmol, 1 equiv), 4-ethyloctanoyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 13 (75% yield).

[0084]

[0085] 1 H NMR (600MHz, CDCl3) δ7.43-7.36 (m, 1H), 7.22-7.14 (m, 3H), 6.74-6.63 (m, 2H), 6.42 (dd, J=15.6, 0.8Hz, 1H), 2.81 (t, J=8.0Hz, 2H), 2.45 (ddd . 13 C NMR (151MHz, CDCl3) δ194.0, 154.1, 139.7, 136.2, 135.4, 131.6, 129.1, 127.7, 127.7, 126.5, 125.9, 44.8, 33.9, 29.6, 27.6, 27.3, 23.3, 22.8, 14.0, 11.8.HRMS m / z(ESI)calcd for C 20 H 27 O + [M+H] + 283.2056, found 283.2053.

[0086] Example 14

[0087] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 3,4-dihydronaphthyl-1-yltrifluoromethanesulfonate (0.2 mmol, 1 equiv), propionyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 14 (79% yield).

[0088]

[0089] 1 H NMR (600MHz, CDCl3) δ7.53-7.42(m, 1H), 7.23-7.15(m, 3H), 6.78(td, J=12.4, 11.5, 8.2Hz, 2H), 6.33(d d, J=17.3, 1.7Hz, 1H), 5.89 (dd, J=10.6, 1.6Hz, 1H), 2.80 (t, J=8.0Hz, 2H), 2.46 (td, J=7.9, 5.0Hz, 2H). 13 C NMR (151MHz, CDCl3) δ193.6, 138.9, 137.4, 136.2, 135.2, 131.2, 129.8, 127.9, 127.7, 126.6, 126.0, 27.5, 23.4.HRMS m / z (ESI)calcdfor C 13 H 13 O + [M+H] + 185.0961, found 185.0960.

[0090] Example 15

[0091] In a reaction tube equipped with a stir bar, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), Xantphos as ligand (0.03 mmol, 15 mol%), 3,4-dihydronaphthyl-1-yltrifluoromethanesulfonate (0.2 mmol, 1 equiv), octanoic acid methyl ester chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent toluene. The mixture was stirred at 40 °C for 16 h. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, finally yielding compound 15 (42% yield).

[0092]

[0093] 1 H NMR (600MHz, CDCl3) δ7.41-7.36 (m, 1H), 7.22-7.15 (m, 3H), 6.91 (dt, J=15.4, 6.9Hz, 1H), 6.67 (t, J=4.7Hz, 1H), 6.48 (dt, J=15.6 , 1.5Hz, 1H), 3.67 (s, 3H), 2.80 (t, J=8.0Hz, 2H), 2.50-2.41 (m, 2H), 2.37-2.24 (m, 4H), 1.67 (p, J=7.5Hz, 2H), 1.58-1.47 (m, 2H). 13 C NMR (151MHz, CDCl3) δ193.8, 173.8, 148.8, 139.5, 136.2, 135.8, 131.5, 129.4 ,127.74,127.70,126.6,125.9,51.6,33.8,32.2,27.6,27.5,24.5,23.3.HRMS m / z(ESI)calcd for C 19 H 23 O3 + [M+H] + 299.1642, found 299.1640.

[0094] Example 16 Synthesis of the target product using different base reagents

[0095] In a reaction tube equipped with a stir bar, under a nitrogen atmosphere, the following substances were added sequentially: catalyst Pd₂dba₃ (0.01 mmol, 5 mol%), ligand Xantphos (0.03 mmol, 15 mol%), alkenyl trifluoromethanesulfonate (0.2 mmol, 1 equiv), alkyl acyl chloride (0.4 mmol, 2 equiv), and base reagent (0.6 mmol, 3 equiv). The solvent was toluene. The reaction was stirred at 40 °C for 16 h. The reaction results are shown in Table 1.

[0096] Table 1. Synthesis results of different base reagents

[0097] N,N-Diisopropylethylamine 99％ Triethylamine 6％

[0098] Example 17 Synthesis of the target product using different organic solvents

[0099] In a reaction tube equipped with a stir bar, under a N2 atmosphere, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), ligand Xantphos (0.03 mmol, 15 mol%), alkenyl trifluoromethanesulfonate (0.2 mmol, 1 equiv), alkyl acyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and organic solvent. The mixture was stirred at 40 °C for 16 h. The reaction results are shown in Table 2.

[0100] Table 2 Synthesis results with different organic solvents

[0101] Toluene 90％ 1,4-Dioxane 48％ Tetrahydrofuran 68％

[0102] Example 18 Synthesis of the target product using different palladium salts

[0103] In a reaction tube equipped with a stir bar, under a N2 atmosphere, palladium catalyst (0.01 mmol, 5 mol%), ligand Xantphos (0.03 mmol, 15 mol%), alkenyl trifluoromethanesulfonate (0.2 mmol, 1 equiv), alkyl acyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent were added sequentially, and the mixture was stirred at 40 °C for 16 h. The reaction results are shown in Table 3.

[0104] Table 3. Synthesis results of different palladium salts

[0105] <![CDATA[Pd2dba3]]> 99％ <![CDATA[Pd(OAc)2]]> 80％ <![CDATA[PdCl2]]> 30％

[0106] Example 19 Synthesis of the target product with different phosphine ligands

[0107] In a reaction tube equipped with a stir bar, under a N2 atmosphere, the following components were added sequentially: catalyst Pd2dba3 (0.01 mmol, 5 mol%), ligand (0.03 mmol, 15 mol%), alkenyl trifluoromethanesulfonate (0.2 mmol, 1 equiv), alkyl acyl chloride (0.4 mmol, 2 equiv), N,N-diisopropylethylamine (0.6 mmol, 3 equiv), and solvent. The mixture was stirred at 40 °C for 16 h. The reaction results are shown in Table 4.

[0108] Table 4. Synthesis results of different phosphine ligands

[0109] Xantphos 99％ <![CDATA[PPh3]]> 0％

[0110] Although the invention has been described through specific embodiments above, it should not be construed as being limited thereto; rather, the invention encompasses the general aspects previously disclosed. Various modifications and embodiments are possible without departing from the spirit and scope of the invention.

Claims

1. A method for the palladium-catalyzed synthesis of 1,4-dien-3-one compounds, characterized in that, The method includes the following procedures: Alkenyl trifluoromethanesulfonate, alkyl acyl chloride, palladium catalyst, phosphine ligand, and base were dispersed in a solvent and reacted under a nitrogen atmosphere. After the reaction was completed, a 1,4-dien-3-one compound was obtained. The structural formula of the alkenyl trifluoromethanesulfonate is: Structural formula of alkyl acyl chloride The structural formula of the 1,4-dien-3-one compound is as follows: The alkenyl trifluoromethanesulfonate thereof is selected from any one or more of the following: The alkyl acyl chloride is selected from any one or more of the following: The palladium catalyst is selected from any one or more of the following: Pd2dba3, PdCl2, and Pd(OAc)2; The phosphine ligands include any one or more of the following structures: 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene (Xantphos) and triphenylphosphine (PPh3); The base is selected from any one or more of the following: iPr2NEt and Et3N; The solvent is selected from any one or more of the following: toluene, 1,4-dioxane, and tetrahydrofuran.

2. The method according to claim 1, characterized in that, The molar ratio of alkenyl trifluoromethanesulfonate to alkyl acyl chloride is 1:

2.

3. The method according to claim 1, characterized in that, The amount of phosphine ligand relative to alkenyl trifluoromethanesulfonate is 15 mol.

4. The method according to claim 1, characterized in that, The amount of palladium catalyst relative to alkenyl trifluoromethanesulfonate is 5 mol%.

5. The method according to claim 1, characterized in that, The molar ratio of the base to the alkenyl trifluoromethanesulfonate is 3:1.

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