Method for synthesizing 1, 3-conjugated diene carboxylate by palladium-catalyzed conjugated eneyne hydrogen esterification reaction

Abstract

The invention discloses a method for synthesizing 1, 3-conjugated diene carboxylate by palladium-catalyzed conjugated eneyne hydrogen esterification reaction, and belongs to the field of organic synthesis. Under the protection of nitrogen, conjugated eneyne and formic acid aryl ester are used as raw materials and react in an organic solvent system containing a palladium catalyst and a ligand to obtain the 1, 3-conjugated diene carboxylic ester. The one-step method is adopted, under the combined action of the ligand and the palladium catalyst, preparation and synthesis of the 1, 3-conjugated diene carboxylic ester with good selectivity are achieved, the system is simple, and the target product can be obtained without additional treatment. The method is easy to operate, mild in condition, wide in substrate range and good in functional group compatibility, different types of conjugated enyne show good tolerance, amplification is easy, atom economy is high, and the method is superior to a traditional synthesis method in multiple aspects.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing 1,3-conjugated diene carboxylic acid esters by palladium-catalyzed hydrogen esterification of conjugated alkynes. Background Technology

[0002] 1,3-Conjugated diene carboxylic acid esters have wide applications in organic synthesis, medicinal chemistry, materials science, natural product synthesis, catalysis, biochemistry, and analytical chemistry, demonstrating their multifunctionality and importance. Containing multiple carbon-carbon double bonds, the diversity of substituent groups, and ester groups endows them with unique biological activities and physicochemical properties. They are often key synthetic intermediates for many active pharmaceutical molecules; therefore, developing new reaction strategies or catalytic systems for the synthesis of novel 1,3-conjugated diene carboxylic acid esters is of great significance.

[0003] Ester-substituted 1,3-conjugated dienes offer greater research value than other multifunctionalized conjugated dienes due to their ability to flexibly transform carboxyl groups or other functional groups in organic synthesis. However, traditional synthetic methods often suffer from harsh reaction conditions (such as strong acid / base environments, high temperature and pressure), limited functional group compatibility, difficulty in controlling regioselectivity, and low yields, hindering the widespread application of ester-substituted 1,3-conjugated dienes. Developing innovative synthetic strategies with milder conditions and greater versatility has become a key research focus and challenge in this field. Recent studies have shown that the introduction of novel catalytic systems such as transition metal catalysis and photoredox catalysis provides breakthrough ideas for overcoming this synthetic challenge. Summary of the Invention

[0004] This invention addresses the shortcomings of existing technologies by providing a method for synthesizing 1,3-conjugated diene carboxylic acid esters via palladium-catalyzed hydrogen esterification of conjugated enyne. This method overcomes the drawbacks of traditional catalytic systems, such as cumbersome steps, poor substrate regioselectivity, the need for pre-functionalized substrates, reliance on expensive transition metal catalysts, the use of toxic and harmful CO gas and air and moisture-sensitive organometallic reagents, difficulty in preparation and storage, harsh reaction conditions, numerous reaction steps, low efficiency, limited substrate range, and the generation of large amounts of metal waste.

[0005] The design concept of this invention is to achieve regioselective hydrogen esterification of conjugated alkynes and alkenes based on a palladium-catalyzed CH bond activation strategy, efficiently constructing carboxylic acid ester derivatives with a 1,3-conjugated diene structure. This method utilizes readily available and inexpensive raw materials, enabling more efficient and milder synthesis of carboxylic acid ester derivatives with a 1,3-conjugated diene structure. It boasts higher atom and step economy, and is expected to have a lasting impact on the field of synthetic organic chemistry. However, due to the lack of functional groups to guide positional or regioselectivity, the diversity of reaction sites in unsaturated hydrocarbons often leads to product complexity, posing a significant challenge to regioselectivity control in most transformation processes. This characteristic largely limits its synthetic application value. Therefore, developing highly selective catalytic systems has become a core research issue in this field, particularly achieving precise control of reaction selectivity through strategies such as ligand selection and catalyst regulation, which has significant scientific implications.

[0006] The present invention relates to a method for synthesizing 1,3-conjugated diene carboxylic acid esters by palladium-catalyzed hydrogen esterification of conjugated enyne. The method involves reacting conjugated enyne and aryl formate as raw materials under nitrogen protection in an organic solvent system containing a palladium catalyst and ligands to obtain 1,3-conjugated diene carboxylic acid esters.

[0007] The reaction route is shown below:

[0008] .

[0009] R1 is selected from phenyl, substituted phenyl, or naphthyl. The substituents of the substituted phenyl include C1-C6 alkyl substitution, C1-C6 alkoxy substitution, halogen substitution, and ester group (RCOO-, where R is selected from H or C1-C6 alkyl).

[0010] R2 is selected from phenyl, substituted phenyl, or naphthyl. The substituents of the substituted phenyl include one or more of C1-C6 alkyl substitution, C1-C6 alkoxy substitution, halogen substitution, trifluoromethyl substitution, and phenyl substitution.

[0011] Further, the conjugated enyne is selected from 1-phenyl-3-en-1-butyne, 1-p-methoxyphenyl-3-en-1-butyne, 4-(but-3-en-1-yn-1-yl)phenyl acetate, 2-(3-buten-1-yn-1-yl)naphthalene, 1-(3-buten-1-yn-1-yl)-4-(tert-butyl)benzene, or 1-(3-buten-1-ynyl)-4-fluorobenzene. The aromatic formate is selected from phenyl formate, p-toluene formate, 4-fluorophenyl formate, 4-chlorophenyl formate, 4-methoxyphenyl formate, 4-trifluoromethylphenyl formate, or 4-phenylphenyl formate.

[0012] The palladium catalyst is selected from any one of palladium acetate, bis(acetylacetone)palladium, palladium chloride, palladium neopentanoate, and allyl palladium chloride dimer.

[0013] The ligand is selected from any one of bis(dicyclohexylphosphinophenyl) ether, dimethyl-p-tolylphosphine, triphenylphosphine, tri-p-benzylphosphine, 4-(dimethylamino)triphenylphosphine, and tris(4-dimethylaminophenyl)phosphine.

[0014] The organic solvent is selected from one or a combination of several of acetone, 1,4-dioxane, ethyl acetate, toluene, tetrahydrofuran, ethyl acetate, and N,N-dimethylformamide, preferably a 1:1 (V / V) combination of ethyl acetate and N,N-dimethylformamide.

[0015] During the reaction, the molar ratio of conjugated alkyne to aryl formate is 1:3.

[0016] The molar ratio of conjugated alkyne to palladium catalyst is 1:0.01 to 1:0.20, preferably 1:0.05.

[0017] The molar ratio of conjugated alkyne to ligand is 1:0.05 to 1:0.30, preferably 1:0.20.

[0018] The reaction temperature is 80-110℃, preferably 100℃; the reaction time is 12-36 hours, preferably 24 hours.

[0019] Compared with the prior art, the beneficial effects of the present invention are reflected in:

[0020] 1. This invention reports for the first time a method for synthesizing 1,3-conjugated diene carboxylic acid esters by palladium-catalyzed hydrogen esterification of conjugated alkynes.

[0021] 2. This invention obtains non-cyclic long-chain 1,3-conjugated diene carboxylic acid esters by regulating ligands.

[0022] 2. This invention uses conjugated alkynes as raw materials, which are inexpensive and readily available. No substrate pre-activation is required, the operation is simple, and it has higher atom economy.

[0023] 3. This invention uses abundant palladium as a catalyst, resulting in low reaction cost, mild conditions, a broad substrate range, good functional group compatibility, and good tolerance to different types of conjugated alkenes and alkynes. It is also easily scaled up. This provides a practical synthetic method for synthesizing high-value-added 1,3-conjugated diene carboxylic esters from simple unsaturated hydrocarbon feedstocks, demonstrating atom economy and promising industrial applications. Attached Figure Description

[0024] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, and the advantages of the present invention as described above or otherwise will become clearer.

[0025] Figure 1 This is the reaction route diagram of the present invention.

[0026] Figure 2 This is the proton NMR spectrum of compound 3a.

[0027] Figure 3 The carbon spectrum of compound 3a;

[0028] Figure 4 This is the proton NMR spectrum of compound 3b.

[0029] Figure 5 This is the carbon spectrum of compound 3b.

[0030] Figure 6 This is the hydrogen spectrum of compound 3c.

[0031] Figure 7 This is the carbon spectrum of compound 3c.

[0032] Figure 8 This is the proton NMR spectrum of compound 3d.

[0033] Figure 9 This is the carbon spectrum of compound 3d.

[0034] Figure 10 This is the hydrogen spectrum of compound 3e.

[0035] Figure 11 This is the carbon spectrum of compound 3e.

[0036] Figure 12 This is the proton NMR spectrum of compound 3f.

[0037] Figure 13 This is the carbon spectrum of compound 3f.

[0038] Figure 14 The image shows the hydrogen spectrum of compound 3g.

[0039] Figure 15 This is the carbon spectrum of compound 3g.

[0040] Figure 16 This is the proton NMR spectrum of compound 3h.

[0041] Figure 17 This is the carbon spectrum of compound 3h.

[0042] Figure 18 This is the proton NMR spectrum of compound 3i.

[0043] Figure 19 This is the carbon spectrum of compound 3i.

[0044] Figure 20 This is the proton NMR spectrum of compound 3j.

[0045] Figure 21 This is the carbon spectrum of compound 3j.

[0046] Figure 22 This is the proton NMR spectrum of compound 3k.

[0047] Figure 23 This is the carbon spectrum of compound 3k.

[0048] Figure 24 This is the proton NMR spectrum of compound 3l.

[0049] Figure 25 This is the carbon spectrum of compound 3l. Detailed Implementation

[0050] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0051] The following examples illustrate the reaction process following these steps:

[0052] Under a nitrogen atmosphere, palladium neopentanoate (0.0031 g, 5 mol%) and bis(dicyclohexylphosphine) ether (0.0113 g, 20 mol%) were added to a reaction tube, followed by the sequential addition of aryl formate (0.6 mmol, 3.0 equiv), conjugated enyne (0.2 mmol, 1.0 equiv), ethyl acetate (0.5 mL), and N,N-dimethylformamide (0.5 mL). The mixture was stirred at 100 °C for 24 hours. After the reaction was complete, dichloromethane was added, and the mixture was filtered through diatomaceous earth. The filtrate was concentrated to obtain a crude product. After vacuum concentration, the residue was purified by rapid column chromatography on silica gel (200-300 mesh) using petroleum ether / ethyl acetate (19:1) as the eluent to obtain the desired product 3. The product yield was calculated by weighing the separated components.

[0053] The 1,3-conjugated diene carboxylic acid ester compounds shown in Table 1 are all products synthesized by the method of this invention and confirmed by NMR characterization. Some NMR spectra are as follows: Figures 2-13 As shown.

[0054]

[0055] Example 1:

[0056] Under a nitrogen atmosphere, palladium neopentanoate (0.0031 g, 5 mol%) and bis(dicyclohexylphosphine) ether (0.0113 g, 20 mol%) were added to a reaction tube, followed by aryl formate (0.6 mmol, 3.0 equiv), conjugated enyne (0.2 mmol, 1.0 equiv), and solvent (1 mL). The mixture was stirred at 100 °C for 24 hours. After the reaction was complete, dichloromethane was added, and the mixture was filtered through diatomaceous earth. The filtrate was concentrated to obtain a crude product. After vacuum concentration, the residue was purified by rapid column chromatography on silica gel (200-300 mesh) using petroleum ether / ethyl acetate (19:1) as the eluent to obtain the desired product 3. The product yield was calculated by weighing the separated components.

[0057]

[0058] Among the numerous solvents screened, we used a mixed solvent approach. The results showed that using 0.5 mL each of N,N-dimethylformamide and ethyl acetate (1:1) resulted in the highest reaction yield (95%) and the highest E:Z configuration ratio (95:5), with a separation yield of 92%. Using ethyl acetate alone or 1 mL of N,N-dimethylformamide alone did not yield as high a yield as the mixed solvent approach, despite the difference in NMR yield and configuration ratio.

[0059] Through extensive comparative experiments, we determined that 0.5 mL each of N,N-dimethylformamide and ethyl acetate were the optimal reaction solvent conditions for this reaction.

[0060] Example 2: Synthesis of compound 3a

[0061] Under a nitrogen atmosphere at 0 °C, diethylamine (0.5 mL / 1 mmol acetylene), vinyl bromide (1.3 equiv, 1 mol / L in THF), and phenylacetylene (1.0 equiv) were successively added to a round-bottom flask containing tetra-triphenylphosphine palladium (0.3 mol%) and cuprous iodide (0.2 mol%). After reacting at room temperature for 10 hours, the crude product was filtered through diatomaceous earth and extracted, followed by column chromatography to obtain compound 1a, 1-phenyl-3-ene-1-butyne.

[0062] Under a nitrogen atmosphere, palladium neopentanoate (0.0031 g, 5 mol%) and bis(dicyclohexylphosphinophenyl) ether (0.0113 g, 20 mol%) were added to a reaction tube, followed by phenyl formate (0.6 mmol, 3.0 equiv), 1-phenyl-3-ene-1-butyne (0.2 mmol, 1.0 equiv), ethyl acetate (0.5 mL), and N,N-dimethylformamide (0.5 mL). The mixture was stirred at 100 °C for 24 hours. After the reaction was complete, dichloromethane was added, and the mixture was filtered through diatomaceous earth. The filtrate was concentrated to obtain the crude product. After vacuum concentration, the residue was purified by silica gel column chromatography using petroleum ether / ethyl acetate (19:1, V / V) as the eluent to obtain the target product 3a. The separation yield was 91% (E:Z = 92:8).

[0063] 1 H NMR (400 MHz, CDCl3) δ 7.83 (s, 1H), 7.52-7.49 (m, 2H), 7.46-7.36(m, 5H), 7.29-7.25 (m, 1H), 7.20-7.17 (m, 2H), 6.72 (ddd, J = 17.7, 17.6, 0.9Hz, 1H), 6.00 (dd, J = 17.6, 1.5 Hz, 1H), 5.51 (dt, J = 11.7, 1.4 Hz, 1H). 13 CNMR (151 MHz, cdcl3) δ 165.8, 150.9, 141.0, 135.0, 130.3, 129.5, 129.4, 129.2, 129.1, 128.5, 125.9, 121.8, 121.6.

[0064] Example 3: Synthesis of compound 3b

[0065] Similar to Method 2 in Example, except that 4-ethynyl anisole was used to synthesize compound 1b. 1-p-methoxyphenyl-3-ene-1-butyne participated in the reaction, with a yield of 90% (E:Z=92:8). After column chromatography separation, product 3b was obtained.

[0066] 1H NMR (400 MHz, CDCl3) δ 7.80 (s, 1H), 7.50-7.40 (m, 4H), 7.27-7.17(m, 4H), 6.94 (d, J = 7.8 Hz, 2H), 6.72 (dd, J = 17.7, 17.6 Hz, 1H), 6.00(dd, J = 17.9 Hz, 1H), 5.52 (dt, J = 11.7 Hz, 1H), 3.86 (s, 3H). 13 C NMR (101MHz, cdcl3) δ 166.0, 160.4, 151.0, 141.0, 132.3, 129.8, 129.5, 127.5, 127.0,125.8, 121.8, 121.1, 113.9, 55.4.

[0067] Example 4: Synthesis of compound 3c

[0068] The method was the same as in Example 2, except that 4-ethynylphenyl acetate was used to synthesize compound 1c. 4-(but-3-en-1-yn-1-yl)phenyl acetate participated in the reaction, with a yield of 51% (E:Z=86:14). After column chromatography separation, product 3c was obtained.

[0069] 1 H NMR (400 MHz, Chloroform-d) δ 8.11 – 8.04 (m, 2H), 7.80 (s, 1H), 7.59 – 7.52 (m, 2H), 7.48 – 7.39 (m, 2H), 7.32 – 7.24 (m, 1H), 7.23 – 7.15(m, 2H), 6.67 (ddd, J = 17.7, 11.7, 1.0 Hz, 1H), 6.01 (dd, J = 17.7, 1.5 Hz,1H), 5.55 (dt, J = 11.7, 1.5 Hz, 1H), 3.94 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 166.57, 165.41, 150.79, 139.45, 139.31, 131.02, 130.27,130.05, 129.65, 129.56, 128.95, 126.02, 122.58, 121.67, 52.32.

[0070] Example 5: Synthesis of compound 3d

[0071] The method was the same as in Example 2, except that 2-ethynylnaphthalene was used to synthesize compound 1c 2-(3-buten-1-yn-1-yl)naphthalene in the reaction, with a yield of 87% (E:Z=90:10). After column chromatography separation, product 3d was obtained.

[0072] 1 H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 3.5 Hz, 2H), 7.90 – 7.77 (m,3H), 7.62 (dt, J = 8.6, 1.8 Hz, 1H), 7.53 (dt, J = 7.1, 2.5 Hz, 2H), 7.44(td, J = 7.9, 1.8 Hz, 2H), 7.32 – 7.17 (m, 3H), 6.81 (ddd, J = 17.8, 11.7,1.8 Hz, 1H), 6.03 (dt, J = 17.7, 1.8 Hz, 1H), 5.56 (dd, J = 11.7, 1.6 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 165.82, 151.01, 141.06, 133.39, 133.06,132.54, 130.52, 129.58, 128.52, 128.09, 127.78, 127.21 (d, J = 4.1 Hz),126.66, 125.93, 121.83.

[0073] Example 6: Synthesis of compound 3e

[0074] The method was the same as in Example 2, except that p-tert-butylphenylacetylene was used to synthesize compound 1c 1-(3-buten-1-yn-1-yl)-4-(tert-butyl)benzene to participate in the reaction, with a yield of 84% (E:Z=93:7). After column chromatography separation, product 3e was obtained.

[0075] 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.41 – 7.29 (m, 7H), 7.21 –7.15 (m, 1H), 7.13 – 7.08 (m, 2H), 6.67 (dd, J = 17.8, 11.7, 1.1 Hz, 1H), 5.92 (ddd, J = 17.8, 1.7, 0.6 Hz, 1H), 5.43 (dt, J = 11.6, 1.5 Hz, 1H), 1.27(s, 9H). 13 C NMR (101 MHz, CDCl3) δ 165.88, 152.64, 151.00, 141.09, 132.16,130.29, 129.69, 129.50, 125.83, 125.46, 121.81, 121.21, 34.87, 31.23.

[0076] Example 7: Synthesis of compound 3f

[0077] The method was the same as in Example 2, except that p-fluorophenylacetylene was used to synthesize compound 1c 1-(3-buten-1-ynyl)-4-fluorobenzene in the reaction, with a yield of 81% (E:Z=90:10). After column chromatography, product 3f was obtained.

[0078] 1 H NMR (400 MHz, CDCl3) δ 7.77 (s, 1H), 7.46 (dtd, J = 29.0, 7.3, 6.5,2.0 Hz, 4H), 7.31 – 7.22 (m, 2H), 7.22 – 7.15 (m, 2H), 7.15 – 7.06 (m, 2H), 6.66 (ddd, J = 17.7, 11.6, 1.1 Hz, 1H), 5.98 (dd, J = 17.8, 1.6 Hz, 1H), 5.54 (dt, J = 11.7, 1.5 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 165.64, 164.25, 150.89,139.68, 132.23 (d, J = 8.3 Hz), 129.52, 129.18, 125.92, 121.92, 121.71,115.64 (d, J = 21.7 Hz).

[0079] Example 8: Synthesis of 3g of compound

[0080] Under a nitrogen atmosphere at 0 °C, diethylamine (0.5 mL / 1 mmol acetylene), vinyl bromide (1.3 equiv, 1 mol / L in THF), and p-methoxyphenylacetylene (1.0 equiv) were successively added to a round-bottom flask containing tetrakis(triphenylphosphine)palladium (0.3 mol%) and cuprous iodide (0.2 mol%). After reacting at room temperature for 10 hours, the crude product was filtered through diatomaceous earth and extracted, followed by column chromatography to obtain compound 1-p-methoxyphenyl-3-ene-1-butyne.

[0081] Under a nitrogen atmosphere, palladium neopentanoate (0.0031 g, 5 mol%) and bis(dicyclohexylphosphinophenyl) ether (0.0113 g, 20 mol%) were added to a reaction tube, followed by the sequential addition of 2 g of p-toluene formate (0.6 mmol, 3.0 equiv), 1-p-methoxyphenyl-3-ene-1-butyne (0.2 mmol, 1.0 equiv), ethyl acetate (0.5 mL), and N,N-dimethylformamide (0.5 mL). The mixture was stirred at 100 °C for 24 hours. After the reaction was complete, dichloromethane was added, and the mixture was filtered through diatomaceous earth. The filtrate was concentrated to obtain the crude product. After vacuum concentration, the residue was purified by silica gel column chromatography using petroleum ether / ethyl acetate (19:1, V / V) as the eluent to obtain 3 g of the target product. The yield was 79% (E:Z = 98:2).

[0082] 1 H NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.48 – 7.33 (m, 2H), 7.14 –7.07 (m, 2H), 6.97 (dd, J = 8.3, 1.4 Hz, 2H), 6.89 – 6.78 (m, 2H), 6.62 (ddt,J = 17.7, 11.6, 1.3 Hz, 1H), 5.88 (dt,J = 17.8, 1.8, 0.8 Hz, 1H), 5.59 –5.36 (m, 1H), 3.75 (s, 3H), 2.27 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.18,160.44, 148.78, 140.81, 135.39, 132.24, 130.00, 129.81, 127.59, 127.16,121.47, 121.06, 113.96, 55.37, 20.93.

[0083] Example 9: Synthesis of compound 3h

[0084] The method was the same as in Example 8, except that the compound 2h formate-4-fluorophenyl ester was involved in the reaction, with a yield of 84% (E:Z=94:6). After column chromatography, product 3h was obtained.

[0085] 1 H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.46 – 7.33 (m, 2H), 7.10 –6.96 (m, 4H), 6.92 – 6.81 (m, 2H), 6.62 (ddd, J = 17.7, 11.6, 1.1 Hz, 1H), 5.87 (ddd, J = 17.8, 1.7, 0.6 Hz, 1H), 5.44 (dt, J = 11.6, 1.5 Hz, 1H), 3.77(s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.93, 160.55, 146.83 (d, J = 2.9 Hz), 141.22, 132.30, 127.44, 126.69, 123.20 (d, J = 8.5 Hz), 121.15, 116.11 (d, J= 23.4 Hz), 113.99, 55.38.

[0086] Example 10: Synthesis of compound 3i

[0087] The method was the same as in Example 8, except that the compound 2i, 4-chlorophenyl formate, was involved in the reaction, with a yield of 72% (E:Z=93:7). After column chromatography, product 3i was obtained.

[0088] 1 H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H), 7.40 (d, J = 8.7 Hz, 2H), 7.33– 7.25 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 6.61 (dd,J = 17.7, 11.7 Hz, 1H), 5.86 (dd,J = 17.8, 1.7 Hz, 1H), 5.44 (dt,J = 11.6,1.5 Hz, 1H), 3.76 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 165.65, 160.60, 149.53,141.38, 132.34, 131.12, 129.70, 129.52, 127.40, 126.58, 123.22, 121.21, 114.01, 55.39.

[0089] Example 11: Synthesis of compound 3j

[0090] The method was the same as in Example 8, except that the compound 2j, formic acid-4-methoxyphenyl ester, was involved in the reaction, with a yield of 81% (E:Z=97:3). After column chromatography, product 3j was obtained.

[0091] 1 H NMR (400 MHz, CDCl3) δ 7.69

[0092] (s, 1H), 7.45 – 7.33 (m, 2H), 7.10 – 6.94 (m, 2H), 6.91 – 6.77 (m,4H), 6.63 (ddd, J = 17.7, 11.6, 1.1 Hz, 1H), 5.88 (dd, J = 17.7, 1.8 Hz, 1H), 5.42 (dt, J = 11.7, 1.5 Hz, 1H), 3.76 (s, 3H), 3.72 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.34, 160.44, 157.24, 144.48, 140.81, 132.24, 129.82, 127.57,127.10, 122.54, 121.05, 114.23 (d, J = 56.2 Hz), 55.50 (d, J = 25.6 Hz).

[0093] Example 12: Synthesis of compound 3k

[0094] The method was the same as in Example 8, except that the compound 2k formic acid-4-trifluoromethylphenyl ester was involved in the reaction, with a yield of 85% (E:Z=92:8). After column chromatography, product 3k was obtained. 1H NMR (400 MHz, CDCl3) δ 7.73(s, 1H), 7.63 – 7.57 (m, 2H), 7.45 – 7.39 (m, 2H), 7.25 – 7.18 (m, 2H), 6.96– 6.82 (m, 2H), 6.62 (ddd, J = 17.8, 11.7, 1.1 Hz, 1H), 5.87 (ddd, J = 17.7,1.7, 0.6 Hz, 1H), 5.45 (dt, J = 11.7, 1.5 Hz, 1H), 3.77 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 165.33, 160.70, 141.72, 132.40, 129.62, 127.31, 126.81 (q, J =3.7 Hz), 126.31, 122.36, 121.30, 114.03, 55.38.

[0095] Example 13: Synthesis of compound 3l

[0096] The method was the same as in Example 8, except that the compound 21, formic acid-4-phenylphenyl ester, was involved in the reaction, with a yield of 76% (E:Z=95:5). After column chromatography, product 31 was obtained. 1 H NMR (400 MHz, Chloroform-d) δ7.92 – 7.79 (m, 5H), 7.65 (d, J = 2.3 Hz, 1H), 7.55 – 7.46 (m, 4H), 7.33 (dd,J = 8.8, 2.3 Hz, 1H), 6.99 – 6.91 (m, 2H), 6.75 (ddd, J = 17.7, 11.7, 1.1 Hz, 1H), 6.01 (dd, J = 17.8, 1.7 Hz, 1H), 5.54 (dt, J = 11.7, 1.5 Hz, 1H), 3.86 (s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 166.13, 160.51, 148.70, 141.09,133.86, 132.29, 131.47, 129.80, 129.41, 127.80, 127.67, 127.57, 127.04,126.54, 125.66, 121.39, 121.16, 118.72, 113.98, 55.38.

[0097] This invention provides a method for synthesizing 1,3-conjugated diene carboxylic acid esters via palladium-catalyzed hydrogen esterification of conjugated enyne. Many methods and approaches exist for implementing this technical solution; the above description is merely a preferred embodiment of the invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of this invention, and these improvements and modifications should also be considered within the scope of protection of this invention. All components not explicitly stated in this embodiment can be implemented using existing technologies.

Claims

1. A method for synthesizing 1,3-conjugated diene carboxylic acid esters by palladium-catalyzed hydrogen esterification of conjugated enyne, characterized in that: Under nitrogen protection, 1,3-conjugated diene carboxylic acid esters were obtained by reacting conjugated alkynes and aromatic formates in an organic solvent system containing a palladium catalyst and ligands. The reaction route is shown below: ； R1 is selected from phenyl, substituted phenyl, or naphthyl, and the substituents of the substituted phenyl in R1 include C1-C6 alkyl substitution, C1-C6 alkoxy substitution, halogen substitution, and ester group; R2 is selected from phenyl, substituted phenyl, or naphthyl, and the substituents of the substituted phenyl in R2 include one or more of C1-C6 alkyl substitution, C1-C6 alkoxy substitution, halogen substitution, trifluoromethyl substitution, and phenyl substitution.

2. The method according to claim 1, characterized in that: The palladium catalyst is selected from any one of palladium acetate, bis(acetylacetone)palladium, palladium chloride, palladium neopentanoate, and allyl palladium chloride dimer.

3. The method according to claim 2, characterized in that: The molar ratio of conjugated alkyne to palladium catalyst is 1:0.01 to 1:0.

20.

4. The method according to claim 1, characterized in that: The ligand is selected from any one of bis(dicyclohexylphosphinophenyl) ether, dimethyl-p-tolylphosphine, triphenylphosphine, tri-p-benzylphosphine, 4-(dimethylamino)triphenylphosphine, and tris(4-dimethylaminophenyl)phosphine.

5. The method according to claim 4, characterized in that: The molar ratio of conjugated alkynes to ligands is 1:0.05 to 1:0.

30.

6. The method according to claim 1, characterized in that: The organic solvent is selected from one or a combination of several of acetone, 1,4-dioxane, ethyl acetate, toluene, tetrahydrofuran, ethyl acetate, and N,N-dimethylformamide.

7. The method according to claim 6, characterized in that: The organic solvent is a mixture of ethyl acetate and N,N-dimethylformamide in a volume ratio of 1:

1.

8. The method according to claim 1, characterized in that: During the reaction, the molar ratio of conjugated alkyne to aryl formate is 1:

3.

9. The method according to claim 1, characterized in that: The reaction temperature is 80-110℃, and the reaction time is 12-36 hours.

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