Method for preparing heterocyclic 1, 4-diene compound through cycloisomerization reaction of 1, 6-eneyne compound

Abstract

The invention discloses a preparation method of a heterocyclic 1, 4-diene compound, which comprises the following steps: by taking 1, 6-eneyne as a raw material, cobalt salt as a metal catalyst, organic phosphine as a ligand, 4CzIPN as a photosensitizer and Et3N as an additive, carrying out cycloisomerization reaction in an organic solvent under the illumination condition to obtain the heterocyclic 1, 4-diene compound, in the structural formula, R is phenyl, p-fluorophenyl, p-chlorphenyl, p-bromophenyl, p-methylphenyl, p-tert-butylphenyl, p-phenylphenyl, p-methoxyphenyl, p-thiomethylphenyl, N, N-dimethylphenyl, p-chlorophenyl, p-chlorophenyl, p-bromophenyl, p-methylphenyl, p-phenylphenyl, p-methylphenyl, p- the phenyl group is one of N, N-dimethylaniline, p-hydroxymethyl phenyl, p-acetoxyphenyl, p-trifluoromethoxy phenyl, p-oxygen phenyl, p-methyl formate phenyl, p-trifluoromethyl phenyl, 1-naphthyl, 2-thienyl, 3-thienyl, methyl and ethyl. Cheap and easy-to-obtain Co and light are adopted for concerted catalysis, conditions are simple and mild, and regioselectivity is high.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for preparing heterocyclic 1,4-diene compounds by selective cycloisomerization of 1,6-enyne. Background Technology

[0002] Heterocyclic 1,4-diene compounds are key substances in the fields of pharmaceuticals, fine chemicals, and functional materials. In pharmaceuticals, they serve as the core framework for antibacterial agents and antitumor drugs, and are important structural units in highly active drug intermediates. In materials science, they can serve as monomers for heat-resistant polyesters, functional resins, and other polymers, helping to improve material performance. Therefore, developing efficient, green, and low-cost methods for synthesizing heterocyclic 1,4-diene compounds is of great significance for the upgrading of related industries. Currently, there are two main types of catalytic systems for achieving this reaction, both of which have technical bottlenecks. Traditional metal catalytic systems rely on precious metal catalysts such as palladium and rhodium, which have significant drawbacks: first, precious metals are scarce and expensive (e.g., palladium catalyst costs approximately 100,000 RMB / kg), limiting large-scale applications; second, they require high-temperature (120-180℃) and high-pressure conditions, resulting in high energy consumption, difficult operation, and a tendency to trigger side reactions, with the selectivity of the target product often below 60%; and third, some precious metals leave toxic residues, requiring additional purification in pharmaceutical applications, increasing costs. Although single photocatalytic systems can react at room temperature and pressure, they have significant drawbacks: they rely on ultraviolet light or specific visible light to excite photosensitizers, and ultraviolet light easily causes substrate degradation; the electron transfer efficiency is low, and the reaction cycle requires 24-48 hours, making it difficult to meet the efficiency requirements for mass production; the photosensitizer is easily decomposed, requiring frequent replenishment, which increases costs and affects product purity.

[0003] Both types of systems struggle to balance efficiency, conditions, selectivity, and cost. Traditional metal catalysis increases rates but sacrifices cost and selectivity, while single photocatalysis optimizes conditions but reduces efficiency. Therefore, developing synergistic catalysis for the application of 1,6-enyne cycloisomerization is of significant research importance. Summary of the Invention

[0004] The technical problem to be solved by this invention is how to prepare heterocyclic 1,4-diene compounds cleanly and efficiently.

[0005] The present invention solves the above-mentioned technical problems through the following technical means:

[0006] A method for preparing a heterocyclic 1,4-diene compound, comprising using a 1,6-enyne compound as a raw material, a cobalt salt as a metal catalyst, an organophosphorus compound as a ligand, 4CzIPN as a photosensitizer, and triethylamine (Et3N) as an additive, and carrying out a cycloisomerization reaction in an organic solvent under light irradiation to obtain the heterocyclic 1,4-diene compound; wherein the structural formula of the 1,6-enyne compound is as follows: R represents phenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-methylphenyl, p-tert-butylphenyl, p-phenylphenyl, p-methoxyphenyl, p-thiomethylphenyl, N,N-dimethylaniline, p-hydroxymethylphenyl, p-acetoxyphenyl, p-trifluoromethoxyphenyl, p-oxyphenylphenyl, methyl p-formate phenyl, p-trifluoromethylphenyl, 1-naphthyl, 2-thienyl, 3-thienyl, methyl, ethyl, One of them, in which wavy lines Indicates the position where it is attached to the alkynyl group; structural formula The wavy line in the figure represents the Z / E heterogeneity.

[0007] Preferably, the structural formula of the 1,6-enyne compound is as follows:

[0008] One of them.

[0009] Preferably, the cobalt salt is one or a mixture of CoBr2, CoCl2, and CoI2.

[0010] Preferably, the cobalt salt is CoCl2.

[0011] Preferably, the organophosphine is one or a mixture of triphenylphosphine, racemic binaphthalene diphenylphosphine, and 1,3-bis(diphenylphosphino)propane.

[0012] Preferably, the organophosphine is 1,3-bis(diphenylphosphine)propane.

[0013] Preferably, the organic solvent is one or a mixture of acetonitrile, tetrahydrofuran, dichloromethane, and N,N-dimethylformamide.

[0014] Preferably, the organic solvent is N,N-dimethylformamide.

[0015] Preferably, the molar ratio of the metal catalyst to the 1,6-enyne compound is 0.05:1.

[0016] Preferably, the molar ratio of the ligand to the 1,6-enyne compound is 0.06:1.

[0017] Preferably, the ratio of the 1,6-enyne compound to the organic solvent is 1 mmol: 5 mL.

[0018] Preferably, the molar ratio of the photosensitizer and the 1,6-enyne compound is 0.02:1.

[0019] Preferably, the molar ratio of the 1,6-enyne compound to the additive is 1:1.2.

[0020] Preferably, the reaction is carried out under blue light irradiation.

[0021] Preferably, the reaction time is 12-24 hours.

[0022] Preferably, the organic solvent is N,N-dimethylformamide, and the reaction time is 12 hours.

[0023] Preferably, the method for preparing the heterocyclic 1,4-diene compound includes the following steps: mixing the 1,6-enyne compound with a metal catalyst, a ligand, and a photosensitizer, then adding an organic solvent and a triethylamine (Et3N) additive, and reacting under blue light irradiation to obtain the heterocyclic 1,4-diene compound.

[0024] Preferably, the method further includes a step of separating and purifying the product after the reaction; the separation and purification method includes at least one of column chromatography, vacuum distillation and recrystallization.

[0025] The heterocyclic 1,4-diene compound prepared in this invention has the structural formula of Formula I:

[0026]

[0027] Preferably, in Formula I, R is one of an alkyl substituent and an aryl substituent.

[0028] Preferably, in Formula I, R is phenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-methylphenyl, p-tert-butylphenyl, p-phenylphenyl, p-methoxyphenyl, p-thiomethylphenyl, N,N-dimethylaniline, p-hydroxymethylphenyl, p-acetoxyphenyl, p-trifluoromethoxyphenyl, p-oxyphenylphenyl, p-methylformate phenyl, p-trifluoromethylphenyl, 1-naphthyl, 2-thiophene, 3-thiophene, methyl, ethyl, One of them; In Indicates the location of the connection.

[0029] Photocobalt synergistic catalysis offers the advantages of being economical and environmentally friendly. It can promote intermolecular / intramolecular carbon-carbon unsaturated bond rearrangement reactions in unsaturated or multi-substituted compounds, constructing multi-component carbon heterocyclic compounds. In the preparation method of this invention, 1,6-enyne compounds are used as raw materials, cobalt as a metal catalyst, 1,3-bis(diphenylphosphine)propane as a ligand, 4CzIPN as a photosensitizer, and triethylamine Et3N as an additive. A cyclization reaction is carried out in an organic solvent to obtain the 1,6-enyne cycloisomerization product. This method utilizes photocobalt synergistic catalysis to construct multi-substituted products in one step through the carbon-carbon unsaturated bond isomerization of 1,6-enyne. Furthermore, it employs an inexpensive metal catalyst, avoiding the use of metal reducing agents, and the reaction conditions are simple and mild with high regioselectivity, making it suitable for the development of heterocyclic drug molecules.

[0030] The advantages of this invention are:

[0031] (1) The metal catalyst used in this invention is inexpensive, readily available, and easy to operate;

[0032] (2) The reaction conditions of this invention are mild and simple;

[0033] (3) This invention can obtain heterocyclic 1,4-diene compounds with high regioselectivity and good yield;

[0034] (4) The synthesis method used in this invention is green and environmentally friendly;

[0035] (5) The yield and selectivity of the method described in this invention can be maintained after scale-up;

[0036] (6) The synthesis method described in this invention has a wide range of applications and can synthesize various substituted 1,6-enyne ring isomerization products, which can be used for the development of heterocyclic drug molecules. Attached Figure Description

[0037] Figure 1 The hydrogen NMR spectrum of the product prepared in Example 2 of this invention;

[0038] Figure 2 The carbon NMR spectrum of the product prepared in Example 2 of this invention;

[0039] Figure 3 The hydrogen NMR spectrum of the product prepared in Example 3 of this invention;

[0040] Figure 4 The carbon NMR spectrum of the product prepared in Example 3 of this invention;

[0041] Figure 5 The NMR fluorine spectrum of the product prepared in Example 3 of this invention;

[0042] Figure 6 The hydrogen NMR spectrum of the product prepared in Example 4 of this invention;

[0043] Figure 7 The carbon NMR spectrum of the product prepared in Example 4 of this invention;

[0044] Figure 8 The hydrogen NMR spectrum of the product prepared in Example 5 of this invention;

[0045] Figure 9 The carbon NMR spectrum of the product prepared in Example 5 of this invention;

[0046] Figure 10 The hydrogen NMR spectrum of the product prepared in Example 6 of this invention;

[0047] Figure 11 The carbon NMR spectrum of the product prepared in Example 6 of this invention;

[0048] Figure 12 The hydrogen NMR spectrum of the product prepared in Example 7 of this invention;

[0049] Figure 13 The carbon NMR spectrum of the product prepared in Example 7 of this invention;

[0050] Figure 14 The hydrogen NMR spectrum of the product prepared in Example 8 of this invention;

[0051] Figure 15 The carbon NMR spectrum of the product prepared in Example 8 of this invention;

[0052] Figure 16 The hydrogen NMR spectrum of the product prepared in Example 9 of this invention;

[0053] Figure 17 The carbon NMR spectrum of the product prepared in Example 9 of this invention;

[0054] Figure 18 The image shows the hydrogen NMR spectrum of the product prepared in Example 10 of this invention.

[0055] Figure 19 The image shows the carbon NMR spectrum of the product prepared in Example 10 of this invention.

[0056] Figure 20 The image shows the hydrogen NMR spectrum of the product prepared in Example 11 of this invention.

[0057] Figure 21 The image shows the carbon NMR spectrum of the product prepared in Example 11 of this invention.

[0058] Figure 22 The image shows the hydrogen NMR spectrum of the product prepared in Example 12 of this invention.

[0059] Figure 23 The image shows the carbon NMR spectrum of the product prepared in Example 12 of this invention.

[0060] Figure 24 The image shows the hydrogen NMR spectrum of the product prepared in Example 13 of this invention.

[0061] Figure 25 The image shows the carbon NMR spectrum of the product prepared in Example 13 of this invention.

[0062] Figure 26 The image shows the hydrogen NMR spectrum of the product prepared in Example 14 of this invention.

[0063] Figure 27 The image shows the carbon NMR spectrum of the product prepared in Example 14 of this invention. Detailed Implementation

[0064] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0065] Unless otherwise specified, all test materials and reagents used in the following examples are commercially available.

[0066] Unless otherwise specified in the embodiments, the techniques or conditions described in the literature in this field or in accordance with the product manual may be followed.

[0067] Example 1

[0068] Preparation of enyne compounds: Enyne compounds were synthesized according to previously reported methods (J. Am. Chem. Soc. 2020, 142, 9510; Org. Chem. Front., 2021, 8, 4785), and the experimental procedures were basically consistent with those reported in the literature; among which... The preparation method includes the following steps:

[0069]

[0070] Propyleneamine protected by Ts (p-toluenesulfonyl group) under an ice-water bath at 0°C To a 25.0 mmol solution of acetonitrile (25 mL), K₂CO₃ (38.0 mmol) and 2-butenyl bromide (40.0 mmol) were added. The mixture was heated under reflux for 24 hours. The solvent was removed by rotary evaporation. The resulting solid was dissolved in ethyl acetate, washed with water, extracted, and dried to obtain a crude product for direct use in the next step. Under a nitrogen atmosphere, iodobenzene (11.0 mmol), Pd(PPh₃)₂Cl₂ (0.2 mmol), CuI (0.2 mmol), and tetrahydrofuran (20 mL) were added to a 10.0 mmol solution of the crude product in Et₃N (20 mL). The mixture was stirred under a nitrogen atmosphere for 16 hours. The resulting product was washed with water, dried, and separated by column chromatography to obtain the final product.

[0071] Other enyne compounds used in the embodiments of this invention were all prepared by the above method.

[0072] The alkenyne compounds used are Z / E isomers, and the wavy lines in their structural formulas represent the Z / E isomers.

[0073] Example 2

[0074] Preparation of heterocyclic 1,4-diene compounds

[0075] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0076]

[0077] 1,6-enyne 0.1 mmol of N,N-dimethylformamide solvent and 0.12 mmol of Et3N additive were added to a 4 mL screw-top flask. Then, 0.5 mL of N,N-dimethylformamide solvent and 0.12 mmol of Et3N were added. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 40:1), with a yield of 91%.

[0078] The corresponding NMR spectra of the products are as follows: Figure 1 and Figure 2 As shown, the data is as follows: 1H NMR(400MHz, CDCl3)δ7.72(d,J=8.3Hz,2H),7.36–7.30(m,4H),7.24(m,1H ),7.15–7.12(m,2H),6.20(q,J=2.5Hz,1H),5.63–5.53(m,1H),5.21(s,1H ),5.19–5.15(m,1H),4.31(m,1H),4.00(dt,J=14.9,2.4Hz,1H),3.63(dd, J=9.4,7.6Hz,1H),3.46–3.39(m,1H),2.86(t,J=9.0Hz,1H),2.41(s,3H). 13 C NMR (101MHz, CDCl3) δ143.9,139.1,136.4,136.1,132.9,129.9,128.7,128.2,127.7,127.3,124.3,118.6,52.2,50.8,49.4,21.6.

[0079] Example 3

[0080] Preparation of heterocyclic 1,4-diene compounds

[0081] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0082]

[0083] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 40:1), with a yield of 90%.

[0084] The corresponding NMR spectra of the products are as follows: Figure 3-5 As shown, the data is as follows: 1H NMR (600MHz, CDCl3) δ7.71(d,J=8.0Hz,2H),7.31(d,J=8.0Hz,2H),7.22(m,1H ),7.11(dd,J=6.5,3.7Hz,2H),7.04–7.00(m,1H),6.36–6.31(m,1H),5.60(m, 1H),5.22–5.17(m,2H),4.27–4.17(m,1H),3.92(dd,J=15.0,2.3Hz,1H),3.64 (dd,J=9.5,7.8Hz,1H),3.47–3.31(m,1H),2.89(d,J=9.0Hz,1H),2.42(s,3H). 13 C NMR (101MHz, CDCl3) δ161.8 (d, J = 247.6Hz), 144.0, 138.8, 136.0, 132.9, 132.6 (d, J = 3.3Hz), 129.9, 129.8 (d, J = 8.0Hz), 127.9, 123.2, 118.8, 115.7 (d, J = 21.6Hz), 52.2, 50.7, 49.4, 21.7. 19 F NMR (377MHz, CDCl3) δ-114.23.

[0085] Example 4

[0086] Preparation of heterocyclic 1,4-diene compounds

[0087] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0088]

[0089] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 40:1), with a yield of 92%.

[0090] The corresponding NMR spectra of the products are as follows: Figure 6 and Figure 7 As shown, the data is as follows: 1H NMR (600MHz, CDCl3) δ7.74–7.70(m,2H),7.47–7.43(m,2H),7.33(d,J=7.9Hz,2H),7.01–6.98(m,2H),6.12(d,J=2.5Hz,1H),5.56(m,1H),5.2 2–5.17(m,2H),4.26(m,1H),3.95–3.90(m,1H),3.64(dd,J=9.5,7.7Hz,1H),3.43(dd,J=12.5,5.0Hz,1H),2.85(t,J=9.1Hz,1H),2.42(s,3H). 13 CNMR (101MHz, CDCl3) δ144.0,140.1,135.8,135.4,132.8,131.8,130.0,129.7,127.9,123.2,121.2,118.9,52.1,50.8,49.5,21.7.

[0091] Example 5

[0092] Preparation of heterocyclic 1,4-diene compounds

[0093] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0094]

[0095] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA volume ratio = 40:1) with a yield of 87%.

[0096] The corresponding NMR spectra of the products are as follows: Figure 8 and Figure 9 As shown, the data is as follows: 1H NMR (600MHz, CDCl3) δ7.73(d,J=8.0Hz,2H),7.32(d,J=7.9Hz,2H),7.15(d,J=7.8 Hz,2H),7.04(d,J=7.8Hz,2H),6.16(d,J=2.6Hz,1H),5.58(m,1H),5.21–5.16(m,2 H),4.30(dt,J=14.8,2.0Hz,1H),3.99(dt,J=14.8,2.5Hz,1H),3.63(dd,J=9.4,7 .6Hz,1H),3.42(q,J=8.4Hz,1H),2.85(t,J=9.0Hz,1H),2.42(s,3H),2.34(s,3H). 13 C NMR (151MHz, CDCl3) δ143.9,138.0,137.2,136.2,133.7,132.9,129.9,129.4,128.2,127.9,124.2,118.6,52.2,50.9,49.4,21.7,21.3.

[0097] Example 6

[0098] Preparation of heterocyclic 1,4-diene compounds

[0099] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0100]

[0101] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 40:1), with a yield of 88%.

[0102] The corresponding NMR spectra of the products are as follows: Figure 10 and Figure 11 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3)δ

[0103] 7.73(d,J=7.9Hz,2H),7.37(d,J=8.0Hz,2H),7.32(d,J=7.9Hz,2H),7.09( d,J=8.0Hz,2H),6.16(q,J=2.7Hz,1H),5.61–5.53(m,1H),5.21–5.16(m,2H ),4.31(d,J=14.9Hz,1H),4.00(dt,J=14.9,2.5Hz,1H),3.63(t,J=8.5Hz,1 H), 3.43 (q, J = 8.3Hz, 1H), 2.85 (t, J = 9.0Hz, 1H), 2.42 (s, 3H), 1.32 (s, 9H). 13 C NMR (151MHz, CDCl3) δ150.4,143.9,138.2,136.3,133.7,132.9,129.9,128.0,127.9,125.7,124.1,118.6,52.2,50.9,49.4,34.7,31.4,21.7.

[0104] Example 7

[0105] Preparation of heterocyclic 1,4-diene compounds

[0106] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0107]

[0108] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 40:1), with a yield of 80%.

[0109] The corresponding NMR spectra of the products are as follows: Figure 12 and Figure 13 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3)δ

[0110] 7.76(d,J=8.1Hz,2H),7.63–7.58(m,4H),7.46(t,J=7.6Hz,2H),7.38–7. 32(m,3H),7.23(d,J=8.0Hz,2H),6.24(d,J=2.5Hz,1H),5.61(m,1H),5.2 4–5.20(m,2H),4.37(m,1H),4.06(dt,J=14.9,2.5Hz,1H),3.66(dd,J=9. 4,7.7Hz,1H),3.47(q,J=8.4Hz,1H),2.88(t,J=9.1Hz,1H),2.43(s,3H). 13 C NMR (151MHz, CDCl3) δ143.9,140.5,140.0,139.2,136.1,135.5,132.7,129.9,1 29.0,128.7,127.9,127.6,127.3,127.1,123.9,118.7,52.2,51.0,49.6,21.7.

[0111] Example 8

[0112] Preparation of heterocyclic 1,4-diene compounds

[0113] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0114]

[0115] 1,6-enyne 0.1 mmol of N,N-dimethylformamide solvent and 0.12 mmol of Et3N additive were added to a 4 mL screw-top flask. Then, 0.5 mL of N,N-dimethylformamide solvent and 0.12 mmol of Et3N were added. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 20:1), with a yield of 71%.

[0116] The corresponding NMR spectra of the products are as follows: Figure 14 and Figure 15 As shown, the data is as follows: 1H NMR(600MHz, CDCl3)δ7.74–7.70(m,2H),7.32(d,J=7.4Hz,2H),7.10–7.05(m,2H) ,6.87(d,J=7.1Hz,2H),6.17–6.07(m,1H),5.61–5.52(m,1H),5.18(dd,J=13.3,5 .1Hz,2H),4.28(d,J=14.4Hz,1H),3.98(s,1H),3.81(t,J=3.8Hz,3H),3.64–3.59 (m,1H),3.41(q,J=8.4Hz,1H),2.84(dt,J=8.8,4.4Hz,1H),2.41(t,J=3.8Hz,3H). 13 C NMR (101MHz, CDCl3) δ158.8,143.9,136.7,136.3,133.0,129.9,129.5,129.3,127.9,123.7,118.5,114.2,55.4,52.2,50.8,49.4,21.7.

[0117] Example 9

[0118] Preparation of heterocyclic 1,4-diene compounds

[0119] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0120]

[0121] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 30:1), with a yield of 73%.

[0122] The corresponding NMR spectra of the products are as follows: Figure 16 and Figure 17 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3)δ

[0123] 7.72(d,J=8.0Hz,2H),7.32(d,J=7.9Hz,2H),7.21(d,J=8.2Hz,2H),7.06( d,J=8.1Hz,2H),6.13(q,J=2.6Hz,1H),5.57(m,1H),5.21–5.16(m,2H),4.3 1–4.27(m,1H),3.97(dt,J=14.9,2.5Hz,1H),3.63(dd,J=9.4,7.7Hz,1H),3 .42(q,J=8.8,8.0Hz,1H),2.85(t,J=9.1Hz,1H),2.49(s,3H),2.42(s,3H). 13 C NMR (151MHz, CDCl3) δ 143.9, 138.6, 137.8, 136.1, 133.3, 129.9, 128.6, 127.9, 126.5, 123.7 (two peaks overlap), 118.7, 52.2, 50.9, 49.5, 21.7, 15.8.

[0124] Example 10

[0125] Preparation of heterocyclic 1,4-diene compounds

[0126] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0127]

[0128] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 30:1), with a yield of 75%.

[0129] The corresponding NMR spectra of the products are as follows: Figure 18 and Figure 19 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3)δ

[0130] 7.74–7.70(m,2H),7.31(d,J=8.1Hz,2H),7.05–7.02(m,2H),6.70–6.66 (m,2H),6.07(d,J=2.5Hz,1H),5.57(m,1H),5.16(m,2H),4.30(dt,J=14. 8,2.0Hz,1H),3.99(dt,J=14.6,2.5Hz,1H),3.60(dd,J=9.3,7.6Hz,1H),3.40(d,J=8.4Hz,1H),2.97(s,6H),2.82(t,J=9.0Hz,1H),2.41(s,3H). 13 C NMR (151MHz, CDCl3) δ149.5,143.8,136.6,134.2,133.0,129.9,129.3,127.9,124.9,124.0,118.2,112.4,52.3,51.0,49.4,40.5,21.7.

[0131] Example 11

[0132] Preparation of heterocyclic 1,4-diene compounds

[0133] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0134]

[0135] 1,6-enyne 0.1 mmol of N,N-dimethylformamide solvent and 0.12 mmol of Et3N additive were added to a 4 mL screw-top flask. Then, 0.5 mL of N,N-dimethylformamide solvent and 0.12 mmol of Et3N were added. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 10:1), with a yield of 73%.

[0136] The corresponding NMR spectra of the products are as follows: Figure 20 and Figure 21 As shown, the data is as follows: 1H NMR (600MHz, CDCl3) δ7.71 (d, J=8.0Hz, 2H), 7.32 (dd, J=12.0, 7.9Hz, 4H), 7.12 (d,J=7.9Hz,2H),6.18(d,J=2.6Hz,1H),5.58(m,1H),5.22–5.17(m,2H),4.68(s ,2H),4.30(dt,J=14.9,1.9Hz,1H),4.00–3.96(m,1H),3.63(dd,J=9.4,7.7Hz,1 H),3.43(q,J=8.3,6.6Hz,1H),2.85(t,J=9.0Hz,1H),2.41(s,3H),1.96(s,1H). 13 C NMR (101MHz, CDCl3) δ144.0,139.9,139.2,136.1,135.9,132.9,129.9,128.4,127.9,127.4,124.0,118.7,65.1,52.2,50.9,49.5,21.7.

[0137] Example 12

[0138] Preparation of heterocyclic 1,4-diene compounds

[0139] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0140]

[0141] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA, volume ratio = 40:1), with a yield of 83%.

[0142] The corresponding NMR spectra of the products are as follows: Figure 22 and Figure 23 As shown, the data is as follows: 1H NMR (600MHz, CDCl3) δ7.75–7.72(m,2H),7.33(d,J=8.0Hz,2H),7.30(dd,J=5.0, 2.9Hz,1H),7.04–7.01(m,1H),6.97(dd,J=5.0,1.4Hz,1H),6.21(q,J=2.6Hz,1H ),5.55(m,1H),5.20–5.16(m,2H),4.27–4.23(m,1H),3.94(dt,J=14.9,2.5Hz,1 H),3.65(dd,J=9.4,7.6Hz,1H),3.42(m,1H),2.84(t,J=9.1Hz,1H),2.42(s,3H). 13 C NMR (151MHz, CDCl3) δ 144.0, 138.0 (two peaks overlap), 136.0, 132.7, 129.9, 127.9, 127.7, 126.0, 122.9, 118.7, 118.2, 52.6, 51.2, 49.1, 21.7.

[0143] Example 13

[0144] Preparation of heterocyclic 1,4-diene compounds

[0145] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0146]

[0147] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA volume ratio = 30:1) with a yield of 76%.

[0148] The corresponding NMR spectra of the products are as follows: Figure 24 and Figure 25 As shown, the data is as follows: 1H NMR (600MHz, CDCl3) δ8.14(d,J=7.7Hz,1H),7.90(d,J=1.7Hz,1H),7.74(d,J=8.2Hz,2H),7.62(t,J=7.8Hz,2H),7. 57–7.54(m,2H),7.50–7.47(m,1H),7.45–7.41(m,2H),7.37(d,J=8.5Hz,1H),7.31(dd,J=8.0,6.3Hz,3H),7.21(dd, J=8.6,1.7Hz,1H),6.40(t,J=2.5Hz,1H),5.69–5.60(m,2H),5.22(d,J=2.1Hz,1H),4.44(dt,J=14.6,2.1Hz,1H),4 .11(dt,J=14.7,2.5Hz,1H),3.67(dd,J=9.3,7.6Hz,1H),3.49(q,J=8.4Hz,1H),2.90(t,J=9.0Hz,1H),2.41(s,3H). 13 CNMR (151MHz, CDCl3) δ 143.8, 141.4, 140.0, 137.6, 136.6, 136.4, 133.0, 130.1, 129.9, 128.7, 127.9, 127.8, 127.1, 126.4 (two peaks overlap), 124.9, 123.7, 123.3, 120.5, 120.3, 120.1, 118.6, 110.1, 110.0, 52.3, 50.9, 49.5, 21.7.

[0149] Example 14

[0150] Preparation of heterocyclic 1,4-diene compounds

[0151] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0152]

[0153] 1,6-enyne 0.1 mmol of CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphino)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature. The target product compound was obtained by column chromatography (petroleum ether PE: ethyl acetate EA volume ratio = 40:1) with a yield of 72%.

[0154] The corresponding NMR spectra of the products are as follows: Figure 26 and Figure 27 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3) δ7.73(d,J=7.9Hz,2H),7.34(d,J=7.9Hz,2H),5.43(dt,J=17.5 ,8.9Hz,1H),5.09–5.03(m,2H),4.60–4.50(m,1H),4.07(d,J=13.9Hz,1H),3.80(d,J =14.0Hz,1H),3.59(t,J=8.5Hz,1H),3.21(q,J=8.6Hz,1H),2.79(t,J=9.1Hz,1H),2. 44(s,3H),1.16(dt,J=8.7,4.5Hz,1H),0.72(t,J=8.0Hz,2H),0.31(t,J=6.5Hz,2H). 13 C NMR (101MHz, CDCl3) δ143.8,136.5,135.5,132.9,129.8,128.1,128.0,117.8,53.2,50.0,47.8,21.7,11.5,7.0,6.9.

[0155] Example 15

[0156] Preparation of heterocyclic 1,4-diene compounds

[0157] Heterocyclic 1,4-diene compounds were prepared according to the reaction equation shown below:

[0158]

[0159] The only difference from Example 2 is that the equivalent of triethylamine was reduced to 0.5; the product yield was reduced to 42 percent.

[0160] Comparative Example 1

[0161] Preparation of heterocyclic 1,4-diene compounds

[0162] Prepared according to the reaction equation shown below:

[0163]

[0164] 1,6-enyne (0.1 mmol), CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphine)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature, but no product was obtained.

[0165] Comparative Example 2

[0166] Preparation of heterocyclic 1,4-diene compounds

[0167] Prepared according to the reaction equation shown below:

[0168]

[0169] 1,8-enyne (0.1 mmol), CoCl2 (0.005 mmol), 1,3-bis(diphenylphosphine)propane (0.006 mmol), and 4CzIPN (0.002 mmol) were added to a 4 mL screw-top flask, followed by 0.5 mL of N,N-dimethylformamide solvent and Et3N (0.12 mmol) additive. The mixture was stirred for 12 hours under blue light at room temperature, but no product was obtained.

[0170] The alkenynes used in Comparative Examples 1 and 2 are not very stable and neither can react.

[0171] Comparative Example 3

[0172] The only difference from Example 2 is that the photosensitizers used are eosin Y, 9-mesine-10-methylacridine perchlorate (Mes-Acr-Me), and benzophenone, and the product yields are all less than 5%.

[0173] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a heterocyclic 1,4-diene compound, characterized in that: The heterocyclic 1,4-diene compound was obtained by cycloisomerization in an organic solvent under photoluminescence using a 1,6-enyne compound as a raw material, a cobalt salt as a metal catalyst, an organophosphorus ligand, 4CzIPN as a photosensitizer, and triethylamine as an additive; wherein the structural formula of the 1,6-enyne compound is as follows. R represents phenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-methylphenyl, p-tert-butylphenyl, p-phenylphenyl, p-methoxyphenyl, p-thiomethylphenyl, N,N-dimethylaniline, p-hydroxymethylphenyl, p-acetoxyphenyl, p-trifluoromethoxyphenyl, p-oxyphenylphenyl, methyl p-formate phenyl, p-trifluoromethylphenyl, 1-naphthyl, 2-thienyl, 3-thienyl, methyl, ethyl, One of them.

2. The method for preparing the heterocyclic 1,4-diene compound according to claim 1, characterized in that: The structural formula of the 1,6-enyne compound is as follows: One of them.

3. The method for preparing the heterocyclic 1,4-diene compound according to claim 1, characterized in that: The cobalt salt is one or a mixture of CoBr2, CoCl2, and CoI2.

4. The method for preparing the heterocyclic 1,4-diene compound according to claim 1, characterized in that: The organophosphine is one or a mixture of triphenylphosphine, racemic binaphthalene diphenylphosphine, and 1,3-bis(diphenylphosphino)propane.

5. The method for preparing the heterocyclic 1,4-diene compound according to claim 1, characterized in that: The organic solvent is one or a mixture of acetonitrile, tetrahydrofuran, dichloromethane, and N,N-dimethylformamide.

6. The method for preparing the heterocyclic 1,4-diene compound according to claim 1, characterized in that: The molar ratio of the metal catalyst to the 1,6-enyne compound is 0.05:

1.

7. The method for preparing the heterocyclic 1,4-diene compound according to claim 1, characterized in that: The molar ratio of the ligand to the 1,6-enyne compound is 0.06:

1.

8. The method for preparing the heterocyclic 1,4-diene compound according to claim 1, characterized in that: The ratio of the 1,6-enyne compound to the organic solvent is 1 mmol: 5 mL.

9. The method for preparing the heterocyclic 1,4-diene compound according to claim 1, characterized in that: The molar ratio of the photosensitizer and the 1,6-enyne compound is 0.02:1; the molar ratio of the 1,6-enyne compound and the additive is 1:1.

2.

10. The method for preparing the heterocyclic 1,4-diene compound according to any one of claims 1-9, characterized in that: Includes the following steps: The 1,6-enyne compound was mixed with a metal catalyst, ligand, and photosensitizer, and then an organic solvent and triethylamine additive were added. The mixture was reacted under blue light irradiation to obtain the heterocyclic 1,4-diene compound.

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