Method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenation cycloaddition reaction

Abstract

The invention discloses a method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenation cycloaddition reaction, which comprises the following steps: by taking an o-hydroxyphenylacetylene compound or an o-aminophenylacetylene compound as a substrate A and a 1, 3-dicarbonyl compound as a substrate B, reacting under the action of a molybdenum catalyst, a ligand and an additive, thereby obtaining the benzofuran and indole compounds. And carrying out an intermolecular deoxygenation cycloaddition reaction in an organic solvent to generate a corresponding benzofuran or indole compound. The invention provides a method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenation cycloaddition reaction, the method takes a molybdenum compound as a catalyst, the reaction condition is mild, the atom economy is high, the functional group compatibility is good, and various substituted benzofuran and indole compounds can be efficiently constructed; and a new path is provided for synthesis of the important heterocyclic compounds.

Description

Technical Field

[0001] This invention relates to a method for synthesizing benzofuran and indole compounds, and more particularly to a method for synthesizing benzofuran and indole compounds via molybdenum-catalyzed intermolecular deoxycycloaddition reaction, belonging to the field of organic synthetic chemistry technology. Background Technology

[0002] Benzofurans and indoles are two important classes of heterocyclic compounds, widely found in natural products, drug molecules, and functional materials. For example, many natural products with anti-inflammatory, antibacterial, and antitumor activities contain benzofuran or indole skeletons. In the field of organic electronic materials, these heterocyclic compounds, due to their unique electronic structures, are often used as core building blocks for organic semiconductors, fluorescent probes, and other applications. Therefore, developing efficient, concise, and atom-economical synthetic methods for benzofurans and indoles has always been a research hotspot in the field of organic synthetic chemistry.

[0003] Currently, the traditional methods for synthesizing benzofuran and indole compounds mainly include: (1) condensation reaction based on ortho-hydroxy / aminobenzaldehyde / ketone and active methylene compounds. This method has a long reaction step and limited functional group compatibility; (2) cyclization reaction catalyzed by transition metals, such as intramolecular coupling cyclization reaction catalyzed by palladium and copper. This type of method often requires pre-functionalization modification of the substrate, has low atom economy, and some noble metal catalysts are expensive and highly toxic, which is not conducive to large-scale industrial application; (3) cyclization reaction catalyzed by photocatalysis or electrocatalysis. Although it is green and environmentally friendly, the reaction conditions are harsh and the equipment requirements are high, making it difficult to popularize.

[0004] Deoxycycloaddition reactions, as an efficient strategy for constructing heterocyclic skeletons, offer advantages such as high atom economy and simple reaction steps. However, existing deoxycycloaddition reactions mainly rely on noble metal catalysts, and intermolecular deoxycycloaddition synthesis methods for benzofurans and indole compounds are rarely reported. Molybdenum, as a transition metal with abundant reserves, low cost, and low toxicity, exhibits unique reactivity and selectivity in catalysis, but research on applying molybdenum catalysts to intermolecular deoxycycloaddition reactions for the synthesis of benzofurans and indole compounds has not yet been reported. Summary of the Invention

[0005] To address the shortcomings of the aforementioned technologies, this invention provides a method for synthesizing benzofurans and indole compounds via molybdenum-catalyzed intermolecular deoxygenation cycloaddition reactions. This method effectively overcomes the problems of high catalyst cost, cumbersome reaction steps, and poor functional group compatibility in existing synthesis methods.

[0006] To solve the above technical problems, the technical solution adopted in this invention is: a method for synthesizing benzofuran and indole compounds via molybdenum-catalyzed intermolecular deoxygenation cycloaddition reaction, using o-hydroxyphenylacetylene compounds or o-aminophenylacetylene compounds as substrate A and 1,3-dicarbonyl compounds as substrate B, and in the presence of a molybdenum catalyst, ligands and additives, an intermolecular deoxygenation cycloaddition reaction occurs in an organic solvent to generate the corresponding benzofuran or indole compounds; Substrate A has the following general structural formula: R 1 C6(C≡CH)XH, where X is O or NH; When X is O, substrate A is an o-hydroxyphenylacetylene compound, which may optionally have 1-4 R¹ groups substituted on its benzene ring. Each R¹ group is independently selected from hydrogen, alkyl, alkoxy, halogen, nitro, cyano, and trifluoromethyl. When X is NH, substrate A is an o-aminophenylacetylene compound, which may optionally have 1-4 R¹ groups substituted on its benzene ring. Each R¹ group is independently selected from hydrogen, alkyl, alkoxy, halogen, nitro, cyano, and trifluoromethyl groups, and the NH group is substituted with an R² group, which is selected from hydrogen, alkyl, and benzyl groups. The substrate B has the following general structural formula: R 1 R 2 C(C=O)R 3 (C=O)R 4 ; In the formula, R¹ and R² are selected from either alkyl or alkoxy groups, and R³ and R₂ are selected from either alkyl or alkoxy groups. 4 It is selected from any one of alkyl, alkoxy, and aryl; the aryl group is phenyl or substituted phenyl, and the substituent of the substituted phenyl group is selected from any one of alkyl, alkoxy, and halogen.

[0007] Preferably, the molybdenum catalyst is selected from one or more of MoCl5, MoO2Cl2, Mo(CO)6, and Cp2MoCl2.

[0008] Preferably, the ligand is selected from one or more of 2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, 1,10-phenanthroline, triphenylphosphine, and tricyclohexylphosphine.

[0009] Preferably, the additive is selected from one or more of trifluoromethanesulfonic acid, p-toluenesulfonic acid, acetic acid, potassium carbonate, and sodium carbonate.

[0010] Preferably, the organic solvent is selected from one or more of dichloromethane, chloroform, 1,2-dichloroethane, toluene, xylene, tetrahydrofuran, and acetonitrile.

[0011] Preferably, the molar ratio of substrate A to substrate B is 1:1.0 to 1:2.0. More preferably, it is 1:1.2 to 1:1.5. This molar ratio range ensures that substrate A reacts fully while avoiding excessive amounts of substrate B, which would lead to waste.

[0012] Preferably, the amount of molybdenum catalyst used is 5%-20% of the molar amount of substrate A. More preferably, it is 8%-12%. Too little catalyst will result in a slow reaction rate and reduced yield; too much catalyst will increase costs and may trigger side reactions.

[0013] Preferably, the molar ratio of ligand to molybdenum catalyst is 1:1 to 3:1. More preferably, it is 1.5:1 to 2:1. The addition of ligand can effectively regulate the active site structure of molybdenum catalyst, improve catalyst selectivity and stability, and this molar ratio range can achieve the best catalytic effect.

[0014] Preferably, the amount of additive used is 10%-30% of the molar amount of substrate A. More preferably, it is 15%-25%. The additive can promote the formation of active intermediates in the reaction system, accelerate the reaction rate, and increase the yield of the target product.

[0015] Preferably, the reaction temperature is 25℃-100℃, the reaction time is 4h-24h, and the reaction is carried out under nitrogen or argon protection. The amount of organic solvent used is 10mL-30mL per 1mmol of substrate A.

[0016] The preferred reaction temperature is 40℃-60℃. Too low a temperature will hinder the reaction; too high a temperature may trigger side reactions such as substrate polymerization and oxidation, reducing product purity and yield. The preferred reaction time is 8h-12h. Too short a reaction time will lead to incomplete reaction; too long a time may increase the formation of byproducts and reduce production efficiency. Inert gas protection can prevent the catalyst and substrate in the reaction system from being oxidized, improving the stability and repeatability of the reaction.

[0017] The reaction mechanism of this invention is as follows: First, the molybdenum catalyst combines with the ligand to form an active catalytic species. The active catalytic species interacts with substrate B (1,3-dicarbonyl compound) to induce enolization isomerization, forming an enol intermediate. The enol intermediate then undergoes an intermolecular addition reaction with substrate A (ortho-hydroxy / aminophenylacetylene compound) to form a carbon-carbon bonded intermediate. Finally, this intermediate undergoes an intramolecular deoxygenation cyclization reaction under the action of additives, eliminating one molecule of water to generate the target product benzofuran or indole compound. Simultaneously, the molybdenum catalyst is regenerated and participates in the next catalytic cycle.

[0018] Compared with the prior art, the present invention has the following beneficial effects: The catalyst is inexpensive and readily available: This invention uses molybdenum compounds as catalysts. Molybdenum is abundant, its cost is much lower than that of precious metals such as palladium and platinum, and its toxicity is low, which helps to reduce industrial production costs and is in line with the concept of green chemistry.

[0019] High atom economy: This invention constructs benzofuran and indole skeletons in one step through intermolecular deoxygenation cycloaddition reaction, eliminating only one molecule of water as a byproduct, resulting in high atom utilization and avoiding the atom waste caused by multi-step reactions in traditional methods.

[0020] The reaction conditions are mild: the reaction temperature of this invention is 25℃-100℃, no high temperature and high pressure are required, and it can be carried out in conventional organic solvents. The reaction equipment requirements are simple and easy to scale up industrially.

[0021] Good functional group compatibility: The method of this invention has good tolerance to a variety of substituents (such as alkyl, alkoxy, halogen, nitro, cyano, etc.), and can synthesize a variety of structurally diverse benzofuran and indole compounds, with a wide range of applications.

[0022] Simple to operate: The reaction steps of this invention are simple, no pre-functionalization modification of the substrate is required, and the post-processing is simple, which is conducive to improving production efficiency.

[0023] This invention provides a method for synthesizing benzofurans and indole compounds via molybdenum-catalyzed intermolecular deoxycycloaddition reactions. This method uses molybdenum compounds as catalysts, has mild reaction conditions, high atom economy, and good functional group compatibility. It can efficiently construct a variety of substituted benzofurans and indole compounds, providing a new route for the synthesis of these important heterocyclic compounds. Detailed Implementation

[0024] The present invention will be further described in detail below with reference to specific embodiments.

[0025] Example 1

[0026] Synthesis of 2-acetylbenzofuran: In a 100 mL dry Shrek tube, o-hydroxyphenylacetylene (1 mmol, 116 mg), acetylacetone (1.2 mmol, 120 mg), MoCl5 (0.1 mmol, 27 mg), 2,2'-bipyridine (0.15 mmol, 23 mg) and p-toluenesulfonic acid (0.2 mmol, 38 mg) were added sequentially. 20 mL of dichloromethane was added as an organic solvent. After purging the tube with nitrogen three times to replace the air, the Shrek tube was sealed and placed in an oil bath at 50 °C with stirring for 10 h.

[0027] After the reaction was complete, the reaction solution was cooled to room temperature, and the reaction was quenched with 20 mL of saturated brine. The mixture was extracted with dichloromethane (3 × 20 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1, v / v) to give the white solid product 2-acetylbenzofuran, in 85% yield.

[0028] Product characterization: ¹H NMR (400MHz, CDCl3) δ: 7.85 (d, J=7.6Hz, 1H), 7.68 (d, J=8.0Hz, 1H), 7.45 (t, J=7.6Hz, 1H), 7.32 (t, J=7.6Hz, 1H), 6.85 (s, 1H), 2.65 (s, 3H); ¹³C NMR (100MHz, CDCl3) δ: 197.5, 157.8, 155.2, 128.9, 124.5, 122.1, 112.8, 107.5, 26.8; MS (EI) m / z: 160 [M]⁺.

[0029] Example 2

[0030] Synthesis of 3-methyl-2-benzoylindole: In a 100 mL dry Shrek tube, N-methyl-o-aminophenylacetylene (1 mmol, 131 mg), benzoylacetone (1.5 mmol, 240 mg), MoO2Cl2 (0.12 mmol, 25 mg), 4,4'-dimethoxy-2,2'-bipyridine (0.24 mmol, 58 mg) and trifluoromethanesulfonic acid (0.25 mmol, 37 mg) were added sequentially. 20 mL of toluene was added as an organic solvent. After purging the tube with argon gas three times to replace the air, the Shrek tube was sealed and placed in an oil bath at 60 °C with stirring for 12 h.

[0031] After the reaction was complete, the reaction solution was cooled to room temperature, and the reaction was quenched by adding 20 mL of saturated sodium carbonate solution. The mixture was extracted with ethyl acetate (3 × 20 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 8:1, v / v) to give the pale yellow solid product 3-methyl-2-benzoylindole, in 82% yield.

[0032] Product characterization: ¹H NMR (400MHz, CDCl₃) δ: 8.12 (d, J=7.2Hz, 2H), 7.75 (d, J=7.6Hz, 1H), 7.58 (t, J=7.2Hz, 1H), 7.46 (t, J=7.6Hz, 2H), 7.35 (t, J=7.6Hz, 1H), 7.22 (t, J=7.6Hz, 1H), 7.05 (d, J=7.6Hz, 1H), 3.85 (s, 3H), 2.45 (s, 3H); ¹³C NMR (100MHz, CDCl₃) δ: 194.2, 158.6, 142.5, 137.8, 132.6, 129.8, 128.5, 124.2, 122.8, 120.5, 110.2, 109.8, 32.5, 12.6; MS (EI) m / z: 259 [M]⁺.

[0033] Example 3:

[0034] Synthesis of 5-methoxy-2-acetylbenzofuran: In a 100 mL dry Shrek tube, 5-methoxy-o-hydroxyphenylacetylene (1 mmol, 146 mg), acetylacetone (1.3 mmol, 130 mg), Cp2MoCl2 (0.09 mmol, 28 mg), 1,10-phenanthroline (0.18 mmol, 33 mg) and acetic acid (0.2 mmol, 12 mg) were added sequentially. 20 mL of tetrahydrofuran was added as an organic solvent. After purging the tube with nitrogen three times, the Shrek tube was sealed and placed in an oil bath at 40 °C with stirring for 8 h.

[0035] After the reaction was completed, the subsequent processing steps were the same as in Example 1. Separation was carried out by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 12:1, v / v) to obtain a white solid product 5-methoxy-2-acetylbenzofuran in 88% yield.

[0036] Product characterization: ¹H NMR (400MHz, CDCl3) δ: 7.65 (d, J=8.8Hz, 1H), 6.95 (d, J=2.4Hz, 1H), 6.85 (dd, J=8.8Hz, 2.4Hz, 1H), 6.75 (s, 1H), 3.85 (s, 3H), 2.62 (s, 3H); ¹³C NMR (100MHz, CDCl3) δ: 197.2, 159.8, 157.5, 155.8, 118.5, 112.6, 108.2, 107.5, 102.8, 55.6, 26.5; MS (EI) m / z: 190 [M]⁺.

[0037] Example 4:

[0038] Synthesis of 6-chloro-3-ethyl-2-propionylindole: In a 100 mL dry Shrek tube, 6-chloro-N-benzyl-o-aminophenylacetylene (1 mmol, 217 mg), 3-pentanedione (1.4 mmol, 140 mg), Mo(CO)6 (0.15 mmol, 41 mg), triphenylphosphine (0.3 mmol, 79 mg), and potassium carbonate (0.22 mmol, 30 mg) were added sequentially. 20 mL of 1,2-dichloroethane was added as an organic solvent. After purging the tube with argon gas three times to replace the air, the Shrek tube was sealed and placed in an oil bath at 70 °C with stirring for 14 h.

[0039] After the reaction was completed, the subsequent processing steps were the same as in Example 2. Separation was carried out by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 15:1, v / v) to obtain the pale yellow solid product 6-chloro-3-ethyl-2-propionylindole, with a yield of 78%.

[0040] Product characterization: ¹H NMR (400MHz, CDCl₃) δ: 7.72 (d, J=8.4Hz, 1H), 7.45 (d, J=1.6Hz, 1H), 7.25 (dd, J=8.4Hz, 1.6Hz, 1H), 7.15 (s, 1H), 5.25 (s, 2H), 7.35–7.20 (m, 5H), 2.95 (q, J=7.2Hz, 2H), 2.75 (q, J=7.2Hz, 2H), 1.25 (t, J=7.2Hz, 3H), 1.05 (t, J=7.2Hz, 3H); ¹³C NMR (100MHz, CDCl₃) δ: 195.8, 157.2, 141.8, 136.5, 133.2, 129.8, 128.5, 127.6, 126.8, 124.5, 121.2, 111.5, 109.2, 50.2,29.8, 22.5, 12.8, 10.5; MS (EI) m / z: 327 [M]⁺.

[0041] Example 5:

[0042] Synthesis of 7-nitro-2-propionylbenzofuran: In a 100 mL dry Shrek tube, 7-nitro-o-hydroxyphenylacetylene (1 mmol, 161 mg), 3-pentanedione (1.3 mmol, 130 mg), MoCl5 (0.11 mmol, 30 mg), 1,10-phenanthroline (0.22 mmol, 40 mg) and p-toluenesulfonic acid (0.22 mmol, 42 mg) were added sequentially. 22 mL of chloroform was added as an organic solvent. After purging the tube with nitrogen three times to replace the air, the Shrek tube was sealed and placed in an oil bath at 55 °C with stirring for 11 h.

[0043] After the reaction was complete, the reaction solution was cooled to room temperature, and the reaction was quenched with 20 mL of saturated brine. The mixture was extracted with chloroform (3 × 20 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 15:1, v / v) to give the pale yellow solid product 7-nitro-2-propionylbenzofuran, in 76% yield.

[0044] Product characterization: ¹H NMR (400MHz, CDCl3) δ: 8.35 (d, J=8.0Hz, 1H), 7.85 (d, J=8.0Hz, 1H), 7.65 (t, J=8.0Hz, 1H), 6.95 (s, 1H), 3.05 (q, J=7.2Hz, 2H), 1.25 (t, J=7.2Hz, 3H); ¹³C NMR (100MHz, CDCl3) δ: 200.2, 158.5, 153.2, 146.8, 130.5, 125.8, 121.2, 113.5, 108.2, 37.5, 7.8; MS (EI) m / z: 233 [M]⁺.

[0045] Example 6:

[0046] Synthesis of 5-cyano-3-phenyl-2-benzoylindole: In a 100 mL dry Shrek tube, 5-cyano-N-benzyl-o-aminophenylacetylene (1 mmol, 212 mg), dibenzoylmethane (1.4 mmol, 308 mg), MoO2Cl2 (0.13 mmol, 27 mg), 4,4'-dimethoxy-2,2'-bipyridine (0.26 mmol, 63 mg) and trifluoromethanesulfonic acid (0.24 mmol, 35 mg) were added sequentially. 24 mL of xylene was added as an organic solvent. After purging the tube with argon gas three times, the Shrek tube was sealed and placed in an oil bath at 65 °C with stirring for 13 h.

[0047] After the reaction was complete, the reaction solution was cooled to room temperature, and the reaction was quenched by adding 20 mL of saturated sodium carbonate solution. The mixture was extracted with ethyl acetate (3 × 20 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain the crude product. The crude product was separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 12:1, v / v) to give the pale yellow solid product 5-cyano-3-phenyl-2-benzoylindole, in yield 73%.

[0048] Product characterization: ¹H NMR (400MHz, CDCl₃) δ: 8.25 (d, J=8.4Hz, 2H), 7.95 (d, J=8.8Hz, 1H), 7.75 (d, J=1.6Hz, 1H), 7.65 (t, J=7.2Hz, 1H), 7.55-7.40 (m, 7H), 7.30 (dd, J=8.8Hz, 1.6Hz, 1H), 5.35 (s, 2H); ¹³C NMR (100MHz, CDCl₃) δ: 193.5, 157.8, 142.2, 137.5, 136.8, 133.5, 130.2, 129.8, 129.2, 128.8, 127.6, 126.5,124.8, 121.5, 118.2, 112.5, 110.8, 50.5; MS (EI) m / z: 362 [M]⁺.

[0049] Example 7:

[0050] Synthesis of 6-trifluoromethyl-2-acetylbenzofuran: In a 100 mL dry Shrek tube, 6-trifluoromethyl-o-hydroxyphenylacetylene (1 mmol, 184 mg), acetylacetone (1.2 mmol, 120 mg), Cp2MoCl2 (0.1 mmol, 31 mg), triphenylphosphine (0.2 mmol, 52 mg), and acetic acid (0.2 mmol, 12 mg) were added sequentially. 20 mL of acetonitrile was added as an organic solvent. After purging the tube with nitrogen three times to replace the air, the Shrek tube was sealed and placed in an oil bath at 45 °C with stirring for 9 h.

[0051] After the reaction was completed, the subsequent processing steps were the same as in Example 1. Separation was carried out by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 18:1, v / v) to obtain a white solid product 6-trifluoromethyl-2-acetylbenzofuran, with a yield of 81%.

[0052] Product characterization: ¹H NMR (400MHz, CDCl3) δ: 7.95 (s, 1H), 7.85 (d, J=8.4Hz, 1H), 7.55 (d, J=8.4Hz, 1H), 6.95 (s, 1H), 2.70 (s, 3H); ¹³C NMR (100MHz, CDCl3) δ: 197.8, 158.2, 154.5, 132.5 (q, J=32.5Hz), 128.8, 124.5 (q, J=270Hz), 122.8, 118.2 (q, J=3.5Hz), 108.5, 26.8; MS (EI) m / z: 228 [M]⁺.

[0053] Example 8:

[0054] Synthesis of 4-methoxy-3-ethyl-2-propionylindole: In a 100 mL dry Shrek tube, 4-methoxy-N-methyl-o-aminophenylacetylene (1 mmol, 161 mg), 3-pentanedione (1.5 mmol, 150 mg), Mo(CO)6 (0.14 mmol, 39 mg), tricyclohexylphosphine (0.28 mmol, 79 mg), and potassium carbonate (0.23 mmol, 32 mg) were added sequentially. 25 mL of 1,2-dichloroethane was added as an organic solvent. After purging the tube with argon gas three times to replace the air, the Shrek tube was sealed and placed in an oil bath at 60 °C with stirring for 12 h.

[0055] After the reaction was completed, the subsequent processing steps were the same as in Example 2. Separation was carried out by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1, v / v) to obtain the pale yellow solid product 4-methoxy-3-ethyl-2-propionylindole, with a yield of 83%.

[0056] Product characterization: ¹H NMR (400MHz, CDCl₃) δ: 7.65 (d, J=8.4Hz, 1H), 7.05 (d, J=2.4Hz, 1H), 6.95 (dd, J=8.4Hz, 2.4Hz, 1H), 7.10 (s, 1H), 3.85 (s, 3H), 3.75 (s, 3H), 2.95 (q, J=7.2Hz, 2H), 2.75 (q, J=7.2Hz, 2H), 1.25 (t, J=7.2Hz, 3H), 1.05 (t, J=7.2Hz, 3H); ¹³C NMR (100MHz, CDCl₃) δ: 196.2, 158.5, 157.2, 142.8,130.5, 124.2, 118.5, 112.2, 110.5, 109.8, 55.6, 32.8, 29.8, 22.5, 12.8, 10.5; MS (EI) m / z: 273 [M]⁺.

[0057] Comparative Experiment: To verify the superiority of the molybdenum catalyst of this invention, the reaction for synthesizing 2-acetylbenzofuran in Example 1 was used as a model reaction. Palladium catalyst (PdCl2) and copper catalyst (CuCl2) were used to replace the molybdenum catalyst of this invention, respectively, while other reaction conditions remained unchanged. The experimental results are shown in the table below:

[0058]

[0059] As shown in the table above, under the same reaction conditions, the molybdenum catalyst (MoCl5) used in this invention has a significantly better catalytic effect than the palladium catalyst and the copper catalyst, and the product yield is significantly higher, which fully demonstrates the superiority of the method of this invention.

[0060] To further verify the universality of the method of the present invention for different substituted substrates and the advantages of the catalyst, reactions containing strong electron-withdrawing substituents (nitro, cyano, trifluoromethyl) were selected as model reactions. PdCl2 and CuCl2 were used to replace molybdenum catalysts, respectively, while other reaction conditions remained unchanged. The comparative experimental results are shown in the table below:

[0061]

[0062] The comparative experimental data above show that even for substrates containing strong electron-withdrawing substituents such as nitro, cyano, and trifluoromethyl, the molybdenum catalyst used in this invention still exhibits significantly better catalytic activity than palladium and copper catalysts, with product yields exceeding those of palladium by more than 20%. The advantages of the molybdenum catalyst are even more pronounced for the synthesis of indole compounds containing cyano groups, further demonstrating that the method of this invention has excellent functional group compatibility and universality.

[0063] The above embodiments are not intended to limit the present invention, and the present invention is not limited to the examples given above. Any changes, modifications, additions or substitutions made by those skilled in the art within the scope of the technical solution of the present invention are also within the protection scope of the present invention.

Claims

1. A method for synthesizing benzofuran and indole compounds by molybdenum-catalyzed intermolecular deoxygenative cycloaddition reaction, characterized in that: an o-hydroxyphenylacetylene compound or an o-aminophenylacetylene compound is used as a substrate A, a 1,3-dicarbonyl compound is used as a substrate B, and intermolecular deoxygenative cycloaddition reaction occurs in an organic solvent under the action of a molybdenum catalyst, a ligand and an additive to generate a corresponding benzofuran or indole compound; when X is O, the substrate A is an o-hydroxyphenylacetylene compound, and the benzene ring of the substrate A is optionally substituted with 1-4 R¹ groups, each R¹ being independently selected from any one of hydrogen, an alkyl group, an alkoxy group, a halogen, a nitro group, a cyano group and a trifluoromethyl group; when X is NH, the substrate A is an o-aminophenylacetylene compound, the benzene ring of the substrate A is optionally substituted with 1-4 R¹ groups, each R¹ being independently selected from any one of hydrogen, an alkyl group, an alkoxy group, a halogen, a nitro group, a cyano group and a trifluoromethyl group, and NH is substituted with an R² group, R² being selected from any one of hydrogen, an alkyl group and a benzyl group; the molybdenum catalyst is selected from one or more of MoCl5, MoO2Cl2, Mo(CO)6 and Cp2MoCl2; the ligand is selected from one or more of 2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, 1,10-phenanthroline, triphenylphosphine and tricyclohexylphosphine; the additive is selected from one or more of trifluoromethanesulfonic acid, p-toluenesulfonic acid, acetic acid, potassium carbonate and sodium carbonate; the organic solvent is selected from one or more of dichloromethane, chloroform, 1,2-dichloroethane, toluene, xylene, tetrahydrofuran and acetonitrile; the molar ratio of the substrate A to the substrate B is 1:1.0-1:2.0; the amount of the molybdenum catalyst is 5%-20% of the molar amount of the substrate A; the molar ratio of the ligand to the molybdenum catalyst is 1:1-3:1; the amount of the additive is 10%-30% of the molar amount of the substrate A; the reaction temperature is 25°C-100°C, the reaction time is 4h-24h, and the reaction is carried out under the protection of nitrogen or argon, and the amount of the organic solvent is 10mL-30mL per 1mmol of the substrate A.

2. The method according to claim 1, wherein the substrate A is an o-hydroxyphenylacetylene compound, and the benzene ring of the substrate A is optionally substituted with 1-4 R¹ groups, each R¹ being independently selected from any one of hydrogen, an alkyl group, an alkoxy group, a halogen, a nitro group, a cyano group and a trifluoromethyl group. Substrate A has the general structure: R 1 C6 (C=CH)XH, X is O or NH; 3. The method according to claim 1, wherein the substrate A is an o-aminophenylacetylene compound, the benzene ring of the substrate A is optionally substituted with 1-4 R¹ groups, each R¹ being independently selected from any one of hydrogen, an alkyl group, an alkoxy group, a halogen, a nitro group, a cyano group and a trifluoromethyl group, and NH is substituted with an R² group, R² being selected from any one of hydrogen, an alkyl group and a benzyl group.

4. The method according to claim 1, wherein the molybdenum catalyst is selected from one or more of MoCl5, MoO2Cl2, Mo(CO)6 and Cp2MoCl2. The substrate B has the following general structure: R 1 R 2 C(C=O)R 3 (C=O)R 4 ; wherein R1, R2are selected from any one of alkyl, alkoxy, R3, R 4 selected from any one of alkyl, alkoxy, aryl; aryl is phenyl or substituted phenyl, the substituents of the substituted phenyl are selected from any one of alkyl, alkoxy, halogen.

2. The process for the synthesis of benzofurans and indoles by molybdenum-catalyzed intermolecular deoxygenative cycloaddition reactions according to claim 1, characterized in that:

5. The method according to claim 1, wherein the ligand is selected from one or more of 2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, 1,10-phenanthroline, triphenylphosphine and tricyclohexylphosphine.

3. The method for synthesizing benzofuran and indole compounds by molybdenum-catalyzed intermolecular deoxygenative cycloaddition reaction according to claim 1, characterized in that:

6. The method according to claim 1, wherein the additive is selected from one or more of trifluoromethanesulfonic acid, p-toluenesulfonic acid, acetic acid, potassium carbonate and sodium carbonate.

4. The method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenation cycloaddition reaction according to claim 1, characterized in that:

7. The method according to claim 1, wherein the organic solvent is selected from one or more of dichloromethane, chloroform, 1,2-dichloroethane, toluene, xylene, tetrahydrofuran and acetonitrile.

5. The method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenative cycloaddition reaction according to claim 1, characterized in that:

8. The method according to claim 1, wherein the molar ratio of the substrate A to the substrate B is 1:1.0-1:2.

0.

6. The method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenative cycloaddition reaction according to claim 1, characterized in that:

9. The method according to claim 1, wherein the amount of the molybdenum catalyst is 5%-20% of the molar amount of the substrate A.

7. The method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenative cycloaddition reaction according to claim 1, characterized in that:

10. The method according to claim 1, wherein the molar ratio of the ligand to the molybdenum catalyst is 1:1-3:

1.

8. The method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenative cycloaddition reaction according to claim 1, characterized in that:

11. The method according to claim 1, wherein the amount of the additive is 10%-30% of the molar amount of the substrate A.

9. The method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenative cycloaddition reaction according to claim 1, characterized in that:

12. The method according to claim 1, wherein the reaction temperature is 25°C-100°C, the reaction time is 4h-24h, and the reaction is carried out under the protection of nitrogen or argon, and the amount of the organic solvent is 10mL-30mL per 1mmol of the substrate A.

10. The method for synthesizing benzofuran and indole compounds through molybdenum-catalyzed intermolecular deoxygenative cycloaddition reaction according to claim 1, characterized in that: ​

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