Efficient synthesis method of benzofuranone-containing diheterocyclic compound

Abstract

According to the efficient synthesis method of the benzofuranone-containing diheterocyclic compound, aryl iodide is used as a substrate, in the atmosphere of carbon monoxide, palladium is used as a catalyst, organic phosphine is used as a ligand, potassium carbonate is used as alkali, and indole is used as a nucleophilic reagent, so that the benzofuranone-containing diheterocyclic compound is successfully synthesized. The method adopts a one-pot method and has the characteristics of simplicity in operation, wide substrate range, good functional group compatibility, high bonding efficiency and the like. The benzofuranone-containing bis-heterocyclic compound is an important intermediate for synthesizing complex molecules such as drugs and natural products, and the method has important significance in the fields of medicines, pesticides, chemical engineering and the like.

Description

Technical Field

[0001] This invention relates to an efficient method for synthesizing bicyclic compounds containing benzofuranone, belonging to the field of organic synthesis. Background Technology

[0002] Heterocyclic compounds are one of the largest families of organic compounds, with wide applications in medicinal chemistry and pesticide products. Among them, bicyclic compounds are found in a variety of drugs with unique physicochemical properties and have been identified as a major pillar of medicinal chemistry. Furthermore, bicyclic compounds serve as general synthetic building blocks for constructing specific ligands or catalysts. Therefore, the efficient synthesis of bicyclic compounds has attracted widespread attention from synthetic chemists.

[0003] Benzofuranones are important organic synthetic intermediates widely used in pharmaceuticals, pesticides, and food additives. Their derivatives possess antibacterial, antiviral, and antioxidant bioactivities. There are two traditional synthetic strategies for these compounds. The first is oxidation synthesis, where benzofuran can be oxidized to benzofuranones under the action of a suitable oxidant. This method requires the selection of a suitable oxidant to avoid over-oxidation and the formation of byproducts. The second is carbonylation synthesis of benzofuranones, which typically uses benzofuran and a carbonylating agent as raw materials under high temperature and pressure. The reaction conditions are harsh and require high-pressure equipment. In recent years, chemists have combined the Heck reaction process to achieve a carbonylation-Heck reaction transformation, enabling the efficient construction of carbonyl-containing heterocycles from acyclic substrates. For example, in 2023, Guan's research group efficiently constructed an indanone skeleton via a carbonylation Heck reaction, achieving secondary carbonylation and nucleophilic capture of phenylboronic acid, thus efficiently constructing a series of indanone-linked ester compounds (Org. Lett. 2023, 25, 8110–8115). In 2024, Zhu's research group utilized the carbonylation Heck reaction to construct 1,4-keto ester compounds containing a benzofuranone structure (Chem. Commun. 2024, 60, 9606–9609). We hypothesize that through ingenious substrate design, combining the carbonylation Heck reaction with secondary carbonylation and nucleophilic capture processes, it would be possible to achieve the efficient synthesis of biheterocyclic compounds. If this hypothesis could be realized, it would have significant implications for synthetic chemistry.

[0004] This invention successfully synthesized a bicyclic compound containing benzofuranone and an indole skeleton using aryl iodides as substrates, palladium as catalyst, organophosphine as ligand, potassium carbonate as base, and indole as nucleophile in a carbon monoxide atmosphere. This invention utilizes a zero-valent palladium catalytic cycle system, involving oxidative addition, carbon monoxide migration insertion, Heck carbonylation, and indole nucleophilic capture, providing a novel and efficient synthetic method for bicyclic compounds containing benzofuranone. This invention surpasses previously reported synthetic methods, employing a one-pot process with advantages such as simple operation, broad substrate scope, good functional group compatibility, and high bonding efficiency.

[0005] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: (1) The one-pot series process realizes the construction of double heterocyclic rings, with high bonding efficiency and simple and convenient operation; (2) It has a wide range of substrates and good functional group compatibility. Summary of the Invention

[0006] The purpose of this invention is to provide an efficient method for synthesizing bicyclic compounds containing benzofuranone: using aryl iodides as substrates, in a carbon monoxide atmosphere, using palladium as a catalyst, organophosphorus as a ligand, potassium carbonate as a base, and indole as a nucleophile, bicyclic compounds containing benzofuranone were successfully synthesized.

[0007] To achieve the above-mentioned objectives, this invention proposes an efficient synthetic method for bicyclic compounds containing benzofuranone, the synthetic route of which is shown below:

[0008]

[0009] This invention provides an efficient method for synthesizing a bicyclic compound containing benzofuranone, the steps of which are as follows:

[0010] Palladium catalyst, phosphine ligand, potassium carbonate, aryl iodine (formula 1), and indole (formula 3) were added to a dry Schlenk reaction tube. Carbon monoxide gas 2 was introduced, and solvent was added. The reaction was sealed and the reaction system temperature was controlled at 60–120 °C. After stirring for 1–60 hours, the resulting reaction mixture was transferred to a gai flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain the bicyclic compound containing benzofuranone (formula 4).

[0011] In general formulas 1, 3, and 4, R 1 It is hydrogen, alkyl, or halogen; R 2 It is methyl or phenyl; R 3 It is hydrogen, alkyl, or alkoxy; R 4 It is one of hydrogen, alkyl or phenyl; the carbon monoxide pressure is 1 to 50 atmospheres.

[0012] In the steps of the above method, the palladium catalyst is one of Pd(OAc)2, PdCl2, Pd(PPh3)4, Pd(MeCN)2Cl2, or Pd(TFA)2.

[0013] In the steps of the above method, the ligand is one of triphenylphosphine, bis(triphenylphosphine propane), bis(triphenylphosphine butane), adamantine phosphine, or tricyclohexylphosphine.

[0014] In the steps of the above method, the solvent is one of cyclohexane, toluene, xylene, fluorobenzene, chlorobenzene, or trifluorotoluene.

[0015] In the steps of the above method, the molar ratio of aryl iodine 1: indole 3: palladium catalyst: phosphine ligand: potassium carbonate is 1.0: 1.0~4.0: 0.01~0.3: 0.2~0.3: 1~3. Detailed Implementation

[0016] The following examples will help to understand the present invention, but are not intended to limit the scope of the invention.

[0017] Example 1: Preparation of benzofuranone and indole bicyclic compound 4a

[0018]

[0019] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1a (0.2 mmol, 52 mg, 100 mol%), and indole 3a (0.6 mmol, 70.2 mg, 300 mol%) were mixed with carbon monoxide gas at one atmosphere and 1.0 mL of toluene solvent. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain benzofuranone and indole bicyclic compound 4a in 95% yield with a melting point of 173-174 °C. 1H NMR(500MHz, CDCl3)δ8.29(d,J=7.8Hz,1H),7.77(d,J=7.8Hz,1H),7.64–7.60(m,1H),7.54–7.52(m,1H),7.39(d,J=3.8Hz,1H),7.28–7.2 2(m,2H),7.13(t,J=7.2Hz,1H),7.08(d,J=8.4Hz,1H),6.63(d,J=3.9Hz,1H),3.62(d,J=16.7Hz,1H),3.57(d,J=16.8Hz,1H),1.59(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ202.5,170.7,166.1,137.7,135.5,130.2,125.1,124.7,124.4,1 23.8,122.0,120.8,120.6,116.7,113.3,109.7,86.0,42.6,22.5.HRMS(ESI)m / z:[M+Na] + Calcd.for C 19 H 15 NNaO3 328.0944, found 328.0950.

[0020] Example 2: Preparation of benzofuranone and indole bicyclic compound 4b

[0021]

[0022] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1a (0.2 mmol, 52 mg, 100 mol%), and 2-methylindole 3b (0.6 mmol, 78.6 mg, 300 mol%) were mixed with carbon monoxide gas at one atmosphere and 1.0 mL of toluene solvent. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain benzofuranone and indole bicyclic compound 4b in 93% yield, with a melting point of 236-238 °C. 1H NMR (500MHz, CDCl3) δ7.84–7.77(m,2H),7.63–7.59(m,1H),7.45–7.41(m,1H),7.22–7.18(m,2H),7.13(t,J=7.5Hz ,1H),7.06(d,J=8.4Hz,1H),6.34(s,1H),3.76(d,J=16.6Hz,1H),3.68(d,J=16.5Hz,1H),2.53(s,3H),1.58(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ202.6,170.7,168.2,137.5,137.0,136.2,129.8,124.7,123.5,123 .2,121.9,120.9,119.9,115.1,113.1,109.9,86.4,45.7,22.8,17.4.HRMS(ESI)m / z:[M+Na] + Calcd.for C 20 H 17 NNaO3 342.1101, found 342.1103.

[0023] Example 3: Preparation of benzofuranone and indole bicyclic compound 4c

[0024]

[0025] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1a (0.2 mmol, 52 mg, 100 mol%), and 2-ethylindole 3c (0.6 mmol, 87.0 mg, 300 mol%) were mixed with carbon monoxide gas at one atmosphere (2), and 1.0 mL of toluene solvent was added. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain benzofuranone and indole bicyclic compound 4c in 88% yield, with a melting point of 172-173 °C. 1H NMR (500MHz, CDCl3) δ7.79–7.72(m,2H),7.61(t,J=7.3Hz,1H),7.47(d,J=6.5Hz,1H),7.24–7.19(m,2H),7.13(t,J=7.5Hz,1H),7.05 (d,J=8.4Hz,1H),6.39(s,1H),3.81(d,J=16.5Hz,1H),3.72(d,J=16.4Hz,1H),2.94–2.82(m,2H),1.59(s,3H),1.24(t,J=7.3Hz,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ202.6,170.7,168.4,144.2,137.5,136.0,130.0,124.7,123.4,123.1, 121.9,120.9,120.3,114.6,113.1,107.4,86.5,46.1,23.5,22.8,12.9.HRMS(ESI)m / z:[M+Na] + Calcd.for C 21 H 19 NNaO3 356.1257, found 356.1266.

[0026] Example 4: Preparation of a benzofuranone and indole bicyclic compound 4d

[0027]

[0028] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1a (0.2 mmol, 52 mg, 100 mol%), and 2-phenylindole 3d (0.6 mmol, 115.8 mg, 300 mol%) were mixed with carbon monoxide gas at one atmosphere and 1.0 mL of toluene solvent. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain benzofuranone and indole bicyclic compound 4d, with a yield of 82% and a melting point of 164-165 °C. 1H NMR (500MHz, CDCl3) δ8.04(d,J=7.1Hz,1H),7.71(d,J=7.6Hz,1H),7.58-7.45(m,7H),7.26-7.20(m,2H),7.09(t ,J=7.5Hz,1H),6.96(d,J=8.4Hz,1H),6.64(s,1H),3.01(d,J=16.7Hz,1H),2.95(d,J=16.6Hz,1H),1.18(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ202.3,170.6,169.2,139.1,137.6,137.4,133.7,129.0,128.9,128.9,128.8,1 25.0,124.6,123.7,121.8,120.7,120.30,115.83,113.1,111.7,86.5,46.6,22.4.HRMS(ESI)m / z:[M+H] + Calcd.for C 25 H 20 NO3382.1438, found 382.1443.

[0029] Example 5: Preparation of benzofuranone and indole bicyclic compound 4e

[0030]

[0031] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1a (0.2 mmol, 52 mg, 100 mol%), and 7-methylindole 3e (0.6 mmol, 78.6 mg, 300 mol%) were mixed with carbon monoxide gas at one atmosphere (2), and 1.0 mL of toluene solvent was added. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain benzofuranone and indole bicyclic compound 4e in 86% yield, with a melting point of 150-151 °C. 1H NMR (500MHz, CDCl3) δ7.75(d,J=7.7Hz,1H),7.59(t,J=8.5Hz,1H),7.37(t,J=3.7Hz,2H),7.16(t,J =7.5Hz,1H),7.12–7.05(m,3H),6.62(d,J=3.9Hz,1H),3.64–3.57(m,2H),2.27(s,3H),1.60(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ202.3,170.8,165.6,137.7,135.0,131.9,128.1,126.7,125.7,124. 7,124.2,122.0,120.6,118.4,113.2,109.3,86.6,43.57,22.5,22.0.HRMS(ESI)m / z:[M+Na] + Calcd.for C 20 H 17 NNaO3342.1101, found 342.1103.

[0032] Example 6: Preparation of benzofuranone and indole bicyclic compound 4f

[0033]

[0034] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1a (0.2 mmol, 52 mg, 100 mol%), and 4-methoxyindole 3f (0.6 mmol, 88.2 mg, 300 mol%) were mixed with carbon monoxide gas at one atmosphere and 1.0 mL of toluene solvent. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain benzofuranone and indole bicyclic compound 4f in 81% yield, with a melting point of 172-173 °C. 1HNMR (500MHz, CDCl3) δ7.87(d,J=8.4Hz,1H),7.77(d,J=7.7Hz,1H),7.62(t,J=8.6Hz,1H),7.30(d,J=3.8Hz,1H),7.20–7.07( m,3H),6.77(d,J=3.8Hz,1H),6.68(d,J=8.0Hz,1H),3.92(s,3H),3.62(d,J=16.8Hz,1H),3.57(d,J=16.7Hz,1H),1.58(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ202.5,170.7,166.3,152.7,137.7,136.7,126.1,124.7,122.9,122 .0,120.6,120.4,113.3,109.8,106.7,104.3,86.0,55.4,42.7,22.5.HRMS(ESI)m / z:[M+Na] + Calcd.for C 20 H 17 NNaO4 358.1050, found 358.1059.

[0035] Example 7: Preparation of 4g of a benzofuranone and indole bicyclic compound

[0036]

[0037] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1b (0.2 mmol, 54.8 mg, 100 mol%), and 2-methylindole 3b (0.6 mmol, 78.6 mg, 300 mol%) were introduced. Carbon monoxide gas 2 at one atmosphere was introduced, and 1.0 mL of toluene solvent was added. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain 4 g of a benzofuranone and indole bicyclic compound, with a yield of 92% and a melting point of 130-131 °C. 1H NMR(500MHz,DMSO-d6)δ7.91(d,J=7.7Hz,1H),7.51–7.44(m,3H),7.19–7.06(m,3H),6.47(s ,1H),3.97(d,J=17.4Hz,1H),3.91(d,J=17.3Hz,1H),2.57(s,3H),2.35(s,3H),1.47(s,3H). 13 C{ 1 H}NMR(125MHz,DMSO-d6)δ202.3,169.4,168.6,138.7,136.9,136.1,131.0,129.3,123.61,123. 58,123.3,120.8,119.7,115.6,112.8,109.7,86.8,45.2,22.8,20.2,17.1.HRMS(ESI)m / z:[M+H] + Calcd.for C 21 H 20 NO3 334.1438, found334.1438.

[0038] Example 8: Preparation of a benzofuranone and indole bicyclic compound (4h)

[0039]

[0040] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1c (0.2 mmol, 57.6 mg, 100 mol%), and 2-methylindole 3b (0.6 mmol, 78.6 mg, 300 mol%) were introduced. Carbon monoxide gas 2 at one atmosphere was introduced, and 1.0 mL of toluene solvent was added. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain a benzofuranone and indole bicyclic compound 4h, with a yield of 89% and a melting point of 150-151 °C. 1H NMR (500MHz, CDCl3) δ7.84–7.82(m,1H),7.59(s,1H),7.47–7.42(m,2H),7.22–7.18(m,2H),6.98(d,J=8.5Hz,1H),6.33(s, 1H), 3.74 (d, J = 16.5Hz, 1H), 3.66 (d, J = 16.6Hz, 1H), 2.70 (q, J = 7.6Hz, 2H), 2.53 (s, 3H), 1.58 (s, 3H), 1.28 (t, J = 7.6Hz, 3H). 13 C{ 1 H}NMR(125MHz, CDCl3)δ202.8,169.3,168.3,137.9,137.0,136.2(2C),129.7,123.5,123.2,122 .9,120.6,119.9,115.1,112.8,109.8,86.7,45.6,28.0,22.9,17.3,15.4.HRMS(ESI)m / z:[M+Na] + Calcd.for C 22 H 21 NNaO3 370.1414, found 370.1420.

[0041] Example 9: Preparation of benzofuranone and indole bicyclic compound 4i

[0042]

[0043] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1d (0.2 mmol, 55.6 mg, 100 mol%), and 2-methylindole 3b (0.6 mmol, 78.6 mg, 300 mol%) were mixed with carbon monoxide gas at one atmosphere and 1.0 mL of toluene solvent. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain benzofuranone and indole bicyclic compound 4i in 76% yield, with a melting point of 150-152 °C. 1H NMR(500MHz, CDCl3)δ7.82–7.80(m,1H),7.44–7.41(m,2H),7.33(td,J1=8.8Hz,J2=2.8Hz,1H),7.22–7.18k(m,2H),7.0 1(dd,J1=9.0Hz,J2=3.6Hz,1H),6.34(s,1H),3.77(d,J=16.7Hz,1H),3.70(d,J=16.6Hz,1H),2.52(s,3H),1.57(s,3H). 13 C{ 1 H}NMR(125MHz, CDCl3)δ202.14,168.12,166.76,157.7(d,J=241.3Hz),136.97,136.18,129.79,125.0(d,J=25.0Hz),123.62,123.33,1 21.5(d,J=7.5Hz),119.98,115.08,114.1(d,J=1.5Hz),110.04,109.8(d,J=23.8Hz),87.49,46.08,22.89,17.41.HRMS(ESI)m / z:[M+Na] + Calcd.for C 20 H 16 FNNaO3360.1006, found 360.1011.

[0044] Example 10: Preparation of benzofuranone and indole bicyclic compound 4j

[0045]

[0046] Palladium catalyst Pd(MeCN)₂Cl₂ (0.02 mmol, 5.2 mg, 10 mol%) and phosphine ligand Ad₂P were added to a dry Schlenk reaction tube. n Bu (0.04 mmol, 14.3 mg, 20 mol%), potassium carbonate (0.4 mmol, 55.3 mg, 200 mol%), aryl iodine 1e (0.2 mmol, 64.4 mg, 100 mol%), and 2-methylindole 3b (0.6 mmol, 78.6 mg, 300 mol%) were mixed with carbon monoxide gas at one atmosphere (2), and 1.0 mL of toluene solvent was added. The reaction system was sealed, and the temperature was maintained at 100 °C. After stirring for 36 hours, the reaction was stopped. The resulting reaction mixture was transferred to a round-bottom flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain benzofuranone and indole bicyclic compound 4j, with a yield of 74% and a melting point of 204-205 °C. 1H NMR(500MHz,CDCl3)δ7.79–7.69(m,4H),7.65–7.62(m,1H),7.44–7.32(m,4H),7.22–7.12(m,4H),6.34(s,1H),4.09(d,J=16.7Hz,1H),4.08(d,J=16.7Hz,1H),2.50(s,3H). 13 C{ 1 H}NMR(125MHz,CDCl3)δ199.7,171.0,168.1,137.5,137.2,136.7,136.2,129.8,128.9,128.5,125.0,124.8,123.6,123.3,122.4,121.1,120.0,115.1,112.9,109.9,88.4,47.9,17.39.HRMS(ESI)m / z:[M+Na] + Calcd.for C 25 H 19 NNaO3 404.1257,found404.1257.

Claims

1. An efficient method for synthesizing a bicyclic compound containing benzofuranone, comprising the following steps: ； Aryl iodine (Formula 1), carbon monoxide (CO 2), indole (Formula 3), palladium catalyst, organophosphorus ligand, and potassium carbonate were added to a dry Schlenk reaction tube, along with a solvent. The reaction was sealed, and the temperature of the reaction system was controlled at 60–120 °C. After stirring for 1–60 hours, the resulting reaction mixture was transferred to a gai flask and concentrated. The concentrate was separated by silica gel column chromatography to obtain a bicyclic compound containing benzofuranone (Formula 4). in, In general formulas 1, 3 and 4, R 1 It is hydrogen, alkyl, or halogen; R 2 It is methyl or phenyl; R 3 It is hydrogen, alkyl, or alkoxy; R 4 It is one of hydrogen, alkyl or phenyl; the carbon monoxide pressure is 1 to 50 atmospheres.

2. The efficient method for synthesizing a benzofuranone-containing bicyclic compound according to claim 1, characterized in that... The palladium catalyst is one of Pd(OAc)2, PdCl2, Pd(PPh3)4, Pd(MeCN)2Cl2, or Pd(TFA)2.

3. The efficient method for synthesizing a benzofuranone-containing bicyclic compound according to claim 1, characterized in that the ligand... It is one of triphenylphosphine, bis(triphenylphosphine propane), bis(triphenylphosphine butane), adamantine phosphine, or tricyclohexylphosphine.

4. The efficient method for synthesizing a benzofuranone-containing bicyclic compound according to claim 1, characterized in that... The solvent is one of cyclohexane, toluene, xylene, fluorobenzene, chlorobenzene, or trifluorotoluene.

5. The efficient method for synthesizing a benzofuranone-containing bicyclic compound according to claim 1, characterized in that... The molar ratio of aryl iodine: indole: palladium catalyst: phosphine ligand: potassium carbonate is 1.0 : 1.0 ~ 4.0 : 0.01 ~ 0.3 : 0.2 ~ 0.3 : 1 ~ 3.

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