Tetrasubstituted furan compounds and methods for their preparation

Abstract

The present application relates to tetra-substituted furan compounds and a preparation method thereof, and belongs to the technical field of organic chemical synthesis. In the preparation process, conjugated ene-yne ketone compounds and aldehyde compounds are used as reaction raw materials, nitrogen heterocyclic carbene compounds (NHCs) are used as catalysts, and tetra-substituted furan, an important application value multi-substituted furan derivative, is constructed in a one-step reaction in an alkaline and organic solvent environment. The preparation method does not require transition metal reagents, avoids the use of toxic metals and possible metal residues, and has mild and simple conditions, easy operation, and cheap and easily available raw materials, thereby providing a new friendly and low-cost path for the production and application of tetra-substituted furan, an important bioactive skeleton heterocyclic compound.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, and relates to tetrasubstituted furan compounds and their preparation methods. Background Technology

[0002] Heterocyclic chemistry is one of the most active research areas in organic synthetic chemistry. The efficient synthesis of heterocyclic compounds and their derivatives has always been a research hotspot in heterocyclic construction. Among numerous heterocyclic compounds, the tetrasubstituted furan skeleton has even broader research and application value because it is not only widely found in many natural products, drugs, and bioactive molecules, but also an important organic synthetic intermediate. Studies have found that urofuran acid (CMPF) and its analogues are thought to potentially induce gestational diabetes mellitus (GD) in pregnant women and type 2 diabetes in mice and humans (J. Med. Chem. 2017, 60, 1860-1875). Elevated plasma CMPF levels are not only directly related to glucose-induced insulin secretion decline, but also closely associated with the development of chronic kidney disease (CKD). Therefore, the diverse synthesis and evaluation of tetrasubstituted furans are extremely important.

[0003] Currently, numerous studies have been conducted on the preparation of polysubstituted furans. However, most synthetic strategies suffer from limitations in the availability and diversity of raw materials, relatively harsh reaction conditions, and a focus on the use of transition metal reagents (Org. Biomol. Chem. 2014, 12, 5802-5806; Org. Prep. Proced. Int. 2019, 51, 409-442). This leads to numerous drawbacks, including poor compatibility in diverse preparation methods, poor regioselectivity of the products, low atom utilization, metal residues in the products, and high production costs.

[0004] Organic catalysis, as an efficient catalytic method, generally offers numerous advantages over transition metal catalysis, including lower toxicity, milder conditions, higher selectivity, and avoidance of metal residues. However, reports on the efficient synthesis of polysubstituted furans using small organic molecule catalytic strategies are still scarce, necessitating further research and development. Designing novel and efficient organic catalytic strategies to prepare novel polysubstituted furan compounds will be of great significance. Summary of the Invention

[0005] In view of this, one objective of the present invention is to provide a tetrasubstituted furan compound; another objective of the present invention is to provide a method for preparing a tetrasubstituted furan compound.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] 1. A tetrasubstituted furan compound, the structure of which is shown in general formula I:

[0008]

[0009] Among them, R 1 It is any one of the following: alkyl group with 1 to 30 carbon atoms, heteroalkyl group with 1 to 30 carbon atoms, cycloalkyl group with 3 to 30 carbon atoms, aryl group, heteroaryl group, substituted heteroaryl group, aromatic hydrocarbon group with 6 to 60 carbon atoms, or aromatic heterocyclic group with 3 to 60 carbon atoms; R 2 It is any one of the following groups: alkyl acyl group with 2 to 30 carbon atoms, aryl acyl group with 6 to 60 carbon atoms, heterocyclic acyl group, cyclic alkyl acyl group with 3 to 30 carbon atoms, alkenyl acyl group with 2 to 30 carbon atoms, heterocyclic alkenyl acyl group, amide group, or ester group with 2 to 30 carbon atoms; R 3 It is any one of alkyl, heteroalkyl, aryl, or heteroaryl groups having 1 to 30 carbon atoms; R 4 It is any one of aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkenyl with 2 to 30 carbon atoms, heteroalkenyl with 2 to 30 carbon atoms, heterocyclic alkenyl with 3 to 20 carbon atoms, alkynyl with 2 to 30 carbon atoms, heteroalkynyl with 2 to 30 carbon atoms, heterocyclic alkynyl with 3 to 20 carbon atoms, alkyl with 1 to 30 carbon atoms, or heteroalkyl with 1 to 30 carbon atoms;

[0010] R 1 With R 2 The dashed line between them represents R. 1 and R 2 They can be independent substituents or linked together to form a ring.

[0011] Preferably, the R 1 It is any one of methyl, oxocyclohexyl, 3-methoxy-3-oxopropyl, phenyl, thiophene-2-yl, naphth-1-yl, or naphth-2-yl; the R 2 It is any one of acetyl, benzoyl, methoxyformyl, ethoxyformyl, or diethylaminoformyl; the R 3 It is any one of methyl, butyl, triisopropylsilyl, or phenyl; the R 4 It is any one of phenyl, p-chlorophenyl, p-bromophenyl, p-phenylphenyl, m-fluorophenyl, 4-bromo-3-methylphenyl, 2,4-dichlorophenyl, quinoline-6-yl or 3-pyridyl.

[0012] Preferably, it is any one of the following compounds:

[0013]

[0014]

[0015] 2. A method for preparing the tetrasubstituted furan compound, wherein the preparation method is as follows:

[0016] Provide conjugated enynoids and ketones as shown in general formula A and aldehydes as shown in general formula B, respectively:

[0017]

[0018] The conjugated enynone compound, the aldehyde compound, the nitrogen heterocyclic carbene compound, the basic compound and the organic solvent are mixed, sealed and reacted at room temperature or 50°C for 3 to 24 hours. After the reaction is completed, the reaction product is subjected to crude extraction and purification in sequence to obtain the tetrasubstituted furan compound.

[0019] Among them, R 1 It is any one of the following: alkyl group with 1 to 30 carbon atoms, heteroalkyl group with 1 to 30 carbon atoms, cycloalkyl group with 3 to 30 carbon atoms, aryl group, heteroaryl group, substituted heteroaryl group, aromatic hydrocarbon group with 6 to 60 carbon atoms, or aromatic heterocyclic group with 3 to 60 carbon atoms; R 2 It is any one of the following groups: alkyl acyl group with 2 to 30 carbon atoms, aryl acyl group with 6 to 60 carbon atoms, heterocyclic acyl group, cyclic alkyl acyl group with 3 to 30 carbon atoms, alkenyl acyl group with 2 to 30 carbon atoms, heterocyclic alkenyl acyl group, amide group, or ester group with 2 to 30 carbon atoms; R 3 It is any one of alkyl, heteroalkyl, aryl, or heteroaryl groups having 1 to 30 carbon atoms; R 4 It is any one of aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkenyl with 2 to 30 carbon atoms, heteroalkenyl with 2 to 30 carbon atoms, heterocyclic alkenyl with 3 to 20 carbon atoms, alkynyl with 2 to 30 carbon atoms, heteroalkynyl with 2 to 30 carbon atoms, heterocyclic alkynyl with 3 to 20 carbon atoms, alkyl with 1 to 30 carbon atoms, or heteroalkyl with 1 to 30 carbon atoms;

[0020] R 1 With R 2 The dashed line between them represents R. 1 and R 2 They can be independent substituents or linked together to form a ring.

[0021] Preferably, the molar ratio of the conjugated enynoid ketone compound, aldehyde compound, nitrogen heterocyclic carbene compound and basic compound is 1:1-2:0.1-0.2:1-2.

[0022] Preferably, the nitrogen-containing heterocyclic carbene compound is any one of the following structural formulas:

[0023]

[0024] Preferably, the alkaline compound is any one or more of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, diisopropylethylamine, bis(trimethylsilylaminolithium), diisopropylaminolithium, sodium methoxide, or sodium ethoxide.

[0025] Preferably, the organic solvent is any one or more of tetrahydrofuran, toluene, acetonitrile, diethyl ether, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, dichloroethane, ethyl acetate, methyl tert-butyl ether, isopropyl ether, or N-methylpyrrolidone.

[0026] Preferably, the specific process of crude extraction and purification is as follows: ethyl acetate is added to the reaction product and filtered to obtain a primary filtrate and a filter cake; the filter cake is washed with ethyl acetate at least once to obtain a secondary filtrate; the primary filtrate and the secondary filtrate are mixed and subjected to reduced pressure treatment to remove the solvent to obtain a crude product; the crude product is purified by column chromatography.

[0027] The beneficial effects of this invention are as follows: This invention provides tetrasubstituted furan compounds and their preparation method. In the preparation process, organic small-molecule nitrogen heterocyclic carbene compounds (NHCs) are used as catalysts to catalyze the reaction of conjugated enyneone compounds and aldehyde compounds, ultimately successfully constructing tetrasubstituted furan compounds. This method is mild, avoids the use of toxic metals and metal residue problems, is easy to operate, and uses inexpensive and readily available raw materials, making it a highly atom-efficient and economical green preparation method.

[0028] Other advantages, objectives, and features of the invention will be set forth in part in the description which follows, and in part will be apparent to those skilled in the art from the following examination, or may be learned from practice of the invention. The objectives and other advantages of the invention can be realized and obtained through the following description. Attached Figure Description

[0029] To make the objectives, technical solutions, and advantages of the present invention clearer, the preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings, wherein:

[0030] Figure 1 This is a schematic diagram illustrating the preparation process of the tetrasubstituted furan compounds in this invention;

[0031] Figure 2 The 1H NMR spectrum of the tetrasubstituted furan compound I-1 prepared in Example 1;

[0032] Figure 3 The carbon NMR spectrum of the tetrasubstituted furan compound I-1 prepared in Example 1;

[0033] Figure 4 The 1H NMR spectrum of the tetrasubstituted furan compound I-2 prepared in Example 2;

[0034] Figure 5 The carbon NMR spectrum of the tetrasubstituted furan compound I-2 obtained in Example 2;

[0035] Figure 6 The 1H NMR spectrum of the tetrasubstituted furan compound I-3 prepared in Example 3;

[0036] Figure 7 The image shows the carbon NMR spectrum of the tetrasubstituted furan compound I-3 obtained in Example 3. Detailed Implementation

[0037] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that the illustrations provided in the following embodiments are only schematic representations of the basic concept of the present invention. Unless otherwise specified, the following embodiments and features can be combined with each other.

[0038] The reaction formulas for preparing tetrasubstituted furan compounds in the following examples are as follows, and the schematic diagram of the preparation process is shown in the figure. Figure 1 As shown:

[0039]

[0040] Example 1

[0041] Preparation of tetrasubstituted furan compounds I-1

[0042] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.01 mmol, 10 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 15:1) to obtain the target product (1-(5-benzyl-4-(4-chlorobenzoyl)-2-methylfuran-3-yl)ethane-1-one I-1 (31.8 mg, yield 90%), whose chemical structure is as follows:

[0043]

[0044] The relevant characterization analysis results are as follows: 1 H NMR (600MHz, CDCl3): δ7.75(d,J=8.2Hz,2H),7.39(d,J=8.2Hz,2H),7.25(t,J=8.0Hz,2H ),7.20(t,J=7.3Hz,1H),7.15(d,J=7.5Hz,2H),3.88(s,2H),2.55(s,3H),2.15(s,3H)(such as Figure 2 (as shown); 13 C NMR (151MHz, CDCl3): δ 193.3, 190.9, 156.7, 153.9, 139.9, 136.9, 136.6, 130.6, 129.1, 128.8, 128.7, 127.0, 123.7, 121.1, 77.4, 30.1, 14.4 (e.g.) Figure 3 (as shown); HRMS (ESI): C 21 H 17 ClNaO3[M+Na] + The calculated precise molecular weight is 375.0758, while the measured value is 375.0566.

[0045] Example 2

[0046] Preparation of tetrasubstituted furan compounds I-2

[0047] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.01 mmol, 10 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 8 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product (1-(4-chlorobenzoyl)-5-ethyl-2-methylfuran-3-yl)ethane-1-one I-2 (18.6 mg, yield 64%), whose chemical structure is as follows:

[0048]

[0049] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.77(d,J=8.5Hz,2H),7.41(d,J=8.5Hz,2H),2.55(d,J=4.7Hz,4H),2.52(d,J=7.5Hz,1H),2.15(s,3H),1.15(t,J=7.5Hz,3H) (such as Figure 4 (as shown); 13 C NMR (101MHz, CDCl3): δ 193.6, 191.1, 157.2, 156.1, 139.8, 137.0, 130.6, 129.1, 123.6, 119.8, 30.2, 20.6, 14.3, 12.6 (e.g.) Figure 5 (as shown); HRMS (ESI): C 16 H 15 ClNaO3[M+Na] + The calculated precise molecular weight is 313.0602, while the measured value is 313.0611.

[0050] Example 3

[0051] Preparation of tetrasubstituted furan compounds I-3

[0052] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst (0.01 mmol, 10 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and 1,4-dioxane (1.0 mL) were reacted at room temperature for 8 hours. After the reaction, ethyl acetate was added to the reaction product and filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain the target product (1-(4-chlorobenzoyl)-2-methyl-5-(triisopropylsilyl)methylfuran-3-yl)ethane-1-one I-3 (35.9 mg, yield 83%), whose chemical structure is as follows:

[0053]

[0054] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.72(d,J=8.5Hz,2H),7.38(d,J=8.5Hz,2H),2.49(s ,3H),2.17(s,2H),2.03(s,3H),1.07-1.03(m,3H),0.96(d,J=7.0Hz,18H)(such as Figure 6 (as shown); 13 C NMR (101MHz, CDCl3): δ 194.2, 190.7, 158.1, 154.5, 139.4, 137.5, 130.5, 129.0, 124.0, 118.4, 30.3, 18.4, 13.9, 11.3, 10.1 (e.g.) Figure 7 (as shown); HRMS (ESI): C 24 H 33 ClNaO3Si[M+Na] + The calculated precise molecular weight is 455.1780, while the measured value is 455.1794.

[0055] Example 4

[0056] Preparation of tetrasubstituted furan compounds I-4

[0057] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.01 mmol, 10 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain the target product (4-benzoyl-2-benzyl-5-methylfuran-3-yl)(4-chlorophenyl)methyl ketone I-4 (36.5 mg, yield 88%), whose chemical structure is as follows:

[0058]

[0059] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.34-7.26(m,3H),7.24-7.13(m,9H),7.08-7.06(m,2H),4.06(s,2H),2.35(s,3H); 13 C NMR (101MHz, CDCl3): δ191.1,190.1,157.0,156.6,139.0,138.9,137.4,137.0,132.6,1 29.7,128.9,128.8,128.6,128.5,128.4,127.0,121.8,121.7,33.1,13.4; HRMS(ESI):C 16 H 19 ClNaO3[M+Na] + The calculated precise molecular weight is 437.0915, while the measured value is 437.0920.

[0060] Example 5

[0061] Preparation of tetrasubstituted furan compounds I-5

[0062] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.01 mmol, 10 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 8 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product (4-benzoyl-2-benzyl-5-phenylfuran-3-yl)(4-chlorophenyl)methyl ketone I-5 (46.7 mg, yield 98%), whose chemical structure is as follows:

[0063]

[0064] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.68-7.63(m,2H),7.51-7.48(m,2H),7.39(dd,J=8.5,2.1Hz,3H),7.30(dd,J=8.3,3.7Hz,7H),7.25-7.18(m,5H),4.20(s,2H); 13 CNMR (101MHz, CDCl3): δ191.5,189.9,157.5,153.4,139.2,138.0,137.0,136.7,133.3,130.1,129. 5,129.1,128.9,128.9,128.8,128.7,128.7,128.5,127.2,127.1,123.7,121.2,33.5; HRMS(ESI):C 31 H 21 ClNaO3[M+Na] + The calculated precise molecular weight is 499.1071, while the measured value is 499.1072.

[0065] Example 6

[0066] Preparation of tetrasubstituted furan compounds I-6

[0067] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at 50 °C for 3 hours. After the reaction, ethyl acetate was added to the product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 5:1) to obtain the target product 2-benzyl-3-(4-chlorobenzoyl)-6,7-dihydrobenzofuran-4(5H)one I-6 (23.0 mg, yield 63%), whose chemical structure is as follows:

[0068]

[0069] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.73(d,J=8.5Hz,2H),7.37(d,J=8.5Hz,2H),7.29-7.20(m, 5H),3.99(s,2H),2.86(t,J=6.2Hz,2H),2.40(t,J=6.5Hz,2H),2.18-2.12(m,2H); 13 C NMR (101MHz, CDCl3): δ192.5,190.2,166.1,156.9,139.6,136.8,136.6,130.7, 129.0,128.8,128.7,127.1,120.7,118.4,37.9,33.1,23.5,22.4; HRMS(ESI):C 22 H 17 ClNaO3[M+Na] + The calculated precise molecular weight is 387.0758, while the measured value is 387.0765.

[0070] Example 7

[0071] Preparation of tetrasubstituted furan compounds I-7

[0072] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at 50 °C for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure treatment using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 5:1) to obtain the target product 2-benzyl-3-(4-chlorobenzoyl)-6-methyl-6,7-dihydrobenzofuran-4(5H)one I-7 (22.7 mg, yield 60%), whose chemical structure is as follows:

[0073]

[0074] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.72(d,J=8.5Hz,2H),7.37(d,J=8.5Hz,2H),7.29-7.21(m,5H),4.00(s,2H),2.95(dd,J=16. 9,4.6Hz,1H),2.54(dd,J=16.9,9.8Hz,1H),2.47-2.42(m,2H),2.17(dd,J=17.0,12.1Hz,1H),1.15(d,J=6.2Hz,3H); 13 C NMR (101MHz, CDCl3): δ192.2,190.2,165.8,157.2,139.6,136.8,136.6,130.7,12 9.0,128.8,128.8,127.1,120.4,118.4,46.4,33.1,31.5,30.7,21.1; HRMS(ESI):C 23 H 19 ClNaO3[M+Na] + The calculated precise molecular weight is 401.0915, while the measured value is 401.0930.

[0075] Example 8

[0076] Preparation of tetrasubstituted furan compounds I-8

[0077] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product, methyl 5-benzyl-4-(4-chlorobenzoyl)-2-(naphth-1-yl)furan-3-carboxylic acid ester I-8 (45.2 mg, yield 94%), with the following chemical structure:

[0078]

[0079] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.86(d,J=8.2Hz,1H),7.80(d,J=8.1Hz,1H),7.76-7.74(m,2H),7.65(dd,J=7.1,1.2Hz,1H),7.57( d,J=8.4Hz,1H),7.47-7.39(m,2H),7.37-7.31(m,3H),7.19(d,J=4.4Hz,4H),7.17-7.12(m,1H),4.02(s,2H),3.16(s,3H); 13 C NMR (101MHz, CDCl3): δ190.2,162.8,156.3,156.1,139.6,137.1,136.6,133.6,131.8,130.8,130.4,129. 8,129.0,129.0,128.8,128.6,127.1,126.9,126.3,125.4,124.9,121.6,116.5,51.5,33.4; HRMS(ESI):C 30 H 22 ClO4[M+H] + The calculated precise molecular weight is 481.1201, while the measured value is 481.1192.

[0080] Example 9

[0081] Preparation of tetrasubstituted furan compounds I-9

[0082] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst (0.015 mmol, 15 mol%), p-chlorobenzaldehyde (0.1 mmol, 1.0 equiv) and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product, methyl 5-benzyl-4-(4-chlorobenzoyl)-2-(naphth-2-yl)furan-3-carboxylic acid ester I-9 (46.7 mg, yield 97%), with the following chemical structure:

[0083]

[0084] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ8.48(s,1H),7.95-7.89(m,2H),7.87-7.82(m,2H),7.79(ddd,J=8.6,2.1,1.1Hz,2H),7 .52-7.49(m,2H),7.44-7.41(m,2H),7.30-7.27(m,4H),7.23-7.20(m,1H),4.12(d,J=2.5Hz,2H),3.36(s,3H); 13 C NMR (101MHz, CDCl3): δ190.0,163.5,155.9,155.7,139.5,137.1,136.6,133.8,132.9,130.2,129.1,128.9,1 28.9,128.8,128.3,128.1,127.8,127.3,127.1,126.7,126.2,125.0,122.7,114.3,51.6,33.2; HRMS(ESI):C 30 H 22 ClO4[M+H] + The calculated precise molecular weight is 481.1201, while the measured value is 481.1200.

[0085] Example 10

[0086] Preparation of tetrasubstituted furan compounds I-10

[0087] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 15:1) to obtain the target product, methyl 5-benzyl-4-(4-chlorobenzoyl)-2-methylfuran-3-carboxylic acid ester I-10 (31.4 mg, yield 85%), with the following chemical structure:

[0088]

[0089] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.72(d,J=8.6Hz,2H),7.39(d,J=8.6Hz,2H),7.26-7.19(m,5H),3.94(s,2H),3.41(s,3H),2.54(s,3H); 13 C NMR (101MHz, CDCl3): δ190.6,163.5,158.5,154.3,139.4,137.2,136.8,130.3,128.9,128.7,127.0,120.9,113.8,51.3,33.0,13.7; HRMS (ESI): C 21 H 17 ClNaO4[M+Na] + The calculated precise molecular weight is 391.0708, while the measured value is 391.0709.

[0090] Example 11

[0091] Preparation of tetrasubstituted furan compounds I-11

[0092] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product, ethyl 5-benzyl-4-(4-chlorobenzoyl)-2-(thiophen-2-yl)furan-3-carboxylic acid I-11 (43.7 mg, yield 97%), with the following chemical structure:

[0093]

[0094] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.97(dd,J=3.9,1.4Hz,1H),7.78(d,J=8.8Hz,2H),7.44-7.39(m,3H),7.25(d,J=4. 4Hz,4H),7.21-7.18(m,1H),7.11-7.09(m,1H),4.03(s,2H),3.89(q,J=7.2Hz,2H),0.85(t,J=7.3Hz,3H); 13 C NMR (101MHz, CDCl3): δ189.9,162.6,154.5,151.8,139.6,137.0,136.4,130.5,130.4,129 .4,129.0,128.9,128.8,128.7,127.6,127.0,122.1,112.1,61.0,33.0,13.5; HRMS(ESI):C 25 H 19 ClNaO4S[M+Na] + The calculated precise molecular weight is 473.0585, while the measured value is 473.0587.

[0095] Example 12

[0096] Preparation of tetrasubstituted furan compounds I-12

[0097] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.1 mmol, 1.0 equiv) and ethyl acetate (2.0 mL) were added to the reaction mixture and reacted at room temperature for 24 hours. After the reaction was completed, ethyl acetate was added to the product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 15:1) to obtain the target product, methyl 4-(4-chlorobenzoyl)-5-pentyl-2-phenylfuran-3-carboxylic acid ester I-12 (40.3 mg, yield 98%), with the following chemical structure:

[0098]

[0099] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.94 (dd, J=7.9, 1.8Hz, 2H), 7.79 (d, J=8.6Hz, 2H), 7.47-7.42 (m, 5H), 3 .35(s,3H),2.73(t,J=7.6Hz,2H),1.70(t,J=7.4Hz,2H),1.31-1.26(m,4H),0.88-0.83(m,3H); 13 C NMR (101MHz, CDCl3): δ190.2,163.6,158.3,155.0,139.3,137.2,130.2,129.8,12 9.0,128.5,128.1,121.9,113.9,51.6,31.3,28.0,27.0,22.3,14.0; HRMS(ESI):C 24 H 24 ClO4[M+H] + The calculated precise molecular weight is 411.1358, while the measured value is 411.1361.

[0100] Example 13

[0101] Preparation of tetrasubstituted furan compounds I-13

[0102] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv, E / Z = 4:1), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen-containing heterocyclic carbene catalyst (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product, methyl 4-(4-chlorobenzoyl)-2-(3-methoxy-3-oxopropyl)-5-pentylfuran-3-carboxylic acid ester I-13 (37.0 mg, yield 88%), with the following chemical structure:

[0103]

[0104] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.73(d,J=8.6Hz,2H),7.41(d,J=8.6Hz,2H),3.71(s,3H),3.43(s,3H),3.31(t,J=7.7Hz ,2H),2.74(t,J=7.6Hz,2H),2.59(t,J=7.6Hz,2H),1.63-1.56(m,2H),1.26-1.23(m,4H),0.83(t,J=6.8Hz,3H); 13 CNMR (101MHz, CDCl3): δ190.6,172.6,163.3,158.9,157.1,139.4,137.2,130.3,128 .9,120.2,113.9,52.0,51.4,32.0,31.2,27.8,26.8,23.1,22.3,14.0; HRMS(ESI):C 22 H 25 ClNaO6[M+Na] + The calculated precise molecular weight is 443.1232, while the measured value is 443.1238.

[0105] Example 14

[0106] Preparation of tetrasubstituted furan compounds I-14

[0107] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-chlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 7:1) to obtain the target product 5-benzyl-4-(4-chlorobenzoyl)-N,N-diethyl-2-phenylfuran-3-carboxamide I-14 (29.7 mg, yield 63%), whose chemical structure is as follows:

[0108]

[0109] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.76 (d, J=8.5Hz, 2H), 7.66 (dd, J=7.1, 1.6Hz, 2H), 7.40-7.34 (m, 4H),7.31-7.26(m,3H),7.23-7.18(m,3H),4.07(s,2H),3.19(s,4H),0.92-0.86(m,6H); 13 C NMR (101MHz, CDCl3): δ190.0,164.5,157.2,148.7,139.6,136.6,136.6,130.9,129.1,12 8.8,128.8,128.7,127.0,125.4,122.5,117.4,43.4,39.2,33.8,13.8,12.1; HRMS(ESI):C 29 H 26 ClNNaO3[M+Na] + The calculated precise molecular weight is 494.1493, while the measured value is 494.1490.

[0110] Example 15

[0111] Preparation of tetrasubstituted furan compounds I-15

[0112] The compound, consisting of an enyne ketone, was added to a dry, sealed tube. (0.1 mmol, 1.0 equiv), benzaldehyde (0.15 mmol, 1.5 equiv), nitrogen-containing heterocyclic carbene catalyst (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product, methyl 4-benzoyl-5-benzyl-2-(naphth-2-yl)furan-3-carboxylic acid ester I-15 (40.7 mg, yield 91%), with the following chemical structure:

[0113]

[0114] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ8.49 (d, J=1.8Hz, 1H), 7.95 (dd, J=8.7, 1.8Hz, 1H), 7.92 -7.90(m,1H),7.87-7.82(m,4H),7.56-7.54(m,1H),7.52-7.45(m,4H),7.33-7.26(m,4H),7.24-7.21(m,1H),4.14(s,2H),3.29(s,3H); 13 C NMR (101MHz, CDCl3): δ191.3,163.7,156.0,155.3,138.8,136.8,133.7,133.1,133.0,128.9,128.8,1 28.8,128.2,128.1,127.8,127.3,127.0,126.6,126.3,124.9,123.1,114.5,51.5,33.2; HRMS(ESI):C 30 H 23 O4[M+H] + The calculated precise molecular weight is 447.1591, while the measured value is 447.1592.

[0115] Example 16

[0116] Preparation of tetrasubstituted furan compounds I-16

[0117] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-bromobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product, methyl 5-benzyl-4-(4-bromobenzoyl)-2-(naphth-2-yl)furan-3-carboxylic acid ester I-16 (50.9 mg, yield 97%), with the following chemical structure:

[0118]

[0119] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ8.48(s,1H),7.95-7.90(m,2H),7.88-7.83(m,2H),7.71(d,J=8.2Hz, 2H),7.60(d,J=8.1Hz,2H),7.53-7.50(m,2H),7.29-7.20(m,5H),4.12(s,2H),3.36(s,3H); 13 C NMR (101MHz, CDCl3): δ190.2,163.5,156.0,155.7,137.6,136.6,133.8,133.0,132.1,130.3,129.0,128.9,1 28.9,128.4,128.2,128.1,127.8,127.4,127.1,126.7,126.2,125.0,122.7,114.3,51.7,33.3; HRMS(ESI):C 30 H 21 BrNaO4[M+Na] + The calculated precise molecular weight is 547.0515, while the measured value is 547.0516.

[0120] Example 17

[0121] Preparation of tetrasubstituted furan compounds I-17

[0122] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), p-phenylbenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product, methyl 4-([1,1'-biphenyl]-4-carbonyl)-5-benzyl-2-(naphth-2-yl)furan-3-carboxylic acid ester I-17 (51.2 mg, yield 98%), with the following chemical structure:

[0123]

[0124] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ8.42(s,1H),7.89-7.82(m,4H),7.80-7.74(m,2H),7.61(d,J=8.1Hz,2H),7.56(d,J=7.6H z,2H),7.45-7.37(m,4H),7.32(t,J=7.3Hz,1H),7.26-7.19(m,4H),7.16-7.12(m,1H),4.07(s,2H),3.28(s,3H); 13 C NMR (101MHz, CDCl3): δ190.8,163.7,155.7,155.5,145.7,139.9,137.5,136.8,133.8,133.0,129.5,129.1,129.0,128. 8,128.4,128.2,128.1,127.8,127.4,127.3,127.3,127.0,126.6,126.3,125.0,123.2,114.6,51.6,33.3; HRMS(ESI):C 36 H 26 NaO4[M+Na] + The calculated precise molecular weight is 545.1723, and the measured value is 545.1725.

[0125] Example 18

[0126] Preparation of tetrasubstituted furan compounds I-18

[0127] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), m-fluorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen-containing heterocyclic carbene catalyst Potassium carbonate (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the target product, methyl 5-benzyl-4-(3-fluorobenzoyl)-2-(naphth-2-yl)furan-3-carboxylic acid ester I-18 (41.8 mg, yield 90%), with the following chemical structure:

[0128]

[0129] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ8.40 (d, J = 1.8Hz, 1H), 7.87-7.81 (m, 2H), 7.9-7.74 (m, 2H), 7.52-7.4 7(m,2H),7.45-7.39(m,2H),7.36-7.31(m,1H),7.24-7.11(m,6H),4.05(s,2H),3.27(s,3H); 13 C NMR (101MHz, CDCl3): δ189.9,164.2,163.5,161.7,156.1,155.7,141.0,140.9,136.6,133.8,133.0,130.4,130.4,129.0,128.9,128.8,128. 4,128.1,127.8,127.4,127.1,127.1,126.7,126.2,125.0,124.7,124 .7,122.7,120.2,119.9,115.4,115.2,114.3,51.6,33.3; HRMS(ESI):C 30 H 22 FO4[M+H] + The calculated precise molecular weight is 465.1497, while the measured value is 465.1498.

[0130] Example 19

[0131] Preparation of tetrasubstituted furan compounds I-19

[0132] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), 4-bromo-3-methylbenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the target product, methyl 5-benzyl-4-(4-bromo-3-methylbenzoyl)-2-(naphth-2-yl)furan-3-carboxylic acid ester I-19 (52.8 mg, yield 98%), with the following chemical structure:

[0133]

[0134] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ8.47(d,J=1.9Hz,1H),7.92(ddd,J=12.4,6.5,2.1Hz,2H),7.87-7.81(m,2H),7.71(d,J=2.2Hz,1H ),7.61(d,J=8.3Hz,1H),7.52-7.49(m,3H),7.29-7.27(m,4H),7.23-7.21(m,1H),4.10(s,2H),3.39(s,3H),2.42(s,3H); 13 C NMR (101MHz, CDCl3): δ190.4,163.6,155.7,155.5,138.7,137.7,136.6,133.7,133.0,132.9,130.8,130.7,128.9,128 .9,128.8,128.2,128.1,127.8,127.7,127.3,127.0,126.7,126.2,124.9,122.9,114.4,51.7,33.3,23.0; HRMS(ESI):C 31 H 24 BrO4[M+H] + The calculated precise molecular weight is 539.0852, while the measured value is 539.0850.

[0135] Example 20

[0136] Preparation of tetrasubstituted furan compounds I-20

[0137] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), 2,4-dichlorobenzaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain the target product (4-benzoyl-2-benzyl-5-phenylfuran-3-yl)(2,4-dichlorophenyl) methyl ketone I-20 (46.0 mg, yield 90%), whose chemical structure is as follows:

[0138]

[0139] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ7.58 -7.55(m,2H),7.49-7.45(m,2H),7.43-7.38(m,1H),7.25-7.15(m,10H),7.08(s,1H),6.98(d,J=1.2Hz,2H),4.15(s,2H); 13 CNMR (101MHz, CDCl3): δ191.7,188.1,159.8,151.9,137.4,136.8,136.3,133.8,132.8,130.8,130. 1,129.3,129.2,128.9,128.9,128.8,128.7,127.2,127.1,126.6,124.1,120.6,33.8; HRMS(ESI):C 31 H 21 Cl2O3[M+H] + The calculated precise molecular weight is 511.0862, while the measured value is 511.0868.

[0140] Example 21

[0141] Preparation of tetrasubstituted furan compounds I-21

[0142] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), quinoline-6-carbaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst Potassium carbonate (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 15:1) to obtain the target product, methyl 5-benzyl-2-(naphth-2-yl)-4-(quinoline-6-carbonyl)furan-3-carboxylic acid ester I-21 (48.8 mg, yield 98%), with the following chemical structure:

[0143]

[0144] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ8.92(dd,J=4.4,1.7Hz,1H),8.42(d,J=1.7Hz,1H),8.17-8.08(m,4H),7.88(dd,J=8.6,1.8Hz,1H),7.84 -7.74(m,3H),7.45-7.41(m,2H),7.37(dd,J=8.3,4.2Hz,1H),7.22-7.15(m,4H),7.12-7.08(m,1H),4.07(s,2H),3.18(s,3H); 13 C NMR (101MHz, CDCl3): δ190.5,163.6,155.9,155.6,152.7,150.0,137.7,136.6,136.6,133.8,133.0,130.4,130.3,128.9,1 28.8,128.3,128.2,128.1,127.8,127.5,127.3,127.1,126.7,126.2,124.9,123.0,122.1,114.5,51.6,33.3; HRMS(ESI):C 33 H 23 NNaO4[M+Na] + The calculated precise molecular weight is 520.1519, while the measured value is 520.1525.

[0145] Example 22

[0146] Preparation of tetrasubstituted furan compounds I-22

[0147] Add enyne ketone to a dry, sealed tube (0.1 mmol, 1.0 equiv), 3-pyridinecarboxaldehyde (0.15 mmol, 1.5 equiv), nitrogen heterocyclic carbene catalyst (0.015 mmol, 15 mol%), potassium carbonate (0.1 mmol, 1.0 equiv), and ethyl acetate (2.0 mL) were reacted at room temperature for 3 hours. After the reaction, ethyl acetate was added to the reaction product and the mixture was filtered to obtain a primary filtrate and a filter cake. The filter cake was then washed three times with ethyl acetate to obtain a secondary filtrate. The primary and secondary filtrates were mixed and subjected to reduced pressure evaporation using a rotary evaporator to remove the solvent, yielding a crude product. Finally, the crude product was purified by rapid silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain the target product, methyl 5-benzyl-2-(naphth-2-yl)-4-nicotinylfuran-3-carboxylic acid ester I-22 (41.1 mg, yield 92%), with the following chemical structure:

[0148]

[0149] The relevant characterization analysis results are as follows: 1 H NMR (400MHz, CDCl3): δ8.95(d,J=2.2Hz,1H),8.69(dd,J=4.9,1.7Hz,1H),8.38(d,J=1.7Hz,1H),8.03-8.00(m,1H),7.86-7.82(m,2H ),7.80-7.75(m,2H),7.46-7.40(m,2H),7.31(dd,J=8.0,4.8Hz,1H),7.23-7.17(m,4H),7.14-7.10(m,1H),4.06(s,2H),3.29(s,3H); 13 C NMR (101MHz, CDCl3): δ189.8,163.2,156.4,156.1,153.3,150.2,136.4,135.8,134.2,133.8,132.9,129.0,128. 9,128.9,128.6,128.1,127.8,127.4,127.1,126.7,126.1,125.1,123.6,122.4,114.0,51.7,33.3; HRMS(ESI):C 29 H 22 NO4[M+H] + The calculated precise molecular weight is 448.1543, while the measured value is 448.1544.

[0150] In summary, this invention provides tetrasubstituted furan compounds and their preparation method. Using conjugated enyneones and aldehydes as reactants, tetrasubstituted furan compounds are generated through a step-by-step reaction catalyzed by a nitrogen-containing heterocyclic carbene compound. The reaction conditions are mild, the reactants are inexpensive and readily available, and no toxic metals are introduced, making this a highly efficient, economical, and atom-utilizing preparation method. This method provides a new approach for the efficient synthesis of polysubstituted furans using small-molecule organic catalysis.

[0151] Finally, it should be noted that 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 preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A method for preparing tetrasubstituted furan compounds, characterized in that: The preparation method is as follows: Provide conjugated enynoids and ketones as shown in general formula A and aldehydes as shown in general formula B, respectively: The conjugated enynone compound, the aldehyde compound, the nitrogen heterocyclic carbene compound, the basic compound and the organic solvent are mixed, sealed and reacted at room temperature or 50°C for 3 to 24 hours. After the reaction is completed, the reaction product is subjected to crude extraction and purification in sequence to obtain the tetrasubstituted furan compound. Wherein, the R 1 It is any one of methyl, oxocyclohexyl, 3-methoxy-3-oxopropyl, phenyl, thiophene-2-yl, naphth-1-yl, or naphth-2-yl; the R 2 It is any one of acetyl, benzoyl, methoxyformyl, ethoxyformyl, or diethylaminoformyl; the R 3 It is any one of methyl, butyl, triisopropylsilyl or phenyl; the R 4 It is any one of phenyl, p-chlorophenyl, p-bromophenyl, p-phenylphenyl, m-fluorophenyl, 4-bromo-3-methylphenyl, 2,4-dichlorophenyl, quinoline-6-yl or 3-pyridyl; R 1 With R 2 The dashed line between them represents R. 1 and R 2 These can be independent substituents or linked together to form a ring; The nitrogen-containing heterocyclic carbene compound is any one of the following structural formulas: 、 ； The alkaline compound is potassium carbonate; The organic solvent is any one or more of ethyl acetate or 1,4-dioxane; The structure of the tetrasubstituted furan compound is shown in general formula I: 。 2. The preparation method according to claim 1, characterized in that: The molar ratio of the conjugated enynoids, aldehydes, nitrogen-containing heterocyclic carbene compounds and basic compounds is 1:1~2:0.1~0.2:1~2.

3. The preparation method according to claim 1, characterized in that: The specific process of crude extraction and purification is as follows: Ethyl acetate is added to the reaction product and filtered to obtain a primary filtrate and a filter cake; the filter cake is washed with ethyl acetate at least once to obtain a secondary filtrate; the primary filtrate and the secondary filtrate are mixed and subjected to reduced pressure treatment to remove the solvent to obtain a crude product; the crude product is purified by column chromatography.

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