A method for directly stringing together 2,5-diaryl furan by aryl phosphorus ylide one-pot method

Abstract

The application belongs to the technical field of catalytic synthesis of fine chemical products, and discloses a method for directly synthesizing 2,5-diaryl furan through one-pot cascade of aryl phosphorus ylide. The method directly synthesizes 2,5-diaryl furan through one-pot cascade of the following processes: photo-induced oxidative coupling of aryl phosphorus ylide, reduction of the generated by-product O=PPh3 mediated by enone, and Paal-Knorr cyclization catalyzed by the by-product HCl. The self-coupling, reduction and cyclization of aryl phosphorus ylide are realized through the one-pot cascade strategy, the alkaline, high temperature and multi-step separation operation are avoided, the by-product is used as a catalyst for the next reaction, and the atom economy and step economy are realized. The method has mild reaction conditions, high reaction yield and good application prospect.

Description

Technical Field

[0001] This invention relates to the field of catalytic synthesis technology for fine chemical products, specifically to a method for the direct tandem synthesis of 2,5-diarylfurans from arylphosphine ylide in a one-pot process. Background Technology

[0002] 2,5-Diarylfurans are common structural units in bioactive molecules and functional materials, and have attracted widespread attention over the years. Existing research has developed metal catalytic systems such as Cu, Zn, Pd, and Au complexes, as well as organocatalytic systems, to synthesize the furan skeleton. These methods have made some progress compared to traditional methods in terms of reaction conditions and functional group compatibility. However, in the field of organic synthesis, there is still an urgent need to develop new methods with readily available raw materials, mild reaction conditions, and simple operating procedures.

[0003] Serial reactions have flourished over the past few decades. In these reactions, the products of the upstream steps can often be used directly as starting materials for the downstream steps without further purification, thus significantly improving the atom economy. However, in most cascade reactions, the byproducts generated in each step are often discarded as waste, which greatly reduces the atom economy of the conversion process. If the byproducts of the upstream steps can be used as catalysts for the downstream steps without additional addition, the atom economy of cascade conversions will be greatly improved. To date, chemists have reported the application of this strategy in some synthetic methods. For example, indium species have been recycled through a sequential In(0)-promoted reduction of nitroaromatics and an In(III)-catalyzed azadiels-Alder reaction and Mannich reaction, where In(III) is a byproduct of the previous reaction. However, a method for the direct synthesis of 2,5-diarylfurans via a cascade reaction strategy has not yet been reported.

[0004] Phosphorus ylides are important organic synthons readily obtained from organohalides or alcohols. In recent years, visible light-induced catalysis has attracted significant attention due to its green and sustainable characteristics, and has become one of the key technologies in organic synthesis. 1,4-enediones can be conveniently prepared using light-promoted phosphorus ylide oxidation self-coupling reactions. However, a direct one-pot tandem synthesis of 2,5-diarylfurans from phosphorus ylides, via photocatalytic aryl phosphorus ylide oxidation self-coupling, the resulting byproduct O=PPh3 mediating the reduction of the enone, and the byproduct HCl catalyzing Paal-Knorr cyclization in the reduction step, has not yet been reported.

[0005] In summary, the study of multi-component transformations involving photoinduced self-coupling, reduction, and cyclization of phosphorus ylides via tandem transformation is an important research area in synthetic chemistry. Among these, the tandem transformation of carbonyl-stabilized phosphorus ylides through self-coupling, reduction, and cyclization to obtain the corresponding 2,5-diarylfurans is a problem that urgently needs to be solved. Summary of the Invention

[0006] To address the technical problem of existing methods failing to achieve the tandem transformation of photoinduced phosphorus ylide self-coupling, reduction, and cyclization in a one-pot tandem synthesis of 2,5-diaryl-substituted furans, this invention provides a method for the direct tandem synthesis of 2,5-diaryl furans from aryl phosphorus ylides in a one-pot tandem process. This invention achieves self-coupling, reduction, and cyclization of aryl phosphorus ylides through a one-pot tandem strategy, avoiding the need for alkali, high temperatures, and multi-step separation operations. Byproducts serve as catalysts for subsequent reactions, achieving both atom economy and step economy. This method features mild reaction conditions, high reaction yields, and shows great promise for application.

[0007] In this invention, arylphosphine ylide substrates, photosensitizers, and organic solvents are mixed and added to a reaction tube. The arylphosphine ylide self-coupling is then carried out under visible light irradiation in air. After the reaction is complete, a reducing agent is added to reduce the enone. Once the conversion is complete, an additive is added to complete the cascade cyclization process, directly yielding 2,5-diarylfuran. This method utilizes photocatalytic oxidative coupling of arylphosphine ylides, with the generated byproduct O=PPh3 mediating the enone reduction, and the byproduct HCl catalyzing the Paal-Knorr cyclization cascade pathway, enabling a more gentle and efficient direct synthesis of 2,5-diarylfuran.

[0008] To achieve the above objectives, the present invention provides a method for synthesizing 2,5-diarylfuran, using aryl phosphorus ylidene shown in Formula I as a substrate, and sequentially preparing 2,5-diarylfuran shown in Formula II through a three-step tandem reaction: ; Wherein, R is selected from any one of methyl, methoxy, methylthio, halogen substituents (fluorine, chlorine, bromine), and trifluoromethyl; Ar is selected from substituted or unsubstituted C6-C20 aryl groups; The three-step cascade reaction includes: (1) Photocatalytic oxidative coupling step: Under an oxygen-containing atmosphere, the substrate arylphosphine ylide, photosensitizer and organic solvent are mixed and added to the reaction vessel. The reaction is carried out under visible light irradiation to generate 1,4-enedione and the byproduct triphenylphosphine oxide. (2) Conjugate reduction step: Add a reducing agent to the reaction system of step (1), and use the byproduct triphenylphosphine oxide generated in step (1) as a catalyst to carry out a 1,4-conjugate reduction reaction of 1,4-enedione to generate a 1,4-dione intermediate, and at the same time generate the byproduct hydrogen chloride. (3) Cycling reaction step: Additives are added dropwise to the reaction system of step (2), and hydrogen chloride generated in step (2) is used as a catalyst to cause the 1,4-diketone intermediate to undergo Paal-Knorr cyclization reaction to obtain 2,5-diarylfuran.

[0009] Furthermore, the photosensitizer is cobalt porphyrin, preferably Co(TPP).

[0010] Furthermore, the molar amount of the porphyrin cobalt is 0.1 mol%-0.2 mol% of the molar amount of arylphosphine ylide.

[0011] Furthermore, the organic solvent is dichloromethane or dichloroethane. Even further, 5-10 L of organic solvent is added for every 1 mol of the substrate arylphosphine ylide.

[0012] Furthermore, the wavelength of the visible light is 515 nm-520 nm, and the light intensity is generally 50 mW / cm²-100 mW / cm².

[0013] Furthermore, the temperature of the oxidative self-coupling reaction is room temperature, generally 25℃-30℃, and the reaction time is 1.5h-2h.

[0014] Furthermore, the reducing agent is trichlorosilane.

[0015] Furthermore, the molar amount of the trichlorosilane is 1-3 times, preferably 2 times, the molar amount of the arylphosphine ylide.

[0016] Furthermore, the reduction reaction is carried out at room temperature, typically 25°C-30°C, and the reaction endpoint is determined by thin-layer chromatography.

[0017] Furthermore, the additive is methanol, and adding a small amount of methanol promotes the generation of HCl.

[0018] Furthermore, the molar amount of methanol is 1 mol%-5 mol% of the molar amount of arylphosphine ylide.

[0019] Furthermore, the atmospheric condition is air.

[0020] Furthermore, the yield of the 2,5-diarylfuran is 50%-91%.

[0021] Furthermore, the three-step tandem reaction does not require the separation of intermediates, and the byproducts generated in the previous step are directly used as catalysts for the next step, thus realizing a one-pot tandem reaction.

[0022] Compared with the prior art, the present invention has at least the following beneficial effects: (1) This invention realizes the three-step tandem transformation of photoinduced phosphorus ylide oxidation self-coupling, byproduct triphenylphosphine oxide (O=PPh3) mediated ketene reduction, and byproduct hydrogen chloride catalyzed Paal-Knorr cyclization, successfully solving the technical problem that existing methods cannot complete the above-mentioned photoinduced self-coupling, reduction and cyclization tandem process in the same system.

[0023] (2) Compared with known methods, the present invention uses photocatalytic conditions, and the reaction process is mild (room temperature, visible light), avoiding the strong base, high temperature or multi-step separation operations that may be required in traditional synthesis, which greatly improves the functional group compatibility and operational safety. At the same time, the present invention makes full use of O=PPh3 and hydrogen chloride generated by the reaction itself as catalysts, achieving high atom economy and step economy, and reducing by-product emissions.

[0024] In summary, this invention provides an efficient and simple one-pot synthesis route that can directly obtain 2,5-diarylfuran, and has excellent process economy and large-scale application prospects. Attached Figure Description

[0025] Figure 1 The hydrogen spectrum of 2,5-diphenylfuran obtained in Example 1; Figure 2 The carbon spectrum of 2,5-diphenylfuran obtained in Example 1; Figure 3 The hydrogen spectrum of 2,5-di-p-methylphenylfuran obtained in Example 2; Figure 4 The carbon spectrum of 2,5-di-p-methylphenylfuran obtained in Example 2; Figure 5 The hydrogen spectrum of 2,5-di-p-methylthiophenylfuran obtained in Example 3; Figure 6 The carbon spectrum of 2,5-di-p-methylthiophenylfuran obtained in Example 3; Figure 7 The hydrogen spectrum of 2,5-di-p-fluorophenylfuran obtained in Example 4; Figure 8 The carbon spectrum of 2,5-di-p-fluorophenylfuran obtained in Example 4; Figure 9 The fluorine spectrum of 2,5-di-p-fluorophenylfuran obtained in Example 4; Figure 10The hydrogen spectrum of 2,5-di-2,5-dimethoxyphenylfuran obtained in Example 5; Figure 11 The carbon spectrum of 2,5-di-2,5-dimethoxyphenylfuran obtained in Example 5; Figure 12 The hydrogen spectrum of 2,5-di-2-chlorophenylfuran obtained in Example 6; Figure 13 The carbon spectrum of 2,5-di-2-chlorophenylfuran obtained in Example 6; Figure 14 The hydrogen spectrum of 2,5-bis(2-naphthyl)furan obtained in Example 7; Figure 15 The carbon spectrum of 2,5-bis(2-naphthyl)furan obtained in Example 7; Figure 16 The hydrogen spectrum of 2,5-bis-4-trifluoromethylphenylfuran obtained in Example 8; Figure 17 The carbon spectrum of 2,5-bis-4-trifluoromethylphenylfuran obtained in Example 8; Figure 18 The fluorine spectrum of 2,5-bis-4-trifluoromethylphenylfuran obtained in Example 8; Figure 19 The hydrogen spectrum of 2,5-di-p-bromophenylfuran obtained in Example 9; Figure 20 The carbon spectrum of 2,5-di-p-bromophenylfuran obtained in Example 9; Figure 21 This is a schematic diagram of a preferred embodiment of the present invention, showing a method for directly synthesizing 2,5-diarylfuran by a one-pot tandem synthesis of arylphosphine ylide. Detailed Implementation

[0026] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0027] According to one embodiment of the present invention, a one-pot multi-component transformation direct synthesis of 2,5-diarylfuran via arylphosphine ylide self-coupling, reduction, and cyclization is provided, as follows: Under air or other oxygen-containing atmosphere conditions, the substrate arylphosphine ylide, photosensitizer, and organic solvent are mixed and added to a reaction tube. The arylphosphine ylide is self-coupled under visible light irradiation, followed by reduction by adding a reducing agent. Finally, an additive is added dropwise to carry out a cascade process of cyclization, generating the 2,5-diarylfuran product in a one-pot manner.

[0028] In some embodiments, the photosensitizer is cobalt porphyrin, and the amount of cobalt porphyrin is 0.1 mol%-0.2 mol% of the amount of phosphorus ylide, and the main solvent is dichloromethane or dichloroethane.

[0029] In some embodiments, the phosphorus ylide self-coupling reaction is carried out under air conditions.

[0030] In some embodiments, the reducing agent is trichlorosilane, and the amount used is 1-3 times that of arylphosphine ylidemolar, preferably 2 times.

[0031] In some embodiments, the additive is methanol.

[0032] In some embodiments, the general structural formula of the phosphorus ylide is further as follows: R is selected from any one of methyl, methoxy, methylthio, halogen substituents (fluorine, chlorine, bromine), cyano or trifluoromethyl.

[0033] In some embodiments, the apparatus used for this tandem reaction is a sealable glass or quartz reactor.

[0034] The embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. It should be understood that the following embodiments are for illustrative purposes only and are not intended to limit the invention. For those skilled in the art, other equivalent embodiments based on the present invention can be obtained without creative effort, and all such embodiments should be considered to fall within the protection scope of the present invention.

[0035] Unless otherwise specified, all raw materials used in the following examples are publicly available in the prior art, such as those that can be directly purchased or prepared according to publicly available methods. Dichloromethane in the examples is a commercially available analytical grade solvent; other reagents and solvents are commercially available without further purification. All phosphorus ylide coupling reactions were carried out in an oxygen atmosphere, and reduction and cyclization were carried out in air. Nuclear magnetic resonance (NMR) spectra were determined using a Bruker Avance-400 spectrometer in the specified solvents; chemical shifts are reported in ppm. 1 The H spectrum was defined with the TMS resonance peak at 0.00 ppm or the CHCl3 resonance peak in CDCl3 at 7.26 ppm as a reference. 13The C-spectrum was referenced with the CDCl3 resonance peak set at 77.00 ppm. Coupling constants were reported in Hertz (Hz), and peak splitting modes were labeled as: s (single), d (double), t (triple), q (quartet), and m (multiple).

[0036] This invention provides a tandem reaction system for the one-pot synthesis of 2,5-diarylfuran via photoinduced arylphosphine ylide self-coupling, reduction, and cyclization. The system uses cobalt porphyrin as a photocatalyst, trichlorosilane as a reducing agent, and methanol as an additive to efficiently synthesize 2,5-diarylfuran.

[0037] This method can be performed as follows: (1) First add solid reagents into the glass tube, such as cobalt porphyrin or solid arylphosphine ylide raw materials; (2) Add dichloromethane or dichloroethane as solvent under air conditions, and seal; (3) Irradiate with green light with a wavelength of 515 nm-520 nm for 1.5-2 h; (4) After the arylphosphine ylide self-coupling reaction is complete, trichlorosilane reducing agent is added and the mixture is stirred under air to carry out reduction. (5) After the reduction reaction is complete, methanol is added dropwise to promote the cyclization reaction; (6) After the reaction is complete, the solvent is removed by vacuum distillation, and the product is obtained by column chromatography.

[0038] Preparation Example 1 The method for synthesizing phosphorus ylide is as follows: ketone ( R is selected from any one of methyl, methoxy, methylthio, halogen substituent, and trifluoromethyl; purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (1.0 equivalent) was dissolved in a mixed solvent of distilled CHCl3 and EtOAc (volume ratio 1:1, ketone concentration 1.25 M). CuBr2 (1.1 equivalent) was added at room temperature under nitrogen protection, and the mixture was then heated to reflux for 20 minutes. Distilled EtOH (volume fraction 50%) was added to the reaction system, and reflux was continued for 2 hours. The reaction suspension was then filtered while hot, and the residue was washed with a mixed solvent of CHCl3 and EtOAc (volume ratio 1:1). The organic phases were combined and washed with water until neutral. The organic phase was removed by vacuum distillation to obtain the crude α-bromocarbonyl compound. To a toluene solution (0.30 M) of the obtained α-bromocarbonyl compound (1.0 equivalent), distilled Et3N (0.1 equivalent) was added, followed by a toluene solution of PPh3 (1.0 equivalent) with stirring. The reaction mixture was stirred at room temperature, and TLC was monitored until the carbonyl compound was completely consumed. The reaction mixture was filtered, and the precipitate was washed with Et2O to obtain crude phosphonium salt. Subsequently, the crude phosphonium salt was added to a mixed solvent of water and methanol (1:1, 0.25 M, v / v), stirred at room temperature for 1 hour, and then the pH was adjusted to 7–8 with 2 mol / L NaOH aqueous solution, and stirred vigorously for 2–3 hours. The suspension was rapidly filtered, and the precipitate was washed with water and dried to obtain the phosphorus ylide substrate.

[0039] Example 1: Synthesis of 2,5-diphenylfuran from benzoylmethylene triphenylphosphine First, prepare the Co(TPP) solution: Dissolve 3.4 mg of Co(TPP) in 10 mL of dichloromethane (DCM) to obtain a concentration of 5 × 10⁻⁶. -4 A solution of mol / L was prepared. Then, benzoylmethylenetriphenylphosphine (0.20 mmol, 1 equivalent) was added to a Schlenk tube equipped with a magnetic stir bar. Next, 10 μL of the above Co(TPP) solution (volume 2.5 × 10⁻⁶) was injected sequentially into the reaction tube using a 10 μL microsyringe. -32 mL of DCM was injected using a standard syringe. The reaction mixture was placed in a Wattecs parallel light reactor and stirred under a green (515-520 nm) LED light source at room temperature. After stirring for 1.5-2 hours, once the reaction was complete, HSiCl3 (27.1 mg, 20 μL, 0.2 mmol) was added in one go, and the reaction mixture was stirred vigorously. After confirming the complete conversion of the intermediate enone by TLC, methanol was added dropwise to the mixture, and vigorous stirring was continued to promote the conversion of the intermediate 1,4-dione to the furan product. The solvent was then removed under reduced pressure, and the residue was directly separated by rapid column chromatography using petroleum ether / ethyl acetate as eluent to obtain 17.2 mg of 2,5-diphenylfuran 2a, with a reaction yield of 78%. The structural formula of product 2a is shown below: like Figure 1 The proton NMR spectrum of product 2a is shown below: 1 H NMR (400 MHz, CDCl3) δ 7.72–7.60 (m, 4H),7.31 (t, J = 7.6 Hz, 4H), 7.17 (dd, J = 14.8 (7.2 Hz, 2H), 6.64 (s, 2H). Wherein the chemical shift (unit: ppm) 1 H NMR (400 MHz, Chloroform- d ) δ7.72–7.60 (m, 4H), 7.31 (t, J = 7.6 Hz, 4H), 7.17 (dd, J = 14.8, 7.2 Hz, 2H) represents the hydrogen atoms in the benzene ring of the structure, and 6.64 (s, 2H) represents the hydrogen atoms in the furan ring double bond.

[0040] like Figure 2 The carbon spectrum of product 2a is shown below: 13 C NMR (100 MHz, CDCl3) δ 153.3 (2C), 130.8 (2C), 128.7 (4C), 127.3 (2C), 123.7 (4C), 107.2 (2C). Among them, the chemical shifts (unit: ppm) δ153.3 (2C) are quaternary carbons of the furan ring, 130.8 (2C), 128.7 (4C), 127.3 (2C), 123.7 (4C) are carbons of the benzene ring, and 107.2 (2C) is a carbon of the furan ring double bond.

[0041] Example 2: Synthesis of 2,5-di-p-methylphenylfuran from p-methylbenzoylmethylenetriphenylphosphine First, prepare the Co(TPP) solution: Dissolve 3.4 mg of Co(TPP) in 10 mL of dichloromethane (DCM) to obtain a concentration of 5 × 10⁻⁶. -4 A solution of mol / L was prepared. Then, 0.20 mmol (1 equivalent) of p-methylbenzoylmethylenetriphenylphosphine was added to a Schlenk tube equipped with a magnetic stir bar. Next, 10 μL of the above Co(TPP) solution (volume 2.5 × 10⁻⁶) was injected sequentially into the reaction tube using a 10 μL microsyringe. -3 2 mL of DCM was injected using a standard syringe. The reaction mixture was placed in a Wattecs parallel light reactor and stirred under a green (515-520 nm) LED light source at room temperature. After stirring for 1.5-2 hours, once the reaction was complete, HSiCl3 (27.1 mg, 20 μL, 0.2 mmol) was added in one go, and the reaction mixture was stirred vigorously. After confirming complete conversion of the intermediate enone by TLC, 80 μL of methanol was added to the mixture, and vigorous stirring was continued to promote the conversion of the intermediate 1,4-dione to the furan product. The solvent was then removed under reduced pressure, and the residue was directly separated by rapid column chromatography using petroleum ether / ethyl acetate as eluent to obtain 22.4 mg of 2,5-di-p-methylphenylfuran 2b, with a reaction yield of 90%. The structural formula of product 2b is shown below: like Figure 3 The proton NMR spectrum of product 2b is shown below: 1 H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.4 Hz, 4H), 7.12 (d, J = 8.4 Hz (4H), 6.58 (s, 2H), 2.29 (s, 6H). Wherein chemical shifts (unit: ppm) 1 H NMR (400 MHz, Chloroform- d ) δ 7.55 (d, J = 8.4 Hz, 4H), 7.12 (d, J = 8.4 Hz, 4H) is the hydrogen atom of the benzene ring in the structure, 6.58 (s, 2H) is the hydrogen atom of the furan ring double bond, and 2.29 (s, 6H) is the hydrogen atom of the methyl ring.

[0042] like Figure 4 The carbon spectrum of product 2b is shown below: 13C NMR (100 MHz, CDCl3) δ 153.2 (2C), 137.0 (2C), 129.4 (4C), 128.2 (2C), 123.6 (4C), 106.4 (2C), 21.3 (2C). Chemical shifts (in ppm): δ 153.2 (2C) represents the quaternary carbon of the furan ring, 137.0 (2C), 129.4 (4C), 128.2 (2C), and 123.6 (4C) represent carbons in the benzene ring, 106.4 (2C) represents the carbon of the furan ring double bond, and 21.3 (2C) represents the methyl carbon.

[0043] Example 3: Synthesis of 2,5-di-p-methylthiophenylfuran from p-methylthiobenzoylmethylenetriphenylphosphine First, prepare the Co(TPP) solution: Dissolve 3.4 mg of Co(TPP) in 10 mL of dichloromethane (DCM) to obtain a concentration of 5 × 10⁻⁶. -4 A solution of mol / L was prepared. Then, 0.20 mmol (1 equivalent) of p-methylthiobenzoylmethylenetriphenylphosphine was added to a Schlenk tube equipped with a magnetic stir bar. Next, 10 μL of the above Co(TPP) solution (volume of 2.5 × 10⁻⁶) was injected sequentially into the reaction tube using a 10 μL microsyringe. -3 2 mL of DCM was injected using a standard syringe. The reaction mixture was placed in a Wattecs parallel light reactor and stirred under a green (515-520 nm) LED light source at room temperature. After stirring for 1.5-2 hours, once the reaction was complete, HSiCl3 (27.1 mg, 20 μL, 0.2 mmol) was added in one go, and the reaction mixture was stirred vigorously. After confirming complete conversion of the intermediate enone by TLC, 80 μL of methanol was added to the mixture, and vigorous stirring was continued to promote the conversion of the intermediate 1,4-dione to the furan product. The solvent was then removed under reduced pressure, and the residue was directly separated by rapid column chromatography using petroleum ether / ethyl acetate as eluent to obtain 25.1 mg of 2,5-di-p-methylthiophenylfuran 2c, with a reaction yield of 80%. The structural formula of product 2c is shown below: like Figure 5 The hydrogen spectrum of product 2c is shown below: 1 H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.4 Hz, 4H), 7.21 (d, J = 8.4 Hz, 4H), 6.61 (s, 2H), 2.44 (s, 6H). Wherein chemical shifts (unit: ppm)1 H NMR (400 MHz, Chloroform- d 7.57 (d, J = 8.4 Hz, 4H), 7.21 (d, J = 8.4 Hz, 4H) is the hydrogen atom of the benzene ring in the structure, 6.61 (s, 2H) is the hydrogen atom of the furan ring double bond, and 2.44 (s, 6H) is the hydrogen atom of the thiomethyl ring.

[0044] like Figure 6 The carbon spectrum of product 2c is shown below: 13 C NMR (100 MHz, CDCl3) δ 152.9 (2C), 137.6 (2C), 127.7 (2C), 126.8 (4C), 124.1 (4C), 107.0 (2C), 15.9 (2C). Chemical shifts (in ppm): 152.9 (2C) represents the quaternary carbon of the furan ring; 137.6 (2C), 127.7 (2C), 126.8 (4C), and 124.1 (4C) represent carbons in the benzene ring; 107.0 (2C) represents the carbon of the furan ring double bond; and 15.9 (2C) represents the carbon of the furan ring double bond. Example 4: Synthesis of 2,5-di-p-fluorophenylfuran from p-fluorobenzoylmethylenetriphenylphosphine First, prepare the Co(TPP) solution: Dissolve 3.4 mg of Co(TPP) in 10 mL of dichloromethane (DCM) to obtain a concentration of 5 × 10⁻⁶. -4 A solution of mol / L was prepared. Then, p-fluorobenzoylmethylenetriphenylphosphine (0.20 mmol, 1 equivalent) was added to a Schlenk tube equipped with a magnetic stir bar. Next, 10 μL of the above Co(TPP) solution (volume 2.5 × 10⁻⁶) was sequentially injected into the reaction tube using a 10 μL microsyringe. -3 2 mL of DCM was injected using a standard syringe. The reaction mixture was placed in a Wattecs parallel light reactor and stirred under a green (515-520 nm) LED light source at room temperature. After stirring for 1.5-2 hours, once the reaction was complete, HSiCl3 (27.1 mg, 20 μL, 0.2 mmol) was added in one go, and the reaction mixture was stirred vigorously. After TLC monitoring confirmed complete conversion of the intermediate enone, 80 μL of methanol was added to the mixture, and vigorous stirring was continued to promote the conversion of the intermediate 1,4-dione to the furan product. The solvent was then removed under reduced pressure, and the residue was directly separated by rapid column chromatography using petroleum ether / ethyl acetate as eluent to obtain 16.5 mg of 2,5-di-p-fluorophenylfuran 2d, with a reaction yield of 66%. The structural formula of product 2d is shown below: like Figure 7 The 1H NMR spectrum of the product at 2d is shown below: 1 H NMR (400 MHz, CDCl3) δ 7.61 (dd, J = 8.8, 5.6 Hz, 4H), 7.02 (t, J = 8.8 Hz (4H), 6.57 (s, 2H). Wherein chemical shift (unit: ppm) 1 HNMR (400 MHz, Chloroform- d ) δ 7.61 (dd, J = 8.8, 5.6 Hz, 4H), 7.02 (t, J = 8.8 Hz, 4H) represents the hydrogen atom in the benzene ring in the structure, and 6.57 (s, 2H) represents the hydrogen atom in the furan ring double bond.

[0045] like Figure 8 The carbon spectrum of the product at 2d is shown below: 13 C NMR (100 MHz, CDCl3) δ 162.2 (d, 1 J C-F =245.7 Hz, 2C), 152.6 (2C), 127.1 (d, J = 3.4 Hz, 2C), 125.4 (d, 3 J C-F = 8.0 Hz, 4C), 115.8 (d, 2 J C-F = 22.0 Hz, 4C), 106.9 (2C). The chemical shift (unit: ppm) δ152.6 (2C) is 162.2 (d, ) of the furan ring quaternary carbon. 1 J C-F = 245.7 Hz, 2C), 127.1 (d, J = 3.4 Hz, 2C), 125.4(d, 3 J C-F = 8.0 Hz, 4C), 115.8 (d, 2 J C-F = 22.0 Hz, 4C) is carbon in the benzene ring region, 106.9 (2C) is carbon in the furan ring double bond.

[0046] like Figure 9 The fluorine spectrum of the product at 2d is shown below: 19 F NMR (376 MHz, CDCl3) δ -114.08. Example 5: Synthesis of 2,5-di-2,5-dimethoxyphenylfuran from 2,5-dimethoxybenzoylmethylenetriphenylphosphine First, prepare the Co(TPP) solution: Dissolve 3.4 mg of Co(TPP) in 10 mL of dichloromethane (DCM) to obtain a concentration of 5 × 10⁻⁶. -4 A solution of mol / L was prepared. Then, 0.20 mmol (1 equivalent) of 2,5-methoxybenzoylmethylenetriphenylphosphine was added to a Schlenk tube equipped with a magnetic stir bar. Next, 10 μL of the above Co(TPP) solution (volume of 2.5 × 10⁻⁶) was injected sequentially into the reaction tube using a 10 μL microsyringe. -3 2 mL of DCM was injected using a standard syringe. The reaction mixture was placed in a Wattecs parallel light reactor and stirred under a green (515-520 nm) LED light source at room temperature. After stirring for 1.5-2 hours, once the reaction was complete, HSiCl3 (27.1 mg, 20 μL, 0.2 mmol) was added in one go, and the reaction mixture was stirred vigorously. After confirming complete conversion of the intermediate enone by TLC, 80 μL of methanol was added to the mixture, and vigorous stirring was continued to promote the conversion of the intermediate 1,4-dione to the furan product. The solvent was then removed under reduced pressure, and the residue was directly separated by rapid column chromatography using petroleum ether / ethyl acetate as eluent to obtain 27.5 mg of 2,5-di-2,5-dimethoxyphenylfuran 2e, with a reaction yield of 81%. The structural formula of product 2e is shown below: like Figure 10 The hydrogen spectrum of product 2e is shown below: 1 H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 3.2Hz, 2H), 6.99 (s, 2H), 6.81 (d, J = 8.8 Hz, 2H), 6.70 (dd, J = 8.8 (2.8 Hz, 2H), 3.83 (s, 6H), 3.77 (s, 6H). Wherein chemical shifts (unit: ppm) 1 H NMR (400 MHz, Chloroform- d ) δ7.46 (d, J= 3.2 Hz, 2H), 6.81 (d, J = 8.8 Hz, 2H), 6.70 (dd, J =8.8, 2.8 Hz, 2H) are hydrogen atoms in the benzene ring in the structure, 6.99 (s, 2H) are hydrogen atoms in the furan ring double bond, and 3.83 (s, 6H) and 3.77 (s, 6H) are hydrogen atoms in the methoxy ring.

[0047] like Figure 11 The carbon spectrum of product 2e is shown below: 13 C NMR (100 MHz, CDCl3) δ 153.7 (2C), 150.1 (2C), 148.6 (2C), 120.6 (2C), 112.8 (2C), 112.7 (2C), 112.2 (2C), 111.6 (2C), 56.0 (2C), 55.8 (2C). The chemical shifts (in ppm) are as follows: δ153.7 (2C) represents the quaternary carbon of the furan ring; 150.1 (2C), 148.6 (2C), 120.6 (2C), 112.8 (2C), 112.7 (2C), and 112.2 (2C) represent carbons in the benzene ring; 111.6 (2C) represents the carbon of the furan ring double bond; and 56.0 (2C) and 55.8 (2C) represent methoxy carbons.

[0048] Example 6: Synthesis of 2,5-di-2-chlorophenylfuran from 2-chlorobenzoylmethylenetriphenylphosphine First, prepare the Co(TPP) solution: Dissolve 3.4 mg of Co(TPP) in 10 mL of dichloromethane (DCM) to obtain a concentration of 5 × 10⁻⁶. -4 A solution of mol / L was prepared. Then, 0.20 mmol (1 equivalent) of 2-chlorobenzoylmethylenetriphenylphosphine was added to a Schlenk tube equipped with a magnetic stir bar. Next, 10 μL of the above Co(TPP) solution (volume 2.5 × 10⁻⁶) was injected sequentially into the reaction tube using a 10 μL microsyringe. -32 mL of DCM was injected using a standard syringe. The reaction mixture was placed in a Wattecs parallel light reactor and stirred under a green (515-520 nm) LED light source at room temperature. After stirring for 1.5-2 hours, once the reaction was complete, HSiCl3 (27.1 mg, 20 μL, 0.2 mmol) was added in one go, and the reaction mixture was stirred vigorously. After confirming complete conversion of the intermediate enone by TLC, 80 μL of methanol was added to the mixture, and vigorous stirring was continued to promote the conversion of the intermediate 1,4-dione to the furan product. The solvent was then removed under reduced pressure, and the residue was directly separated by rapid column chromatography using petroleum ether / ethyl acetate as eluent to obtain 17.5 mg of 2,5-di-2-chlorophenylfuran 2f, with a reaction yield of 61%. The structural formula of product 2f is shown below: like Figure 12 The hydrogen spectrum of product 2f is shown below: 1 H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 7.6Hz, 4H), 7.39 (d, J = 8.0 Hz, 2H), 7.28 (t, J = 7.6 Hz, 2H), 7.20-7.12 (m, 4H). Wherein chemical shift (unit: ppm) 1 H NMR (400 MHz, Chloroform- d 7.90 (d, J = 7.6 Hz, 4H), 7.39 (d, J = 8.0 Hz, 2H), 7.28 (t, J = 7.6 Hz, 2H), 7.20-7.12 (m, 2H) are hydrogen atoms in the benzene ring in the structure, and 7.20-7.12 (m, 2H) are hydrogen atoms in the furan double bond.

[0049] like Figure 13 The carbon spectrum of product 2f is shown below: 13C NMR (100 MHz, CDCl3) δ 149.7 (2C), 130.8 (2C), 130.3 (2C), 128.9 (2C), 128.3 (2C), 128.0 (2C), 126.9 (2C), 113.0 (2C). Among them, the chemical shifts (unit: ppm) δ 149.7 (2C) are quaternary carbons of the furan ring, 130.8 (2C), 130.3 (2C), 128.9 (2C), 128.3 (2C), 128.0 (2C), 126.9 (2C) are carbons in the benzene ring, and 113.0 (2C) is a carbon in the furan ring double bond.

[0050] Example 7: Synthesis of 2,5-di(2-naphthyl)furan from naphthylmethylenetriphenylphosphine First, prepare the Co(TPP) solution: Dissolve 3.4 mg of Co(TPP) in 10 mL of dichloromethane (DCM) to obtain a concentration of 5 × 10⁻⁶. -4 A solution of mol / L was prepared. Then, naphthylmethylenetriphenylphosphine (0.20 mmol, 1 equivalent) was added to a Schlenk tube equipped with a magnetic stir bar. Next, 10 μL of the above Co(TPP) solution (volume 2.5 × 10⁻⁶) was injected sequentially into the reaction tube using a 10 μL microsyringe. -3 2 mL of DCM was injected using a standard syringe. The reaction mixture was placed in a Wattecs parallel light reactor and stirred under a green (515-520 nm) LED light source at room temperature. After stirring for 1.5-2 hours, once the reaction was complete, HSiCl3 (27.1 mg, 20 μL, 0.2 mmol) was added in one go, and the reaction mixture was stirred vigorously. After confirming complete conversion of the intermediate enone by TLC, 80 μL of methanol was added to the mixture, and vigorous stirring was continued to promote the conversion of the intermediate 1,4-dione to the furan product. The solvent was then removed under reduced pressure, and the residue was directly separated by rapid column chromatography using petroleum ether / ethyl acetate as eluent to obtain 2 g of 2,5-bis(2-naphthyl)furan (total yield 15.9 mg), with a reaction yield of 50%. The structural formula of the 2 g product is shown below: like Figure 14 The hydrogen spectrum of 2g of product is shown below: 1 H NMR (400 MHz, CDCl3) δ 8.21 (s, 2H),7.92–7.73 (m, 8H), 7.42 (dt, J= 14.8 (7.6 Hz, 4H), 6.84 (s, 2H). Wherein chemical shift (unit: ppm) 1 H NMR (400 MHz, Chloroform- d ) δ7.72–7.60 (m, 4H), 7.31 (t, J = 7.6Hz, 4H), 7.17 (dd, J = 14.8, 7.2 Hz, 2H) represents the hydrogen atoms in the benzene ring of the structure, and 6.64 (s, 2H) represents the hydrogen atoms in the furan ring double bond.

[0051] like Figure 15 The carbon spectrum of 2g of product is shown below: 13 C10 NMR (100 MHz, CDCl3) δ 153.8 (2C), 133.6 (2C), 132.8 (2C), 128.5 (2C), 128.2 (2C), 128.1 (2C), 127.8 (2C), 126.6 (2C), 125.9 (2C), 122.3 (2C), 122.1 (2C), 108.1 (2C). Chemical shifts (in ppm) δ 153.8 (2C) represents a furan ring quaternary carbon, 133.6 (2C), 132.8 (2C), 128.5 (2C), 128.2 (2C), 128.1 (2C), 127.8 (2C), 126.6 (2C), 125.9 (2C), 122.3 (2C), 108.1 (2C). (2C), 122.1 (2C) is a carbon in the benzene ring region, and 108.1 (2C) is a carbon in the furan ring double bond. Example 8: Synthesis of 2,5-di-4-trifluoromethylphenylfuran from 4-trifluoromethylbenzoylmethylenetriphenylphosphine First, prepare the Co(TPP) solution: Dissolve 3.4 mg of Co(TPP) in 10 mL of dichloromethane (DCM) to obtain a concentration of 5 × 10⁻⁶. -4 A solution of mol / L was prepared. Then, 0.20 mmol (1 equivalent) of 4-trifluoromethylbenzoylmethylenetriphenylphosphine was added to a Schlenk tube equipped with a magnetic stir bar. Next, 10 μL of the above Co(TPP) solution (volume 2.5 × 10⁻⁶) was injected sequentially into the reaction tube using a 10 μL microsyringe. -32 mL of DCM was injected using a standard syringe. The reaction mixture was placed in a Wattecs parallel light reactor and stirred under a green (515-520 nm) LED light source at room temperature. After stirring for 1.5-2 hours, once the reaction was complete, HSiCl3 (27.1 mg, 20 μL, 0.2 mmol) was added in one go, and the reaction mixture was stirred vigorously. After confirming complete conversion of the intermediate enone by TLC, 80 μL of methanol was added to the mixture, and vigorous stirring was continued to promote the conversion of the intermediate 1,4-dione to the furan product. The solvent was then removed under reduced pressure, and the residue was directly separated by rapid column chromatography using petroleum ether / ethyl acetate as eluent to obtain 19.6 mg of 2,5-bis-4-trifluoromethylphenylfuran 2h, with a reaction yield of 55%. The structural formula of the product 2h is shown below: like Figure 16 The 1H NMR spectrum of the product is shown below: 1 H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.4Hz, 4H), 7.59 (d, J = 8.0 Hz (4H), 6.81 (s, 2H). Wherein chemical shift (unit: ppm) 1 H NMR (400 MHz, Chloroform- d ) δ7.77 (d, J = 8.4 Hz, 4H), 7.59 (d, J = 8.0 Hz, 4H) represents the hydrogen atom in the benzene ring in the structure, and 6.81 (s, 2H) represents the hydrogen atom in the furan ring double bond.

[0052] like Figure 17 The carbon spectrum of the product after 2 hours is shown below: 13 C NMR (100 MHz, CDCl3) δ 152.9 (2C), 133.4(2C), 129.4 (d, 2 J C-F = 32.2 Hz, 2C), 125.8 (dt, 3 J C-F = 37.2, 18.6 Hz, 8C), 123.3(d, 1 J C-F= 116.3 Hz, 2C), 109.4 (2C). The chemical shifts (in ppm) δ152.9 (2C) are furan cyclic quaternary carbons, 33.4 (2C), 129.4 (d, 2 J C-F = 32.2 Hz, 2C), 125.8 (dt, 3 J C-F = 37.2, 18.6 Hz,8C), 123.3 (d, 1 J C-F = 116.3 Hz, 2C) is carbon in the benzene ring region, and 109.4 (2C) is carbon in the furan ring double bond.

[0053] like Figure 18 The fluorine spectrum of the product after 2 hours is shown below: 19 F NMR (376 MHz, CDCl3) δ -62.56. Example 9: Synthesis of 2,5-di-p-bromophenylfuran from 4-bromobenzoylmethylenetriphenylphosphine First, prepare the Co(TPP) solution: Dissolve 3.4 mg of Co(TPP) in 10 mL of dichloromethane (DCM) to obtain a concentration of 5 × 10⁻⁶. -4 A solution of mol / L was prepared. Then, 0.20 mmol (1 equivalent) of 4-bromobenzoylmethylenetriphenylphosphine was added to a Schlenk tube equipped with a magnetic stir bar. Next, 10 μL of the above Co(TPP) solution (volume of 2.5 × 10⁻⁶) was injected sequentially into the reaction tube using a 10 μL microsyringe. -3 2 mL of DCM was injected using a standard syringe. The reaction mixture was placed in a Wattecs parallel light reactor and stirred under a green (515-520 nm) LED light source at room temperature. After stirring for 1.5-2 hours, once the reaction was complete, HSiCl3 (27.1 mg, 20 μL, 0.2 mmol) was added in one go, and the reaction mixture was stirred vigorously. After confirming complete conversion of the intermediate enone by TLC, 80 μL of methanol was added to the mixture, and vigorous stirring was continued to promote the conversion of the intermediate 1,4-dione to the furan product. The solvent was then removed under reduced pressure, and the residue was directly separated by rapid column chromatography using petroleum ether / ethyl acetate as eluent to obtain 20.9 mg of 2,5-di-p-bromophenylfuran 2i, with a reaction yield of 55%. The structural formula of product 2i is shown below: like Figure 19As shown, the proton NMR spectrum of product 2i is: δ 7.52 (d, J = 8.0 Hz, 4H), 7.45 (d, J = 8.4 Hz (4H), 6.66 (s (2H)). Wherein the chemical shift (unit: ppm) 1 H NMR (400 MHz, Chloroform- d ) δ7.52 (d, J = 8.0 Hz, 4H), 7.45 (d, J = 8.4 Hz, 4H) represents the hydrogen atom in the benzene ring in the structure, and 6.66 (s, 2H) represents the hydrogen atom in the furan ring double bond.

[0054] like Figure 20 The carbon spectrum of product 2i is shown below: 13 C NMR (100 MHz, CDCl3) δ 152.7 (2C), 131.9 (4C), 129.4 (2C), 125.2 (4C), 121.3 (2C), 107.9 (2C). Among them, the chemical shifts (unit: ppm) δ152.7 (2C) are quaternary carbons of the furan ring, 131.9 (4C), 129.4 (2C), 125.2 (4C), 121.3 (2C) are carbons of the benzene ring, and 107.9 (2C) is a double bond carbon of the furan ring.

[0055] The above description is merely a preferred embodiment of the present invention, and the present invention is not limited to the above embodiments. It is understood that other improvements and variations that are directly derived or conceived by those skilled in the art without departing from the spirit and concept of the present invention should be considered to be included within the protection scope of the present invention.

Claims

1. A method for synthesizing 2,5-diarylfuran, characterized in that, Using arylphosphine ylides of Formula I as substrates, 2,5-diarylfurans of Formula II were prepared sequentially through a three-step tandem reaction: Wherein, R is selected from any one of methyl, methoxy, methylthio, halogen substituent, and trifluoromethyl; Ar is selected from substituted or unsubstituted C6-C20 aryl groups; The three-step cascade reaction includes: (1) Photocatalytic oxidative coupling step: Under an oxygen-containing atmosphere, the substrate arylphosphine ylide, photosensitizer and organic solvent are mixed and added to the reaction vessel. The reaction is carried out under visible light irradiation to generate 1,4-enedione and the byproduct triphenylphosphine oxide. (2) Conjugate reduction step: Add a reducing agent to the reaction system of step (1), and use the byproduct triphenylphosphine oxide generated in step (1) as a catalyst to carry out a 1,4-conjugate reduction reaction of 1,4-enedione to generate a 1,4-dione intermediate, and at the same time generate the byproduct hydrogen chloride. (3) Cycling reaction step: Additives are added dropwise to the reaction system of step (2), and hydrogen chloride generated in step (2) is used as a catalyst to cause the 1,4-diketone intermediate to undergo Paal-Knorr cyclization reaction to obtain 2,5-diarylfuran.

2. The method according to claim 1, characterized in that, In step (1), the photosensitizer is cobalt porphyrin, and the molar amount of cobalt porphyrin is 0.1 mol%-0.2 mol% of the molar amount of arylphosphine ylide.

3. The method according to claim 1, characterized in that, In step (1), the organic solvent is dichloromethane or dichloroethane; 5-10 L of organic solvent is added for every 1 mol of substrate arylphosphine ylide.

4. The method according to claim 1, characterized in that, In step (1), the wavelength of the visible light is 515 nm-520 nm.

5. The method according to claim 1, characterized in that, In step (1), the reaction time of the oxidative self-coupling reaction is 1.5h-2h.

6. The method according to claim 1, characterized in that, In step (2), the reducing agent is trichlorosilane, and the molar amount of trichlorosilane is 1-3 times the molar amount of arylphosphine ylide.

7. The method according to claim 1, characterized in that, In step (2), the endpoint of the reduction reaction is monitored by thin-layer chromatography.

8. The method according to claim 1, characterized in that, In step (3), the additive is methanol, and the molar amount of methanol is 1 mol%-5 mol% of the molar amount of arylphosphine ylidene.

9. The method according to claim 1, characterized in that, In step (3), the yield of the 2,5-diarylfuran is 50%-91%.

10. The method according to claim 1, characterized in that, The three-step tandem reaction does not require the separation of intermediates, and the byproducts generated in the previous step are directly used as catalysts for the next step, thus realizing a one-pot tandem reaction.

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