Method for synthesizing polysubstituted furan compound through ring opening of gem-difluorocyclopropane

Abstract

The invention discloses a method for synthesizing a polysubstituted furan compound through ring opening of gem-difluorocyclopropane, and belongs to the technical field of compound synthesis. The preparation method comprises the following steps: carrying out ring-opening defluorination-nucleophilic addition reaction on a gem-difluorocyclopropane compound, a carbonyl compound and a ligand in a solvent, and sequentially carrying out filtration, rotary evaporation and column chromatography after the reaction to obtain the polysubstituted furan compound. The method is simple and convenient to operate, the raw materials are easy to obtain, the reaction conditions are mild, the furan ring is efficiently constructed through the one-pot cascade reaction, and an efficient and practical new way is provided for synthesis of the polysubstituted furan compound.

Description

Technical Field

[0001] This invention belongs to the field of compound synthesis technology, and particularly relates to a method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane. Background Technology

[0002] Furans, as an important class of five-membered oxygen-containing heterocyclic structures, have molecular skeletons widely found in natural products, pharmaceutical active molecules, and organic functional materials. Among them, polysubstituted furans, due to their unique electronic structure characteristics and diverse biological activities, show significant application value in medicinal chemistry and materials science. However, the efficient and highly regioselective synthesis of these compounds still faces serious challenges.

[0003] Traditional synthetic methods, such as the Feist-Bénary reaction (route a), can directly construct furan rings, but they are heavily dependent on specific α-halocarbonyl and β-dicarbonyl substrates, and mainly generate furan derivatives with an acyl group at the 3-position (Ber. Dtsch.chem. Ges. 1911, 44, 489−493; Eur. J. Org. Chem. 2016, 2016, 5169−5179).

[0004] Route a:

[0005] ,

[0006] In route a, R 1 For substituted or unsubstituted aromatic or alkyl groups; R 2 For substituted or unsubstituted aromatic or alkyl groups; R 3 R is a hydrogen atom, a substituted or unsubstituted aromatic group or alkyl group; 4 It can be a substituted or unsubstituted aromatic group or alkyl group.

[0007] To obtain furans with other substitution modes, a multi-step strategy (route b) is usually required: the ketone is enolized and coupled with an α-haloketone to give a 1,4-diketone, followed by dehydration and cyclization via the Paal-Knorr reaction (J. Org. Chem. 1995, 60, 301-307; Eur. J. Med. Chem. 2018, 148, 86-94). However, this reaction is not suitable for acid-sensitive substrates.

[0008] Route b:

[0009] ,

[0010] In route b, R 1 For substituted or unsubstituted aromatic or alkyl groups; R 2For substituted or unsubstituted aromatic or alkyl groups; R 3 For substituted or unsubstituted aromatic or alkyl groups; R 4 It can be a substituted or unsubstituted aromatic group or alkyl group.

[0011] To overcome the limitations of traditional methods, transition metal catalysis strategies have emerged. Among them, gold-catalyzed cycloisomerization reactions (route c) and other methods have made significant progress in reaction efficiency (Org. Lett. 2019, 21, 5552-5555), but still face the following problems: high cost of precious metal catalysts, poor adaptability to specific substrates, and poor control of regioselectivity.

[0012] Route C:

[0013] ,

[0014] In route c, R 1 For substituted or unsubstituted aromatic groups, alkyl groups, or thiophene groups; R 2 R is a hydrogen atom, alkyl group, or aromatic group; 3 It can be a hydrogen atom, alkyl group, or aromatic group.

[0015] In summary, existing metal catalysis systems still have significant shortcomings in terms of functional group compatibility, making it difficult to meet the needs of rapid construction of complex functional molecules in drug development. Summary of the Invention

[0016] To address the aforementioned technical problems, this invention proposes a method for synthesizing polysubstituted furan compounds via ring-opening of gem-difluorocyclopropane. This method is achieved through a one-pot series reaction, featuring simple steps, readily available raw materials, and mild reaction conditions. During the reaction, the main byproduct is inorganic fluoride, which allows for more efficient conversion of raw material atoms into the target product, reducing the generation and emission of organic waste at the source and aligning with the atom-economical green synthesis concept.

[0017] To achieve the above objectives, the present invention provides the following technical solution:

[0018] This invention provides a method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane, comprising the following steps:

[0019] In the presence of a metal catalyst and an alkali metal compound, the compound shown in Formula I and the compound shown in Formula II undergo a ring-opening defluorination-nucleophilic addition reaction with the ligand in a solvent. After the reaction, the compound is successively filtered, rotary evaporated and column chromatography to obtain the polysubstituted furan compound shown in Formula III.

[0020] The general structural formula of the compound shown in Formula I is: , where R 1Selected from substituted or unsubstituted aromatic groups and ferrocene groups;

[0021] The general structural formula of the compound shown in Formula II is: , where R 2 Selected from substituted or unsubstituted aromatic groups, substituted or unsubstituted thiophene groups, R 3 Selected from cyano, substituted or unsubstituted sulfonyl, substituted or unsubstituted ester groups;

[0022] The general structural formula of the polysubstituted furan compound shown in Formula III is: , where R 1 Selected from ferrocene, substituted or unsubstituted aryl groups, R 2 Selected from substituted or unsubstituted aromatic groups, substituted or unsubstituted thiophene groups, R 3 Selected from cyano, substituted or unsubstituted sulfonyl, substituted or unsubstituted ester groups. Preferably, the R group... 1 The R is selected from substituted or unsubstituted phenyl or substituted or unsubstituted naphthyl groups, with 1 to 5 substituents, preferably monosubstituted, and the substituents are selected from alkyl, alkoxy, aryl, halogen, fluoroalkyl or ester groups, preferably from methoxycarbonyl, halogen, trifluoromethyl, pyridyl or (Z)-hexanoic acid-3-hexenyl ester group; 2 Selected from substituted or unsubstituted phenyl or substituted or unsubstituted thiophene groups, wherein the number of substituents is 1 to 5; the R 3 The group is selected from substituted or unsubstituted sulfonyl, cyano, or substituted or unsubstituted ester groups, with the number of substituents ranging from 1 to 5. More preferably, the R group... 1 Selected from 2-naphthyl, 4-methoxycarbonylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-pyridylphenyl, or ferrocene; wherein R 2 It is phenyl; the R 3 Selected from sulfonyl or cyano groups, preferably R 3 It is a sulfonyl group.

[0023] This invention develops a synthetic strategy based on a Pd(0) / phosphine ligand catalytic system, which effectively overcomes the problems of poor regioselectivity, limited functional group compatibility, and cumbersome steps in existing technologies. The core mechanism of this invention is as follows: the distal C-C bond of gem-difluorocyclopropane (Formula I) is selectively oxidized and added by a Pd(0) species, followed by β-F elimination to generate the key π-fluoroallylpalladium intermediate; then, the enol salt of Formula II, stabilized by a strongly electron-withdrawing group (such as a sulfonyl group), acts as a nucleophile, highly regioselectively attacking the sterically less hindrance terminal carbon of this intermediate; the fluorocarbonyl intermediate generated therefrom does not need to be separated, and under the basic conditions of the reaction system, it undergoes intramolecular CF bond breaking and cyclization sequentially, thereby efficiently constructing a furan ring (Formula III). The above mechanism ensures the specificity and regioselectivity of the reaction, and the tandem process allows for the immediate conversion of the active intermediate, which helps to suppress side reaction pathways, thus achieving excellent yields (e.g., 96% in Example 1). It is noteworthy that the strong electron-withdrawing group (R³) is not only well-compatible in this method, but also plays a crucial role in stabilizing the nucleophilic precursor and driving the reaction equilibrium, breaking through the limitations of traditional methods on this type of sensitive functional group. Unlike existing technologies (Li Zhiping / Lv Leiyang research group, Chem. Sci., 2021, 12, 15511-15518) that disclose divergent synthesis through ligand regulation, this invention provides a different technical solution. The core differences compared to this technology are: 1. Different catalytic system: This invention uses phosphine ligands (such as the electron-rich, sterically hindered single phosphine ligand BrettPhos) to construct the catalytic system. This ligand, through its unique spatial and electronic environment, is beneficial for stabilizing the key intermediate π-fluoroallylpalladium generated in the reaction and precisely controlling its reactivity, thereby achieving linear selectivity different from existing technologies. 2. Different nucleophiles: This invention uses active methylene compounds containing strong electron-withdrawing groups (such as sulfonyl or cyano groups) as nucleophiles. The strong electron-withdrawing group significantly enhances the acidity of the methylene proton, promoting the in-situ formation of highly reactive enols and providing a highly efficient nucleophile for subsequent transformations. 3. Different product selectivity: The synergistic effect of the above features allows the reaction to specifically generate 2,3,5-trisubstituted furan compounds via intramolecular cyclization from a linear selective intermediate, rather than a divergent pathway starting from a branched intermediate that could lead to different products. Therefore, this invention provides a synthetic route different from the aforementioned strategy.

[0024] Furthermore, the molar ratio of the compound shown in Formula I, the compound shown in Formula II, the metal catalyst, the ligand, and the alkali metal compound is 1:(1.5~2):0.1:0.1:(1.5~6).

[0025] Furthermore, the metal catalyst is selected from one of Pd(TFA)2, Pd2(dba)3 and Pd(OAc)2.

[0026] Furthermore, the alkali metal compound is selected from Cs2CO3 and CsOH•H2O.

[0027] Furthermore, the ligand is selected from one of XPhos, XantPhos, and BrettPhos.

[0028] Furthermore, the ring-opening defluorination-nucleophilic addition reaction is carried out at a temperature of 100 °C for 3 to 6 hours.

[0029] Furthermore, the solvent is selected from one of tetrahydrofuran, 1,4-dioxane, and toluene.

[0030] For example, the polysubstituted furan compound is selected from 5-(naphthyl-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan, methyl 4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)benzoate, 5-(4-fluorobenzyl)-2-phenyl-3-(benzenesulfonyl)furan, 2-phenyl-3-(benzenesulfonyl)-5-(4-(trifluoromethyl)benzyl)furan, 2-(4- ((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)phenyl)pyridine, (5-phenyl-4-(benzenesulfonyl)furan-2-yl)methylferrocene, 5-(4-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)benzyl)-2-phenyl-3-(benzenesulfonyl)furan or 5-(naphthalene-2-methylene)-2-phenylfuran-3-carboxynitrile.

[0031] Compared with the prior art, the present invention has the following advantages and technical effects:

[0032] 1. The reaction conditions of the method of the present invention are relatively mild, and can be carried out at 100 °C, with low requirements for reaction equipment.

[0033] 2. This invention achieves multi-step transformation through a one-pot series reaction, eliminating the need for intermediate separation and purification, and making the reaction steps simple and efficient. The atoms in the raw materials are mainly converted into the target product, with the main byproducts being easily processed inorganic fluorides. This method offers high atom economy, conforms to green chemistry principles, and effectively reduces synthesis costs and process complexity.

[0034] 3. The multifunctionalized furan compounds prepared by the method of this invention have shown important potential application value in the fields of medicinal chemistry and materials science. Attached Figure Description

[0035] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. In the drawings:

[0036] Figure 1 The 1H NMR spectrum of 5-(naphthyl-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan as shown in Formula III-1;

[0037] Figure 2 The carbon NMR spectrum of 5-(naphthalene-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan as shown in Formula III-1;

[0038] Figure 3 The 1H NMR spectrum of methyl 4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)benzoate as shown in Formula III-2;

[0039] Figure 4 The carbon NMR spectrum of methyl 4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)benzoate as shown in Formula III-2;

[0040] Figure 5 The 1H NMR spectrum of 5-(4-fluorobenzyl)-2-phenyl-3-(benzenesulfonyl)furan as shown in Formula III-3;

[0041] Figure 6 The carbon NMR spectrum of 5-(4-fluorobenzyl)-2-phenyl-3-(benzenesulfonyl)furan as shown in Formula III-3;

[0042] Figure 7 The 1H NMR spectrum of 2-phenyl-3-(benzenesulfonyl)-5-(4-(trifluoromethyl)benzyl)furan, as shown in Formula III-4;

[0043] Figure 8 The carbon NMR spectrum of 2-phenyl-3-(benzenesulfonyl)-5-(4-(trifluoromethyl)benzyl)furan as shown in Formula III-4;

[0044] Figure 9 The 1H NMR spectrum of 2-(4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)phenyl)pyridine as shown in Formula III-5;

[0045] Figure 10 The carbon NMR spectrum of 2-(4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)phenyl)pyridine as shown in Formula III-5;

[0046] Figure 11 The 1H NMR spectrum of (5-phenyl-4-(benzenesulfonyl)furan-2-yl)methylferrocene, as shown in Formula III-6;

[0047] Figure 12 The carbon NMR spectrum of (5-phenyl-4-(benzenesulfonyl)furan-2-yl)methylferrocene as shown in Formula III-6;

[0048] Figure 13 The 1H NMR spectrum of 5-(4-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)benzyl)-2-phenyl-3-(benzenesulfonyl)furan is shown in Formula III-7.

[0049] Figure 14 The carbon NMR spectrum of 5-(4-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)benzyl)-2-phenyl-3-(benzenesulfonyl)furan is shown in Formula III-7.

[0050] Figure 15 The 1H NMR spectrum of 5-(naphthalene-2-methylene)-2-phenylfuran-3-carboxynitrile, as shown in Formula III-8;

[0051] Figure 16 The carbon NMR spectrum of 5-(naphthalene-2-methylene)-2-phenylfuran-3-carboxynitrile as shown in Formula III-8;

[0052] Figure 17 The 1H NMR spectrum of (1S,4R)-4-(naphth-2-ylmethyl)-1-phenyl-2-(benzenesulfonyl)-1,4-dihydro-1,4-epoxynaphthalene in Application Example 1 of this invention;

[0053] Figure 18 The image shows the carbon NMR spectrum of (1S,4R)-4-(naphth-2-ylmethyl)-1-phenyl-2-(benzenesulfonyl)-1,4-dihydro-1,4-epoxynaphthalene in Application Example 1 of this invention. Detailed Implementation

[0054] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0055] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0056] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0057] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0058] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0059] Embodiments of the present invention provide a method for synthesizing polysubstituted furan compounds via ring-opening of gem-difluorocyclopropane, comprising the following steps: in the presence of a metal catalyst and an alkali metal compound, the compounds shown in Formula I and Formula II undergo a ring-opening defluorination-nucleophilic addition reaction with ligands in a solvent; after the reaction, the compounds are sequentially filtered, rotary evaporated, and column chromatography to obtain the polysubstituted furan compound shown in Formula III. The synthetic route is as follows:

[0060] ;

[0061] The general structural formula of the compound shown in Formula I is: , where R 1 Selected from ferrocene, substituted or unsubstituted aryl groups;

[0062] The general structural formula of the compound shown in Formula II is: , where R 2 Selected from substituted or unsubstituted aromatic groups or substituted or unsubstituted thiophene groups, R 3 Selected from cyano, substituted or unsubstituted sulfonyl, substituted or unsubstituted ester groups;

[0063] The general structural formula of the polysubstituted furan compound shown in Formula III is: , where R 1 Selected from substituted or unsubstituted aromatic groups, R 2 Selected from substituted or unsubstituted aromatic groups, substituted or unsubstituted thiophene groups, R 3 Selected from cyano, substituted or unsubstituted sulfonyl, substituted or unsubstituted ester groups. Preferably R 1Selected from substituted or unsubstituted phenyl or substituted or unsubstituted naphthyl groups, with the number of substituents ranging from 1 to 5; R 2 Selected from substituted or unsubstituted phenyl groups, substituted or unsubstituted thiophene groups, with 1 to 5 substituents, preferably trisubstituted, R 1 The substituents are selected from alkyl, alkoxy, aryl, halogen, fluoroalkyl, or ester groups, preferably R. 1 The substituents in R are selected from methoxycarbonyl, halogen, trifluoromethyl, pyridyl, and (Z)-hexanoic acid-3-hexenyl ester; 3 It is selected from cyano, substituted or unsubstituted sulfonyl, substituted or unsubstituted ester groups, wherein the number of substituents is 1 to 5. More preferably R 1 Selected from 2-naphthyl, 4-methoxycarbonylphenyl, 4-pyridylphenyl, ferrocene; R 2 Selected from phenyl; R 3 Selected from sulfonyl or cyano groups.

[0064] In embodiments of the present invention, the molar ratio of the compound shown in Formula I, the compound shown in Formula II, the metal catalyst, the ligand and the alkali metal compound is 1:(1.5~2):0.1:0.1:(1.5~6), preferably 1:2:0.1:0.1:6.

[0065] In embodiments of the present invention, the metal catalyst is selected from Pd(TFA)2, Pd2(dba)3, and Pd(OAc)2, preferably Pd(OAc)2. As a catalyst precursor, the metal catalyst can generate highly active Pd(0) species in situ within the reaction system, which is a necessary condition for initiating the catalytic cycle. Different precursors exhibit differences in reduction efficiency and complex formation kinetics, thus affecting the final yield.

[0066] In embodiments of the present invention, the alkali metal compound is selected from Cs₂CO₃ and CsOH•H₂O, preferably CsOH•H₂O. The alkali metal compound plays a dual role in the reaction: firstly, it promotes the deprotonation of the active methylene compound to form a nucleophile; secondly, it drives subsequent intramolecular CF bond breaking and cyclization steps. The strength, solubility, and properties of the basic anion of the base collectively determine its overall efficiency in promoting these steps.

[0067] In embodiments of the present invention, the ligand is selected from XPhos, XantPhos, and BrettPhos, preferably BrettPhos. The ligand, by coordinating with the metal center, modulates the electron density and spatial configuration of the catalytic center, which is crucial for stabilizing key intermediates and controlling the regioselectivity of nucleophilic attack.

[0068] In embodiments of the present invention, the ring-opening defluorination-nucleophilic addition reaction is carried out at a temperature of 100 °C for 3 to 6 hours; preferably, the ring-opening defluorination-nucleophilic addition reaction is carried out at a temperature of 100 °C for 6 hours. A suitable temperature provides the necessary activation energy for the multi-step cascade reaction, while the optimized reaction time aims to balance the degree of reaction completion with the suppression of excessive reactions or side reactions.

[0069] In embodiments of the present invention, the solvent is selected from tetrahydrofuran, 1,4-dioxane, and toluene, preferably 1,4-dioxane. The solvent mainly affects the homogeneity of the reaction system, the solubility of the reactants, and the upper limit of the reaction temperature, thereby indirectly affecting the reaction rate and yield.

[0070] In an embodiment of the present invention, the eluent used in column chromatography is a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1.

[0071] For example, the polysubstituted furan compounds are selected from 5-(naphthyl-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan, methyl 4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)benzoate, 5-(4-fluorobenzyl)-2-phenyl-3-(benzenesulfonyl)furan, 2-phenyl-3-(benzenesulfonyl)-5-(4-(trifluoromethyl)benzyl)furan, 2-(4-( (5-Phenylacetyl-4-(benzenesulfonyl)furan-2-yl)methyl)phenyl)pyridine, (5-Phenylacetyl-4-(benzenesulfonyl)furan-2-yl)methylferrocene, 5-(4-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)benzyl)-2-phenyl-3-(benzenesulfonyl)furan or 5-(naphthalene-2-methylene)-2-phenylfuran-3-carboxynitrile.

[0072] The synthetic method provided by this invention can efficiently and selectively construct a series of furan derivatives, particularly by conveniently introducing key functional groups such as sulfonyl, ester, and cyano groups. Therefore, the obtained polysubstituted furan compounds have the following potential applications:

[0073] (1) In the field of drug development: Multisubstituted furan compounds can serve as important organic synthesis intermediates or active molecular skeletons for constructing diverse compound libraries and conducting high-throughput drug screening. Among them, sulfonyl and ester groups are common pharmacophores or prodrug groups in drug molecules, while cyano groups can serve as hydrogen bond acceptors or metabolic stabilizers. This makes these compounds valuable for the development of small molecule inhibitors or probe molecules targeting specific targets (such as kinases, proteases, etc.).

[0074] (2) In the field of functional materials: polysubstituted furans are the classic building blocks for constructing π-conjugated organic functional materials. The method of this invention can flexibly adjust the electronic properties and steric hindrance of each substituent on the furan ring. The synthesized polysubstituted furan compounds are expected to serve as key building blocks for the molecular design and performance research of organic semiconductor materials, organic light-emitting diode (OLED) light-emitting layer materials or fluorescent sensing materials.

[0075] Unless otherwise specified, the room temperature in this invention is 25±2℃.

[0076] Unless otherwise specified, all raw materials and reagents used in this invention are commercially available products and can be obtained through conventional commercial channels. For example, XPhos was purchased from Jiangsu Xinnoco Catalyst Co., Ltd. (whose product brand is "Little Chili Reagent"); SPhos was purchased from Beijing Leyan Technology Co., Ltd.; XantPhos, tBu-BrettPhos, and BrettPhos were all purchased from Beijing Innocare Technology Co., Ltd.

[0077] It should be noted that any aspects not described in detail in this invention are conventional practices in the field and are not the focus of this invention.

[0078] In this invention, to determine the optimal conditions for the ring-opening defluorination-nucleophilic addition reaction, the synthesis of 5-(naphthyl-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan (i.e., the target product of Example 1) was used as a model reaction. The effects of catalyst, ligand, base, solvent, temperature, and reaction time on reaction efficiency and selectivity were systematically investigated. All experiments were conducted in a one-pot process in a reaction tube under argon protection. After the reaction, the target product was obtained by column chromatography, and the yield was calculated. Key screening data are summarized in Table 1.

[0079] Table 1 Results of reaction condition screening

[0080]

[0081] As shown in Table 1:

[0082] 1. The optimal combination of conditions for the synthesis method of this invention is to use Pd(OAc)2 as a catalyst, BrettPhos as a ligand, CsOH·H2O as a base, and 1,4-dioxane as a solvent, and to react at 100°C for 6 hours. The yield of the model product (polysubstituted furan compound) can reach 96% (No. 3).

[0083] 2. Defining the Scope of Options: Data screening demonstrates that the synthesis method of this invention remains effective even with variations within the following ranges:

[0084] The catalyst can be replaced by Pd(OAc)2 with Pd(TFA)2 (number 1, 48%) or Pd2(dba)3 (number 2, 44%), but the yield decreases. The ligand can be replaced by BrettPhos with XPos (number 4, 53%) or XantPhos (number 6, 69%). BrettPhos exhibits the best performance as a single phosphine ligand. The base can be replaced by CsOH•H2O with Cs2CO3 (number 9, 74%), but CsOH•H2O is more effective. The solvent can be replaced by 1,4-dioxane with tetrahydrofuran (number 11, 76%) or toluene (number 12, 81%).

[0085] The technical solution of the present invention will be further illustrated by the following embodiments.

[0086] Example 1: Synthesis of 5-(naphthalene-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan as shown in Formula III-1

[0087] The synthesis route is as follows:

[0088]

[0089] Formula III-1

[0090] The specific synthesis method is as follows: Under argon atmosphere, 2-(2,2-difluorocyclopropyl)naphthalene (0.1 mmol), 1-phenyl-2-(benzenesulfonyl)ethane-1-one (0.2 mmol), Pd(OAc)2 (0.01 mmol), BrettPhos (0.01 mmol), CsOH•H2O (0.6 mmol) and 1,4-dioxane (1.0 mL) were added sequentially to the reaction tube. The temperature was raised to 100℃ and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was filtered from the reaction tube into a 100 mL pear-shaped flask, evaporated by rotary evaporation, and subjected to column chromatography (the eluent was petroleum ether / ethyl acetate (10:1, volume ratio, the same below)).

[0091] After weighing, column chromatography was used to separate 40.8 mg of 5-(naphthalene-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan, with a yield of 96%.

[0092] Figure 1 and Figure 2 The 1H and 1C NMR spectra of 5-(naphthalene-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan prepared in Example 1 of this invention are characterized as follows:

[0093] 1H NMR (400 MHz, CDCl3) δ 7.81-7.75 (m, 7H), 7.69 (s, 1H), 7.49-7.43(m, 3H), 7.38-7.35 (m, 6H), 6.49 (s, 1H), 4.13 (s, 2H); 13 C NMR (100 MHz, CDCl3) δ 154.3, 154.1, 141.9, 133.7, 133.5, 133.1, 132.4, 129.8, 128.9,128.6, 128.5, 128.3, 128.2, 127.7, 127.6, 127.4, 127.0, 126.9, 126.2, 125.8,124.2, 109.1, 34.4. HRMS (ESI) m / z: Calcd for C 27 H 21 O3S [M+H] + : 425.1206; found: 425.1207.

[0094] As can be seen from the above analysis, the target compound was successfully prepared in this embodiment.

[0095] Example 2 Synthesis of methyl 4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)benzoate as shown in Formula III-2

[0096] The synthesis route is as follows:

[0097]

[0098] Formula III-2

[0099] The specific synthesis method is as follows: Under argon atmosphere, methyl 4-(2,2-difluorocyclopropyl)benzoate (0.1 mmol), 1-phenyl-2-(benzenesulfonyl)ethane-1-one (0.2 mmol), Pd(OAc)2 (0.01 mmol), BrettPhos (0.01 mmol), Cs2CO3 (0.6 mmol) and 1,4-dioxane (1.0 mL) were added sequentially to the reaction tube. The temperature was raised to 100 °C and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was filtered from the reaction tube into a 100 mL pear-shaped flask, evaporated by rotary evaporation, and subjected to column chromatography (eluent: petroleum ether / ethyl acetate (10:1)).

[0100] After weighing, 42.8 mg of methyl 4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)benzoate was obtained by column chromatography, with a yield of 99%.

[0101] Figure 3 and Figure 4 The proton and carbon NMR spectra of methyl 4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)benzoate prepared in Example 2 of this invention are characterized as follows:

[0102] 1 H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.3 Hz, 2H), 7.81-7.76 (m, 4H), 7.49 (t, J = 7.4 Hz, 1H), 7.41-7.37 (m, 5H), 7.32 (d, J = 8.2 Hz, 2H), 6.49 (s, 1H), 4.03 (s, 2H), 3.90 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 166.7, 154.4,153.0, 141.7, 141.5, 133.1, 130.0, 129.9, 128.9, 128.9, 128.8, 128.5, 128.2,128.1, 126.9, 124.2, 109.3, 52.1, 34.1. HRMS (ESI) m / z: Calcd for C 25 H 21 O5S [M+H] + : 433.1104; found: 433.1102.

[0103] As can be seen from the above analysis, the target compound was successfully prepared in this embodiment.

[0104] Example 3 Synthesis of 5-(4-fluorobenzyl)-2-phenyl-3-(benzenesulfonyl)furan as shown in Formula III-3

[0105] The synthesis route is as follows:

[0106]

[0107] Formula III-3

[0108] The specific synthesis method is as follows: Under argon atmosphere, 1-(2,2-difluorocyclopropyl)-4-fluorobenzene (0.1 mmol), 1-phenyl-2-(benzenesulfonyl)ethane-1-one (0.2 mmol), Pd(OAc)2 (0.01 mmol), BrettPhos (0.01 mmol), Cs2CO3 (0.6 mmol) and 1,4-dioxane (1.0 mL) were added sequentially to the reaction tube. The temperature was raised to 100℃ and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was filtered from the reaction tube into a 100 mL pear-shaped flask, evaporated by rotary evaporation, and subjected to column chromatography (eluent was petroleum ether / ethyl acetate (10:1)).

[0109] After weighing, 18.2 mg of 5-(4-fluorobenzyl)-2-phenyl-3-(benzenesulfonyl)furan was obtained by column chromatography, with a yield of 46%.

[0110] Figure 5 and Figure 6 The 1H and 1C NMR spectra of 5-(4-fluorobenzyl)-2-phenyl-3-(benzenesulfonyl)furan prepared in Example 3 of this invention are shown below, and the data characterization is as follows:

[0111] 1 H NMR (400 MHz, CDCl3) δ 7.82-7.76 (m, 4H), 7.50 (t, J = 7.5 Hz, 1H), 7.41-7.37 (m, 5H), 7.23-7.19 (m, 2H), 7.01 (t, J = 8.6 Hz, 2H), 6.44 (s, 1H),3.95 (s, 2H); 13 C NMR (100 MHz, CDCl3) δ 161.9 (d, J C-F = 245.3 Hz), 154.3,153.9, 141.8, 133.1, 131.9 (d, J C-F = 3.5 Hz), 130.3 (d, J C-F = 8.0 Hz), 129.8,128.9, 128.5, 128.2, 126.9, 124.1, 115.6 (d, J C-F = 21.4 Hz), 108.9, 33.4.HRMS (ESI) m / z: Calcd for C 23 H 18 FO3S [M+H] + : 393.0955; found: 393.0951.

[0112] As can be seen from the above analysis, the target compound was successfully prepared in this embodiment.

[0113] Example 4 Synthesis of 2-phenyl-3-(benzenesulfonyl)-5-(4-(trifluoromethyl)benzyl)furan as shown in Formula III-4

[0114] The synthesis route is as follows:

[0115]

[0116] Formula III-4

[0117] The specific synthesis method is as follows: Under argon conditions, 1-(2,2-difluorocyclopropyl)-4-(trifluoromethyl)benzene (0.1 mmol), 1-phenyl-2-(benzenesulfonyl)ethane-1-one (0.2 mmol), Pd(OAc)2 (0.01 mmol), BrettPhos (0.01 mmol), CsOH•H2O (0.6 mmol) and 1,4-dioxane (1.0 mL) were added sequentially to the reaction tube. The temperature was raised to 100 °C and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was filtered from the reaction tube into a 100 mL pear-shaped flask, evaporated by rotary evaporation, and subjected to column chromatography (eluent was petroleum ether / ethyl acetate (10:1)).

[0118] After weighing, column chromatography was used to separate 30.1 mg of 2-phenyl-3-(benzenesulfonyl)-5-(4-(trifluoromethyl)benzyl)furan, with a yield of 68%.

[0119] Figure 7 and Figure 8 The 1H and 1C NMR spectra of 2-phenyl-3-(benzenesulfonyl)-5-(4-(trifluoromethyl)benzyl)furan prepared in Example 4 of this invention are shown below, and the data characterization is as follows:

[0120] 1 H NMR (400 MHz, CDCl3) δ 7.81-7.76 (m, 4H), 7.59 (d, J = 8.1 Hz, 2H), 7.51 (t, J = 7.4 Hz, 1H), 7.42-7.36 (m, 7H), 6.50 (s, 1H), 4.04 (s, 2H); 13 CNMR (100 MHz, CDCl3) δ 154.5, 152.8, 141.7, 140.3, 133.2, 130.0, 129.1,128.9, 128.5 128.3, 128.1, 127.0, 125.7 (q, JC-F = 3.7 Hz), 124.2, 109.4,34.0. HRMS (ESI) m / z: Calcd for C 24 H 18 F3O3S [M+H] + : 443.0923; found: 443.0925.

[0121] As can be seen from the above analysis, the target compound was successfully prepared in this embodiment.

[0122] Synthesis of 2-(4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)phenyl)pyridine as shown in Example 5 III-5

[0123] The synthesis route is as follows:

[0124]

[0125] Formula III-5

[0126] The specific synthesis method is as follows: Under argon atmosphere, 2-(4-(2,2-difluorocyclopropyl)phenyl)pyridine (0.1 mmol), 1-phenyl-2-(benzenesulfonyl)ethane-1-one (0.2 mmol), Pd(OAc)2 (0.01 mmol), BrettPhos (0.01 mmol), CsOH•H2O (0.6 mmol) and 1,4-dioxane (1.0 mL) were added sequentially to the reaction tube. The temperature was raised to 100 °C and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was filtered from the reaction tube into a 100 mL pear-shaped flask, evaporated by rotary evaporation, and subjected to column chromatography (eluent was petroleum ether / ethyl acetate (10:1)).

[0127] After weighing, column chromatography was used to separate 32.1 mg of 2-(4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)phenyl)pyridine, with a yield of 71%.

[0128] Figure 9 and Figure 10 The proton and carbon NMR spectra of 2-(4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)phenyl)pyridine prepared in Example 5 of this invention are characterized as follows:

[0129] 1H NMR (400 MHz, CDCl3) δ 8.69 (d, J = 4.5 Hz, 1H), 7.96 (d, J = 8.2Hz, 2H), 7.83-7.80 (m, 2H), 7.77 (d, J = 7.4 Hz, 3H), 7.73 (t, J = 7.7 Hz,1H), 7.50 (t, J = 7.5 Hz, 1H), 7.41-7.36(m, 7H), 7.24 (t, J = 6.9 Hz, 1H),6.48 (s, 1H), 4.04 (s, 2H); 13 C NMR (100 MHz, CDCl3) δ 157.0, 154.3, 153.9,149.6, 141.8, 138.2, 137.1, 136.8, 133.1, 129.8, 129.3, 128.9, 128.5, 128.3,128.2, 127.3, 127.0, 124.1, 122.1, 120.5, 109.0, 34.0. HRMS (ESI) m / z: Calcdfor C 28 H 22 NO3S [M+H] + : 452.1315; found: 452.1304.

[0130] As can be seen from the above analysis, the target compound was successfully prepared in this embodiment.

[0131] Synthesis of (5-phenyl-4-(benzenesulfonyl)furan-2-yl)methylferrocene as shown in Example 6 III-6

[0132] The synthesis route is as follows:

[0133]

[0134] Formula III-6

[0135] The specific synthesis method is as follows: Under argon atmosphere, (2,2-difluorocyclopropyl)ferrocene (0.1 mmol), 1-phenyl-2-(benzenesulfonyl)ethane-1-one (0.2 mmol), Pd(OAc)2 (0.01 mmol), BrettPhos (0.01 mmol), CsOH•H2O (0.6 mmol) and 1,4-dioxane (1.0 mL) were added sequentially to the reaction tube. The temperature was raised to 100℃ and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was filtered from the reaction tube into a 100 mL pear-shaped flask, evaporated by rotary evaporation, and subjected to column chromatography (eluent was petroleum ether / ethyl acetate (10:1)).

[0136] After weighing, column chromatography yielded 8.2 mg of (5-phenyl-4-(benzenesulfonyl)furan-2-yl)methylferrocene, with a yield of 17%.

[0137] Figure 11 and Figure 12 The proton and carbon NMR spectra of (5-phenyl-4-(benzenesulfonyl)furan-2-yl)methylferrocene prepared in Example 6 of this invention are characterized as follows:

[0138] 1 H NMR (400 MHz, CDCl3) δ 7.86-7.84 (m, 2H), 7.78 (d, J = 7.8 Hz, 2H), 7.49 (t, J = 7.4 Hz, 1H), 7.42-7.37 (m, 5H), 6.48 (s, 1H), 4.15 (s, 2H), 4.11(s, 2H), 4.07 (s, 5H), 3.70 (s, 2H); 13 C NMR (100 MHz, CDCl3) δ 154.4, 153.6,141.9, 133.1, 129.8, 128.9, 128.5, 128.4, 128.3, 126.9, 124.0, 108.3, 83.4,68.7, 68.5, 67.8, 67.1, 28.3. HRMS (ESI) m / z: Calcd for C 27 H 23 FeO3S [M+H] + :483.0712; found: 483.0685.

[0139] As can be seen from the above analysis, the target compound was successfully prepared in this embodiment.

[0140] Synthesis of 5-(4-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)benzyl)-2-phenyl-3-(benzenesulfonyl)furan as shown in Example 7 III-7

[0141] The synthesis route is as follows:

[0142]

[0143] Formula III-7

[0144] The specific synthesis method is as follows: Under argon atmosphere, 1-(2,2-difluorocyclopropyl)-4-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)benzene (0.1 mmol), 1-phenyl-2-(benzenesulfonyl)ethane-1-one (0.2 mmol), Pd(OAc)2 (0.01 mmol), BrettPhos (0.01 mmol), CsOH•H2O (0.6 mmol) and 1,4-dioxane (1.0 mL) were added sequentially to the reaction tube. The temperature was raised to 100 °C and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was filtered from the reaction tube into a 100 mL pear-shaped flask, evaporated by rotary evaporation, and subjected to column chromatography (eluent was petroleum ether / ethyl acetate (10:1)).

[0145] After weighing, column chromatography yielded 41.8 mg of 5-(4-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)benzyl)-2-phenyl-3-(benzenesulfonyl)furan, with a yield of 77%.

[0146] Figure 13 and Figure 14 The 1H and 1C NMR spectra of 5-(4-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)benzyl)-2-phenyl-3-(benzenesulfonyl)furan prepared in Example 7 of this invention are characterized as follows:

[0147] 1H NMR (400 MHz, CDCl3) δ 7.81-7.79 (m, 2H), 7.76 (d, J = 7.7 Hz, 2H), 7.50 (t, J = 7.4 Hz, 1H), 7.41-7.37 (m, 5H), 7.31 (d, J = 7.9 Hz, 2H), 7.23(d, J = 7.9 Hz, 2H), 6.43 (s, 1H), 4.64 (d, J = 11.4 Hz, 1H), 4.38 (d, J =11.3 Hz, 1H), 3.96 (s, 2H), 3.20-3.14 (m, 1H), 2.33-2.25 (m, 1H), 2.20 (d, J= 12.3 Hz, 1H), 1.67-1.60 (m, 3H), 1.28-1.26 (m, 2H), 0.94 (d, J = 6.6 Hz, 4H), 0.89 (d, J = 7.1 Hz, 4H), 0.70 (d, J = 6.9 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 154.2, 154.1, 141.9, 137.9, 135.4, 133.1, 129.7, 128.9, 128.8,128.5, 128.3, 128.2, 126.9, 124.0, 108.8, 78.7, 70.1, 48.2, 40.2, 34.5, 34.0,31.5, 25.4, 23.1, 22.4, 21.0, 16.0. HRMS (ESI) m / z: Calcd for C 34 H 38 NaO4S [M+Na] + : 565.2383; found: 565.2372.

[0148] As can be seen from the above analysis, the target compound was successfully prepared in this embodiment.

[0149] Example 8 Synthesis of 5-(naphthalene-2-methylene)-2-phenylfuran-3-carboxynitrile as shown in Formula III-8

[0150] The synthesis route is as follows:

[0151]

[0152] Formula III-8

[0153] The specific synthesis method is as follows: Under argon atmosphere, 2-(2,2-difluorocyclopropyl)naphthalene (0.1 mmol), 3-oxo-3-phenylpropionitrile (0.2 mmol), Pd(OAc)2 (0.01 mmol), BrettPhos (0.01 mmol), CsOH•H2O (0.6 mmol) and 1,4-dioxane (1.0 mL) were added sequentially to the reaction tube. The temperature was raised to 100 °C and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was filtered from the reaction tube into a 100 mL pear-shaped flask, evaporated by rotary evaporation, and subjected to column chromatography (eluent was petroleum ether / ethyl acetate (10:1)).

[0154] After weighing, 15.8 mg of 5-(naphthalene-2-methylene)-2-phenylfuran-3-carboxynitrile was obtained by column chromatography, with a yield of 51%.

[0155] Figure 15 and Figure 16 The proton and carbon NMR spectra of 5-(naphthalene-2-methylene)-2-phenylfuran-3-carboxynitrile prepared in Example 8 of this invention are characterized as follows:

[0156] 1 H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.0 Hz, 2H), 7.81 (t, J = 8.2Hz, 3H), 7.70 (s, 1H), 7.51-7.37 (m, 6H), 6.28 (s, 1H), 4.18 (s, 2H); 13 C NMR(100 MHz, CDCl3) δ 159.0, 154.9, 133.6, 133.5, 132.4, 129.8, 129.0, 128.5,128.2, 127.7, 127.6, 127.3, 126.8, 126.3, 125.9, 125.2, 115.1, 109.8, 92.0,34.4. HRMS (ESI) m / z: Calcd for C 22 H 16 NO [M+H] + : 310.1226; found: 310.1225.

[0157] As can be seen from the above analysis, the target compound was successfully prepared in this embodiment.

[0158] Therefore, the preparation method of furan compounds described in this invention can be achieved in a one-pot process, with simple operation steps, which helps to reduce production costs and achieve efficient synthesis.

[0159] Application Example 1: Derivatization reaction of furan product III-1

[0160] Synthesis route:

[0161]

[0162] The specific synthesis method is as follows: Under argon atmosphere, 5-(naphthyl-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan (0.1 mmol), 2-(trimethylsilyl)phenyltrifluoromethanesulfonate (0.2 mmol), CsF (0.2 mmol), and acetonitrile (1.0 mL) were added sequentially to the reaction tube, and the reaction was carried out at room temperature for 12 hours. After the reaction was completed, saturated NaCl solution was added to the reaction tube, and the mixture was extracted with ethyl acetate. The combined organic phases were washed twice with saturated brine, dried over anhydrous sodium sulfate, rotary evaporated, and subjected to column chromatography (the eluent was a mixture of petroleum ether and ethyl acetate, with a volume ratio of 10:1).

[0163] After weighing, column chromatography yielded 48.1 mg of (1S,4R)-4-(naphth-2-ylmethyl)-1-phenyl-2-(benzenesulfonyl)-1,4-dihydro-1,4-epoxynaphthalene, with a yield of 96%.

[0164] Figure 17 and Figure 18 The proton and carbon NMR spectra of (1S,4R)-4-(naphth-2-ylmethyl)-1-phenyl-2-(benzenesulfonyl)-1,4-dihydro-1,4-epoxynaphthalene prepared from product III-1 of Example 1 of this invention are characterized as follows:

[0165] 1 H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H), 7.86 - 7.81 (m, 3H), 7.76 (s,1H), 7.70 -7.67 (m, 2H), 7.59 (d, J = 7.5 Hz, 1H), 7.52 - 7.44 (m, 2H), 7.40(d, J = 7.0 Hz, 1H), 7.36 - 7.29 (m, 5H), 7.16 - 7.01 (m, 6H), 3.94 - 3.78(m, 2H); 13C NMR (100 MHz, CDCl3) δ 159.4, 156.6, 149.6, 148.2, 139.0, 133.4,133.3, 132.8, 132.5, 132.4, 128.6, 128.5, 128.4, 128.2, 128.1, 128.0, 127.7,127.6, 127.5, 127.2, 126.1, 125.9, 125.8, 121.3, 120.3, 92.4, 91.5, 35.4.HRMS (ESI) m / z: Calcd for C 33 H 25 O3S [M+H] + : 501.1519; found: 501.1528.

[0166] As can be seen from the above analysis, the target compound was successfully prepared from product Ⅲ-1 in Example 1.

[0167] The above are merely preferred embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for synthesizing polysubstituted furan compounds via ring-opening of gem-difluorocyclopropane, characterized in that, Includes the following steps: In the presence of a metal catalyst and an alkali metal compound, the compound shown in Formula I and the compound shown in Formula II undergo a ring-opening defluorination-nucleophilic addition reaction with the ligand in a solvent. After the reaction, the compound is successively filtered, rotary evaporated and column chromatography to obtain the polysubstituted furan compound shown in Formula III. The general structural formula of the compound shown in Formula I is: , where R 1 Selected from ferrocene or substituted or unsubstituted aromatic groups; The general structural formula of the compound shown in Formula II is: , where R 2 Selected from substituted or unsubstituted aromatic groups, substituted or unsubstituted thiophene groups, R 3 Selected from cyano, substituted or unsubstituted sulfonyl, substituted or unsubstituted ester groups; The general structural formula of the polysubstituted furan compound shown in Formula III is: , where R 1 Selected from substituted or unsubstituted aryl or ferrocene groups; R 2 Selected from substituted or unsubstituted aromatic groups or substituted or unsubstituted thiophene groups; R 3 Selected from substituted or unsubstituted sulfonyl, cyano, and substituted or unsubstituted ester groups.

2. The method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane according to claim 1, characterized in that, The R 1 It is selected from substituted or unsubstituted phenyl or substituted or unsubstituted naphthyl groups, with the number of substituents being 1 to 5; The R 2 It is selected from substituted or unsubstituted phenyl, substituted or unsubstituted thiophene group, with the number of substituents being 1 to 5, and the substituents being selected from alkyl, alkoxy, aryl, halogen, fluoroalkyl or ester group; The R 3 It is selected from substituted or unsubstituted sulfonyl groups, substituted or unsubstituted cyano groups, and substituted or unsubstituted ester groups, wherein the number of substituents is 1 to 5.

3. The method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane according to claim 2, characterized in that, The R 1 Selected from 2-naphthyl, 4-methoxycarbonylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-pyridylphenyl, or ferrocene; wherein R 2 It is phenyl; the R 3 Selected from sulfonyl or cyano groups.

4. The method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane according to claim 3, characterized in that, The molar ratio of the compound represented by Formula I, the compound represented by Formula II, the metal catalyst, the ligand, and the alkali metal compound is 1:(1.5~2):0.1:0.1:(1.5~6).

5. The method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane according to claim 4, characterized in that, The metal catalyst is selected from one of Pd(OAc)2, Pd(TFA)2 and Pd2(dba)3.

6. The method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane according to claim 4, characterized in that, The alkali metal compound is selected from Cs2CO3 and CsOH•H2O.

7. The method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane according to claim 4, characterized in that, The ligand is selected from one of XPhos, XantPhos and BrettPhos.

8. The method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane according to claim 1, characterized in that, The ring-opening defluorination-nucleophilic addition reaction was carried out at a temperature of 100 °C for 3 to 6 hours.

9. The method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane according to claim 1, characterized in that, The solvent is selected from one of tetrahydrofuran, 1,4-dioxane, and toluene.

10. The method for synthesizing polysubstituted furan compounds by ring-opening of gem-difluorocyclopropane according to claim 1, characterized in that, The polysubstituted furan compounds are selected from 5-(naphthyl-2-methylene)-2-phenyl-3-(benzenesulfonyl)furan, methyl 4-((5-phenyl-4-(benzenesulfonyl)furan-2-yl)methyl)benzoate, 5-(4-fluorobenzyl)-2-phenyl-3-(benzenesulfonyl)furan, 2-phenyl-3-(benzenesulfonyl)-5-(4-(trifluoromethyl)benzyl)furan, 2-(4-((5-phenyl-2-methylene)furan, methyl ... -Phenylacetyl-4-(benzenesulfonyl)furan-2-yl)methyl)phenyl)pyridine, (5-phenyl-4-(benzenesulfonyl)furan-2-yl)methylferrocene, 5-(4-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methyl)benzyl)-2-phenyl-3-(benzenesulfonyl)furan or 5-(naphthalene-2-methylene)-2-phenylfuran-3-carboxynitrile.

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