A method for preparing 2,5-disubstituted and 2,3,5-trisubstituted furan skeleton derivatives

Abstract

A method for preparing 2,5-disubstituted and 2,3,5-trisubstituted furan skeleton derivatives. This invention belongs to the field of heterocyclic compound synthesis technology in organic synthesis. It provides a method for preparing polysubstituted furans, which enables the synthesis of a diverse series of derivatives having the structures of 2,5-disubstituted furans and 2-phenyl-4,5,6,7-tetrahydrobenzofuran shown in formulas (I) and (II). This invention provides a foundation for constructing a library of polysubstituted furan small molecule compounds and lays the material basis for further in-depth exploration of the biological activities of polysubstituted furan compounds. Simultaneously, this invention also provides a new technical means for the rapid synthesis of related active natural products and drug molecules with polysubstituted furan structural skeletons.

Description

Technical Field

[0001] This invention relates to an efficient method for preparing 2,5-disubstituted and 2,3,5-trisubstituted furan derivatives. More specifically, it relates to a novel method for preparing 2,5-disubstituted furans of formula (I) and 2-phenyl-4,5,6,7-tetrahydrobenzofuran derivatives of formula (II). This invention belongs to the field of heterocyclic compound synthesis technology in organic synthesis.

[0002] Background Technology

[0003] Polysubstituted furans are a very important class of oxygen-containing heterocyclic structural skeletons, widely found in many complex and bioactive natural products. [1] and important drug molecules [2] For example, fluticasone furoate, a drug used to treat allergic rhinitis, has a core structure of furan fragments; nitro-substituted furans are mainly used as antibiotics, such as nitrofurantoin, which has been used to treat urinary tract infections since World War II; lapatinib, a mixed inhibitor of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), has a main structure containing multi-substituted furan fragments. Furthermore, multi-substituted furan structures are also an important basic synthetic module, widely used in the synthesis of various complex natural components. Multi-substituted furan fragments also have important applications in the field of materials science; many important luminescent materials contain multi-substituted furan fragments. [3] Therefore, developing efficient and concise new methods for synthesizing furan structures is of great significance for drug development and other fields. Currently, the main method for synthesizing multisubstituted furan structures is intramolecular cyclization reaction catalyzed by transition metals. However, the strategy of constructing multisubstituted furans using intermolecular [2+3] cycloaddition reactions catalyzed by transition metals is rarely reported.

[0004] As one of the hot research areas in organic synthetic chemistry in recent years, triazoles have been widely used in the synthesis of heterocyclic compounds. [4] In particular, triazoles with electron-withdrawing groups substituted at the nitrogen atom, such as N-sulfonyl-1,2,3-triazole, have been widely used as novel and efficient synthons in the synthesis of various novel heterocycles. Although triazoles play an important role in the synthesis of nitrogen-containing heterocyclic compounds, their application in the synthesis of oxygen-containing heterocycles has been rarely reported.

[0005] Against this background, we developed a novel method for constructing 2,5-disubstituted or 2,3,5-trisubstituted furans using triazoles and enamine ketones as substrates, thus achieving the inventive results of this invention. This invention not only provides a completely new method for the synthesis of polysubstituted furans but also greatly expands the chemical reactivity of triazoles and enamine ketones.

[0006] References

[0007] [1]Y.-H.Zhou,M.Zhang,R.-X.Zhu,J.-Z.Zhang,F.Xie,X.-B.Li,W.-Q.Chang,X.-N.Wang,Z.-T.Zhao,H.-X.Lou,J.Nat.Prod.2016,79,2149-2157.

[0008] [2]MDDelost,DTSmith,BJAnderson,JTNjardarson,J.Med.Chem.2018,61,10996-11020.

[0009] [3]CHDuan,A.Furlan,JJFraneker,REMWillems,MMWienk,RAJJanssen,Adv.Mater.2015,27,4461-4468.

[0010] [4] B. Chattopadhyay, V. Gevorgyan, Angew. Chem. Int. Ed. 2012, 51, 862-872. Summary of the Invention

[0011] The purpose of this invention is to provide a method for preparing 2,5-disubstituted and 2,3,5-trisubstituted furan derivatives.

[0012] To achieve the above objectives, the present invention employs the following technical means:

[0013] Based on the understanding of the chemical properties of 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole 1, (E)-3-(dimethylamino)-1-phenylpropyl-2-enone 2 and (E)-2-((dimethylamino)methylene)cyclohexyl-1-enone 4, this invention synthesizes a series of 2,5-disubstituted furan derivatives 3 and 2-phenyl-4,5,6,7-tetrahydrobenzofuran structural derivatives 5 by extensive screening of reaction conditions such as metal Rh catalysts, reaction solvents, and reaction temperatures through [2+3] cycloaddition reactions.

[0014]

[0015] In equation (I), R 1 This represents 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the benzene ring are optionally replaced by the following groups: hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms; R in formula (I) 2 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, 1,2,3,4-tetrahydronaphthyl, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, pregnenolone derivative, musk derivative, phenyl, 1 to 2 phenyl groups substituted at any position, wherein the substituents on the phenyl group are optionally substituted with the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0016] In equation (II), R 1 Represents 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the benzene ring are optionally replaced by the following groups: hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, straight-chain or branched saturated alkyl groups containing 1 to 6 carbon atoms; R in formula (II) 3 This indicates 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the phenyl group are optionally replaced by the following groups: hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0017] In equation (II), n is selected from integers 1 and 2.

[0018] This invention first utilizes simple substrates to explore the feasibility of the reaction by screening reaction conditions such as catalyst type, reaction solvent, and reaction temperature. Using phenyl-substituted triazole 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole 1a and phenyl-substituted (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one enamino ketone 2a as model substrates, condition screening was conducted, and 2,5-diphenylfuran 3a was synthesized through a formal [2+3] cycloaddition reaction. Similarly, using phenyl-substituted triazole 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole 1a and (E)-2-((dimethylamino)methylene)cyclohexane-1-one 4a as model substrates, condition screening was conducted, and 2-phenyl-4,5,6,7-tetrahydrobenzofuran 5a was synthesized through a formal [2+3] cycloaddition reaction. Based on this, substrate tolerance was investigated by synthesizing several substrate derivatives of 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole 1, (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one enamino ketone 2 and (E)-2-((dimethylamino)methylene)cyclohexane-1-one 4. A series of 2,5-disubstituted furan derivatives 3 and 2-phenyl-4,5,6,7-tetrahydrobenzofuran derivatives 5 were synthesized using optimized reaction conditions.

[0019]

[0020] The general structural formulas of 2,5-disubstituted furan derivative 3 and 2-phenyl-4,5,6,7-tetrahydrobenzofuran derivative 5 are shown in formulas (I) and (II) below:

[0021]

[0022] In equation (I), R 1 This represents 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the benzene ring are optionally replaced by the following groups: hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms; R in formula (I) 2 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, 1,2,3,4-tetrahydronaphthyl, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, pregnenolone derivative, musk derivative, phenyl, 1 to 2 phenyl groups substituted at any position, wherein the substituents on the phenyl group are optionally substituted with the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0023] In equation (II), R1 Represents 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the benzene ring are optionally replaced by the following groups: hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, straight-chain or branched saturated alkyl groups containing 1 to 6 carbon atoms; R in formula (II) 3 This indicates 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the benzene ring are optionally replaced by the following groups: hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms.

[0024] In equation (II), n is selected from integers 1 and 2.

[0025] The method includes the following steps:

[0026] Using Rh2(esp)2 as a metal catalyst and DCE as a reaction solvent, 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative 1 and (E)-3-(dimethylamino)-1-phenylprop-2-en-1-one enamino ketone derivative 2 were mixed and heated at 90°C for 2 hours to synthesize 2,5-disubstituted furan derivative 3 as shown in formula (I); 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative 1 and (E)-2-((dimethylamino)methylene)cyclohexane-1-one derivative 4 were mixed and heated at 90°C for 2 hours to synthesize 2-phenyl-4,5,6,7-tetrahydrobenzofuran derivative 5 as shown in formula (II);

[0027]

[0028] Preferably, in formula (I), R 1 The benzene ring contains 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the benzene ring are optionally replaced by the following groups: hydrogen, F, Cl, Br, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, and n-hexyl.

[0029] Preferably, in formula (I), R 2The derivatives include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, dodecyl, cyclopropyl, cyclobutanealkyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 1,2,3,4-tetrahydronaphthyl, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, pregnenolone derivatives, musk derivatives, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-nitrophenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-phenoxyphenyl, 4-trifluoromethylphenyl, 4-hydroxyphenyl, 4- Cyanophenyl, 4-methylphenyl, 4-ethylphenyl, 4-n-propylphenyl, 4-n-butylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-n-pentylphenyl, 4-n-ethylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl, 3-nitrophenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-phenoxyphenyl, 3-trifluoromethylphenyl, 3-hydroxyphenyl, 3-cyanophenyl, 3-methylphenyl, 3-ethylphenyl, 3-n-propylphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-nitrophenyl, 2-methoxyphenyl, 2-ethoxyphenyl, 2-methylphenyl, 2-ethylphenyl.

[0030] Preferably, in formula (II), R 1 The benzene ring contains 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the benzene ring are optionally replaced by the following groups: hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, and n-hexyl.

[0031] Preferably, in formula (II), R 3 The following are examples of phenyl groups: hydrogen, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-nitrophenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-phenoxyphenyl, 4-trifluoromethylphenyl, 4-hydroxyphenyl, 4-cyanophenyl, 4-methylphenyl, 4-ethylphenyl, 4-n-propylphenyl, 4-n-butylphenyl, 4-isopropylphenyl, 4-isobutylphenyl, 4-n-pentylphenyl, 4-n-ethylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl, 3-nitrophenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-phenoxyphenyl, 3-trifluoromethylphenyl, 3-hydroxyphenyl, 3-cyanophenyl, 3-methylphenyl, 3-ethylphenyl, 3-n-propylphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-nitrophenyl, 2-methoxyphenyl, 2-ethoxyphenyl, 2-methylphenyl, and 2-ethylphenyl.

[0032] Preferably, the amount of 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative 1 is twice the molar amount of (E)-3-(dimethylamino)-1-phenylpropyl-2-enone 2 or (E)-2-((dimethylamino)methylene)cyclohexyl-1-enone 4, the amount of metal Rh2(esp)2 as catalyst is 2% of the molar amount of enone 2 or enone 4 derivative, the reaction temperature is 90°C, and the reaction time is 2 hours.

[0033] Preferably, the method further includes monitoring the reaction process using thin-layer chromatography. After the reaction is completed, the reaction solvent DCE is removed by vacuum distillation. The residue is separated by silica gel column chromatography, with petroleum ether-ethyl acetate as the eluent. The volume ratio of petroleum ether to ethyl acetate is 6:1. Solid or oily products are obtained, which are the purified 2,5-disubstituted furan derivative 3 and 2-phenyl-4,5,6,7-tetrahydrobenzofuran derivative 5 shown in formulas (I) and (II).

[0034] The preparation process of this invention can be represented by the following reaction formula:

[0035]

[0036] Raw materials 1, 2, and 4 in the preparation method of this invention can be purchased directly or prepared by existing methods. For example, they can be prepared by the following methods:

[0037] 1) Different substituted phenylacetylene derivatives 6 and equimolar amounts of p-toluenesulfonyl azide 7 were stirred in toluene, and catalyst CuTc (20%) was added. The mixture was stirred at room temperature for 2 hours to obtain 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative 1.

[0038]

[0039] 2) Different alkyl or aryl ketone derivatives 8 and N,N-dimethylformamide dimethyl acetal 9 were refluxed in toluene for 12 hours to obtain (E)-3-(dimethylamino)-1-phenylpropyl-2-enone 2 derivative; different cyclohexanone derivatives 10 and N,N-dimethylformamide dimethyl acetal 9 were refluxed in toluene for 12 hours to obtain (E)-2-((dimethylamino)methylene)cyclohexane-1-one 4 derivative;

[0040]

[0041] Compared with the prior art, the beneficial effects of the present invention are:

[0042] This invention provides a method for the efficient synthesis of 2,5-disubstituted furans and 2,3,5-trisubstituted furans and their derivatives using triazole and enamine ketones. This method enables the synthesis of a diverse range of 2,5-disubstituted furan derivatives 3 and 2-phenyl-4,5,6,7-tetrahydrobenzofuran derivatives 5, as shown in formulas (I) and (II). Compared with traditional methods for synthesizing polysubstituted furans, this new method offers significant advantages: 1) the substrates triazole and enamine ketones can be prepared from simple and inexpensive precursors; 2) this new method synthesizes a variety of 2,5-disubstituted furans and their derivatives with different substitution types and substituents in excellent yields, demonstrating good substrate versatility; 3) this new method can synthesize 2,3,5-trisubstituted furans and their derivatives with fused ring structures that are difficult to synthesize using other methods. This invention provides a method for constructing a library of small furan compounds and lays a solid material foundation for subsequent in-depth research on their biological activities. Meanwhile, this invention also provides a new technical means for the synthesis of active natural products with furan-like structural skeletons. Detailed Implementation

[0043] To further illustrate the present invention, a series of embodiments are given below. These embodiments are purely illustrative and are only used to specifically describe the present invention, and should not be construed as limiting the present invention.

[0044] The specific implementation method is as follows:

[0045] Example 1: Preparation of 2,5-diphenylfuran

[0046]

[0047] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 35 mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2,5-diphenylfuran 3a (36.5 mg, 83%). 1 H NMR (CDCl3, 500MHz): δ = 7.78 (d, J = 8.0, 4H), 7.43 (t, J = 8.0, 4H), 7.30 (t, J = 7.5, 2H), 6.76 (s, 2H) ppm; 13C NMR (CDCl3, 125MHz): δ = 153.5, 130.9, 128.9, 127.5, 123.9, 107.4ppm; HRMS m / z calcd for C 16 H 12 O[M+H] + :221.2474; found:221.2471.

[0048] Example 2: Preparation of 2-(4-methylphenyl)-5-phenylfuran (2-phenyl-5-(p-tolyl)furan)

[0049]

[0050] Weigh 125.2 mg of 4-methylphenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 1b and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenyldipropionic acid)rhodium] catalyst and 35 mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-methylphenyl)-5-phenylfuran 3b (43.5 mg, 93%). 1 H NMR (CDCl3, 500MHz): δ = 7.79 (d, J = 7.5Hz, 2H), 7.69 (d, J = 8.0Hz, 2H), 7.44 (t, J = 7.5Hz, 2H), 7.30 (t ,J=7.0Hz,1H),7.25(d,J=8.0Hz,2H),6.76(d,J=3.5Hz,1H),6.71(d,J=3.5Hz,1H),2.42(s,3H)ppm; 13 CNMR (CDCl3, 125MHz): δ=153.8,153.1,137.3,131.0,129.5,128.8,128.3,127.3,123.8,123.8,107.3,106.6,21.4ppm; HRMS m / z calcd for C 17 H 14 O[M+H] + :235.1113; found:225.1117.

[0051] Example 3: Preparation of 2-(4-tert-butylphenyl)-5-phenylfuran

[0052]

[0053] Weigh 142 mg of 4-tert-butylphenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 1c and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 35 mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90 °C for 2 hours, remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-tert-butylphenyl)-5-phenylfuran 3c (48 mg, 87%). 1 H NMR (CDCl3, 500MHz): δ = 7.78 (d, J = 7.5Hz, 2H), 7.72 (d, J = 8.5Hz, 2H), 7.47 (d, J = 8.5Hz, 2H), 7.43 (t ,J=7.5Hz,2H),7.29(d,J=7.5Hz,1H),6.75(d,J=3.5Hz,1H),6.72(d,J=3.0Hz,1H),1.39(s,9H)ppm; 13 C NMR (CDCl3, 125MHz): δ=153.7,153.2,150.6,131.0,128.8,128.3,127.3,125.8,123.8,123.7,107.3,106.8,34.8,31.4ppm; HRMS m / z calcd for C 20 H 20 O[M+H] + :277.1582; ​​found:277.1587.

[0054] Example 4: Preparation of 2-(4-n-butylphenyl)-5-phenylfuran

[0055]

[0056] Weigh 142 mg of 4-n-butylphenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 1d and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenyldipropionic acid)rhodium] catalyst and 35 mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90 °C for 2 hours, remove the organic solvent under reduced pressure and perform column chromatography to give 48 mg (87%) of white solid 2-(4-n-butylphenyl)-5-phenylfuran 3d. 1H NMR (CDCl3, 500MHz): δ = 7.78 (d, J = 7.0Hz, 2H), 7.70 (d, J = 8.0Hz, 2H), 7.43 (t, J = 8.0Hz, 2H), 7.29 (t, J = 8.0Hz, 1H), 7.25 (d, J = 8.0Hz, 2H) ),6.75(d,J=3.5Hz,1H),6.71(d,J=3.5Hz,1H),2.67(t,J=7.5Hz,2H),1.69-1.63(m,2H),1.45-1.38(m,2H),0.98(t,J=7.0Hz,3H)ppm; 13 C NMR (CDCl3, 125MHz): δ=153.8,153.1,142.4,131.0,128.9,128.8,128.5,127.3,123.9,123.8,107.3,106.7,35.6,33.7,22.5,14.1ppm; HRMS m / z calcd for C 20 H 20 O[M+H] + :277.1584; found:277.1587.

[0057] Example 5: Preparation of 2-(4-biphenyl)-5-phenylfuran (2-([1,1'-biphenyl]-4-yl)-5-phenylfuran)

[0058]

[0059] Weigh 150 mg of 4-biphenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 1e and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenyldipropionic acid)rhodium] catalyst and 35 mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90 °C for 2 hours, remove the organic solvent under reduced pressure and perform column chromatography to give 54 mg of 2-(4-biphenyl)-5-phenylfuran 3e, a white solid. 1 H NMR (CDCl3, 500MHz): δ = 7.84 (d, J = 8.0Hz, 2H), 7.80 (d, J = 8.0Hz, 2H), 7.68-7.66 (m, 4H), 7.48 (t, J = 7.5Hz, 2H), 7. 45(t,J=7.5Hz,2H),7.39(t,J=7.0Hz,1H),7.31(t,J=7.5Hz,1H),6.80(d,J=3.0Hz,1H),6.78(d,J=3.0Hz,1H)ppm;13 C NMR (CDCl3, 125MHz): δ=153.6,153.3,140.7,140.1,130.9,129.9,129.0,128.9,127.5,127.0,124.3,123.9,107.6,107.5ppm; HRMS m / z calcd for C 22 H 16 O[M+H] + :297.1271; found:297.1274.

[0060] Example 6: Preparation of 2-(4-chlorophenyl)-5-phenylfuran

[0061]

[0062] Weigh 133 mg of 4-chlorophenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole 1f and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenyldipropionic acid)rhodium] catalyst and 35 mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-chlorophenyl)-5-phenylfuran 3f (44.5 mg, 81%). 1 H NMR (CDCl3, 500MHz): δ = 7.75 (d, J = 7.5Hz, 2H), 7.67 (d, J = 8.5Hz, 2H), 7.43 (t, J = 7.5Hz, 2H), 7 .38(d,J=7.5Hz,2H),7.30(t,J=7.0Hz,1H),6.74(d,J=3.0Hz,1H),6.72(d,J=3.0Hz,1H)ppm; 13 C NMR (CDCl3, 125MHz): δ=153.8,152.4,133.1,130.7,129.4,129.0,128.9,127.7,125.0,123.9,107.8,107.4,107.4ppm; HRMS m / z calcd for C 16 H 11 ClO[M+H] + :255.0567; found:255.0571.

[0063] Example 7: Preparation of 2-(4-trifluoromethylphenyl)-5-phenylfuran

[0064]

[0065] Weigh 1 g (146.8 mg) of 4-trifluoromethylphenyl-1-p-toluenesulfonyl-1H-1,2,3-triazole and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 2a (35 mg) of (E)-3-(dimethylamino)-1-phenyl-2-enone. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 3 g (47 mg, 83%) of white solid 2-(4-chlorophenyl)-5-phenylfuran. 1 H NMR (CDCl3, 500MHz): δ = 7.83 (d, J = 8.0Hz, 2H), 7.77 (d, J = 8.0Hz, 2H), 7.65 (d, J = 8.5Hz, 2H), 7 .44(d,J=8.0Hz,2H),7.32(t,J=7.5Hz,1H),6.85(d,J=3.0Hz,1H),6.77(d,J=3.0Hz,1H)ppm; 13 C NMR (CDCl3, 125MHz): δ = 154.6, 151.9, 134.0, 130.5, 129.0 (q, J = 31.3Hz), 128.9, 1 28.0,125.9(q,J=3.75Hz),124.4(q,J=270.0Hz),124.1,123.8,109.4,107.6ppm; 19 F NMR (CDCl3, 470MHz, 500M): δ = -62.4 (s) ppm; HRMS m / z calcd for C 17 H 11 F3O[M+H] + :289.1248; found:289.1232.

[0066] Example 8: Preparation of 2-(3-methylphenyl)-5-phenylfuran (2-phenyl-5-(m-tolyl)furan)

[0067]

[0068] Weigh 125.2 mg of 4-(3-methylphenyl)-1-p-toluenesulfonyl-1,2,3-triazole 1h and add it to 1.5 mL of solvent DCE with stirring. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenyldipropionic acid)rhodium] catalyst and 35 mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90 °C for 2 hours, remove the organic solvent under reduced pressure and perform column chromatography to give 44.5 mg (95%) of white solid 2-(3-methylphenyl)-5-phenylfuran 3h. 1 H NMR (CDCl3, 500MHz): δ = 7.80 (d, J = 7.5Hz, 2H), 7.61-7.59 (m, 2H), 7.45 (t, J = 8.0Hz, 2H), 7.35-7 .29(m,2H),7.13(d,J=7.5Hz,1H),6.77(d,J=3.0Hz,1H),6.75(d,J=3.0Hz,1H),2.45(s,3H)ppm; 13 C NMR (CDCl3, 125MHz): δ=153.7,153.4,138.4,131.0,130.8,128.8,128.8,128.3,127.4,124.5,123.8,121.1,107.3,107.3,21.7ppm; HRMS m / z calcd for C 17 H 14 O[M+H] + :235.1116; found:235.1117.

[0069] Example 9: Preparation of 2-(3-fluorophenyl)-5-phenylfuran

[0070]

[0071] Weigh 126.8 mg of 4-(3-fluorophenyl)-1-p-toluenesulfonyl-1,2,3-triazole 1i and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenyldipropionic acid)rhodium] catalyst and 35 mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 41 mg (86%) of white solid 2-(3-fluorophenyl)-5-phenylfuran 3i. 1H NMR (CDCl3, 500MHz): δ = 7.77 (d, J = 7.5Hz, 2H), 7.52 (d, J = 8.0Hz, 1H), 7.47-7.42 (m, 3H), 7.39-7.35 ( m,1H),7.31(t,J=7.0Hz,1H),6.98(t,J=8.0Hz,1H),6.77(d,J=3.5Hz,1H),6.75(d,J=3.5Hz,1H)ppm; 13 CNMR (CDCl3, 125MHz): δ = 163.3 (d, J = 243.75Hz), 154.0, 152.2, 123.9 (d, J = 7.5Hz), 130.6, 130.4 (d, J=7.5Hz),128.9,127.8,124.0,119.5,114.2(d,J=21.25Hz),110.6(d,J=22.5Hz),108.4,107.4ppm; 19 F NMR (CDCl3, 376MHz): δ = -112.9--113.0(m)ppm; HRMS m / zcalcd for C 16 H 11 FO[M+H] + :239.0865; found:239.0867.

[0072] Example 10: Preparation of 2-(2-methoxyphenyl)-5-phenylfuran

[0073]

[0074] Weigh 131.6 mg of 4-(2-methoxyphenyl)-1-p-toluenesulfonyl-1,2,3-triazole 1j and add it to 1.5 mL of solvent DCE with stirring. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenyldipropionic acid)rhodium] catalyst and 35 mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 40 mg (80%) of white solid 2-(2-methoxyphenyl)-5-phenylfuran 3j. 1H NMR (CDCl3, 500MHz): δ = 8.04-8.01 (m, 1H), 7.80 (d, J = 6.5Hz, 2H), 7.45-7.40 (m, 2H), 7.31-7 .26(m,2H),7.11-7.06(m,2H),6.99(d,J=8.5Hz,1H),6.89(t,J=3.5Hz,1H),3.97(s,3H)ppm; 13 C NMR (CDCl3, 125MHz): δ=155.6,152.4,149.9,131.1,128.8,128.1,127.3,126.0,123.9,120.9,120.0,112.4,111.1,107.5,55.5ppm; HRMS m / zcalcd for C 17 H 14 O2[M+H] + :251.1064; found:251.1067.

[0075] Example 11: Preparation of 2-(3-thiophenyl)-5-phenylfuran

[0076]

[0077] Weigh 1k (122mg) of 4-(3-thienyl)-1-p-toluenesulfonyl-1,2,3-triazole and add it to 1.5mL of solvent DCE with stirring. Add 3.1mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenyldipropionic acid)rhodium] catalyst and 35mg of (E)-3-(dimethylamino)-1-phenyl-2-enone 2a. React at 90°C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 3k (36mg, 80%) of white solid 2-(3-thienyl)-5-phenylfuran. 1 H NMR (CDCl3, 500MHz): δ = 7.75 (d, J = 7.5Hz, 2H), 7.57 (d, J = 1.5Hz, 1H), 7.44-7.36 (m,4H),7.29(t,J=7.5Hz,1H),6.72(d,J=3.5Hz,1H),6.57(d,J=3.0Hz,1H)ppm; 13 C NMR (CDCl3, 125MHz): δ=152.8,150.6,132.7,130.9,128.8,127.4,126.4,124.8,123.8,119.0,107.1,107.0ppm; HRMS m / z calcd forC 17H 10 OS[M+H] + :227.0522; found:227.0525.

[0078] Example 12: Preparation of 2-(4-fluorophenyl)-5-phenylfuran

[0079]

[0080] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 38.6 mg of (E)-3-(dimethylamino)-1-(4-fluorophenyl)-2-enone 2b. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 41 mg (82%) of white solid 2-(4-fluorophenyl)-5-phenylfuran 3l. 1 H NMR (CDCl3, 500MHz): δ = 7.76-7.71 (m, 4H), 7.43 (t, J = 8.0Hz, 2H), 7.30 (t, J = 7.5 Hz,1H),7.12(t,J=8.5Hz,2H),6.74(d,J=3.0Hz,1H),6.68(d,J=3.0Hz,1H)ppm; 13 C NMR (CDCl3, 125MHz): δ = 162.3 (d, J = 245.0Hz), 153.5, 152.6, 130.8, 128.9, 12 7.5, 127.3, 125.6 (d, J = 7.5Hz), 123.8, 115.9 (d, J = 21.3Hz), 107.4, 107.0ppm; 19 F NMR (CDCl3, 376MHz, 400M): δ = -114.16--114.26(m)ppm; HRMS m / z calcd for C 16 H 11 FO[M+H] + :239.0863; found:239.0867.

[0081] Example 13: Preparation of 2-(4-bromophenyl)-5-phenylfuran

[0082]

[0083] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 50.6 mg of (E)-3-(dimethylamino)-1-(4-bromophenyl)-2-enone 2c. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-bromophenyl)-5-phenylfuran 3m (49 mg, 82%). 1 H NMR (CDCl3, 500MHz): δ = 7.75 (d, J = 8.0Hz, 2H), 7.60 (d, J = 8.5Hz, 2H), 7.53 (d, J = 8.0Hz, 2H), 7.43 (t, J = 7.5Hz, 2H), 7.30 (t, J = 7.0Hz, 1H), 6.74 (s, 2H) ppm; 13 C NMR (CDCl3, 125MHz): δ=153.9,152.4,132.0,130.7,129.8,128.9,127.7,125.3,123.9,121.2,107.9,107.4ppm; HRMS m / z calcd forC 16 H 11 BrO[M+H] + :299.0064; found:299.0066.

[0084] Example 14: Preparation of 2-(4-iodophenyl)-5-phenylfuran

[0085]

[0086] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 60.2 mg of (E)-3-(dimethylamino)-1-(4-iodophenyl)-2-enone 2d. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-iodophenyl)-5-phenylfuran 3n (62 mg, 90%). 1 H NMR (CDCl3, 500MHz): δ = 7.74 (t, J = 7.5Hz, 4H), 7.47 (d, J = 7.5Hz, 2H), 7.42 (t, J = 7.0Hz, 2H), 7.30 (t, J = 6.5Hz, 1H), 6.74 (s, 2H) ppm;13 C NMR (CDCl3, 125MHz): δ=153.9,152.4,137.9,130.6,130.3,128.9,127.7,125.5,123.9,108.1,107.5,92.5ppm; HRMS m / z calcd for C 16 H 11 IO[M+H] + :345.9846; found:345.9849.

[0087] Example 15: Preparation of 2-(4-nitrophenyl)-5-phenylfuran

[0088]

[0089] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 44 mg of (E)-3-(dimethylamino)-1-(4-nitrophenyl)-2-enone 2e. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-nitrophenyl)-5-phenylfuran 3o (22 mg, 42%). 1 H NMR (CDCl3, 500MHz): δ = 8.30-8.25 (m, 2H), 7.88-7.77 (m, 4H), 7.49-7.44 (m, 2H), 7.39-7.34 (m, 1H), 6.99-6.96 (m, 1H), 6.84-6.80 (m, 1H), ppm; 13 C NMR (CDCl3, 125MHz): δ=155.7,151.1,146.4,136.4,130.1,129.0,128.4,124.5,124.3,123.8,111.5,108.0ppm; HRMS m / z calcd for C 16 H 11 NO3[M+H] + :266.0806found:266.0812.

[0090] Example 16: Preparation of 2-(4-phenoxyphenyl)-5-phenylfuran

[0091]

[0092] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 53.4 mg of (E)-3-(dimethylamino)-1-(4-phenoxyphenyl)-2-enone 2f. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-phenoxyphenyl)-5-phenylfuran 3p (57 mg, 91%). 1 H NMR (CDCl3, 500MHz): δ = 7.77 (d, J = 8.0Hz, 2H), 7.74 (d, J = 8.5Hz, 2H), 7.43 (t, J = 7.5Hz, 2H), 7.39 (t, J = 8.0Hz, 2H), 7 .30(t,J=7.0Hz,1H),7.16(t,J=7.5Hz,1H),7.09(d,J=8.5Hz,4H),6.76(d,J=3.5Hz,1H),6.68(d,J=3.5Hz,1H)ppm; 13 C NMR (CDCl3, 125MHz): δ=157.2,156.8,153.3,153.1,130.9,129.9,128.8,127.4,126.3,125.4,123.8,123.5,119.3,119.1,107.4,106.7ppm; HRMS m / z calcd for C 22 H 16 O2[M+H] + :313.1216; found:313.1223.

[0093] Example 17: Preparation of 2-(4-pentylphenyl)-5-phenylfuran

[0094]

[0095] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 2 g (49 mg) of (E)-3-(dimethylamino)-1-(4-pentylphenyl)-2-enone. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-pentylphenyl)-5-phenylfuran 3q (49 mg, 85%). 1H NMR (CDCl3, 500MHz): δ = 7.78 (d, J = 7.5Hz, 2H), 7.70 (d, J = 8.0Hz, 2H), 7.43 (t, J = 7.5Hz, 2H), 7.29 (t, J = 7.5Hz, 1H), 7.25 (d, J = 8.0Hz, 2H) ,6.75(d,J=2.0Hz,1H),6.71(d,J=3.0Hz,1H),2.66(t,J=8.0Hz,2H),1.68(t,J=7.0Hz,2H),1.39-1.38(m,4H),0.95(t,J=7.0Hz,3H)ppm; 13 C NMR (CDCl3, 125MHz): δ=153.8,153.1,142.5,131.0,128.9,128.8,128.5,127.3,123.8,123.8,107.3,106.7,35.9,31.6,31.2,22.7,14.2ppm; HRMS m / z calcd for C 21 H 22 O[M+H] + :291.1739; found:291.1743.

[0096] Example 18: Preparation of 2-(4-isobutylphenyl)-5-phenylfuran

[0097]

[0098] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 46.2 mg of (E)-3-(dimethylamino)-1-(4-isobutylphenyl)-2-enone 2h. React at 90 °C for 2 h, remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-isobutylphenyl)-5-phenylfuran 3r (48.5 mg, 88%). 1H NMR (CDCl3, 500MHz): δ = 7.78 (d, J = 7.5Hz, 2H), 7.70 (d, J = 8.0Hz, 2H), 7.43 (t, J = 7.5Hz, 2H), 7.29 (t, J = 7.0Hz, 1H), 7.22 (d, J = 8 .0Hz,2H),6.76(d,J=3.0Hz,1H),6.71(d,J=3.5Hz,1H),2.53(d,J=7.0Hz,2H),1.97-1.89(m,1H),0.97(s,3H),0.96(s,3H)ppm; 13 C NMR (CDCl3, 125MHz): δ=153.8,153.1,141.2,131.0,129.6,128.8,128.5,127.3,123.8,123.7,107.3,106.7,45.4,30.4,22.5ppm; HRMS m / z calcd for C 20 H 20 O[M+H] + :277.1578; found:277.1587.

[0099] Example 19: Preparation of 2-(4-cyclohexylphenyl)-5-phenylfuran

[0100]

[0101] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 51.4 mg of (E)-3-(dimethylamino)-1-(4-cyclohexylphenyl)-2-enone 2i. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-(4-cyclohexylphenyl)-5-phenylfuran 3s (47 mg, 78%). 1H NMR (CDCl3, 500MHz): δ = 7.78 (d, J = 8.0Hz, 2H), 7.70 (d, J = 8.0Hz, 2H), 7.43 (t, J=7.5Hz,2H),7.29(t,J=8.5Hz,3H),6.75(d,J=3.5Hz,1H),6.70(d,J=3.5Hz, 1H),2.56(td,J1=11.0Hz,J1=2.5Hz,1H),1.94(d,J=10.0Hz,2H),1.90(d,J=1 0.0Hz,2H),1.80(d,J=12.5Hz,1H),1.52-1.40(m,4H),1.34-1.30(m,1H)ppm; 13 C NMR (CDCl3, 125MHz): δ=153.8,153.1,147.6,131.0,128.8,128.6,127.3,123.9,123.8,107.3,106.7,44.5,34.5,27.0,26.3ppm; HRMS m / z calcd forC 22 H 22 O[M+H] + 303.1739; found: 303.1743.

[0102] Example 20: Preparation of 2-(2-naphthyl)-5-phenylfuran

[0103]

[0104] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 45 mg of (E)-3-(dimethylamino)-1-(2-naphthyl)-2-enone 2j. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 47 mg (87%) of white solid 2-(2-naphthyl)-5-phenylfuran 3t. 1 H NMR (CDCl3, 500MHz): δ = 8.25 (s, 1H), 7.93 (d, J = 8.0Hz, 1H), 7.89-7.84 (s, 5H), 7.55- 7.46(s,4H),7.34(t,J=7.5Hz,1H),6.88(d,J=3.0Hz,1H),6.81(d,J=3.0Hz,1H)ppm; 13C NMR (CDCl3, 125MHz): δ=153.8,153.6,133.7,132.8,130.9,128.9,128.5,128.3 ,128.2,127.9,127.5,126.6,126.0,123.9,122.4,122.1,108.1,107.5ppm; HRMS m / z calcd for C 20 H 14 O[M+H] + :271.1109; found:271.1117.

[0105] Example 21: Preparation of 2-(2-thiophen-5-phenylfuran)

[0106]

[0107] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 36.2 mg of (E)-3-(dimethylamino)-1-(2-thiophene)-2-enone 2k. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 13.5 mg (30%) of white solid 2-(2-naphthyl)-5-phenylfuran 3u. 1 H NMR (CDCl3, 500MHz): δ = 7.91 (d, J = 7.5Hz, 2H), 7.59 (t, J = 7.5Hz, 2H), 7.52 (d, J = 3.0Hz, 1H) ,7.47-7.43(m,2H),7.25(t,J=4.0Hz,1H),6.89(d,J=3.5Hz,1H),6.78(d,J=3.5Hz,1H)ppm; 13 CNMR (CDCl3, 125MHz): δ=153.1,149.1,133.9,130.7,128.9,127.8,127.5,124.3,123.9,122.7,107.4,107.3ppm; HRMS m / z calcd for C 14 H 10 OS[M+H] + :227.0521; found:227.0525.

[0108] Example 22: Preparation of 2-isobutyl-5-phenylfuran

[0109]

[0110] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 31 mg of (E)-3-(dimethylamino)-1-(2-isobutyl)-2-enone 2l. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 29 mg (76%) of white solid 2-isobutyl-5-phenylfuran 3v. 1 H NMR (CDCl3, 500MHz): δ = 7.65 (d, J = 8.0Hz, 2H), 7.37 (t, J = 7.5Hz, 2H), 7.23 (t, J = 7.5Hz, 1H), 6.57 (d, J = 3.0Hz,1H),6.09(d,J=2.0Hz,1H),2.57(d,J=7.0Hz,2H),2.09-2.01(m,1H),1.00(d,J=7.0Hz,6H)ppm; 13 C NMR (CDCl3, 125MHz): δ=155.7,152.3,131.4,128.7,126.8,123.5,108.1,105.8,37.5,28.2,22.5ppm; HRMS m / z calcd for C 14 H 16 O[M+H] + :201.1274; found:201.1274.

[0111] Example 23: Preparation of 2-(2,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthalen)-5-phenylfuran (2-(3,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-5-phenyl furan)

[0112]

[0113] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediamine)rhodium] catalyst and 62.6 mg of (E)-3-(dimethylamino)-1-(2,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthalene)-2-enone 2m. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 62 mg (76%) of white solid 2-(2,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthalene)-5-phenylfuran 3w. 1 H NMR (CDCl3, 500MHz): δ = 7.79 (d, J = 7.5Hz, 2H), 7.75 (s, 1H), 7.46 (t, J = 7.5H) z,2H),7.33-7.31(m,2H),6.81(d,J=3.0Hz,1H),6.64(d,J=3.0Hz,1H),2.6 0(s,3H),1.99-1.95(m,1H),1.74(t,J=13.0Hz,1H),1.50-1.46(m,1H),1.4 4(s,3H),1.42(s,3H),1.39(s,3H),1.17(s,3H),1.07(d,J=6.5Hz,3H)ppm; 13 C NMR (CDCl3, 125MHz): δ=153.8,152.8,145.8,142.7,131.9,131.1,129.9,128.9,127.7,127.3, 125.3,123.7,110.0,107.0,43.8,37.7,34.7,34.2,32.6,32.3,28.7,25.0,21.9,17.0ppm; HRMS m / zcalcd for C 26 H 30 O[M+H] + :359.2362; found:359.2369.

[0114] Example 24: Preparation of 2-((3S,8S,9S,10R,13S,14S,17S)-3-methoxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopentane)-5-phenylfuran((2-((3S,8S,9S,10R,13S,14S,17S)-3-methoxy-10,13-dimethyl-2,3,4,7,8,910,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-5-phenylfuran)

[0115]

[0116] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 77 mg of (E)-3-(dimethylamino)-1-((3S,8S,9S,10R,13S,14S,17S)-3-methoxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecanohydro-1H-cyclopentane)-2-en-one 2n. The reaction was carried out at 90 °C for 2 hours, the organic solvent was removed under reduced pressure and the mixture was subjected to column chromatography to give a white solid 2-((3S,8S,9S,10R,13S,14S,17S)-3-methoxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecano-1H-cyclopentane)-5-phenylfuran 3x (53 mg, 62%). 1HNMR (CDCl3, 500MHz): δ = 7.63 (d, J = 7.5Hz, 2H), 7.36 (t, J = 7.5Hz, 2H), 7.21 (t, J = 7.0Hz, 1H), 6.57 (d, J = 3. 0Hz,1H),6.10(d,J=2.5Hz,1H),5.39(d,J=2.0Hz,1H),3.37(s,3H),3.11-3.06(m,1H),2.74(t,J=9.5Hz,1H ),2.42(d,J=11.0Hz,1H),2.18(t,J=11.5Hz,1H),2.09-2.00(m,4H),1.96-1.89(m,2H),1.80-1.78(m,1H) ,1.65-1.60(m,2H),1.56-1.31(m,6H),1.22-1.16(m,1H),1.11-1.05(m,1H),1.02(s,3H),0.58(s,3H)ppm; 13 C NMR (CDCl3, 125MHz): δ = 157.4, 152.3, 141.2, 131.5, 128.7, 126.8, 123.4, 121.5, 107.6, 105.5, 80.5, 56. 0,55.7,50.5,50.2,44.3,38.9,38.2,37.4,37.1,32.4,32.1,28.2,25.4,24.7,21.1,19.6,13.2ppm; HRMS m / z calcd for C 30 H 38 O2[M+H] + :431.2931; found:431.2945.

[0117] Example 25: Preparation of 2-phenyl-4,5,6,7-tetrahydrobenzofuran

[0118]

[0119] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 30.6 mg of (E)-2-(dimethylaminomethylene)cyclohexane-1-one 4a. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give a white solid 2-phenyl-4,5,6,7-tetrahydrobenzofuran 5a (33 mg, 83%). 1H NMR (CDCl3, 500MHz): δ = 7.63 (d, J = 7.5Hz, 2H), 7.36 (t, J = 8.0Hz, 2H), 7.21 (t, J = 7.0Hz, 1H), 6.4 9(s,1H),2.68(t,J=6.0Hz,2H),2.48(t,J=6.0Hz,2H),1.90-1.86(m,2H),1.80-1.76(m,2H)ppm; 13 C NMR (CDCl3, 125MHz): δ=151.7,150.9,131.6,128.7,126.7,123.4,119.1,106.1,23.4,23.3,23.2,22.3ppm; HRMS m / z calcd for C 14 H 14 O[M+H] + :199.1118; found:199.1117.

[0120] Example 26: Preparation of 2-phenyl-4,5-dihydronaphtho[1,2-b]furan

[0121]

[0122] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 40.2 mg of (E)-2-(dimethylaminomethylene)-3,4-dihydronaphthyl-1-enone 4b. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 43.2 mg (88%) of white solid 2-phenyl-4,5-dihydronaphtho[1,2-b]furan. 1 H NMR (CDCl3, 500MHz): δ = 7.76 (d, J = 7.5Hz, 2H), 7.61 (d, J = 7.5Hz, 1H), 7.43 (t, J = 8.0Hz, 2H), 7.29 (t, J = 7.0Hz, 2 H),7.22(d,J=7.0Hz,1H),7.16(t,J=8.0Hz,1H),6.65(s,1H),3.02(t,J=8.0Hz,2H),2.80(t,J=8.0Hz,2H)ppm; 13C NMR (CDCl3, 125MHz): δ=153.3,149.8,134.8,131.1,128.8,128.1,128.1,127.3,126.9,126.5,123.7,121.6,119.3,106.7,29.2,21.2ppm; HRMS m / z calcd for C 18 H 14 O[M+H] + :247.1114; found:247.1117.

[0123] Example 27: Preparation of 2-(4-biphenyl)-4,5-dihydronaphtho[1,2-b]furan (2-([1,1'-biphenyl]-4-yl)-4,5-dihydronaphtho[1,2-b]furan)

[0124]

[0125] Weigh 150 mg of 4-biphenyl-1-p-toluenesulfonyl-1,2,3-triazole 1e and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 40.2 mg of (E)-2-(dimethylaminomethylene)-3,4-dihydronaphthyl-1-enone 4b. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 52 mg (81%) of white solid 2-(4-biphenyl)-4,5-dihydronaphtho[1,2-b]furan. 1 H NMR (CDCl3, 500MHz): δ = 7.84 (d, J = 8.0Hz, 2H), 7.69-7.65 (m, 5H), 7.50 (t, J = 8.0Hz, 2H), 7.42-7.39 (m, 1H), 7.33 (t, J =7.0Hz,1H),7.27-7.25(m,1H),7.19(t,J=7.0Hz,1H),6.69(s,1H),3.05(t,J=8.0Hz,2H),2.82(t,J=7.5Hz,2H)ppm; 13 C NMR (CDCl3, 125MHz): δ=153.1,149.9,140.7,139.8,134.8,130.1,128.9,128.1,128. 1,127.5,127.5,127.0,126.9,126.5,124.1,121.7,119.3,106.9,29.1,21.1ppm; HRMS m / z calcd for C 24 H18 O[M+H] + :323.1430; found:323.1430.

[0126] Example 28: Preparation of 2-(4-trifluoromethylphenyl)-4,5-dihydronaphtho[1,2-b]furan

[0127]

[0128] Weigh 1 g (146.8 mg) of 4-trifluoromethylphenyl-1-p-toluenesulfonyl-1,2,3-triazole and add it to 1.5 mL of solvent DCE. Stir and add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 40.2 mg of (E)-2-(dimethylaminomethylene)-3,4-dihydronaphtho-1-en-one 4b. React at 90 °C for 2 hours, remove the organic solvent under reduced pressure and perform column chromatography to give 5 d (53 mg, 85%) of white solid 2-(4-trifluoromethylphenyl)-4,5-dihydronaphtho[1,2-b]furan. 1 HNMR (CDCl3, 500MHz): δ = 7.80 (d, J = 8.0Hz, 2H), 7.64 (d, J = 8.0Hz, 2H), 7.60 (d, J = 7.5Hz, 1H), 7.29 (t, J = 7.5Hz, 1H),7.22(d,J=7.0Hz,1H),7.18(t,J=7.5Hz,1H),6.72(s,1H),3.01(t,J=8.0Hz,2H),2.79(t,J=8.0Hz,2H)ppm; 13 C NMR (CDCl3, 125MHz): δ = 151.7, 150.9, 135.1, 134.2, 128.7 (q, J = 32.5Hz), 128.2, 127.7, 127.1, 127.0, 125.8 (q, J = 3.75Hz), 124.4 (q, J = 270.0Hz), 123.6, 121.7, 119.6, 108.7, 29.0, 21.0ppm; 19 F NMR (CDCl3, 470MHz, 500M): δ = -62.4 (s) ppm; HRMS m / z calcd for C 19 H 13 F3O[M+H] + 315.1741; found: 315.1743.

[0129] Example 29: Preparation of 2-phenyl-7-methoxy-4,5-dihydronaphtho[1,2-b]furan

[0130]

[0131] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE with stirring. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 46.2 mg of (E)-2-(dimethylaminomethylene)-6-methoxy-3,4-dihydronaphthyl-1-en-one 4c. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 47 mg (85%) of white solid 2-phenyl-7-methoxy-4,5-dihydronaphthyl-[1,2-b]furan 5e. 1 HNMR (CDCl3, 500MHz): δ = 7.72 (d, J = 7.5Hz, 2H), 7.51 (d, J = 7.5Hz, 1H), 7.40 (t, J = 7.5Hz, 2H), 7.25 (t, J = 7 .5Hz,1H),6.82-6.80(m,2H),6.61(s,1H),3.83(s,3H),2.97(t,J=7.5Hz,2H),2.76(t,J=7.5Hz,2H)ppm; 13 C NMR (CDCl3, 125MHz): δ=158.6,152.5,149.9,136.9,131.3,128.8,127.0,123.5,121.5,120.5,119.4,114.6,111.5,106.7,55.4,29.6,21.1ppm; HRMS m / z calcd for C 19 H 16 O2[M+H] + :277.1218; found:277.1223.

[0132] Example 30: Preparation of 2-phenyl-5,6-(dihydro-4H-benzocyclohepta)furan

[0133]

[0134] Weigh 120 mg of 4-phenyl-1-p-toluenesulfonyl-1,2,3-triazole 1a and add it to 1.5 mL of solvent DCE with stirring. Add 3.1 mg of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediol)rhodium] catalyst and 43 mg of (E)-3-(dimethylaminomethylene)chromogen-4-one 4d. React at 90 °C for 2 hours. Remove the organic solvent under reduced pressure and perform column chromatography to give 35.2 mg (68%) of white solid 2-phenyl-5,6-(dihydro-4H-benzocycloheptane)furan 5f. 1 H NMR (CDCl3, 400MHz): δ = 7.93 (d, J = 7.6Hz, 1H), 7.71-7.68 (m, 2H), 7.38-7.34 (m, 2H), 7.27-7.20 (m, 2H) ),7.13-7.08(m,2H),6.57(s,1H),2.88(t,J=5.6Hz,2H),2.80(t,J=6.4Hz,2H),2.00-1.94(m,2H)ppm; 13 CNMR (CDCl3, 125MHz): δ=152.4,147.8,139.1,130.9,130.4,129.6,128.8, 127.4,126.7,126.4,125.1,124.6,123.9,109.7,36.2,27.9,24.9ppm; HRMS m / z calcd for C 19 H 16 O[M+H] + :261.1270; found:261.1274.

Claims

1. A method for preparing 2,5-disubstituted furans as shown in general formula (I) and 2-phenyl-4,5,6,7-tetrahydrobenzofuran derivatives as shown in general formula (II): (I) (II) in, In formula (I) R 1 Represents 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the benzene ring are optionally substituted by the following groups: hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, straight-chain or branched saturated alkyl groups containing 1 to 6 carbon atoms; R in formula (I) 2 The term refers to a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, a cyclic alkyl group with 3 to 8 carbon atoms, 1,2,3,4-tetrahydronaphthyl, 2-thienyl, 2-furanyl, naphthyl, biphenyl, pyridyl, piperidinyl, morpholinyl, phenyl, 1 to 2 phenyl groups with substituents at any position, wherein the substituents on the phenyl group are optionally substituted with the following groups: halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, or a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms; In formula (II) R 1 Represents 1 to 2 substituents located at any position on the benzene ring, wherein the substituents are selected from hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, and straight-chain or branched saturated alkyl groups containing 1 to 6 carbon atoms; R in formula (II) 3 It represents 1 to 2 substituents located at any position on the benzene ring, wherein the substituents on the phenyl group are optionally replaced by the following groups: hydrogen, halogen, phenyl, NO2, methoxy, ethoxy, phenoxy, trifluoromethyl, cyano, hydroxyl, straight-chain or branched saturated alkyl groups containing 1 to 6 carbon atoms. In equation (II), n is selected from integers 1 and 2; The method includes the following steps: Under the conditions of using divalent metal Rh2(esp)2 as a catalyst and DCE as a reaction solvent, 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative 1 reacts with ( E )-3-(dimethylamino)-1-phenylpropyl-2-enone 2 when heated to 90 o At time C, the 2,5-disubstituted furan derivative 3 of formula (I) was synthesized by cycloaddition reaction; under the conditions of divalent metal Rh2(esp)2 as catalyst and DCE as reaction solvent, the 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative 1 reacted with ( E )-2-((dimethylamino)methylene)cyclohexyl-1-enone 4- when heated to 90°C o C Derivative 5, with the structure of 2-phenyl-4,5,6,7-tetrahydrobenzofuran shown in formula (II), was synthesized by cycloaddition reaction; 。 2. The method as described in claim 1, characterized in that, In the aforementioned formula (I), R 1 When the alkyl group is a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms, it may be selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, or n-hexyl; the halogen is selected from F, Cl, Br, and I.

3. The method as described in claim 1, characterized in that, In the aforementioned formula (I), R 2 When R is a straight-chain or branched saturated alkyl group with 1 to 12 carbon atoms, it may be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, or dodecyl; 2 When the alkyl group has 3 to 8 carbon atoms, it may be optionally cyclopropane, cyclobutane, cyclopentane, cyclohexyl, cycloheptane, or cyclooctane; R in formula (I) 2 When the substituent on the phenyl group is a straight-chain or branched saturated alkyl group with 1 to 6 carbon atoms, it may be selected as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, or n-hexyl.

4. The method as described in claim 1, characterized in that, In the above formula (II), R 1 When the alkyl group is a straight-chain or branched saturated alkyl group containing 1 to 6 carbon atoms, it may be selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, or n-hexyl; the halogen is selected from F, Cl, Br, and I; R in formula (II) 3 When the substituent on the phenyl group is a straight-chain or branched saturated alkyl group with 1 to 6 carbon atoms, it may be selected as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, n-pentyl, or n-hexyl.

5. The method as described in claim 1, characterized in that, The amount of 4-phenyl-1-toluenesulfonyl-1H-1,2,3-triazole derivative 1 used is ( E )-3-(dimethylamino)-1-phenylpropyl-2-enone 2 or ( E The reaction mixture consisted of 2 molar amounts of 2-((dimethylamino)methylene)cyclohexyl-1-enone 4, with metal Rh2(esp)2 as a catalyst at 2% of the molar amount of either enone 2 or enone 4, and the reaction temperature was 90°C. o C, reaction time 2 hours.

6. The method as described in claim 1, characterized in that, The method further includes monitoring the reaction process using thin-layer chromatography, removing the reaction solvent DCE by direct vacuum distillation after the reaction is complete, separating the residue by silica gel column chromatography, using petroleum ether-ethyl acetate as the eluent, wherein the volume ratio of petroleum ether to ethyl acetate is 6:1, to obtain solid or oily products, namely the purified 2,5-disubstituted furan derivative 3 and 2-phenyl-4,5,6,7-tetrahydrobenzofuran derivative 5 shown in Formula I and Formula II.

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