A multi-substituted tetrahydrofuran and tetrahydropyran diene compound and its preparation method

Abstract

The present invention belongs to the field of organic synthesis and provides a polysubstituted tetrahydrofuran and tetrahydropyran dienophile compound represented by formula I, wherein R 1 is selected from aryl or heteroaryl; R 2 and R 3 are each independently selected from hydrogen or C1-C6 alkyl; R 4 and R 5 are each independently selected from aryl, heteroaryl, C1-C6 alkyl or hydrogen; R 6 and R 7 are selected from cyano, nitro, C1-C6 alkyl, ester group or hydrogen. The target product of the present invention is synthesized through two steps, and the steps are as follows: (1) α-alkenyl lactone reacts with a nucleophile (such as nitrile, nitroalkane or ester, etc.) under the action of a base at -78 to 60 °C for 1-48 h to obtain a hemiacetal intermediate. (2) The hemiacetal intermediate is dehydrated under the catalysis of a Lewis acid or a Bronsted acid to form the compound represented by formula I. This method has simple process equipment, easy operation, is environmentally friendly, has low cost and good yield.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a polysubstituted tetrahydrofuran and tetrahydropyran dienophile compound and a preparation method thereof. Background Art

[0002] Polysubstituted tetrahydrofuran and tetrahydropyran dienophiles are very important synthons, which are widely used in the synthesis of various natural products and drug molecules. Such compounds can be used to prepare polysubstituted benzofurans and benzopyrans through D-A / oxidation reactions. Benzofuran is a typical representative of a class of oxygen-containing heterocyclic compounds. Benzofuran derivatives and their analogs are widely present in natural products. Many compounds containing benzofuran structures have the effects of anti-HIV, anti-tumor, anti-fungal, and delaying cardiovascular aging. So far, more than 30 natural benzofuran compounds have been clinically applied, and more than 3,000 benzofuran compounds have been discovered in natural products by humans; in addition, the benzopyran structure is also widely present in various natural products and has good biological activity. Many flower color substances, such as anthocyanins, are also derivatives of benzopyrylium salts.

[0003] In addition, polysubstituted tetrahydrofuran and tetrahydropyran dienophiles are also often used in materials science to synthesize new materials; they can also be used as monomers to synthesize high molecular compounds; and polysubstituted tetrahydrofuran and tetrahydropyran dienophiles themselves may also have certain biological activities and can be used for anti-fungal, anti-inflammatory, anti-cancer, and anti-viral purposes, etc. Therefore, the synthesis of polysubstituted tetrahydrofuran and tetrahydropyran dienophile compounds has very important application significance.

[0004] At present, there are few reports on the methods for synthesizing tetrahydrofuran and tetrahydropyran dienophiles ((a) J. Chem. Soc., Chem. Commun., 1986, 1230 - 1232. (b) Org. Lett. 2018, 20, 4709 - 4712. (c) Angew. Chem., Int. Ed. 2018, 57, 15553 - 15557), and it is challenging to efficiently and rapidly synthesize polysubstituted tetrahydrofuran and tetrahydropyran dienophiles using simple raw materials.

[0005] Therefore, it is very necessary to explore how to efficiently and rapidly synthesize polysubstituted tetrahydrofuran and tetrahydropyran dienophile compounds using simple raw materials. Summary of the Invention

[0006] The object of the present invention is to provide a polysubstituted tetrahydrofuran and tetrahydropyran dienophile compound, which has good reaction activity, can be used in organic synthesis methodology, and can be used as a precursor molecule for synthesizing benzotetrahydrofuran or benzotetrahydropyran.

[0007] Another object of the present invention is to provide a preparation method for efficiently and rapidly synthesizing polysubstituted tetrahydrofuran and tetrahydropyran diene compounds using simple raw materials.

[0008] The present invention is achieved through the following technical solutions:

[0009] The present invention provides polysubstituted tetrahydrofuran and tetrahydropyran diene compounds represented by Formula I,

[0010]

[0011] wherein, R 1 is selected from aryl or heteroaryl; R 2 and R 3 are each independently selected from hydrogen or C1-C6 alkyl; R 4 and R 5 are each independently selected from aryl, heteroaryl, C1-C6 alkyl or hydrogen; R 6 and R 7 are each independently selected from cyano, nitro, C1-C6 alkyl, ester group or hydrogen.

[0012] Among the above groups:

[0013] The aryl or heteroaryl is preferably phenyl or substituted phenyl. Specifically, the substituted phenyl includes phenyl substituted with electron-donating substituents and electron-withdrawing substituents at any position; further specifically, the aryl or heteroaryl is selected from phenyl, methylphenyl, halophenyl, methoxyphenyl, naphthyl, anthryl, thiophene, benzofuran, pyridyl, indolyl, furyl; more preferably phenyl, benzofuran, naphthyl, thiophene, methoxyphenyl, halophenyl or methylphenyl; even more preferably phenyl, thiophene, methoxyphenyl, halophenyl or methylphenyl;

[0014] C1-C6 alkyl refers to a straight-chain or branched-chain alkyl having 1 to 6 carbon atoms, including: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, n-hexyl, cyclohexyl, etc.; preferably an alkyl having 1 to 3 carbon atoms; particularly preferably methyl or ethyl.

[0015] The preparation method of the above-mentioned tetrahydrofuran and tetrahydropyran diene compounds includes the following steps:

[0016] Step 1: The α-alkenyl lactone represented by Formula III undergoes a 1,2 addition reaction with a nucleophile in the presence of a solvent and a base to prepare a hemiacetal represented by Formula II;

[0017]

[0018] Specifically, the reaction steps of Step 1 are as follows:

[0019] A nucleophile is charged into a reactor, a solvent and a base are added, and then an α-alkenyl lactone is added dropwise and reacted. After the reaction is completed, separation and purification are carried out to obtain the hemiacetal shown in Formula II.

[0020] More specifically, in the reaction of Step 1:

[0021] The solvent is selected from one or more of toluene, ethylbenzene, benzene, tetrahydrofuran, 1,4-dioxane, diethyl ether, ethylene glycol dimethyl ether, n-hexane or petroleum ether; the preferred solvent is an ether solvent.

[0022] The nucleophile is selected from one of nitriles, nitroalkanes or esters; preferably nitriles and esters.

[0023] The base is selected from one or more of n-butyllithium, tert-butyllithium, sodium hydride, sodium ethoxide, sodium methoxide, potassium tert-butoxide or Grignard reagent; the preferred base is sodium ethoxide.

[0024] The molar ratio of each material in the reaction satisfies: the molar ratio of α-alkenyl lactone to nucleophile is 1:0.4 to 8; further preferably 1:0.5 to 4. The molar ratio of α-alkenyl lactone to base is 1:0.4 to 8; further preferably 1:1 to 3. Under this reaction condition, the reaction substrates can react fully, avoiding waste of raw materials.

[0025] The reaction temperature is -78°C to 60°C; further preferably 0 to 30°C. The reaction time is 1 to 48 h; further preferably 8 - 10 h. Under this reaction condition, there are fewer reaction impurities and lower energy consumption.

[0026] The separation and purification method in Step 1 can be extractive distillation or column chromatography separation.

[0027] Step 2: The hemiacetal shown in Formula II undergoes a dehydration reaction in the presence of a catalyst and a solvent to prepare a tetrahydrofuran and tetrahydropyran diene compound shown in Formula I;

[0028]

[0029] Specifically, the reaction steps of Step 2 are as follows:

[0030] The hemiacetal shown in Formula II is charged into a reactor, a solvent and a catalyst are added and reacted fully. After the reaction is completed, separation and purification are carried out to obtain the tetrahydrofuran and tetrahydropyran diene compound shown in Formula I.

[0031] More specifically, in the reaction of Step 2:

[0032] The solvent is selected from one or more of toluene, ethylbenzene, benzene, dichloromethane, 1,2-dichloroethane, chloroform, tetrahydrofuran, 1,4-dioxane, ether, ethylene glycol dimethyl ether, n-hexane, petroleum ether, acetonitrile, DMF, DMAC or DMSO; preferably, the solvent is a halogenated alkane, and the halogenated alkane has a low boiling point, which is convenient for subsequent distillation and removal.

[0033] The catalyst is selected from Zn(OAc) 2 ·2H 2 O, CuSO 4 ·5H 2 O, Cu(OTf) 2 , Pd(OAc) 2 , FeSO 4 , Fe(acac) 3 , FeCl 3 , Fe(ox) 3 ·6H 2 O, FeBr 3 , Co(acac) 2 , Ni(acac) 2 , MnCl 2 .4H 2 O, La(OTf) 3 , BF 3 ·Et 2 O, p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, sulfuric acid or acetic acid; preferably, the catalyst is an iron-based catalyst, and the iron-based catalyst has good catalytic activity and low cost.

[0034] The molar ratio of the hemiacetal to the catalyst is 1:0.1 to 2; further preferably 1:0.5 to 1.

[0035] The reaction temperature is 20 °C to 50 °C; further preferably room temperature; the reaction time is 0.5 to 48 h; further preferably 4 to 6 h. Under these reaction conditions, there are few reaction by-products, the energy consumption is low, the raw materials react fully, and the yield is high.

[0036] The separation and purification method in the second step can be extractive distillation.

[0037] It should be noted that the starting material α-alkenyl lactone of this application can be prepared by the following method:

[0038]

[0039] Weigh 3-substituted alkynoic acid and allyl alcohol or crotyl alcohol and add them to a reactor, and then add a solvent, a catalyst and a reducing agent for reaction. After the reaction is completed, separate and purify to obtain the starting material α-alkenyl lactone of this application.

[0040] The beneficial effects of the present invention are as follows:

[0041] 1. The multi-substituted tetrahydrofuran and tetrahydropyran dienophile compounds of the present invention have good reactivity, can be used in organic synthesis methodology, and can be used as precursor molecules for synthesizing benzotetrahydrofuran or benzotetrahydropyran; such compounds can also be used as monomers to synthesize high molecular weight compounds; and the multi-substituted tetrahydrofuran and tetrahydropyran dienophile itself may also have certain biological activities and can be used in the preparation of antifungal, anti-inflammatory, anti-cancer and antiviral drugs, etc.

[0042] 2. The preparation method of the multi-substituted tetrahydrofuran and tetrahydropyran dienophile compounds of the present invention has a simple and rapid synthesis method, the catalyst is cheap and easily available, is environmentally friendly, has low cost, good yield, simple process equipment, easy operation, and has good practical application prospects. Specific Embodiments

[0043] To make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the present invention will be further described below in conjunction with specific embodiments: All reagents used in the present invention are commercially available products.

[0044] The target products in the following embodiments are all prepared by the following Step 1 and Step 2 in sequence:

[0045] Step 1: The α-alkenyl lactone shown in Formula III undergoes a 1,2 addition reaction with a nucleophile in the presence of a solvent and a base to prepare the hemiacetal shown in Formula II;

[0046]

[0047] Step 2: The hemiacetal shown in Formula II undergoes a dehydration reaction in the presence of a catalyst and a solvent to prepare the tetrahydrofuran and tetrahydropyran dienophile compounds shown in Formula I;

[0048]

[0049] Example 1

[0050] Target compound:

[0051]

[0052] Preparation method:

[0053] Step 1: 2.0 g of (E)-2-benzylidene-3,3-dimethylbutyrolactone was dissolved in 10 ml of 1,4-dioxane to form an allyl lactone solution; 1.3 g of malononitrile was weighed into a reaction flask, 10 ml of 1,4-dioxane was added, and the temperature was lowered to 0 - 5 °C; 2.2 g of potassium tert-butoxide was weighed into the reaction flask; the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at 0 - 5 °C for 10 h; after the reaction was completed, water was added for quenching, and extraction was carried out with ethyl acetate. The solvent was removed by distillation under reduced pressure to obtain 2.3 g of an oily hemiacetal with a yield of 85%.

[0054] Step 2: The hemiacetal obtained in the previous step was dissolved in 10 ml of chloroform, and 2 g of Cu(OTf) 2 was added, and then the temperature was raised to 45 °C and the reaction was carried out for 4 h; after the reaction was completed, water was added for quenching, and extraction was carried out with chloroform. The solvent was removed by distillation under reduced pressure to obtain 2 g of an oily substance with a yield of 95%.

[0055] Product characterization:

[0056] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.41 - 7.35 (m, 2H), 7.34 - 7.31 (m, 1H), 7.30 - 7.27 (m, 2H), 6.68 (s, 1H), 3.98 (s, 2H), 1.24 (s, 6H). 13C NMR (101 MHz, CDCl3): δ 184.16, 162.15, 141.53, 129.77, 128.92, 128.51, 128.19, 128.09, 117.27, 84.25, 42.76, 41.27, 25.82.

[0057] Example 2

[0058] Target compound:

[0059]

[0060] Preparation method:

[0061] Step 1: 2.0 g of (E)-2-benzylidene-3,3-dimethylbutyrolactone was dissolved in 10 ml of tetrahydrofuran to form an allyl lactone solution; 0.5 g of acetonitrile was weighed into a reaction flask, 10 ml of tetrahydrofuran was added; n-butyllithium was weighed into the reaction flask (the molar ratio of n-butyllithium to (E)-2-benzylidene-3,3-dimethylbutyrolactone was 0.4:1); the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at 10 °C for 20 h; after the reaction was completed, water was added for quenching, and extraction was carried out with ethyl acetate. Column chromatography separation was carried out to obtain an oily hemiacetal with a yield of 83%.

[0062] Step 2: Dissolve the hemiacetal obtained in the previous step in 10 ml of dichloromethane, add Zn(OAc) 2 ·2H 2 O (the molar ratio of Zn(OAc) 2 ·2H 2 O to the hemiacetal is 0.1:1), then raise the temperature to 20 °C and react for 48 h; after the reaction is completed, quench with water, extract with ethyl acetate, and remove the solvent under reduced pressure to obtain an oily substance with a yield of 95%.

[0063] Product characterization:

[0064] Colorless liquid, 1 H NMR (400 MHz, CDCl 3 ): δ7.39 - 7.33 (m, 2H), 7.32 - 7.29 (m, 1H), 7.28 - 7.25 (m, 2H), 6.75 (s, 1H), 4.32 (s, 1H), 4.09 (s, 2H), 1.28 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ): δ174.17, 141.53, 134.52, 129.77, 128.87, 128.51, 128.09, 117.27, 84.25, 69.09, 42.76, 25.82.

[0065] Example 3

[0066] Target compound:

[0067]

[0068] Preparation method:

[0069] Step 1: Dissolve 2.2 g of (E)-2-benzylidene-3,3-dimethylvalerolactone in 12 ml of diethyl ether to form an allyl lactone solution; weigh 2.6 g of dimethyl malonate into a reaction flask, add 10 ml of diethyl ether; weigh sodium hydride and add it to the reaction flask (the molar ratio of sodium hydride to (E)-2-benzylidene-3,3-dimethylvalerolactone is 0.8:1); drop the alkenyl lactone solution into the reaction system and react at 20 °C for 12 h; after the reaction is completed, quench with water, extract with ethyl acetate, and separate by column chromatography to obtain an oily hemiacetal with a yield of 84%.

[0070] Step 2: Dissolve the hemiacetal obtained in the previous step in 12 ml of n-hexane, add CuSO 4 ·5H 2 O (CuSO 4 ·5H 2The molar ratio of O to the hemiacetal was 0.2:1), and then the temperature was raised to 30 °C and the reaction was carried out for 24 h; after the reaction was completed, water was added to quench the reaction, and the mixture was extracted with ethyl acetate. The solvent was removed by distillation under reduced pressure to obtain an oily substance with a yield of 96%.

[0071] Product characterization:

[0072] Colorless liquid. 1 H NMR(400MHz,CDCl 3 ):δ7.52 - 7.39(m,2H),7.38 - 7.35(m,1H),7.33 - 7.28(m,2H),6.70(s,1H),4.44 - 4.31(t,J=12Hz,2H),3.78(s,6H),1.79 - 1.76(t,J=12Hz,2H),1.18(s,6H). 13 C NMR(101MHz,CDCl 3 ):δ167.61,164.52,144.18,137.25,136.67,127.59,127.40,127.33,118.28,92.15,64.94,52.15,39.52,34.51,28.95.

[0073] Example 4

[0074] Target compound:

[0075]

[0076] Preparation method:

[0077] Step 1: 2.4 g of (E)-2-benzylidene-3-spirocyclohexylbutyrolactone was dissolved in 12 ml of ether to form an allyl lactone solution; 0.7 g of malononitrile was weighed into a reaction flask, and 10 ml of toluene was added; sodium ethoxide was weighed and added to the reaction flask (the molar ratio of sodium ethoxide to (E)-2-benzylidene-3-spirocyclohexylbutyrolactone was 1.2:1); the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at 30 °C for 8 h; after the reaction was completed, water was added to quench the reaction, and the mixture was extracted with ethyl acetate. Column chromatography separation was carried out to obtain an oily substance hemiacetal with a yield of 86%.

[0078] Step 2: The hemiacetal obtained in the previous step was dissolved in 12 ml of ethylbenzene, and Cu(OTf) 2 (Cu(OTf) 2 with a molar ratio of 0.3:1 to the hemiacetal) was added, and then the temperature was raised to 40 °C and the reaction was carried out for 12 h; after the reaction was completed, water was added to quench the reaction, and the mixture was extracted with ethyl acetate. The solvent was removed by distillation under reduced pressure to obtain an oily substance with a yield of 95%.

[0079] Product characterization:

[0080] Colorless liquid. 1 H NMR(400MHz,CDCl 3 ):δ7.47 - 7.33(m,5H),6.78(s,1H),4.22(s,2H),1.83 - 1.76(m,2H),1.74 - 1.63(m,5H),1.33 - 1.19(m,2H),1.14 - 1.02(m,1H). 13 C NMR(101MHz,CDCl 3 ):δ182.88,162.30,138.66,135.23,134.40,129.25,128.87,128.61,128.22,116.83,74.76,43.61,41.52,33.63,24.90,22.48.

[0081] Example 5

[0082] Target compound:

[0083]

[0084] Preparation method:

[0085] Step 1: Dissolve 2.3 g of (E)-2-benzylidene-3-spirocyclopentylbutyrolactone in 14 ml of n-hexane to form an allyl lactone solution; weigh 0.4 g of malononitrile into a reaction flask, add 14 ml of n-hexane; weigh sodium methoxide and add it to the reaction flask (the molar ratio of sodium methoxide to (E)-2-benzylidene-3-spirocyclopentylbutyrolactone is 1.6:1); drop the alkenyl lactone solution into the reaction system and react at 40 °C for 4 h; after the reaction is completed, quench with water, extract with ethyl acetate, and separate by column chromatography to obtain an oily hemiacetal with a yield of 83%.

[0086] Step 2: Dissolve the hemiacetal obtained in the previous step in 12 ml of ethylbenzene, add Cu(OTf) 2 (Cu(OTf) 2 (the molar ratio of Cu(OTf)

[0087] Product characterization:

[0088] Colorless liquid. 1 H NMR(400MHz,CDCl 3): δ 7.43 - 7.35 (m, 5H), 6.85 (s, 1H), 4.08 (s, 2H), 2.09 - 2.01 (m, 2H), 1.82 - 1.72 (m, 2H), 1.70 - 1.59 (m, 4H). 13 C NMR (101 MHz, CDCl 3 ): δ 186.27, 171.02, 137.48, 134.13, 132.93, 129.58, 129.01, 128.82, 128.52, 128.30, 117.33, 79.82, 50.19, 42.11, 36.55, 25.33.

[0089] Example 6

[0090] Target compound:

[0091]

[0092] Preparation method:

[0093] Step 1: Dissolve 3 g of (E)-2-benzylidene-3,3-dimethyl-4-(4-fluorophenyl)butyrolactone in 14 ml of petroleum ether to form an allyl lactone solution; weigh 2.8 g of malononitrile into a reaction flask, add 14 ml of petroleum ether; weigh potassium tert-butoxide and add it to the reaction flask (the molar ratio of potassium tert-butoxide to (E)-2-benzylidene-3,3-dimethyl-4-(4-fluorophenyl)butyrolactone is 2:1); drip the alkenyl lactone solution into the reaction system and react at 50 °C for 2 h; after the reaction is completed, quench with water, extract with ethyl acetate, and separate by column chromatography to obtain an oily hemiacetal with a yield of 84%.

[0094] Step 2: Dissolve the hemiacetal obtained in the previous step in 14 ml of 1,2-dichloroethane, add Pd(OAc) 2 (The molar ratio of Pd(OAc) 2 to the hemiacetal is 0.5:1), then heat to 20 °C and react for 36 h; after the reaction is completed, quench with water, extract with ethyl acetate, and evaporate the solvent under reduced pressure to obtain an oily substance with a yield of 95%.

[0095] Product characterization:

[0096] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.36 (m, 5H), 7.30 - 7.27 (m, 1H), 7.25 (m, 1H), 7.07 (t, J = 8.6 Hz, 2H), 6.79 (s, 1H), 5.14 (s, 1H), 1.26 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3 ): δ 191.71, 164.01, 138.63, 136.07, 134.09, 129.14, 128.84, 128.25, 128.16, 128.08, 115.45, 115.23, 112.33, 87.69, 44.10, 42.41, 24.26, 23.72. 19 F NMR (376 MHz, CDCl 3 ): δ -114.42.

[0097] Example 7

[0098] Target compound:

[0099]

[0100] Preparation method:

[0101] Step 1: 2.6 g of (E)-2-benzylidene-3,3-dimethyl-4-spirocyclopentyl butyrolactone was dissolved in 10 ml of toluene to form an allyl lactone solution; 1.1 g of acetonitrile was weighed into a reaction flask, and 10 ml of toluene was added; a Grignard reagent was weighed and added to the reaction flask (the molar ratio of the Grignard reagent to (E)-2-benzylidene-3,3-dimethyl-4-spirocyclopentyl butyrolactone was 2.4:1); the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at 60 °C for 1 h; after the reaction was completed, water was added for quenching, extracted with ethyl acetate, and separated by column chromatography to obtain an oily hemiacetal with a yield of 82%.

[0102] Step 2: The hemiacetal obtained in the previous step was dissolved in 14 ml of ethylene glycol dimethyl ether, and FeSO 4 (FeSO 4 with a molar ratio of 0.6:1 to the hemiacetal) was added, and then the temperature was raised to 45 °C and the reaction was carried out for 4 h; after the reaction was completed, water was added for quenching, extracted with ethyl acetate, and the solvent was removed under reduced pressure to obtain an oily substance with a yield of 95%. Product characterization:

[0103] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.44 - 7.29 (m, 5H), 6.68 (s, 1H), 4.36 (s, 1H), 1.96 - 1.80 (m, 2H), 1.76 - 1.70 (m, 6H), 1.16 (s, 6H). 13 C NMR (101 MHz, CDCl 3): δ 181.63, 156.25, 138.14, 136.09, 134.60, 128.97, 128.39, 128.05, 112.55, 99.12, 54.67, 43.93, 33.07, 23.38, 23.04.

[0104] Example 8

[0105] Target compound:

[0106]

[0107] Preparation method:

[0108] Step 1: 2.8 g of (E)-2-benzylidene-3,3-dimethyl-4-spirocyclohexylbutyrolactone was dissolved in 10 ml of ethylbenzene to form an allyl lactone solution; 1.8 g of acetonitrile was weighed into a reaction flask, and 10 ml of ethylbenzene was added; n-butyllithium was weighed and added to the reaction flask (the molar ratio of n-butyllithium to (E)-2-benzylidene-3,3-dimethyl-4-spirocyclohexylbutyrolactone was 2.8:1); the vinyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at -70 °C for 48 h; after the reaction was completed, water was added for quenching, extracted with ethyl acetate, and separated by column chromatography to obtain an oily hemiacetal with a yield of 84%.

[0109] Step 2: The hemiacetal obtained in the previous step was dissolved in 10 ml of petroleum ether, and Fe(acac) 3 (The molar ratio of Fe(acac) 3 to the hemiacetal was 0.7:1), and then the temperature was raised to 45 °C and the reaction was carried out for 4 h; after the reaction was completed, water was added for quenching, extracted with ethyl acetate, and the solvent was removed under reduced pressure to obtain an oily substance with a yield of 96%.

[0110] Product characterization:

[0111] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.37 - 7.31 (m, 3H), 7.30 - 7.26 (m, 2H), 6.74 (s, 1H), 4.38 (s, 1H), 1.75 - 1.59 (m, 8H), 1.36 - 1.30 (m, 2H), 1.08 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ): δ 192.55, 158.54, 138.21, 137.07, 134.78, 128.71, 128.28, 128.06, 116.46, 87.68, 46.09, 43.33, 31.05, 25.18, 22.71, 21.95.

[0112] Example 9

[0113] Target compound:

[0114]

[0115] Preparation method:

[0116] Step 1: Dissolve 2.4 g of (E)-2-benzylidene-3,4-cycloheptanobutyrolactone in 12 ml of benzene to form an allyl lactone solution; weigh 0.8 g of acetonitrile into a reaction flask, add 12 ml of benzene; weigh tert-butyllithium and add it to the reaction flask (the molar ratio of tert-butyllithium to (E)-2-benzylidene-3,4-cycloheptanobutyrolactone is 3.2:1); drop the vinyl lactone solution into the reaction system and react at -50 °C for 36 h; after the reaction is completed, quench with water, extract with ethyl acetate, and separate by column chromatography to obtain an oily hemiacetal with a yield of 85%.

[0117] Step 2: Dissolve the hemiacetal obtained in the previous step in 15 ml of acetonitrile, add FeCl 3 (FeCl 3 with a molar ratio of 0.8:1 to the hemiacetal), then heat to 45 °C and react for 4 h; after the reaction is completed, quench with water, extract with ethyl acetate, and evaporate the solvent under reduced pressure to obtain an oily substance with a yield of 95.8%.

[0118] Product characterization:

[0119] Colorless liquid. 1 H NMR(400MHz,DMSO-d 6 ):δ7.62(d,J=1.7Hz,1H),7.57–7.51(m,2H),7.54-7.43(m,2H),6.65(s,1H),4.46(ddd,J=10.9,8.1,4.2Hz,1H),4.34(s,1H),3.64(td,J=7.7,4.0Hz,1H),2.33-2.21(m,2H),1.85-1.54(m,7H),1.16–1.11(m,1H). 13 C NMR(101MHz,DMSO-d 6 ):δ181.59,148.11,136.37,134.22,132.13,130.15,129.71,128.86,116.77,82.89,43.54,42.66,32.50,27.30,26.35,25.09,24.47.

[0120] Example 10

[0121] Target compound:

[0122]

[0123] Preparation method:

[0124] Step 1: Dissolve 3.1 g of (E)-2-benzylidene-3,3,5-trimethyl-5-phenylvalerolactone in 16 ml of tetrahydrofuran to form an allyl lactone solution; weigh 0.6 g of acetonitrile into a reaction flask, add 16 ml of tetrahydrofuran; weigh sodium hydride and add it to the reaction flask (the molar ratio of sodium hydride to (E)-2-benzylidene-3,3,5-trimethyl-5-phenylvalerolactone is 4:1); drop the vinyl lactone solution into the reaction system and react at -30 °C for 24 h; after the reaction is completed, quench with water, extract with ethyl acetate, and separate by column chromatography to obtain an oily hemiacetal with a yield of 86.2%.

[0125] Step 2: Dissolve the hemiacetal obtained in the previous step in 15 ml of acetonitrile, add FeCl 3 (The molar ratio of FeCl 3 to the hemiacetal is 1:1), then raise the temperature to 45 °C and react for 4 h; after the reaction is completed, quench with water, extract with ethyl acetate, and evaporate the solvent under reduced pressure to obtain an oily substance with a yield of 96.3%.

[0126] Product characterization:

[0127] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.38 (d, J = 3.9 Hz, 4H), 7.36 - 7.26 (m, 2H), 7.28 - 7.16 (m, 2H), 7.06 - 6.98 (m, 2H), 6.88 (s, 1H), 4.33 (s, 1H), 2.28 (d, J = 14.6 Hz, 1H), 2.16 (d, J = 14.5 Hz, 1H), 1.74 (s, 3H), 1.09 (s, 3H), 0.65 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ 182.97, 151.44, 144.45, 142.53, 137.47, 137.08, 128.37, 127.82, 127.50, 127.29, 127.22, 124.69, 117.25, 82.56, 50.92, 45.24, 34.78, 32.56, 30.74.

[0128] Example 11

[0129] Target compound:

[0130]

[0131] Preparation method:

[0132] Step 1: 2.2 g of (E)-2-(4-fluorobenzylidene)-3,3-dimethylbutyrolactone was dissolved in 10 ml of 1,4-dioxane to form an allyl lactone solution; 2.2 g of acetonitrile was weighed into a reaction flask, and 10 ml of 1,4-dioxane was added; potassium tert-butoxide was weighed and added to the reaction flask (the molar ratio of potassium tert-butoxide to (E)-2-(4-fluorobenzylidene)-3,3-dimethylbutyrolactone was 4.4:1); the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at -10 °C for 12 h; after the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain an oily hemiacetal with a yield of 85.3%.

[0133] Step 2: The hemiacetal obtained in the previous step was dissolved in 10 ml of DMF, and Fe(ox) 3 ·6H 2 O (the molar ratio of Fe(ox) 3 ·6H 2 O to the hemiacetal was 1.1:1) was added, and then the temperature was raised to 45 °C and the reaction was carried out for 4 h; after the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, and the solvent was removed under reduced pressure to obtain an oily product with a yield of 94.9%.

[0134] Product characterization:

[0135] Colorless liquid. 1 1H NMR (400 MHz, CDCl 3 ): δ 7.35 - 7.30 (m, 2H), 7.13 - 7.08 (m, 2H), 6.63 (s, 1H), 4.35 (s, 1H), 3.99 (s, 2H), 1.31 (s, 6H). 13 13C NMR (101 MHz, CDCl 3 ): δ 185.17, 166.15, 162.65, 136.96, 135.37, 131.36, 131.25, 130.29, 130.18, 115.56, 115.38, 78.98, 45.67, 39.44, 25.65. 19F NMR (376 MHz, CDCl3): δ -114.48.

[0136] Example 12

[0137] Target compound:

[0138]

[0139] Preparation method:

[0140] Step 1: Dissolve 2.4 g of (E)-2-p-chlorobenzylidene-3,3-dimethylbutyrolactone in a mixture of 10 ml of diethyl ether and 1,2-dimethoxyethane to form an allyl lactone solution; weigh 3.2 g of acetonitrile into a reaction flask, add a mixture of 10 ml of diethyl ether and 1,2-dimethoxyethane; weigh potassium tert-butoxide and add it to the reaction flask (the molar ratio of potassium tert-butoxide to (E)-2-p-chlorobenzylidene-3,3-dimethylbutyrolactone is 4.8:1); drop the vinyl lactone solution into the reaction system and react at -5 °C for 10 h; after the reaction is completed, quench with water, extract with ethyl acetate, and separate by column chromatography to obtain an oily hemiacetal with a yield of 86.3%.

[0141] Step 2: Dissolve the hemiacetal obtained in the previous step in 10 ml of DMAC, add FeBr 3 (the molar ratio of FeBr 3 to the hemiacetal is 1.2:1), then heat to 45 °C and react for 4 h; after the reaction is completed, quench with water, extract with ethyl acetate, and distill off the solvent under reduced pressure to obtain an oily substance with a yield of 95.6%.

[0142] Product characterization:

[0143] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.34 (d, J = 8.5 Hz, 2H), 7.28 (d, J = 8.6 Hz, 2H), 6.55 (s, 1H), 3.98 (s, 2H), 1.28 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ): δ 182.16, 144.42, 136.68, 135.96, 134.94, 132.58, 130.61, 128.57, 116.23, 78.90, 44.35, 39.51, 25.66.

[0144] Example 13

[0145] Target compound:

[0146]

[0147] Preparation method:

[0148] Step 1: Dissolve 2.8 g of (E)-2-(p-bromobenzylidene)-3,3-dimethylbutyrolactone in a mixture of 10 ml of n-hexane and petroleum ether to form an allyl lactone solution; weigh 1.5 g of acetonitrile into a reaction flask, add a mixture of 10 ml of n-hexane and petroleum ether; weigh a mixture of potassium tert-butoxide and n-butyllithium and add it to the reaction flask (the molar ratio of the mixture of potassium tert-butoxide and n-butyllithium to (E)-2-(p-bromobenzylidene)-3,3-dimethylbutyrolactone is 5.2:1); drop the vinyl lactone solution into the reaction system and react at 5 °C for 6 h; after the reaction is completed, quench with water, extract with ethyl acetate, and separate by column chromatography to obtain an oily hemiacetal with a yield of 84.5%.

[0149] Step 2: Dissolve the hemiacetal obtained in the previous step in 10 ml of DMSO, add Co(acac) 2 (The molar ratio of Co(acac) 2 to the hemiacetal is 1.3:1), then heat to 45 °C and react for 6 h; after the reaction is completed, quench with water, extract with ethyl acetate, and remove the solvent under reduced pressure to obtain an oily substance with a yield of 96.2%. Product characterization:

[0150] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.51 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.7 Hz, 3H), 6.56 (s, 1H), 4.28 (s, 1H), 3.98 (s, 2H), 1.29 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ): δ 182.18, 144.38, 136.62, 136.11, 133.03, 131.53, 130.81, 123.18, 117.66, 78.85, 45.55, 43.24, 39.52, 25.71.

[0151] Example 14

[0152] Target compound:

[0153]

[0154] Preparation method:

[0155] Step 1: 2.8 g of (E)-2-benzylidene-3,3-dimethylbutyrolactone was dissolved in a mixture of 10 ml of n-hexane and petroleum ether to form an allyl lactone solution; 0.9 g of acetonitrile was weighed into a reaction flask, and 10 ml of a mixture of n-hexane and petroleum ether was added; a mixture of potassium tert-butoxide and n-butyllithium was weighed and added to the reaction flask (the molar ratio of the mixture of potassium tert-butoxide and n-butyllithium to (E)-2-benzylidene-3,3-dimethylbutyrolactone was 5.6:1); the vinyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at 10 °C for 12 h; after the reaction was completed, water was added for quenching, extraction was carried out with ethyl acetate, and column chromatography separation was carried out to obtain an oily hemiacetal with a yield of 86.5%.

[0156] Step 2: The hemiacetal obtained in the previous step was dissolved in 10 ml of DMSO, and Ni(acac) 2 (The molar ratio of Ni(acac) 2 to the hemiacetal was 1.4:1), and then the temperature was raised to 40 °C and the reaction was carried out for 6 h; after the reaction was completed, water was added for quenching, extraction was carried out with ethyl acetate, and the solvent was removed under reduced pressure to obtain an oily substance with a yield of 95.8%. Product characterization:

[0157] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.63 (td, J = 5.7, 2.6 Hz, 4H), 7.49 - 7.45 (m, 4H), 7.40 - 7.36 (m, 1H), 6.72 (s, 1H), 4.26 (s, 1H), 4.02 (s, 2H), 1.38 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ): δ 182.56, 146.48, 141.77, 140.09, 137.80, 135.08, 133.04, 130.10, 129.21, 128.91, 128.75, 127.81, 127.03, 126.91, 117.44, 79.04, 44.51, 39.53, 25.68.

[0158] Example 15

[0159] Target compound:

[0160]

[0161] Preparation method:

[0162] Step 1: 2.3 g of (E)-2-(p-methoxybenzylidene)-3,3-dimethylbutyrolactone was dissolved in a mixture of 14 ml of tetrahydrofuran and diethyl ether to form an allyl lactone solution; 0.4 g of acetonitrile was weighed into a reaction flask, and a mixture of 14 ml of tetrahydrofuran and diethyl ether was added; potassium tert-butoxide was weighed and added to the reaction flask (the molar ratio of potassium tert-butoxide to (E)-2-(p-methoxybenzylidene)-3,3-dimethylbutyrolactone was 6:1); the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at 10 °C for 12 h; after the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain an oily hemiacetal with a yield of 86.2%.

[0163] Step 2: The hemiacetal obtained in the previous step was dissolved in a mixture of 10 ml of n-hexane and petroleum ether, and MnCl 2 .4H 2 O (the molar ratio of MnCl 2 .4H 2 O to the hemiacetal was 1.5:1) was added, and then the temperature was raised to 40 °C and the reaction was carried out for 6 h; after the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, and the solvent was removed under reduced pressure to obtain an oily substance with a yield of 96.2%.

[0164] Product characterization:

[0165] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.37 (d, J = 8.7 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 6.58 (s, 1H), 4.27 (s, 1H), 3.98 (s, 2H), 3.85 (s, 3H), 1.33 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ): δ 182.75, 160.31, 146.25, 138.01, 132.87, 131.59, 126.40, 113.78, 79.09, 55.31, 43.61, 39.29, 25.42.

[0166] Example 16

[0167] Target compound:

[0168]

[0169] Preparation method:

[0170] Step 1: 2.2 g of (E)-2-p-methylbenzylidene-3,3-dimethylbutyrolactone was dissolved in a mixture of 14 ml of tetrahydrofuran and diethyl ether to form an allyl lactone solution; 0.6 g of acetonitrile was weighed into a reaction flask, and a mixture of 14 ml of tetrahydrofuran and diethyl ether was added; potassium tert-butoxide was weighed and added to the reaction flask (the molar ratio of potassium tert-butoxide to (E)-2-p-methylbenzylidene-3,3-dimethylbutyrolactone was 6.4:1); the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at 15 °C for 12 h; after the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, and separated by column chromatography to obtain an oily hemiacetal with a yield of 86.5%.

[0171] Step 2: The hemiacetal obtained in the previous step was dissolved in a mixture of 10 ml of n-hexane and petroleum ether, and La(OTf) 3 (La(OTf) 3 was added (the molar ratio of La(OTf) to the hemiacetal was 1.6:1), and then the temperature was raised to 25 °C and the reaction was carried out for 10 h; after the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, and the solvent was removed under reduced pressure to obtain an oily substance with a yield of 96.9%.

[0172] Product characterization:

[0173] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.27 (d, J = 6.0 Hz, 2H), 7.18 (d, J = 7.9 Hz, 2H), 6.61 (s, 1H), 4.22 (s, 1H), 3.98 (s, 2H), 2.33 (s, 3H), 1.30 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ): δ 182.73, 144.15, 139.16, 138.29, 134.26, 131.27, 129.51, 128.91, 116.94, 79.42, 44.37, 39.48, 25.55, 21.37.

[0174] Example 17

[0175] Target compound:

[0176]

[0177] Preparation method:

[0178] Step 1: 2.5 g of (E)-2-(benzo[d][1,3]dioxol-5-ylmethylene)-3,3-dimethylbutyrolactone was dissolved in 14 ml of tetrahydrofuran to form an allyl lactone solution; 1.6 g of acetonitrile was weighed into a reaction flask, and 14 ml of tetrahydrofuran was added; potassium tert-butoxide was weighed and added to the reaction flask (the molar ratio of potassium tert-butoxide to (E)-2-(benzo[d][1,3]dioxol-5-ylmethylene)-3,3-dimethylbutyrolactone was 6.8:1); the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at 10 °C for 12 h; after the reaction was completed, water was added for quenching, extracted with ethyl acetate, and separated by column chromatography to obtain an oily hemiacetal with a yield of 86.2%.

[0179] Step 2: The hemiacetal obtained in the previous step was dissolved in a mixture of 10 ml of n-hexane and petroleum ether, and BF 3 ·Et 2 O(BF 3 ·Et 2 O was added (the molar ratio of BF

[0180] Product characterization:

[0181] Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): δ 6.94 - 6.85 (m, 2H), 6.81 (d, J = 8.0 Hz, 1H), 6.53 (s, 1H), 6.03 (s, 2H), 3.96 (s, 2H), 1.33 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ): δ 182.66, 148.39, 147.73, 144.45, 137.93, 133.53, 127.94, 124.66, 117.17, 109.62, 108.24, 101.49, 79.08, 43.23, 39.36, 25.51.

[0182] Example 18

[0183] Target compound:

[0184]

[0185] Preparation method:

[0186] Step 1: 2.4 g of (E)-2-(benzofuran-2-ylmethylene)-3,3-dimethylbutyrolactone was dissolved in 14 ml of tetrahydrofuran to form an allyl lactone solution; 0.9 g of acetonitrile was weighed into a reaction flask, and 14 ml of tetrahydrofuran was added; a mixture of tert-butyllithium and sodium hydride was weighed and added to the reaction flask (the molar ratio of the mixture of tert-butyllithium and sodium hydride to (E)-2-(benzofuran-2-ylmethylene)-3,3-dimethylbutyrolactone was 7.2:1); the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at 20 °C for 15 h; after the reaction was completed, water was added for quenching, extraction was carried out with ethyl acetate, and column chromatography separation was carried out to obtain an oily hemiacetal with a yield of 86.3%.

[0187] Step 2: The hemiacetal obtained in the previous step was dissolved in a mixture of 10 ml of n-hexane and petroleum ether, a mixture of p-toluenesulfonic acid and methanesulfonic acid was added (the molar ratio of the mixture of p-toluenesulfonic acid and methanesulfonic acid to the hemiacetal was 1.8:1), and then the temperature was raised to 40 °C and the reaction was carried out for 5 h; after the reaction was completed, water was added for quenching, extraction was carried out with ethyl acetate, and the solvent was removed under reduced pressure to obtain an oily substance with a yield of 96.3%.

[0188] Product characterization:

[0189] Colorless liquid. 1 H NMR (400 MHz, DMSO-d 6 ): δ 7.84 (dd, J = 7.8, 1.0 Hz, 1H), 7.78 (dd, J = 8.3, 0.9 Hz, 1H), 7.56 - 7.51 (m, 1H), 7.49 (s, 1H), 7.46 - 7.38 (m, 1H), 6.62 (s, 1H), 4.27 (s, 2H), 4.23 (s, 2H), 1.66 (s, 6H). 13 C NMR (101 MHz, DMSO-d 6 ): δ 182.27, 155.99, 151.55, 144.17, 134.33, 128.15, 127.28, 124.27, 123.04, 122.69, 117.26, 115.43, 111.85, 79.16, 43.54, 39.11, 26.04.

[0190] Example 19

[0191] Target compound:

[0192]

[0193] Preparation method:

[0194] Step 1: Dissolve 2.1 g of (E)-2-(thiophen-2-ylmethylene)-3,3-dimethylbutyrolactone in 14 ml of tetrahydrofuran to form an allyl lactone solution; weigh 1.0 g of acetonitrile into a reaction flask, add 14 ml of tetrahydrofuran; weigh a mixture of tert-butyllithium and sodium hydride into the reaction flask (the molar ratio of the mixture of tert-butyllithium and sodium hydride to (E)-2-(thiophen-2-ylmethylene)-3,3-dimethylbutyrolactone is 7.6:1); drop the vinyl lactone solution into the reaction system and react at -10 °C for 16 h; after the reaction is completed, quench with water, extract with ethyl acetate, and separate by column chromatography to obtain an oily hemiacetal with a yield of 84.9%.

[0195] Step 2: Dissolve the hemiacetal obtained in the previous step in a mixture of 10 ml of n-hexane and petroleum ether, add hydrochloric acid (the molar ratio of hydrochloric acid to the hemiacetal is 1.9:1), and then heat to 30 °C and react for 6 h; after the reaction is completed, quench with water, extract with ethyl acetate, and evaporate the solvent under reduced pressure to obtain an oily substance with a yield of 96.5%.

[0196] Product characterization:

[0197] Colorless liquid. 1 H NMR(400MHz,CDCl 3 ):δ7.52(d,J=4.6Hz,1H),7.33(d,J=3.7Hz,1H),7.11(dd,J=5.1,3.7Hz,1H),6.71(s,1H),4.21(s,2H),4.01(s,2H),1.47(s,6H). 13 CNMR(101MHz,CDCl 3 ):δ182.88,144.56,136.04,134.31,130.83,130.54,130.20,127.79,117.28,79.43,42.58,38.51,24.65.

[0198] Example 20

[0199] Target compound:

[0200]

[0201] Preparation method:

[0202] Step 1: 2.5 g of (E)-2-(naphthalen-1-ylmethylene)-3,3-dimethylbutyrolactone was dissolved in 14 ml of tetrahydrofuran to form an allyl lactone solution; 2.1 g of acetonitrile was weighed into a reaction flask, and 14 ml of tetrahydrofuran was added; a mixture of tert-butyllithium and sodium methoxide was weighed and added to the reaction flask (the molar ratio of the mixture of tert-butyllithium and sodium methoxide to (E)-2-(naphthalen-1-ylmethylene)-3,3-dimethylbutyrolactone was 8:1); the alkenyl lactone solution was added dropwise to the reaction system, and the reaction was carried out at -20 °C for 24 h; after the reaction was completed, water was added for quenching, and extraction was carried out with ethyl acetate, and column chromatography separation was carried out to obtain an oily hemiacetal with a yield of 85.3%.

[0203] Step 2: The hemiacetal obtained in the previous step was dissolved in 10 ml of petroleum ether, acetic acid was added (the molar ratio of acetic acid to the hemiacetal was 2:1), and then the temperature was raised to 50 °C and the reaction was carried out for 5 h; after the reaction was completed, water was added for quenching, and extraction was carried out with ethyl acetate, and the solvent was removed by distillation under reduced pressure to obtain an oily substance with a yield of 97.2%.

[0204] Product characterization:

[0205] Colorless liquid. 1 H NMR(400MHz,CDCl 3 ):δ7.95 - 7.81(m,3H),7.66(q,J=3.1Hz,2H),7.44(dd,J=8.2,7.0Hz,1H),7.39(d,J=7.1Hz,1H),6.88(s,1H),3.98(s,2H),1.19(s,6H). 13 C NMR(101MHz,CDCl 3 ):δ181.97,144.18,137.64,136.75,133.25,131.87,131.23,129.01,128.48,126.59,126.38,126.09,125.07,124.75,117.68,78.84,44.69,39.73,26.10.

[0206] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for preparing a polysubstituted tetrahydrofuran and tetrahydropyran dienophile compound represented by formula I, characterized in that, it comprises the following steps: Step 1: The α-alkenyl lactone represented by formula III undergoes a 1,2 addition reaction with a nucleophile in the presence of a solvent and a base to prepare a hemiacetal represented by formula II; Step 2: The hemiacetal represented by formula II undergoes a dehydration reaction in the presence of a catalyst and a solvent to prepare a tetrahydrofuran and tetrahydropyran dienophile compound represented by formula I; Among them, R 1 is selected from phenyl, benzofuran, naphthyl, thiophene, methoxyphenyl, halophenyl or methylphenyl; R 2 and R 3 are each independently selected from hydrogen or C1-C3 alkyl; R 4 and R 5 are each independently selected from phenyl, thiophene, methoxyphenyl, halophenyl, methylphenyl, C1-C3 alkyl or hydrogen; R 6 is selected from cyano; R 7 is selected from cyano, C1-C3 alkyl or hydrogen; In Step 1, the base is selected from one or more of n-butyllithium, tert-butyllithium, sodium hydride, sodium ethoxide, sodium methoxide or potassium tert-butoxide; In Step 2, the catalyst is selected from Zn(OAc) 2 ·2H 2 O, CuSO 4 ·5H 2 O, Cu(OTf) 2 , Pd(OAc) 2 , FeSO 4 , Fe(acac) 3 , FeCl 3 , Fe(ox) 3 ·6H 2 O, FeBr 3 , Co(acac) 2 , Ni(acac) 2 , MnCl 2 .4H 2 O, La(OTf) 3 , BF 3 ·Et 2 O, p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, sulfuric acid or acetic acid, or one or more thereof.

2. The method for preparing a polysubstituted tetrahydrofuran and tetrahydropyran dienophile compound according to claim 1, characterized in that, In Step 1, the solvent is selected from one or more of toluene, ethylbenzene, benzene, tetrahydrofuran, 1,4-dioxane, diethyl ether, ethylene glycol dimethyl ether, n-hexane or petroleum ether.

3. The method for preparing a polysubstituted tetrahydrofuran and tetrahydropyran dienophile compound according to claim 1, characterized in that, In Step 2, the solvent is selected from one or more of toluene, ethylbenzene, benzene, dichloromethane, 1,2-dichloroethane, chloroform, tetrahydrofuran, 1,4-dioxane, diethyl ether, ethylene glycol dimethyl ether, n-hexane, petroleum ether, acetonitrile, DMF, DMAC or DMSO.

4. The method for preparing a polysubstituted tetrahydrofuran and tetrahydropyran dienophile compound according to claim 1, characterized in that, In Step 1, the molar ratio of the α-alkenyl lactone to the nucleophile is 1:0.4 - 8.

5. The method for preparing a polysubstituted tetrahydrofuran and tetrahydropyran dienophile compound according to claim 1, characterized in that, In Step 1, the molar ratio of the α-alkenyl lactone to the base is 1:0.4 - 8.

6. The method for preparing a polysubstituted tetrahydrofuran and tetrahydropyran dienophile compound according to claim 1, characterized in that, In Step 2, the molar ratio of the hemiacetal to the catalyst is 1:0.1 - 2.

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