CN112142694A - Polysubstituted tetrahydrofuran and tetrahydropyrane diene compound and preparation method thereof - Google Patents

Polysubstituted tetrahydrofuran and tetrahydropyrane diene compound and preparation method thereof Download PDF

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CN112142694A
CN112142694A CN202011010976.9A CN202011010976A CN112142694A CN 112142694 A CN112142694 A CN 112142694A CN 202011010976 A CN202011010976 A CN 202011010976A CN 112142694 A CN112142694 A CN 112142694A
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tetrahydrofuran
reaction
tetrahydropyrane
hemiacetal
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王继宇
张华�
李福裕
张远康
张淑青
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Chengdu Organic Chemicals Co Ltd of CAS
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    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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Abstract

The invention belongs to the field of organic synthesis, and provides a polysubstituted tetrahydrofuran and tetrahydropyrane diene compound shown in a formula I,
Figure DDA0002697547370000011
wherein R is1Selected from aryl or heteroaryl; r2And R3Selected from hydrogen or C1-C6 alkyl; r4And R5Each independently selected from aryl, heteroaryl, C1-C6 alkyl or hydrogen; r6And R7Selected from cyano, nitro, C1-C6 alkyl, ester group or hydrogen. The invention synthesizes a target product through two-step reaction, which comprises the following steps: (1) alpha-alkenyl lactone and nucleophilic reagent (nitrile, nitro alkane or ester, etc.) react for 1-48h under the action of alkali and at-78-60 ℃ to obtain hemiacetal intermediate. (2) The hemiacetal intermediate is dehydrated under the catalysis of Lewis acid or Bronsted acid to form the compound shown in the formula I. The method has the advantages of simple process equipment, easy operation, environmental protection, low cost and better yield.

Description

Polysubstituted tetrahydrofuran and tetrahydropyrane diene compound and preparation method thereof
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a polysubstituted tetrahydrofuran and tetrahydropyrane diene compound and a preparation method thereof.
Background
The polysubstituted tetrahydrofuran and tetrahydropyrane diene are very important synthons, are widely used for synthesizing various natural products and drug molecules, and can be used for preparing polysubstituted benzofuran and benzopyran compounds through D-A/oxidation reaction. Benzofuran is a typical representative of a class of oxygen-containing heterocyclic compounds, benzofuran derivatives and analogues thereof widely exist in natural products, many compounds containing benzofuran structures have the effects of resisting HIV, tumors and fungi and delaying cardiovascular aging, so far, more than 30 natural benzofuran compounds are clinically applied, and more than 3000 benzofuran compounds are found in natural products by human beings; in addition, benzopyran structure is widely existed in various natural products, has good biological activity, and many flower color substances, such as anthocyanidin, are also derivatives of benzopyran salt.
In addition, polysubstituted tetrahydrofuran and tetrahydropyrane diene compounds are also frequently used in material science for the synthesis of new materials; can also be used as a monomer to synthesize a high molecular compound; and the polysubstituted tetrahydrofuran and tetrahydropyrane diene may have certain bioactivity and may be used in resisting fungi, inflammation, cancer, virus, etc. Therefore, the synthesis of the polysubstituted tetrahydrofuran and tetrahydropyrane diene compounds has very important application significance.
At present, few methods for synthesizing tetrahydrofuran and tetrahydropyran diene are reported ((a) j. chem. soc., chem. commu., 1986,1230-1232.(b) org. lett.2018,20,4709-4712.(c) angelw.chem., int. ed.2018,57,15553-15557), and the rapid and efficient synthesis of polysubstituted tetrahydrofuran and tetrahydropyran diene from simple raw materials is challenging in itself.
Therefore, it is necessary to search for how to adopt simple raw materials to efficiently and quickly synthesize the polysubstituted tetrahydrofuran and tetrahydropyrane diene compounds.
Disclosure of Invention
The invention aims to provide a polysubstituted tetrahydrofuran and tetrahydropyrane diene compound which has good reaction activity, can be used in an organic synthesis methodology and can be used as a precursor molecule for synthesizing the benzotetrahydrofuran or the benzotetrahydropyrane.
The invention also aims to provide a preparation method for efficiently and quickly synthesizing the polysubstituted tetrahydrofuran and tetrahydropyrane diene compounds by adopting simple raw materials.
The invention is realized by the following technical scheme:
the invention provides a polysubstituted tetrahydrofuran and tetrahydropyrane diene compound shown in a formula I,
Figure BDA0002697547360000021
wherein R is1Selected from aryl or heteroaryl; r2And R3Each independently selected from hydrogen or C1-C6 alkyl; r4And R5Each independently selected from aryl, heteroaryl, C1-C6 alkyl or hydrogen; r6And R7Each independently selected from cyano, nitro, C1-C6 alkyl, ester group or hydrogen.
In the above groups:
the aryl or heteroaryl group is preferably a phenyl group or a substituted phenyl group, and specifically, the substituted phenyl group includes a phenyl group substituted at an arbitrary position with an electron donating substituent and an electron withdrawing substituent; more specifically, the aryl or heteroaryl group is selected from phenyl, methylphenyl, halophenyl, methoxyphenyl, naphthyl, anthracenyl, thiophene, benzofuran, pyridyl, indolyl, furyl; further preferably a phenyl group, a benzofuran group, a naphthyl group, a thiophene group, a methoxyphenyl group, a halophenyl group or a methylphenyl group, and further preferably a phenyl group, a thiophene group, a methoxyphenyl group, a halophenyl group or a methylphenyl group;
the C1-C6 alkyl refers to a straight chain or branched chain alkyl with 1-6 carbon atoms, and comprises: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, n-hexyl, cyclohexyl and the like; preferably an alkyl group having 1 to 3 carbon atoms; particularly preferred is methyl or ethyl.
The preparation method of the tetrahydrofuran and tetrahydropyrane diene compound comprises the following steps:
the method comprises the following steps: the alpha-alkenyl lactone shown in the formula III and a nucleophilic reagent are subjected to 1,2 addition reaction in the presence of a solvent and alkali to prepare hemiacetal shown in the formula II;
Figure BDA0002697547360000031
specifically, the reaction step of the first step is as follows:
weighing a nucleophilic reagent in a reactor, adding a solvent and alkali, then dripping alpha-alkenyl lactone into the reactor for reaction, and separating and purifying the mixture after the reaction is finished to obtain the hemiacetal shown in the formula II.
More specifically, in the reaction of step one:
the solvent is one or more selected from toluene, ethylbenzene, benzene, tetrahydrofuran, 1, 4-dioxane, diethyl ether, ethylene glycol dimethyl ether, n-hexane or petroleum ether; preferred solvents are ethereal solvents.
The nucleophilic reagent is selected from one of nitrile, nitroalkane or ester; nitriles and esters are preferred.
The base is selected from one or more of n-butyl lithium, tert-butyl lithium, sodium hydride, sodium ethoxide, sodium methoxide, potassium tert-butoxide or Grignard reagent; the preferred base is sodium ethoxide.
The molar ratio of materials in the reaction satisfies the following conditions: the molar ratio of the alpha-alkenyl lactone to the nucleophilic reagent is 1: 0.4-8; more preferably 1:0.5 to 4. The molar ratio of the alpha-alkenyl lactone to the alkali is 1: 0.4-8; more preferably 1:1 to 3. The reaction substrate can fully react under the reaction condition, and the waste of raw materials is avoided.
The reaction temperature is-78 ℃ to 60 ℃; more preferably 0 to 30 ℃. The reaction time is 1-48 h; further preferably 8 to 10 hours. The reaction has less reaction impurities and lower energy consumption under the reaction condition.
The separation and purification mode of the step one can be extractive distillation or column chromatography separation.
Step two: carrying out dehydration reaction on hemiacetal shown as a formula II in the presence of a catalyst and a solvent to prepare a tetrahydrofuran and tetrahydropyrane diene compound shown as a formula I;
Figure BDA0002697547360000041
specifically, the reaction step of the second step is as follows:
weighing hemiacetal shown as a formula II in a reactor, adding a solvent and a catalyst for full reaction, and separating and purifying after the reaction is finished to obtain the tetrahydrofuran and tetrahydropyrane diene compounds shown as the formula I.
More specifically, in the reaction of step two:
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; preferably, the solvent is an alkyl halide, which has a low boiling point and is easily removed by subsequent distillation.
The catalyst is selected from Zn (OAc)2·2H2O、CuSO4·5H2O、Cu(OTf)2、Pd(OAc)2、FeSO4、Fe(acac)3、FeCl3、Fe(ox)3·6H2O、FeBr3、Co(acac)2、Ni(acac)2、MnCl2.4H2O、La(OTf)3、BF3·Et2One or more of O, p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, sulfuric acid or acetic acid; the preferred catalyst is an iron catalyst, which has better catalytic activity and lower cost.
The molar ratio of the hemiacetal to the catalyst is 1: 0.1-2; more preferably 1:0.5 to 1.
The reaction temperature is 20 ℃ to 50 ℃; further preferably room temperature; the reaction time is 0.5-48 h; further preferably 4 to 6 hours. Under the reaction condition, the reaction by-product is less, the energy consumption is lower, the raw material reaction is sufficient, and the yield is higher.
The separation and purification mode of the second step can be extractive distillation.
The α -alkenyl lactone as a starting material in the present application can be prepared by the following method:
Figure BDA0002697547360000051
weighing 3-substituted alkynoic acid and allyl alcohol or alkene butanol, adding the 3-substituted alkynoic acid and allyl alcohol or alkene butanol into a reactor, adding a solvent, a catalyst and a reducing agent for reaction, and separating and purifying after the reaction is finished to obtain the initial raw material alpha-alkenyl lactone.
The invention has the beneficial effects that:
1. the polysubstituted tetrahydrofuran and the tetrahydropyrane diene compound have good reaction activity, can be used in an organic synthesis methodology and can be used as a precursor molecule for synthesizing the benzotetrahydrofuran or the benzotetrahydropyrane; the compound can also be used as a monomer to synthesize a high molecular compound; and the polysubstituted tetrahydrofuran and tetrahydropyrane diene may have certain bioactivity and may be used in preparing antifungal, antiphlogistic, anticancer, antiviral and other medicine.
2. The preparation method of the polysubstituted tetrahydrofuran and tetrahydropyrane diene compound has the advantages of concise and quick synthesis method, cheap and easily-obtained catalyst, environmental friendliness, low cost, better yield, simple process equipment, easy operation and good practical application prospect.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the present invention is further described with reference to specific embodiments as follows: the reagents used in the present invention are all commercially available products.
The synthesis of the target products of the following examples is prepared by the following steps one and two in sequence:
the method comprises the following steps: the alpha-alkenyl lactone shown in the formula III and a nucleophilic reagent are subjected to 1,2 addition reaction in the presence of a solvent and alkali to prepare hemiacetal shown in the formula II;
Figure BDA0002697547360000061
step two: carrying out dehydration reaction on hemiacetal shown as a formula II in the presence of a catalyst and a solvent to prepare a tetrahydrofuran and tetrahydropyrane diene compound shown as a formula I;
Figure BDA0002697547360000071
example 1
Target compound:
Figure BDA0002697547360000072
the preparation method comprises the following steps:
the method comprises the following steps: 2.0g of (E) -2-benzylidene-3, 3-dimethylbutyranolide was dissolved in 10ml of 1, 4-dioxane to form an allylic lactone solution; weighing 1.3g of malononitrile in a reaction bottle, adding 10ml of 1, 4-dioxane, and cooling to 0-5 ℃; 2.2g of potassium tert-butoxide is weighed into a reaction bottle; dripping alkenyl lactone solution into the reaction system, and reacting for 10h at 0-5 ℃; after the reaction, water was added to quench, extraction was carried out with ethyl acetate, and the solvent was distilled off under reduced pressure to obtain 2.3g of an oily hemiacetal, yield 85%.
Step two: the hemiacetal obtained in the previous step was dissolved in 10ml of chloroform, and 2g of Cu (OTf) was added2Then heating to 45 ℃ for reaction for 4 h; after the reaction, water was added to quench, chloroform was used for extraction, and the solvent was distilled off under reduced pressure to obtain 2g of an oily substance with a yield of 95%.
And (3) product characterization:
Colorless liquid.1H NMR(400MHz,CDCl3):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(101MHz,CDCl3):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.
example 2
Target compound:
Figure BDA0002697547360000081
the preparation method comprises the following steps:
the method comprises the following steps: 2.0g of (E) -2-benzylidene-3, 3-dimethylbutyranolide was dissolved in 10ml of tetrahydrofuran to form an allyl lactone solution; weighing 0.5g of acetonitrile in a reaction bottle, and adding 10ml of tetrahydrofuran; weighing n-butyllithium and adding the n-butyllithium into a reaction bottle (the molar ratio of the n-butyllithium to the (E) -2-benzylidene-3, 3-dimethyl butyrolactone is 0.4: 1); dripping alkenyl lactone solution into the reaction system, and reacting for 20h at 10 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separation to obtain the semi-acetal of the oily substance with the yield of 83 percent.
Step two: the hemiacetal obtained in the previous step was dissolved in 10ml of dichloromethane, Zn (OAc) was added2·2H2O(Zn(OAc)2·2H2The molar ratio of O to hemiacetal is 0.1: 1) then raising the temperature to 20 ℃ for reaction48 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by reduced pressure evaporation to obtain oily matter with the yield of 95%.
And (3) product characterization:
Colorless liquid,1H NMR(400MHz,CDCl3):7.39-7.33(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).13C NMR(101MHz,CDCl3):174.17,141.53,134.52,129.77,128.87,128.51,128.09,117.27,84.25,69.09,42.76,25.82.
example 3
Target compound:
Figure BDA0002697547360000091
the preparation method comprises the following steps:
the method comprises the following steps: 2.2g of (E) -2-benzylidene-3, 3-dimethylvalerolactone were dissolved in 12ml of diethyl ether to give an allyl lactone solution; weighing 2.6g dimethyl malonate in a reaction bottle, and adding 10ml diethyl ether; sodium hydride is weighed into a reaction bottle (the molar ratio of the sodium hydride to the (E) -2-benzylidene-3, 3-dimethyl valerolactone is 0.8: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 12h at 20 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separation to obtain the semi-acetal of the oily substance with the yield of 84%.
Step two: dissolving the hemiacetal obtained in the previous step in 12ml of n-hexane, adding CuSO4·5H2O(CuSO4·5H2The molar ratio of O to hemiacetal is 0.2: 1) then heating to 30 ℃ for reaction for 24 hours; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by reduced pressure evaporation to obtain oily matter with the yield of 96%.
And (3) product characterization:
Colorless liquid.1H NMR(400MHz,CDCl3):7.52-7.39(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).13C NMR(101MHz,CDCl3):167.61,164.52,144.18,137.25,136.67,127.59,127.40,127.33,118.28,92.15,64.94,52.15,39.52,34.51,28.95.
example 4
Target compound:
Figure BDA0002697547360000092
the preparation method comprises the following steps:
the method comprises the following steps: 2.4g of (E) -2-benzylidene-3-spirocyclohexylbutyrolactone were dissolved in 12ml of diethyl ether to give an allyl lactone solution; weighing 0.7g of malononitrile in a reaction bottle, and adding 10ml of toluene; weighing sodium ethoxide and adding into a reaction bottle (the molar ratio of the sodium ethoxide to the (E) -2-benzylidene-3-spirocyclohexyl butyrolactone is 1.2: 1); dripping alkenyl lactone solution into the reaction system, and reacting for 8 hours at 30 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separation to obtain the semi-acetal of the oily substance with the yield of 86%.
Step two: the hemiacetal obtained in the previous step was dissolved in 12ml of ethylbenzene, Cu (OTf) was added2(Cu(OTf)2Molar ratio to hemiacetal 0.3: 1) then heating to 40 ℃ and reacting for 12 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by reduced pressure evaporation to obtain oily matter with the yield of 95%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.47-7.33(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).13C NMR(101MHz,CDCl3):182.88,162.30,138.66,135.23,134.40,129.25,128.87,128.61,128.22,116.83,74.76,43.61,41.52,33.63,24.90,22.48.
Example 5
Target compound:
Figure BDA0002697547360000101
the preparation method comprises the following steps:
the method comprises the following steps: 2.3g of (E) -2-benzylidene-3-spirocyclopentylbutyrolactone was dissolved in 14ml of n-hexane to form an allyl lactone solution; weighing 0.4g of malononitrile in a reaction bottle, and adding 14ml of n-hexane; weighing sodium methoxide and adding the sodium methoxide into a reaction bottle (the molar ratio of the sodium methoxide to the (E) -2-benzylidene-3-spirocyclopentylbutyrolactone is 1.6: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 4 hours at 40 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separation to obtain the semi-acetal of the oily substance with the yield of 83 percent.
Step two: the hemiacetal obtained in the previous step was dissolved in 12ml of ethylbenzene, Cu (OTf) was added2(Cu(OTf)2Molar ratio to hemiacetal 0.4: 1) then heating to 50 ℃ to react for 0.5 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by reduced pressure evaporation to obtain oily matter with the yield of 96%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):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).13C NMR(101MHz,CDCl3):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.
Example 6
Target compound:
Figure BDA0002697547360000111
the preparation method comprises the following steps:
the method comprises the following steps: 3g of (E) -2-benzylidene-3, 3-dimethyl-4-p-fluorophenyl-butyrolactone were dissolved with 14ml of petroleum ether to form an allyl lactone solution; weighing 2.8g of malononitrile in a reaction bottle, and adding 14ml of petroleum ether; weighing potassium tert-butoxide and adding the potassium tert-butoxide into a reaction bottle (the molar ratio of the potassium tert-butoxide to the (E) -2-benzylidene-3, 3-dimethyl-4-p-fluorophenyl butyrolactone is 2: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 2h at 50 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separation to obtain the semi-acetal of the oily substance with the yield of 84%.
Step two: the hemiacetal obtained in the previous step was dissolved in 14ml of 1, 2-dichloroethane, and Pd (OAc) was added2(Pd(OAc)2The molar ratio to the hemiacetal is 0.5: 1) then heating to 20 ℃ for reaction for 36 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by reduced pressure evaporation to obtain oily matter with the yield of 95%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.36(m,5H),7.30-7.27(m,1H),7.25(m,1H),7.07(t,J＝8.6Hz,2H),6.79(s,1H),5.14(s,1H),1.26(s,3H),0.86(s,3H).13C NMR(101MHz,CDCl3):191.71,164.01,138.63,136.07,134.09,129.14,128.84,128.25,128.16,128.08,115.45,115.23,112.33,87.69,44.10,42.41,24.26,23.72.19F NMR(376MHz,CDCl3):-114.42.
Example 7
Target compound:
Figure BDA0002697547360000121
the preparation method comprises the following steps:
the method comprises the following steps: 2.6g of (E) -2-benzylidene-3, 3-dimethyl-4-spirocyclopentylbutyrolactone was dissolved in 10ml of toluene to form an allylic lactone solution; weighing 1.1g of acetonitrile into a reaction bottle, and adding 10ml of toluene; weighing Grignard reagent and adding into a reaction bottle (the molar ratio of the Grignard reagent to the (E) -2-benzylidene-3, 3-dimethyl-4-spirocyclopentylbutyrolactone is 2.4: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 1h at 60 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separation to obtain the semi-acetal of oil substance with the yield of 82%.
Step two: dissolving the hemiacetal obtained in the last step in 14ml of ethylene glycol dimethyl ether, adding FeSO4(FeSO4Molar ratio to hemiacetal 0.6: 1) then heating to 45 ℃ for reaction for 4 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by reduced pressure evaporation to obtain oily matter with the yield of 95%. And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):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).13C NMR(101MHz,CDCl3):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.
Example 8
Target compound:
Figure BDA0002697547360000131
the preparation method comprises the following steps:
the method comprises the following steps: 2.8g of (E) -2-benzylidene-3, 3-dimethyl-4-spirocyclohexylbutyrolactone were dissolved in 10ml of ethylbenzene to give an allylic lactone solution; weighing 1.8g of acetonitrile in a reaction bottle, and adding 10ml of ethylbenzene; weighing n-butyllithium and adding the n-butyllithium into a reaction bottle (the molar ratio of the n-butyllithium to the (E) -2-benzylidene-3, 3-dimethyl-4-spirocyclohexyl butyrolactone is 2.8: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 48 hours at the temperature of-70 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separation to obtain the semi-acetal of the oily substance with the yield of 84%.
Step two: dissolving the hemiacetal obtained in the previous step in 10ml of petroleum ether, adding Fe (acac)3(Fe(acac)3Molar ratio to hemiacetal 0.7: 1) then heating to 45 ℃ for reaction for 4 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by reduced pressure evaporation to obtain oily matter with the yield of 96%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):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).13C NMR(101MHz,CDCl3):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.
Example 9
Target compound:
Figure BDA0002697547360000141
the preparation method comprises the following steps:
the method comprises the following steps: 2.4g of (E) -2-benzylidene-3, 4-cycloheptylbutyrolactone was dissolved in 12ml of benzene to give an allylic lactone solution; weighing 0.8g of acetonitrile in a reaction bottle, and adding 12ml of benzene; tert-butyllithium was weighed into the reaction flask (molar ratio of tert-butyllithium to (E) -2-benzylidene-3, 4-cycloheptanebutyrolactone 3.2: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 36 hours at-50 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separation to obtain the semi-acetal of the oily substance with the yield of 85%.
Step two: the hemiacetal obtained in the previous step was dissolved in 15ml acetonitrile and FeCl was added3(FeCl3Molar ratio to hemiacetal 0.8: 1) then heating to 45 ℃ for reaction for 4 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by evaporation under reduced pressure to obtain oily matter with the yield of 95.8%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,DMSO-d6):7.62(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).13C NMR(101MHz,DMSO-d6):181.59,148.11,136.37,134.22,132.13,130.15,129.71,128.86,116.77,82.89,43.54,42.66,32.50,27.30,26.35,25.09,24.47.
Example 10
Target compound:
Figure BDA0002697547360000151
the preparation method comprises the following steps:
the method comprises the following steps: 3.1g of (E) -2-benzylidene-3, 3, 5-trimethyl-5-phenylpentanedione dissolved in 16ml of tetrahydrofuran to form an allyl lactone solution; weighing 0.6g of acetonitrile in a reaction bottle, and adding 16ml of tetrahydrofuran; weighing sodium hydride and adding the sodium hydride into a reaction bottle (the molar ratio of the sodium hydride to the (E) -2-benzylidene-3, 3, 5-trimethyl-5-phenyl valerolactone is 4: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 24 hours at-30 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 86.2%.
Step two: the hemiacetal obtained in the previous step was dissolved in 15ml acetonitrile and FeCl was added3(FeCl3The molar ratio to the hemiacetal is 1: 1) then heating to 45 ℃ for reaction for 4 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by evaporation under reduced pressure to obtain oily matter with the yield of 96.3 percent.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.38(d,J＝3.9Hz,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＝14.6Hz,1H),2.16(d,J＝14.5Hz,1H),1.74(s,3H),1.09(s,3H),0.65(s,3H).13C NMR(101MHz,CDCl3):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.
Example 11
Target compound:
Figure BDA0002697547360000161
the preparation method comprises the following steps:
the method comprises the following steps: 2.2g of (E) -2-p-fluorobenzylidene-3, 3-dimethylbutyrolactone dissolved in 10ml of 1, 4-dioxane to form an allylic lactone solution; weighing 2.2g of acetonitrile in a reaction bottle, and adding 10ml of 1, 4-dioxane; weighing potassium tert-butoxide and adding the potassium tert-butoxide into a reaction bottle (the molar ratio of the potassium tert-butoxide to the (E) -2-p-fluorobenzylidene-3, 3-dimethylbutyrolactone is 4.4: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 12 hours at-10 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 85.3%.
Step two: the hemiacetal obtained in the previous step was dissolved in 10ml DMF and Fe (ox) was added3·6H2O(Fe(ox)3·6H2The molar ratio of O to hemiacetal is 1.1: 1) then heating to 45 ℃ for reaction for 4 h; after the reaction, water was added to quench, ethyl acetate was used for extraction, and the solvent was distilled off under reduced pressure to obtain an oily substance with a yield of 94.9%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):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).13C NMR(101MHz,CDCl3):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(376MHz,CDCl3):-114.48.
Example 12
Target compound:
Figure BDA0002697547360000171
the preparation method comprises the following steps:
the method comprises the following steps: 2.4g of (E) -2-p-chlorobenzylidene-3, 3-dimethylbutyramide dissolved in 10ml of a mixture of diethyl ether and ethylene glycol dimethyl ether to form an allyl lactone solution; weighing 3.2g of acetonitrile in a reaction bottle, and adding 10ml of a mixture of diethyl ether and ethylene glycol dimethyl ether; weighing potassium tert-butoxide and adding the potassium tert-butoxide into a reaction bottle (the molar ratio of the potassium tert-butoxide to the (E) -2-p-chlorobenzylidene-3, 3-dimethylbutyrolide is 4.8: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 10 hours at-5 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 86.3%.
Step two: dissolving the hemiacetal obtained in the last step in 10ml DMAC, adding FeBr3(FeBr3The molar ratio to hemiacetal is 1.2: 1) then heating to 45 ℃ for reaction for 4 h; after the reaction, water was added to quench, ethyl acetate was used for extraction, and the solvent was distilled off under reduced pressure to obtain an oily substance with a yield of 95.6%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.34(d,J＝8.5Hz,2H),7.28(d,J＝8.6Hz,2H),6.55(s,1H),3.98(s,2H),1.28(s,6H).13C NMR(101MHz,CDCl3):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.
Example 13
Target compound:
Figure BDA0002697547360000181
the preparation method comprises the following steps:
the method comprises the following steps: 2.8g of (E) -2-p-bromobenzylidene-3, 3-dimethylbutyrolactone dissolved in 10ml of a mixture of n-hexane and petroleum ether to form an allyl lactone solution; weighing 1.5g of acetonitrile in a reaction bottle, and adding 10ml of a mixture of n-hexane and petroleum ether; weighing a mixture of potassium tert-butoxide and n-butyllithium, and adding the mixture into a reaction bottle (the molar ratio of the mixture of potassium tert-butoxide and n-butyllithium to (E) -2-p-bromobenzylidene-3, 3-dimethyl butyrolactone is 5.2: 1); dripping alkenyl lactone solution into the reaction system, and reacting for 6h at 5 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 84.5%.
Step two: the hemiacetal obtained in the previous step was dissolved in 10ml DMSO, Co (acac) was added2(Co(acac)2The molar ratio to hemiacetal is 1.3: 1) then heating to 45 ℃ for reaction for 6 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by evaporation under reduced pressure to obtain oily matter with the yield of 96.2%. And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.51(d,J＝8.4Hz,2H),7.25(d,J＝8.7Hz,3H),6.56(s,1H),4.28(s,1H),3.98(s,2H),1.29(s,6H).13C NMR(101MHz,CDCl3):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.
Example 14
Target compound:
Figure BDA0002697547360000191
the preparation method comprises the following steps:
the method comprises the following steps: 2.8g of (E) -2-p-phenylbenzylidene-3, 3-dimethylbutyrolactone dissolved in 10ml of a mixture of n-hexane and petroleum ether to form an allyl lactone solution; weighing 0.9g of acetonitrile in a reaction bottle, and adding 10ml of a mixture of n-hexane and petroleum ether; weighing a mixture of potassium tert-butoxide and n-butyllithium, and adding the mixture into a reaction bottle (the molar ratio of the mixture of potassium tert-butoxide and n-butyllithium to (E) -2-p-phenylbenzylidene-3, 3-dimethyl butyrolactone is 5.6: 1); dripping alkenyl lactone solution into the reaction system, and reacting for 12h at 10 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 86.5%.
Step two: the hemiacetal obtained in the previous step was dissolved in 10ml of DMSO, Ni (acac) was added2(Ni(acac)2The molar ratio to hemiacetal is 1.4: 1) then heating to 40 ℃ for reaction for 6 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by evaporation under reduced pressure to obtain oily matter with the yield of 95.8%. And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.63(td,J＝5.7,2.6Hz,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).13C NMR(101MHz,CDCl3):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.
Example 15
Target compound:
Figure BDA0002697547360000201
the preparation method comprises the following steps:
the method comprises the following steps: 2.3g of (E) -2-p-methoxybenzylidene-3, 3-dimethylbutyrolactone dissolved in 14ml of a mixture of tetrahydrofuran and diethyl ether to form an allylic lactone solution; weighing 0.4g of acetonitrile in a reaction bottle, and adding 14ml of a mixture of tetrahydrofuran and diethyl ether; weighing potassium tert-butoxide and adding the potassium tert-butoxide into a reaction bottle (the molar ratio of the potassium tert-butoxide to the (E) -2-p-methoxybenzylidene-3, 3-dimethylbutyrolactone is 6: 1); dripping alkenyl lactone solution into the reaction system, and reacting for 12h at 10 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 86.2%.
Step two: dissolving the hemiacetal obtained in the previous step in 10ml of a mixture of n-hexane and petroleum ether, and adding MnCl2.4H2O(MnCl2.4H2The molar ratio of O to hemiacetal is 1.5: 1) then heating to 40 ℃ for reaction for 6 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by evaporation under reduced pressure to obtain oily matter with the yield of 96.2%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.37(d,J＝8.7Hz,2H),6.93(d,J＝8.8Hz,2H),6.58(s,1H),4.27(s,1H),3.98(s,2H),3.85(s,3H),1.33(s,6H).13C NMR(101MHz,CDCl3):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.
Example 16
Target compound:
Figure BDA0002697547360000202
the preparation method comprises the following steps:
the method comprises the following steps: 2.2g of (E) -2-p-methylbenzylidene-3, 3-dimethylbutyramide dissolved in 14ml of a mixture of tetrahydrofuran and diethyl ether to form an allylic lactone solution; weighing 0.6g of acetonitrile in a reaction bottle, and adding 14ml of a mixture of tetrahydrofuran and diethyl ether; weighing potassium tert-butoxide and adding the potassium tert-butoxide into a reaction bottle (the molar ratio of the potassium tert-butoxide to the (E) -2-p-methylbenzylidene-3, 3-dimethylbutyrolactone is 6.4: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 12h at 15 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 86.5%.
Step two: dissolving the hemiacetal obtained in the previous step in 10ml of a mixture of n-hexane and petroleum ether, adding La (OTf)3(La(OTf)3The molar ratio to hemiacetal is 1.6: 1) then heating to 25 ℃ for reaction for 10 h; after the reaction, water was added to quench, ethyl acetate was used for extraction, and the solvent was distilled off under reduced pressure to obtain an oily substance with a yield of 96.9%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.27(d,J＝6.0Hz,2H),7.18(d,J＝7.9Hz,2H),6.61(s,1H),4.22(s,1H),3.98(s,2H),2.33(s,3H),1.30(s,6H).13C NMR(101MHz,CDCl3):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.
Example 17
Target compound:
Figure BDA0002697547360000211
the preparation method comprises the following steps:
the method comprises the following steps: 2.5g of (E) -2- (benzo [ d ] [1,3] dioxan-5-ylmethylene) -3, 3-dimethylbutyrolactone dissolved in 14ml of tetrahydrofuran to form an allylic lactone solution; weighing 1.6g of acetonitrile in a reaction bottle, and adding 14ml of tetrahydrofuran; weighing potassium tert-butoxide and adding to the reaction flask (molar ratio of potassium tert-butoxide to (E) -2- (benzo [ d ] [1,3] dioxan-5-ylmethylene) -3, 3-dimethylbutyrolactone is 6.8: 1); dripping alkenyl lactone solution into the reaction system, and reacting for 12h at 10 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 86.2%.
Step two: dissolving the hemiacetal obtained in the previous step in 10ml of a mixture of n-hexane and petroleum ether, and adding BF3·Et2O(BF3·Et2The molar ratio of O to hemiacetal is 1.7: 1) then heating to 45 ℃ for reaction for 4 h; after the reaction, water was added to quench, ethyl acetate was used for extraction, and the solvent was distilled off under reduced pressure to obtain an oily substance with a yield of 96.9%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):6.94-6.85(m,2H),6.81(d,J＝8.0Hz,1H),6.53(s,1H),6.03(s,2H),3.96(s,2H),1.33(s,6H).13C NMR(101MHz,CDCl3):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.
Example 18
Target compound:
Figure BDA0002697547360000221
the preparation method comprises the following steps:
the method comprises the following steps: 2.4g of (E) -2- (benzofuran-2-ylmethylene) -3, 3-dimethylbutyrolactone dissolved in 14ml of tetrahydrofuran to form an allyl lactone solution; weighing 0.9g of acetonitrile in a reaction bottle, and adding 14ml of tetrahydrofuran; weighing a mixture of tert-butyllithium and sodium hydride into a reaction flask (molar ratio of the mixture of tert-butyllithium and sodium hydride to (E) -2- (benzofuran-2-ylmethylene) -3, 3-dimethylbutyrolactone is 7.2: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 15h at 20 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 86.3%.
Step two: dissolving the hemiacetal obtained in the last step into 10ml of a mixture of n-hexane and petroleum ether, adding a mixture of p-toluenesulfonic acid and methanesulfonic acid (the molar ratio of the mixture of p-toluenesulfonic acid and methanesulfonic acid to the hemiacetal is 1.8: 1), and then heating to 40 ℃ for reaction for 5 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by evaporation under reduced pressure to obtain oily matter with the yield of 96.3 percent.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,DMSO-d6):7.84(dd,J＝7.8,1.0Hz,1H),7.78(dd,J＝8.3,0.9Hz,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).13C NMR(101MHz,DMSO-d6):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.
Example 19
Target compound:
Figure BDA0002697547360000231
the preparation method comprises the following steps:
the method comprises the following steps: 2.1g of (E) -2- (thien-2-ylmethylene) -3, 3-dimethylbutyrolactone dissolved in 14ml of tetrahydrofuran to form an allylic lactone solution; weighing 1.0g of acetonitrile in a reaction bottle, and adding 14ml of tetrahydrofuran; weighing a mixture of tert-butyllithium and sodium hydride into a reaction flask (molar ratio of the mixture of tert-butyllithium and sodium hydride to (E) -2- (thien-2-ylmethylene) -3, 3-dimethylbutyrolactone is 7.6: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 16h at-10 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 84.9%.
Step two: dissolving the hemiacetal obtained in the last step into 10ml of a mixture of normal hexane and petroleum ether, adding hydrochloric acid (the molar ratio of the hydrochloric acid to the hemiacetal is 1.9: 1), and then heating to 30 ℃ for reaction for 6 h; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by evaporation under reduced pressure to obtain oily matter with the yield of 96.5%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.52(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).13C NMR(101MHz,CDCl3):182.88,144.56,136.04,134.31,130.83,130.54,130.20,127.79,117.28,79.43,42.58,38.51,24.65.
Example 20
Target compound:
Figure BDA0002697547360000241
the preparation method comprises the following steps:
the method comprises the following steps: 2.5g of (E) -2- (naphthalen-1-ylmethylene) -3, 3-dimethylbutyrolactone dissolved in 14ml of tetrahydrofuran to form an allyl lactone solution; weighing 2.1g of acetonitrile in a reaction bottle, and adding 14ml of tetrahydrofuran; weighing a mixture of tert-butyllithium and sodium methoxide into a reaction bottle (the molar ratio of the mixture of tert-butyllithium and sodium methoxide to (E) -2- (naphthalene-1-ylmethylene) -3, 3-dimethylbutyrolactone is 8: 1); dripping alkenyl lactone solution into a reaction system, and reacting for 24 hours at the temperature of minus 20 ℃; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and column chromatography is used for separating oily hemiacetal, wherein the yield is 85.3%.
Step two: dissolving the hemiacetal obtained in the last step into 10ml of petroleum ether, adding acetic acid (the molar ratio of the acetic acid to the hemiacetal is 2: 1), and then heating to 50 ℃ for reaction for 5 hours; after the reaction is finished, water is added for quenching, ethyl acetate is used for extraction, and the solvent is removed by evaporation under reduced pressure to obtain oily matter with the yield of 97.2%.
And (3) product characterization:
a colorless liquid.1H NMR(400MHz,CDCl3):7.95-7.81(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).13C NMR(101MHz,CDCl3):181.97,144.18,137.64,136.75,133.25,131.87,131.23,129.01,128.48,126.59,126.38,126.09,125.07,124.75,117.68,78.84,44.69,39.73,26.10.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A polysubstituted tetrahydrofuran and tetrahydropyrane diene compound shown in formula I is characterized in that,
Figure FDA0002697547350000011
wherein R is1Selected from aryl or heteroaryl; r2And R3Each independently selected from hydrogen or C1-C6 alkyl; r4And R5Each independently selected from aryl, heteroaryl, C1-C6 alkyl or hydrogen; r6And R7Each independently selected from cyano, nitro, C1-C6 alkyl, ester group or hydrogen.
2. The process for preparing tetrahydrofuran and tetrahydropyrane diene compounds according to claim 1, comprising the steps of:
the method comprises the following steps: the alpha-alkenyl lactone shown in the formula III and a nucleophilic reagent are subjected to 1,2 addition reaction in the presence of a solvent and alkali to prepare hemiacetal shown in the formula II;
Figure FDA0002697547350000012
step two: carrying out dehydration reaction on hemiacetal shown as a formula II in the presence of a catalyst and a solvent to prepare a tetrahydrofuran and tetrahydropyrane diene compound shown as a formula I;
Figure FDA0002697547350000021
3. the method for preparing multi-substituted tetrahydrofuran and tetrahydropyrane diene compounds according to claim 2, wherein in the first step, the solvent is one or more selected from toluene, ethylbenzene, benzene, tetrahydrofuran, 1, 4-dioxane, diethyl ether, ethylene glycol dimethyl ether, n-hexane and petroleum ether.
4. The method for preparing poly-substituted tetrahydrofuran and tetrahydropyrane diene compounds according to claim 2, wherein in the step one, the nucleophile is selected from one of nitrile, nitroalkane or ester.
5. The method for preparing poly-substituted tetrahydrofuran and tetrahydropyrane diene compounds according to claim 2, wherein in the first step, the base is selected from one or more of n-butyllithium, t-butyllithium, sodium hydride, sodium ethoxide, sodium methoxide, potassium t-butoxide and Grignard reagent.
6. The method for preparing polysubstituted tetrahydrofuran and tetrahydropyrane diene compounds according to claim 2, wherein in the first step, the molar ratio of the α -alkenyl lactone to the nucleophile is 1: 0.4-8.
7. The method for preparing polysubstituted tetrahydrofuran and tetrahydropyrane diene compounds according to claim 2, wherein in the first step, the molar ratio of the α -alkenyl lactone to the base is 1: 0.4-8.
8. The method for preparing polysubstituted tetrahydrofuran and tetrahydropyrane diene compounds according to claim 2, wherein in the second step, 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.
9. The method for preparing polysubstituted tetrahydrofuran and tetrahydropyran diene compounds according to claim 2, wherein in step two, the catalyst is selected from Zn (OAc)2·2H2O、CuSO4·5H2O、Cu(OTf)2、Pd(OAc)2、FeSO4、Fe(acac)3、FeCl3、Fe(ox)3·6H2O、FeBr3、Co(acac)2、Ni(acac)2、MnCl2.4H2O、La(OTf)3、BF3·Et2One or more of O, p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, sulfuric acid or acetic acid.
10. The method for preparing polysubstituted tetrahydrofuran and tetrahydropyrane diene compounds according to claim 2, wherein in the second step, the molar ratio of the hemiacetal to the catalyst is 1: 0.1-2.
CN202011010976.9A 2020-09-23 2020-09-23 Polysubstituted tetrahydrofuran and tetrahydropyrane diene compound and preparation method thereof Pending CN112142694A (en)

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CN114605361A (en) * 2022-04-14 2022-06-10 河南师范大学 Method for synthesizing gamma-hydroxy-gamma-perfluoromethylbutenolide compound
CN114634471A (en) * 2022-04-14 2022-06-17 河南师范大学 Method for synthesizing gamma-hydroxy-gamma-perfluoromethyl exocyclic double bond butyrolactone compound
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