阅读说明：本技术 一种吡喃并[3,2-b]吲哚-2-酮类化合物的合成方法 (Synthesis method of pyrano [3,2-b ] indole-2-ketone compound ) 是由 鲁神赐 王霞 刘世飞 张司辰 蒋建锋 胡丹 范子翔 于 2021-10-19 设计创作，主要内容包括：本发明公开了一种吡喃并[3,2-b]吲哚-2-酮类化合物的合成方法,包括以下步骤：氮气氛围下,将N-对甲苯磺酰基吲哚-3-酮衍生物、取代苯丙炔醛、氮杂环卡宾盐、氧化剂、碱及有机溶剂混合,搅拌均匀得到混合体系；混合体系于25～35℃下充分反应12～36h；反应后冷却至室温,进行后处理得到目标产物。该方法操作简便,反应温和,区域选择性高,是一种廉价且具有很好应用前景的方法,可应用于天然产物、药物、材料的高效合成中。(The invention discloses a synthetic method of pyrano [3,2-b ] indole-2-ketone compounds, which comprises the following steps: under the atmosphere of nitrogen, mixing the N-p-toluenesulfonyl indol-3-one derivative, substituted phenylpropylaldehyde, N-heterocyclic carbene salt, an oxidant, alkali and an organic solvent, and uniformly stirring to obtain a mixed system; fully reacting the mixed system at 25-35 ℃ for 12-36 h; and cooling to room temperature after reaction, and carrying out post-treatment to obtain the target product. The method is simple and convenient to operate, mild in reaction and high in regioselectivity, is a cheap method with good application prospect, and can be applied to efficient synthesis of natural products, medicines and materials.)

1. A synthetic method of pyrano [3,2-b ] indole-2-ketone compounds is characterized by comprising the following steps:

under the atmosphere of nitrogen, mixing the N-p-toluenesulfonyl indol-3-one derivative, substituted phenylpropylaldehyde, N-heterocyclic carbene salt, an oxidant, alkali and an organic solvent, and uniformly stirring to obtain a mixed system;

fully reacting the mixed system at 25-35 ℃ for 12-36 h;

and cooling to room temperature after reaction, and carrying out post-treatment to obtain the target product.

2. The method for synthesizing pyrano [3,2-b ] indol-2-one compounds according to claim 1, wherein the oxidant is 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone.

3. The method for synthesizing pyrano [3,2-b ] indol-2-one compounds according to claim 1, wherein the base is at least one selected from N, N-diethylpropylamine, triethylamine, cesium carbonate, potassium carbonate, N-ethyldiisopropylamine and potassium phosphate.

4. The method for synthesizing pyrano [3,2-b ] indol-2-one compounds according to claim 1, wherein the organic solvent is at least one selected from 1, 4-dioxane, chloroform, dichloromethane, 1, 2-dichloromethane and toluene.

5. The method for synthesizing pyrano [3,2-b ] indol-2-one compounds according to claim 1, wherein the molar ratio of the N-p-toluenesulfonyl indol-3-one derivatives to the substituted phenylpropargylaldehydes is 1: (1.5-2.0), wherein the concentration of the N-p-toluenesulfonyl indol-3-one derivative in the reaction system is 0.05-0.2 mol/L.

6. The synthesis method of pyrano [3,2-b ] indol-2-one compounds according to claim 1, characterized in that the amount of the azacyclo-carbene salt added is 5-20 mol% of the molar amount of the N-p-toluenesulfonyl indol-3-one derivatives.

7. The method for synthesizing pyrano [3,2-b ] indol-2-one compounds according to claim 1, wherein the amount of the oxidant is 1.2-1.5 times that of the N-p-toluenesulfonyl indol-3-one derivatives.

8. The method for synthesizing pyrano [3,2-b ] indol-2-one compounds according to claim 1, wherein the amount of the base is 1 to 1.5 times that of the N-p-toluenesulfonyl indol-3-one derivatives.

9. The synthesis method of pyrano [3,2-b ] indol-2-one compounds according to claim 1, characterized in that the post-treatment specifically comprises:

after the reaction is finished, dichloromethane is added, the mixture is filtered, then is washed for many times by dichloromethane, the solvent is removed under reduced pressure, and the pyrano [3,2-b ] indole-2-ketone compound is obtained by column chromatography separation.

Technical Field

The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthetic method of pyrano [3,2-b ] indole-2-ketone compounds.

Background

In recent years, N-heterocyclic carbene (NHC) catalysis has become a synthetic method for the effective synthesis of important biological substances (S.Mondal, S.R.Yetra, S.Mukherjee, A.T.Biju, Acc.chem.Res.,2019,52, 425; C. -H.Zhang, J.F.Hooper, D.W.Lunton, ACS Catal.,2017,7, 2583). The catalyst is a novel nucleophilic organic small molecule catalyst developed in recent years, and can form Breslow intermediate with alpha, beta unsaturated olefine aldehyde, and according to NHC, type structure skeleton, proton migration capability and isomerization capability, the Breslow intermediate can form acyl anion intermediate (acyl anion), enol intermediate (enol) and high enol intermediate (homoenol). Effectively catalyzing the polarity reversal of the aldehyde which in turn reacts with a series of electrophiles.

In addition to the polarity inversion strategy, Breslow intermediates can be oxidized to form acylazole intermediates (acyl azolium). Alkynyl acylazole intermediates (alkyne acyl azolium) are another important intermediate and have been rarely studied, compared to the more studied α, β -unsaturated acylazole intermediates (α, β -unsaturated acyl azolium). Alkynylacylazoles can be generated up to now by NHC combining different precursors such as alkynylaldehydes (c.zheng, x.liu, c.ma, j.org.chem.,2017,82,6940.), alkynoic acids (k.sun, s.jin, j.zhu, x.zhang, m.gao, w.zhang, t.lu, d.du, adv.synth.cat., 2018,360,4515.) or their alkyne esters (c.mou, j.wu, z.huang, j.sun, z.jin, y.r.chi, chem.commu., 2017,53,13359.) by different strategies.

Pyrano [3,2-b ] indol-2-one backbone is widely found in active natural products as well as pharmaceutical intermediates, and has antitumor, anticancer and antitubercular effects (c.mao, n.m.patterson, m.t.cherian, i.o.aniye, c.zhang, j.b.montoya, j.cheng, k.s.putt, p.j.hererother, e.m.wilson, a.m.nardulli, s.k.nordeen, d.j.sharro, j.biol.chem. 2008,283,12819.; n.s.masterova, s.y.rybova, l.m.alekseeva, m.i.evstrova, s.s.kisel, v.g.granik, russ.chem.59, bule.637).

Currently pyrano [3,2-b ]]The indole-2-ones are prepared mainly by high temperature non-catalytic multistep reactions, for example, McNab in 2010 reported that pure indoxyl, isomer, can be obtained by fast vacuum pyrolysis of 2' -azidoacetophenone at 650 ℃Fast vacuum pyrolysis of 2-methylene compounds gave pyrano [3,2-b ] in 42% yield]Indol-2-ones (a.p. gaywood, h.mcnab, Synthesis,2010,8, 1361); 2019 Duding group reports that N-heterocyclic carbene catalyzes [3+3 ] of N-acetyl indole-3-ketone and alkyne acid ester]Preparation of pyran [3,2-b ] by cyclization reaction]Methods for indol-2-ones (k.sun, s.jin, s.fang, r.ma, x.zhang, m.gao, w.zhang, t.lu, d.du, org.chem.front.,2019,6, 2291.); 2021, Makarov reported the synthesis of pyrano [3,2-b ] using indole via a seven step reaction]Indole-2-ones (N.Monakhova, J.Kordul a kov a, A.Vocat, A.Egorova, A.Lepioshkin, E.G.Salina, J.Nosek, E.Repkov a, J.Zemanov a, H.Jurd a kov a, R.G b rov a, J.Roh, G.Degiacomi, J.C.Sammatino, M.R.Pasca, S.T.Cole, K).V.Makarov,ACS Infect.Dis,2021,7,88)。

The above methods usually require high temperature, vacuum, long synthesis route, difficult preparation of raw materials, and the like.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides a synthetic method of pyrano [3,2-b ] indole-2-ketone compounds, which has the advantages of simple and convenient operation, mild reaction and high regioselectivity, is a method with low price and good application prospect, and can be applied to the high-efficiency synthesis of natural products, medicaments and materials.

In order to achieve the purpose, the invention adopts the following technical scheme to realize the purpose:

a synthetic method of pyrano [3,2-b ] indole-2-ketone compounds comprises the following steps:

under the atmosphere of nitrogen, mixing the N-p-toluenesulfonyl indol-3-one derivative, substituted phenylpropylaldehyde, N-heterocyclic carbene salt, an oxidant, alkali and an organic solvent, and uniformly stirring to obtain a mixed system;

fully reacting the mixed system at 25-35 ℃ for 12-36 h;

and cooling to room temperature after reaction, and carrying out post-treatment to obtain the target product.

As a further improvement of the invention, the oxidizing agent is 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone.

As a further improvement of the invention, the base is at least one selected from the group consisting of N, N-diethylpropylamine, triethylamine, cesium carbonate, potassium carbonate, N-ethyldiisopropylamine, and potassium phosphate.

As a further improvement of the invention, the organic solvent is at least one selected from 1, 4-dioxane, chloroform, dichloromethane, 1, 2-dichloromethane and toluene.

As a further improvement, the molar ratio of the N-p-toluenesulfonyl indol-3-one derivative to the substituted phenylpropargyl aldehyde is 1: (1.5-2.0), wherein the concentration of the N-p-toluenesulfonyl indol-3-one derivative in the reaction system is 0.05-0.2 mol/L.

As a further improvement of the invention, the addition amount of the N-heterocyclic carbene salt is 5-20 mol% of the molar amount of the N-p-toluenesulfonyl indol-3-one derivative.

As a further improvement of the invention, the dosage of the oxidant is 1.2-1.5 times of that of the N-p-toluenesulfonyl indol-3-one derivative.

As a further improvement of the invention, the dosage of the alkali is 1-1.5 times of the N-p-toluenesulfonyl indol-3-one derivative.

As a further improvement of the present invention, the post-treatment specifically comprises:

after the reaction is finished, dichloromethane is added, the mixture is filtered, then is washed for many times by dichloromethane, the solvent is removed under reduced pressure, and the pyrano [3,2-b ] indole-2-ketone compound is obtained by column chromatography separation.

Compared with the prior art, the method has the following technical effects and advantages:

the substituted phenylpropargyl aldehyde and the N-p-toluenesulfonyl indole-3-one derivative are used as raw materials, reaction catalysts are available in the market, the raw materials are simple and easy to obtain, the reaction conditions are room temperature, the pyrano [3,2-b ] indole-2-one compound is obtained in one step under the catalysis of organic small molecular nitrogen heterocyclic carbene and the action of alkali and an oxidant, the operation is simple and convenient, the reaction is mild, the regioselectivity is high, the method is a method which is low in price and has a good application prospect, and the method can be applied to efficient synthesis of natural products, medicines and materials.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of a sample prepared in example 1 of the present invention;

FIG. 2 is a nuclear magnetic carbon spectrum of a sample obtained in example 1 of the present invention;

FIG. 3 is a nuclear magnetic hydrogen spectrum of a sample prepared in example 2 of the present invention;

FIG. 4 is a nuclear magnetic carbon spectrum of a sample prepared in example 2 of the present invention;

FIG. 5 is a nuclear magnetic hydrogen spectrum of a sample prepared in example 3 of the present invention;

FIG. 6 is a nuclear magnetic carbon spectrum of a sample obtained in example 3 of the present invention;

FIG. 7 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 4 of the present invention;

FIG. 8 is a nuclear magnetic carbon spectrum of a sample obtained in example 4 of the present invention;

FIG. 9 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 5 of the present invention;

FIG. 10 is a nuclear magnetic carbon spectrum of a sample obtained in example 5 of the present invention;

FIG. 11 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 6 of the present invention;

FIG. 12 is a nuclear magnetic carbon spectrum of a sample obtained in example 6 of the present invention.

FIG. 13 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 7 of the present invention;

FIG. 14 is a nuclear magnetic carbon spectrum of a sample obtained in example 7 of the present invention;

FIG. 15 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 8 of the present invention;

FIG. 16 is a nuclear magnetic carbon spectrum of a sample obtained in example 8 of the present invention.

Detailed Description

The invention relates to a synthetic method of pyrano [3,2-b ] indole-2-ketone compounds, which adopts the technical scheme as formula (1):

preferably, the molar ratio of the N-tosylindol-3-one derivative to the substituted phenylpropargyl aldehyde is 1: 1.5, the concentration is 0.05-0.2 mol/L. The mol ratio of the N-p-toluenesulfonyl indole-3-one derivative to the substituted phenylpropargyl aldehyde is (1: 1.5) - (1: 2.0).

Preferably, the amount of the N-heterocyclic carbene is 5-20 mol% of the molar amount of the N-p-toluenesulfonyl indol-3-one derivative.

The dosage of the oxidant is 1.2-1.5 times of that of the N-p-toluenesulfonyl indol-3-one derivative, and the dosage of the organic solvent enables the concentration of the N-p-toluenesulfonyl indol-3-one derivative to be 0.05-0.2 mol/L.

Preferably, the organic solvent is at least one selected from the group consisting of 1, 4-dioxane, chloroform, dichloromethane, 1, 2-dichloromethane, and toluene. Preferably, the base is at least one of triethylamine, cesium carbonate, potassium carbonate, N-ethyldiisopropylamine, and potassium phosphate. The dosage of the alkali is 1-1.5 times of the N-p-toluenesulfonyl indole-3-ketone derivative.

Preferably, the reaction time is 12-36 h.

Preferably, after the reaction is finished, dichloromethane is added, the mixture is filtered, then is washed for 2 to 3 times by dichloromethane, the solvent is removed under reduced pressure, and the pyrano [3,2-b ] indol-2-ketone compound is obtained by column chromatography separation.

The invention will be illustrated below with reference to specific examples. In particular, these examples are only intended to illustrate the invention and are not intended to limit the scope of the invention. In practice, the technical personnel according to the invention make improvements and modifications, which still belong to the protection scope of the invention.

Example 1

Under a nitrogen atmosphere, 42mg of N-p-toluenesulfonylindol-3-one, 36mg of o-methoxyphenylpropargylaldehyde, 6.4mg of a carbene salt, 21. mu. L N, N-diethylpropylamine, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone, and 1mL of 1, 2-dichloroethane were added to a reaction flask. The mixed system is reacted for 20 hours at 30 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed with dichloromethane 3 times. The solvent was removed under reduced pressure, and column chromatography was performed to give the objective product 1(49mg, 73% yield).

The hydrogen spectrum data and the carbon spectrum data are respectively as follows:

¹H NMR(500MHz,CDCl₃)δ8.24(d,J＝8.5Hz,1H),7.66(d,J＝7.8Hz,1H),7.54–7.46(m,2H),7.43(dd,J＝7.6,1.7Hz,1H),7.37(t,J＝7.6Hz,1H),7.16(d,J＝8.4Hz,2H),7.11(t,J＝7.5Hz,1H),7.03(d,J＝8.3Hz,1H),6.98(d,J＝8.1Hz,2H),6.29(s,1H),3.89(s,3H),2.25(s,3H).

¹³C NMR(125MHz,CDCl₃)δ160.90,156.68,149.77,149.55,145.08,139.79,131.93,131.09,129.21,129.10,129.05,126.81,126.64,125.80,122.03,120.89,120.64,119.30,118.53,113.16,111.11,55.72,21.54.

example 2

Under a nitrogen atmosphere, 42mg of N-p-toluenesulfonylindol-3-one, 36mg of m-methoxyphenylpropargylaldehyde, 6.4mg of carbene salt, 21. mu. L N, N-diethylpropylamine, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone, and 1mL of 1, 2-dichloroethane were added to the reaction flask. The mixed system is reacted for 20 hours at 30 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed with dichloromethane 3 times. The solvent was removed under reduced pressure, and column chromatography was performed to give the objective product 2(42mg, yield 63%).

The hydrogen spectrum data and the carbon spectrum data are respectively as follows:

¹H NMR(500MHz,CDCl₃)δ8.22(d,J＝8.4Hz,1H),7.65–7.58(d,1H),7.54(m,J＝8.5,7.3,1.2Hz,1H),7.45(t,J＝7.9Hz,1H),7.39–7.34(m,1H),7.34–7.30(m,1H),7.25(t,J＝2.0Hz,1H),7.10(d,J＝8.2Hz,2H),7.05(ddd,J＝8.4,2.6,1.1Hz,1H),6.96(d,J＝8.1Hz,2H),6.30(s,1H),3.89(s,J＝1.3Hz,3H),2.25(s,3H).

¹³C NMR(125MHz,CDCl₃)δ160.92,159.64,151.82,151.39,145.31,140.69,138.11,130.81,129.71,129.37,129.11,127.04,126.29,122.67,120.19,120.16,119.49,119.27,115.35,113.42,111.01,55.44,21.55.

example 3

Under a nitrogen atmosphere, 42mg of N-p-toluenesulfonylindol-3-one, 36mg of p-methoxyphenylalaninaldehyde, 6.4mg of a carbene salt, 21. mu. L N, N-diethylpropylamine, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone, and 1mL of 1, 2-dichloroethane were added to the reaction flask. The mixed system is reacted for 20 hours at 30 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed with dichloromethane 3 times. The solvent was removed under reduced pressure, and column chromatography was performed to give the objective product 3(51mg, yield 76%).

The hydrogen spectrum data and the carbon spectrum data are respectively as follows:

¹H NMR(500MHz,CDCl₃)δ8.23(d,J＝8.4Hz,1H),7.74(d,J＝8.7Hz,2H),7.59(d,J＝7.8Hz,1H),7.57–7.50(m,1H),7.37(t,J＝7.6Hz,1H),7.12–7.00(m,4H),6.95(d,J＝8.1Hz,2H),6.25(s,1H),3.90(s,3H),2.24(s,3H).

¹³C NMR(125MHz,CDCl₃)δ161.23,161.17,151.63,151.61,145.30,140.84,130.46,129.33,129.27,129.08,129.04,127.10,126.36,122.96,120.44,119.48,119.44,114.08,109.66,55.37,21.55.

example 4

Under a nitrogen atmosphere, 42mg of N-p-toluenesulfonylindol-3-one, 40mg of o-3, 5-dimethoxyphenylpropylaldehyde, 6.4mg of carbene salt, 21. mu. L N, N-diethylpropylamine, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone, and 1mL of 1, 2-dichloroethane were added to a reaction flask. The mixed system is reacted for 20 hours at 30 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed with dichloromethane 3 times. The solvent was removed under reduced pressure, and column chromatography was performed to give the objective product 4(55mg, yield 77%).

The hydrogen spectrum data and the carbon spectrum data are respectively as follows:

¹H NMR(500MHz,CDCl₃)δ8.21(d,J＝8.4Hz,1H),7.62(d,J＝7.5Hz,1H),7.57–7.50(m,1H),7.37(t,J＝7.6Hz,1H),7.12(d,J＝6.4Hz,2H),6.97(d,J＝8.1Hz,2H),6.86(d,J＝2.2Hz,2H),6.60(t,J＝2.3Hz,1H),6.31(s,1H),3.87(s,6H),2.26(s,3H).

¹³C NMR(125MHz,CDCl₃)δ160.93,160.90,160.83,151.84,145.28,140.66,138.62,130.98,129.33,129.11,127.03,126.23,122.60,120.18,119.49,119.21,110.93,106.07,101.71,55.56,21.55.

example 5

Under a nitrogen atmosphere, 42mg of N-p-toluenesulfonylindol-3-one, 54mg of 2-bromo-4-methoxyphenylpropargylaldehyde, 6.4mg of a carbene salt, 21. mu. L N, N-diethylpropylamine, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone, and 1mL of 1, 2-dichloroethane were added to the reaction flask. The mixed system is reacted for 20 hours at 30 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed with dichloromethane 3 times. The solvent was removed under reduced pressure, and column chromatography was performed to give the objective product 5(52mg, yield 67%).

The hydrogen spectrum data and the carbon spectrum data are respectively as follows:

¹H NMR(500MHz,CDCl₃)δ8.26(d,J＝8.6Hz,1H),7.66(dd,J＝8.1,3.9Hz,1H),7.57–7.51(m,1H),7.38(m,J＝14.6,8.0,4.0Hz,2H),7.27–7.22(m,3H),7.06–6.89(m,3H),6.26(s,1H),3.87(s,3H),2.27(s,3H).

¹³C NMR(125MHz,CDCl₃)δ160.54,160.51,150.54,150.34,145.25,140.01,131.69,130.57,130.29,129.41,129.27,127.00,126.06,122.10,121.90,120.23,119.41,118.76,118.43,113.76,113.52,55.62,21.56.

example 6

Under a nitrogen atmosphere, 42mg of N-p-toluenesulfonyl-5-methylindol-3-one, 45mg of o-methoxyphenylpropargylaldehyde, 6.4mg of a carbene salt, 21. mu. L N, N-diethylpropylamine, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone, and 1mL of 1, 2-dichloroethane were added to the reaction flask. The mixed system is reacted for 20 hours at 30 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed with dichloromethane 3 times. The solvent was removed under reduced pressure, and column chromatography was performed to give the objective product 6(54mg, yield 78%).

The hydrogen spectrum data and the carbon spectrum data are respectively as follows:

¹H NMR(500MHz,CDCl₃)δ8.11(d,J＝8.5Hz,1H),7.51–7.46(m,1H),7.46–7.35(m,2H),7.33(dd,J＝8.6,1.7Hz,1H),7.15(d,J＝6.4Hz,2H),7.10(t,J＝7.5Hz,1H),7.01(dd,J＝18.6,8.2Hz,3H),6.27(s,1H),3.89(s,3H),2.44(s,3H),2.26(s,3H).

¹³C NMR(125MHz,CDCl₃)δ160.99,156.68,149.81,149.56,144.95,138.03,135.88,131.90,131.03,130.61,129.19,129.05,126.86,126.67,122.20,120.98,120.61,119.00,118.27,112.89,111.10,55.71,21.55,21.32.

example 7

Under nitrogen atmosphere, 45mg of N-p-toluenesulfonyl-6-methylindol-3-one, 36mg of o-methoxyphenylpropargylaldehyde, 6.4mg of carbene salt, 21. mu.L of triethylamine, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone, and 1mL of 1, 2-dichloroethane were added to a reaction flask. The mixed system is reacted for 20 hours at 30 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed with dichloromethane 3 times. The solvent was removed under reduced pressure, and column chromatography was performed to give the objective product 7(50mg, 73% yield).

The hydrogen spectrum data and the carbon spectrum data are respectively as follows:

¹H NMR(500MHz,CDCl₃)δ8.05(s,1H),7.53(d,J＝8.1Hz,1H),7.50–7.46(m,1H),7.41(dd,J＝7.6,1.8Hz,1H),7.19(d,J＝8.0Hz,1H),7.15(d,J＝8.4Hz,2H),7.10(t,J＝7.5Hz,1H),7.01(dd,J＝15.0,8.1Hz,3H),6.24(s,1H),3.89(s,3H),2.54(s,3H),2.27(s,3H).

¹³C NMR(126MHz,CDCl₃)δ161.06,156.66,150.15,149.64,144.99,140.34,140.06,131.97,131.01,129.18,129.05,127.30,126.81,120.61,120.44,119.82,118.92,118.64,112.29,111.08,55.70,22.44,21.55.

example 8

Under a nitrogen atmosphere, 48mg of N-p-toluenesulfonyl-6-chloroindolone, 36mg of o-methoxyphenylpropargylaldehyde, 6.4mg of a carbene salt, 21. mu. L N, N-diethylpropylamine, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone, and 1mL of 1, 2-dichloroethane were added to the reaction flask. The mixed system is reacted for 20 hours at 30 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed with dichloromethane 3 times. The solvent was removed under reduced pressure, and column chromatography was performed to give the objective product 8(57mg, yield 80%).

The hydrogen spectrum data and the carbon spectrum data are respectively as follows:

¹H NMR(500MHz,CDCl₃)δ8.28(d,J＝1.7Hz,1H),7.59(d,J＝8.3Hz,1H),7.49(m,J＝8.3,7.5,1.7Hz,1H),7.41(dd,J＝7.5,1.7Hz,1H),7.35(dd,J＝8.4,1.7Hz,1H),7.18(d,J＝8.4Hz,2H),7.13–7.08(m,1H),7.03(dd,J＝11.0,8.3Hz,3H),6.29(s,1H),3.88(s,3H),2.29(s,3H).

¹³C NMR(125MHz,CDCl₃)δ160.56,156.68,149.37,148.77,145.43,140.07,135.14,131.94,131.25,129.45,128.97,126.79,126.53,126.39,121.25,120.67,120.36,120.02,118.62,113.41,111.06,55.69,21.59.

example 9

Under a nitrogen atmosphere, 42mg of N-p-toluenesulfonylindol-3-one, 57mg of o-methoxynaphthalene propiolic aldehyde, 6.4mg of carbene salt, 21. mu.L of cesium carbonate, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone, and 2mL of 1, 2-dichloroethane were added to a reaction flask. The mixed system is reacted for 28 hours at 28 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed 4 times with dichloromethane. The solvent is removed under reduced pressure, and the target product 9 is obtained after column chromatography separation.

Example 10

Under a nitrogen atmosphere, 42mg of N-p-toluenesulfonylindol-3-one, 43mg of p-methylphenylacetylene aldehyde, 6.4mg of carbene salt, 21. mu.L of potassium carbonate, 90mg of 3,3 ', 5,5 ' -tetra-tert-butyl-4, 4 ' -diphenoquinone and 1mL of toluene were added to a reaction flask. The mixed system is reacted for 12 hours at 35 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed 4 times with dichloromethane. The solvent is removed under reduced pressure, and the target product 10 is obtained by column chromatography separation.

Example 11

Under a nitrogen atmosphere, 42mg of N-p-toluenesulfonylindol-3-one, 52mg of o-methylphenylpropyraldehyde, 6.4mg of carbene salt, 21. mu.L of potassium phosphate, 90mg of 3,3 ', 5,5 ' -tetra-t-butyl-4, 4 ' -diphenoquinone, and 1mL of chloroform were added to a reaction flask. The mixed system is reacted for 36h at 25 ℃. After the reaction, after the reaction system was cooled to room temperature, 5mL of dichloromethane was added to the system, followed by filtration, and the filter cake was washed with dichloromethane 2 times. The solvent is removed under reduced pressure, and the target product 11 is obtained by column chromatography separation.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be construed as the protection scope of the present invention.