WO2024031753A1 - 一种吲哚啉类化合物及其制备方法 - Google Patents

一种吲哚啉类化合物及其制备方法 Download PDF

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WO2024031753A1
WO2024031753A1 PCT/CN2022/115450 CN2022115450W WO2024031753A1 WO 2024031753 A1 WO2024031753 A1 WO 2024031753A1 CN 2022115450 W CN2022115450 W CN 2022115450W WO 2024031753 A1 WO2024031753 A1 WO 2024031753A1
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刘峰
唐婉
敖桂珍
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苏州大学
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/10—Spiro-condensed systems

Definitions

  • the invention belongs to the technical field of nitrogen-containing heterocyclic compounds, and in particular relates to an indoline compound and a preparation method thereof.
  • nitrogen radical cascade reaction is considered to be one of the most potentially powerful tools for constructing various functionalized N-heterocycles.
  • Free-radical carbonamination of alkenes has also proven to be an attractive, straightforward approach to obtain a variety of dihydropyrazole and benzothiazine fused structures.
  • Many related compounds with aromatic ring fused thiazine structures have been found to exhibit a wide range of biological activities.
  • benzoalactan-I and its derivatives have good calpain-I inhibitory activity
  • benzoalactan-II is a new nuclear
  • the factor NF-KB inhibitor, brinzolid-III has also been identified as an effective drug for the treatment of glaucoma.
  • the object of the present invention is to provide an indoline compound and a preparation method thereof.
  • the indoline compound provided by the present invention has a specific structure, and the preparation method has a simple process and a high yield.
  • the invention provides an indoline compound having the structure of formula I:
  • R 1 is selected from alkyl or substituted alkyl, H, halogen atom, carbonyl or substituted carbonyl, aryl or substituted aryl;
  • R 2 is selected from H, halogen atom, alkyl or substituted alkyl, aryl or substituted aryl, carbonyl or substituted carbonyl;
  • R 3 is selected from H, alkyl or substituted alkyl, and forms a ring with R 4 ;
  • R 4 is selected from H, alkyl or substituted alkyl, and forms a ring with R 3 .
  • the alkyl group in R 1 or R 2 is preferably independently selected from alkyl groups with 1 to 5 carbon atoms, more preferably independently selected from alkyl groups with 1 to 3 carbon atoms, and most preferably is independently selected from methyl;
  • the substituted alkyl group is preferably independently selected from alkoxy or haloalkyl;
  • the alkoxy group is preferably independently selected from alkoxy groups with 1 to 5 carbon atoms, more preferably independently selected
  • the alkoxy group having 1 to 3 carbon atoms is most preferably independently selected from the methoxy group;
  • the haloalkyl group is preferably independently selected from the haloalkyl group having 1 to 5 carbon atoms, and more preferably the haloalkyl group is independently selected from the carbon group.
  • the haloalkyl group having 1 to 3 atoms is more preferably independently selected from halomethyl; the halogen in the haloalkyl group is preferably independently selected from F; the haloalkyl group is most preferably independently selected from -CF 3 .
  • the halogen atom in R 1 or R 2 is preferably independently selected from Br, I, F or Cl.
  • the substituted carbonyl group in R 1 or R 2 is preferably independently selected from an alkoxy-substituted carbonyl group; the number of carbon atoms in the alkoxy-substituted carbonyl group is preferably independently selected from 2 to 5 , more preferably independently selected from 2 to 3; the substituted carbonyl group is most preferably independently selected from methoxycarbonyl or ethoxycarbonyl, and most preferably independently selected from 4-ethoxycarbonyl.
  • the aryl group in R 1 or R 2 is preferably independently selected from phenyl;
  • the substituted aryl group is preferably independently selected from halogen-substituted aryl, alkyl-substituted aryl, substituted alkyl Substituted aryl;
  • the halogen in the halogen-substituted aryl group is preferably independently selected from fluorine, bromine, iodine or chlorine;
  • the aryl group in the halogen-substituted aryl group is preferably independently selected from phenyl;
  • the alkyl group in the base-substituted aryl group is preferably independently selected from alkyl groups with 1 to 5 carbon atoms, more preferably independently selected from alkyl groups with 1 to 3 carbon atoms, and most preferably independently selected from methyl groups.
  • the aryl group in the alkyl-substituted aryl group is preferably independently selected from phenyl; the substituted alkyl group in the substituted alkyl-substituted aryl group is preferably independently selected from halogen-substituted alkyl or alkoxy group ;
  • the halogen in the halogen-substituted alkyl group is preferably independently selected from F; the number of carbon atoms of the alkyl group in the halogen-substituted alkyl group is preferably independently selected from 1 to 5, and more preferably independently selected from 1 to 3 , most preferably independently selected from 1; the number of carbon atoms in the alkoxy group is preferably independently selected from 1 to 5, more preferably independently selected from 1 to 3, most preferably independently selected from 1; the substituted
  • the aryl groups in the alkyl-substituted aryl groups are preferably independently selected from phenyl groups.
  • the substituted aryl group in R 1 or R 2 is preferably independently selected from 4-fluorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-tolyl, 4-chlorophenyl, 5-chlorophenyl or 5-bromophenyl.
  • the alkyl group in R 3 or R 4 is preferably independently selected from alkyl groups with 1 to 5 carbon atoms, more preferably independently selected from alkyl groups with 1 to 3 carbon atoms, and most preferably Preferably, they are independently selected from methyl.
  • the R 3 and R 4 preferably form a cycloalkyl ring having 4 to 6 carbon atoms, and are more preferably a cyclopentyl or cyclobutyl group.
  • the structure of formula I is preferably selected from one of the following structures:
  • the terminal groups not given in the above structural formula are all methyl groups.
  • the invention provides a method for preparing indoline compounds, which includes:
  • the compound of the formula VI structure and a base are subjected to a photocatalytic reaction in a solvent to obtain the compound of the formula I structure;
  • the catalyst is preferably selected from the group consisting of tris(2,2'-bipyridyl)ruthenium bis(hexafluorophosphate) salt, cyclometalated iridium complex, terpyridylruthenium chloride hexahydrate, (4,4 '-Di-tert-butyl-2,2'-bipyridyl)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate, [4,4'-di-tert-butyl 2,2'- Bis[3,5-difluoro-2-(5-trifluoromethyl-2-pyridyl)phenyl]iridium(III) hexafluorophosphate, bis[2-(2,5-difluoro) Phenyl)-5-trifluoromethylpyridine]iridium bis(hexafluorophosphate) salt, bis[2-(2,4-diflu
  • the base is preferably selected from one of potassium phosphate, potassium phosphate triple crystal water, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium pivalate, potassium carbonate, sodium phosphate and tetramethylguanidine or Several kinds.
  • the solvent used in the photocatalytic reaction is recorded as the second solvent;
  • the second solvent is preferably selected from benzene trifluoride, acetonitrile, toluene, fluorobenzene, chlorobenzene, dichloromethane, 1,4-dioxy Hexacyclic ring, acetone and one or more mixed solvents;
  • the mixed solvent includes: trifluorotoluene and tert-butanol; the volume ratio of the trifluorotoluene and tert-butanol is preferably (0.8 ⁇ 1.2): 1, more Preferably 1:1.
  • the molar ratio of the compound of the formula VI structure and the base is preferably 1: (1-2), more preferably 1: (1.3-1.7), and most preferably 1:1.5; the molar ratio of the compound of the formula VI structure is:
  • the molar ratio to the catalyst is preferably 1: (0.01-0.05), more preferably 1: (0.02-0.04), and most preferably 1:0.03.
  • the photocatalytic reaction is preferably carried out in a closed and protective atmosphere;
  • the protective atmosphere is preferably selected from nitrogen and/or inert gases;
  • the light during the photocatalytic reaction is preferably selected from blue light and/or Or green light;
  • the power of the light is preferably 20-25W, more preferably 21-24W, most preferably 22-23W;
  • the temperature of the photocatalytic reaction is preferably 30-60°C, more preferably 40-50°C , most preferably 45°C;
  • the photocatalytic reaction time is preferably 6 to 15 hours, more preferably 8 to 12 hours, and most preferably 10 hours.
  • the photocatalytic reaction after the photocatalytic reaction is completed, it preferably further includes:
  • the solvent is removed from the obtained reaction product under reduced pressure, and the residue is purified by column chromatography to obtain the compound of formula I.
  • the preparation method of the compound of formula VI structure preferably includes:
  • the selection range of R 1 is consistent with the selection range of R 1 in the above formula I.
  • the molar ratio of the compound of formula V structure, arylsulfonyl chloride and pyridine is preferably 1: (1.2 ⁇ 2.5): (3.0 ⁇ 5.0), more preferably 1: (1.5 ⁇ 2.0): (3.5 ⁇ 4.5), most preferably 1: (1.6 ⁇ 1.8): 4;
  • the concentration of the compound of formula V structure in dichloromethane is preferably 2 ⁇ 4mol/L, more preferably 2.5 ⁇ 3.5mol/L, most preferably is 3mol/L.
  • the reaction is preferably carried out under conditions of a closed and protective atmosphere; the temperature of the reaction is preferably room temperature.
  • reaction after the reaction is completed, it preferably further includes:
  • reaction product is washed, extracted, the organic layers are combined for washing, drying, filtration, concentration and column chromatography to obtain a compound of formula VI structure.
  • the washing is preferably carried out with hydrochloric acid solution; the mass concentration of the hydrochloric acid solution is preferably 8 to 12%, more preferably 10%; the extraction is preferably carried out with ethyl acetate; the combined organic
  • the layer is preferably washed with brine; the drying is preferably done with anhydrous sodium sulfate; the column chromatography is preferably Flash column chromatography, and petroleum ether and ethyl acetate are preferably used in the column chromatography process; the petroleum ether
  • the volume ratio to ethyl acetate is preferably (13-17):1, more preferably (14-16):1, and most preferably 15:1.
  • the preparation method of the compound of formula V structure preferably includes:
  • the p-toluenesulfonic acid is preferably p-toluenesulfonic acid ⁇ crystallization water
  • the acetonitrile is preferably an acetonitrile aqueous solution
  • the volume ratio of acetonitrile and water in the acetonitrile aqueous solution is preferably (35-45): (3.5 ⁇ 4.5), more preferably (38 ⁇ 42): (3.8 ⁇ 4.2), most preferably 40:4.
  • the molar ratio of the compound of formula IV structure and p-toluenesulfonic acid is preferably (1-1.2): (0.1-0.3), more preferably 1.1:0.2; the molar ratio of the compound of formula IV structure in acetonitrile
  • the concentration is preferably 2 to 4 mol/L, more preferably 3 mol/L.
  • the rearrangement reaction is preferably carried out in a closed and protective atmosphere; the temperature of the rearrangement reaction is preferably 70 to 90°C, more preferably 75 to 85°C, and most preferably 80°C; the The rearrangement reaction time is preferably overnight.
  • reaction product is cooled, washed, extracted, the combined organic layers are washed, dried, filtered and spin-dried to obtain the compound of formula V structure.
  • the cooling is preferably to room temperature; the washing is preferably with water; the extraction is preferably with ethyl acetate; the combined organic layer washing is preferably with brine; the drying is preferably Dry over anhydrous Na2SO4 .
  • the preparation method of the compound of formula IV structure preferably includes:
  • a compound of formula II, a compound of formula III and tetrakis(triphenylphosphine)palladium are mixed and reacted in a solvent to obtain a compound of formula IV;
  • the molar ratio of the compound of formula II to the compound of formula III is preferably 1: (1-1.5), more preferably 1: (1.1-1.4), most preferably 1: (1.2-1.3) .
  • the molar ratio of the compound of the formula II structure and tetrakis(triphenylphosphine)palladium is preferably 1:(0.02 ⁇ 0.05), and more preferably 1:(0.03 ⁇ 0.04).
  • the solvent used in the mixing reaction process is recorded as the first solvent;
  • the first solvent is preferably selected from one or more types of tetrahydrofuran and N,N diformamide.
  • the mixing reaction is preferably carried out in a closed and protective atmosphere; the time of the mixing reaction is preferably 12 to 24 hours, more preferably 15 to 20 hours, and most preferably 16 to 18 hours; the The temperature of the mixing reaction is preferably 25-80°C, more preferably 30-70°C, more preferably 40-60°C, and most preferably 50°C; the mixing reaction is preferably carried out under stirring conditions.
  • reaction product is washed, extracted, the organic layers are combined, washed, dried, filtered, concentrated and purified to obtain a compound of formula IV.
  • the washing preferably uses saturated ammonium chloride solution; the extraction preferably uses ethyl acetate; the combined organic layer washing preferably uses brine; the drying preferably uses anhydrous sodium sulfate;
  • the purification method is preferably flash chromatography, and the eluent in the flash chromatography process preferably includes petroleum ether and ethyl acetate; the volume ratio of the petroleum ether and ethyl acetate is preferably (55-65): 1 , more preferably (58 ⁇ 62):1, most preferably 60:1.
  • the invention provides an inhibitor, including: the indoline compound described in the above technical solution.
  • the inhibitor is preferably selected from calpain-I inhibitors and/or NF-KB inhibitors.
  • the invention provides a medicine for treating glaucoma, including: the indoline compound described in the above technical solution.
  • the indoline compound provided by the invention has a specific structure, and the product obtained under visible light catalysis is thiazine ring-fused cyclohexadiene.
  • the product has enantioselectivity and can be further oxidized into a benzene ring.
  • the preparation method of indoline compounds provided by the invention has high yield, wide substrate range, low reaction temperature, short reaction time, and only requires a few thousandths of the catalytic amount of the metal complex.
  • the preparation of indoline compounds in the present invention adopts visible light catalysis and reduces the use of transition metal catalysis and no oxidant. It is efficient and environmentally friendly; the conditions are mild and the target product is easy to obtain.
  • the compound of formula 1 is prepared according to the following process route:
  • the IV1 obtained above (2.45g, 15.2mmol) was dissolved in acetonitrile:water (40mL:4mL) solution, p-toluenesulfonic acid ⁇ crystal water (289.7mg, 1.52mmol, 0.1equiv) was added, and under inert protection, 80 The reaction was carried out by heating at °C overnight;
  • Example 1 of the present invention The product prepared in Example 1 of the present invention was subjected to nuclear magnetic resonance, infrared spectrum, high-resolution mass spectrometry, and melting point detection.
  • the detection results are:
  • the melting point m.p is 134 ⁇ 138°C (detected by melting point instrument); the yield is 84%.
  • the compound of formula 2 was prepared according to the method of Example 1 using different raw materials (the para position on one side of the benzene ring is substituted by a monomethyl group).
  • Example 2 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 132 ⁇ 135°C; the yield is 88%.
  • the compound of formula 3 was prepared according to the method of Example 1 using different raw materials (the para position on one side of the benzene ring was substituted by the halogen element F).
  • Example 3 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 127 ⁇ 133°C; the yield is 76%.
  • the compound of formula 4 was prepared according to the method of Example 1 using different raw materials (the para position on one side of the benzene ring was replaced by the halogen element Cl).
  • Example 4 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 125 ⁇ 129°C; the yield is 74%.
  • the compound of formula 5 was prepared according to the method of Example 1 using different raw materials (the para position on one side of the benzene ring was substituted by the halogen element Br).
  • Example 5 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 135 ⁇ 138°C; the yield is 81%.
  • the compound of formula 6 was prepared according to the method of Example 1 using different raw materials (the para position on one side of the benzene ring was substituted by halogen element I).
  • Example 7 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 130 ⁇ 136°C; the yield is 72%.
  • the compound of formula 7 was prepared according to the method of Example 1 using different raw materials (the meta position on one side of the benzene ring is replaced by the halogen element Cl).
  • Example 7 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 126 ⁇ 129°C; the yield is 72%.
  • the compound of formula 8 was prepared according to the method of Example 1 using different raw materials (the meta position on one side of the benzene ring is replaced by the halogen element Br).
  • Example 8 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 140 ⁇ 144°C; the yield is 72%.
  • the compound of formula 9 was prepared according to the method of Example 1 using different raw materials (one side of the benzene ring was replaced by a naphthalene ring).
  • Example 9 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 135 ⁇ 138°C; the yield is 55%.
  • Example 10 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 139 ⁇ 143°C; the yield is 60%.
  • the compound of formula 11 was prepared according to the method of Example 1 using different raw materials (no substitution on one side of the benzene ring).
  • Example 11 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 136 ⁇ 141°C; the yield is 80%.
  • the compound of formula 12 was prepared according to the method of Example 1 using different raw materials (one side of the sulfonamide was replaced by halogen element F).
  • Example 13 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 144 ⁇ 147°C; the yield is 82%.
  • the compound of formula 13 was prepared according to the method of Example 1 using different raw materials (one side of the sulfonamide was replaced by the halogen element Br).
  • Example 13 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 135 ⁇ 139°C; the yield is 85%.
  • the compound of formula 14 was prepared according to the method of Example 1 using different raw materials (one side of the sulfonamide was replaced by halogen element I). The difference from Example 1 is that.
  • Example 14 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 130 ⁇ 135°C; the yield is 77%.
  • the compound of formula 15 was prepared according to the method of Example 1 using different raw materials (one side of the sulfonamide was substituted by trifluoromethyl).
  • Example 15 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 137 ⁇ 139°C; the yield is 71%.
  • the compound of formula 16 was prepared according to the method of Example 1 using different raw materials (one side of the sulfonamide was substituted with a methoxy group).
  • Example 16 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 141 ⁇ 146°C; the yield is 75%.
  • the compound of formula 17 was prepared according to the method of Example 1 using different raw materials (one side of the sulfonamide was substituted by an acetate group).
  • Example 17 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 135 ⁇ 139°C; the yield is 70%.
  • the compound of formula 18 was prepared according to the method of Example 1 using different raw materials (one side of the sulfonamide was substituted by phenyl).
  • Example 18 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 132 ⁇ 135°C; the yield is 65%.
  • the compound of formula 19 was prepared according to the method of Example 1 using different raw materials (the end of the olefin was substituted by a four-membered ring).
  • Example 19 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 133 ⁇ 138°C; the yield is 56%.
  • the compound of formula 20 was prepared according to the method of Example 1 using different raw materials (the end of the olefin was substituted by a five-membered ring).
  • Example 20 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 130 ⁇ 134°C; the yield is 60%.
  • the compound of formula 21 was prepared according to the method of Example 1 using different raw materials (the olefin chain was substituted by a monomethyl group).
  • Example 21 of the present invention was tested according to the method of Example 1, and the test results were:
  • the melting point m.p is 121 ⁇ 126°C; the yield is 52%.
  • the indoline compound provided by the invention has a specific structure, and the product obtained under visible light catalysis is thiazine ring-fused cyclohexadiene.
  • the product has enantioselectivity and can be further oxidized into a benzene ring.
  • the preparation method of indoline compounds provided by the invention has high yield, wide substrate range, low reaction temperature, short reaction time, and only requires a few thousandths of the catalytic amount of the metal complex.
  • the preparation of indoline compounds in the present invention adopts visible light catalysis and reduces the use of transition metal catalysis and no oxidant. It is efficient and environmentally friendly; the conditions are mild and the target product is easy to obtain.

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Abstract

本发明提供了一种吲哚啉类化合物的制备方法，通过可见光和金属络合物催化方法将N-芳基磺酰-2-β,γ-不饱和烯烃取代的苯胺进行环合重排反应，从而制备了吲哚啉类化合物。本发明制备的吲哚啉类化合物具有特定的结构，而且制备方法采用无过渡金属、氧化剂等添加剂的无害环境的催化方法，反应条件温和，操作简单、高效，同时底物适用性广泛。本发明还提供了一种吲哚啉类化合物及其应用。

Description

一种吲哚啉类化合物及其制备方法 
本申请要求于2022年08月09日提交中国专利局、申请号为202210951115.3、发明名称为“一种吲哚啉类化合物及及其制备方法”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明属于含氮杂环化合物技术领域，尤其涉及一种吲哚啉类化合物及其制备方法。
背景技术
随着氮自由基化学的发展，氮自由基级联反应被认为是构建多种功能化N-杂环的最具潜力的强大工具之一。烯烃的自由基碳胺化反应也被证明是一种有吸引力的、直接的方法获得各种二氢吡唑和苯并噻嗪稠合结构。许多具有芳环稠合噻嗪结构的相关化合物被发现表现出广泛的生物活性，比如苯唑舒坦-I及其衍生物具有良好的calpain-I抑制活性，苯唑舒坦-II是一种新型核因子NF-KB抑制剂，布林唑胺-III也被确定为治疗青光眼的有效药物。
目前，吡咯环稠合噻嗪的合成主要有以下几种方法：2004年Chemler首次开发了以Cu(OAc) 2催化的分子内氮自由基氧化环化，得到相应的四环化合物：
Figure PCTCN2022115450-appb-000001
2007年，Chemler以铜作为催化和氧化剂，得到对映选择性吡咯烷稠合苯并噻嗪化合物：
Figure PCTCN2022115450-appb-000002
但是，这两种方法均存在着铜作为催化和氧化剂、用量大；而且反应时间长，或者反应温度高，底物局限性大的缺陷。因而，开发一种更为绿色的合成 吲哚啉类化合物的工艺路线，解决现有技术中存在的上述缺陷，已成为本领域诸多前沿学者广泛关注的焦点，具有重要意义。
发明内容
有鉴于此，本发明的目的在于提供一种吲哚啉类化合物及其制备方法，本发明提供的吲哚啉类化合物具有特定的结构，制备方法工艺简单、产率高。
本发明提供了一种吲哚啉类化合物，具有式I结构：
Figure PCTCN2022115450-appb-000003
式I中，R 1选自烷基或取代的烷基、H、卤素原子、羰基或取代的羰基、芳基或取代的芳基；
R 2选自H、卤素原子、烷基或取代的烷基、芳基或取代的芳基、羰基或取代的羰基；
R 3选自H、烷基或取代的烷基、与R 4成环；
R 4选自H、烷基或取代的烷基、与R 3成环。
在本发明中，所述R 1或R 2中的烷基优选独立的选自碳原子数为1～5的烷基，更优选独立的选自碳原子数为1～3烷基，最优选独立的选自甲基；取代的烷基优选独立的选自烷氧基或卤代烷基；所述烷氧基优选独立的选自碳原子数为1～5的烷氧基，更优选独立的选自碳原子数为1～3的烷氧基，最优选独立的选自甲氧基；所述卤代烷基优选独立的选自碳原子数为1～5的卤代烷基，更优选独立的选自碳原子数为1～3的卤代烷基，更优选独立的选自卤代甲基；所述卤代烷基中的卤素优选独立的选自F；所述卤代烷基最优选独立的选自-CF 3。
在本发明中，所述R 1或R 2中的卤素原子优选独立的选自Br、I、F或Cl。
在本发明中，所述R 1或R 2中的取代的羰基优选独立的选自烷氧基取代的羰基；所述烷氧基取代的羰基中的碳原子数优选独立的选自2～5，更优选独立的选自2～3；所述取代的羰基最优选独立的选自甲氧羰基或乙氧羰基，最最优选独立的选自4-乙氧羰基。
在本发明中，所述R 1或R 2中的芳基优选独立的选自苯基；取代的芳基优选独立的选自卤素取代的芳基、烷基取代的芳基、取代的烷基取代的芳基；所 述卤素取代的芳基中的卤素优选独立的选自氟、溴、碘或氯；所述卤素取代的芳基中的芳基优选独立的选自苯基；所述烷基取代的芳基中的烷基优选独立的选自碳原子数为1～5的烷基，更优选独立的选自碳原子数为1～3的烷基，最优选独立的选自甲基；所述烷基取代的芳基中芳基优选独立的选自苯基；所述取代的烷基取代的芳基中的取代的烷基优选独立的选自卤素取代的烷基或烷氧基；所述卤素取代的烷基中的卤素优选独立的选自F；所述卤素取代的烷基中烷基的碳原子数优选独立的选自1～5，更优选独立的选自1～3，最优选独立的选自1；所述烷氧基中的碳原子数优选独立的选自1～5，更优选独立的选自1～3，最优选独立的选自1；所述取代的烷基取代的芳基中的芳基优选独立的选自苯基。
在本发明中，所述R 1或R 2中的取代的芳基优选独立的选自4-氟苯基、4-溴苯基、4-碘苯基、4-三氟甲基苯基、4-甲氧基苯基、4-甲苯基、4-氯苯基、5-氯苯基或5-溴苯基。
在本发明中，所述R 3或R 4中的烷基优选独立的选自碳原子数为1～5的烷基，更优选独立的选自碳原子数为1～3的烷基，最优选独立的选自甲基。
在本发明中，所述R 3与R 4优选成环为碳原子数为4～6的环烷基，更优选为环戊基或环丁基。
在本发明中，所述式I结构优选选自下式结构中的一种：
Figure PCTCN2022115450-appb-000004
Figure PCTCN2022115450-appb-000005
在本发明中，上述结构式中未给出的端基均为甲基。
本发明提供了一种吲哚啉类化合物的制备方法，包括：
在催化剂的作用下，将式VI结构化合物和碱在溶剂中进行光催化反应，得到式I结构化合物；
Figure PCTCN2022115450-appb-000006
式VI中，R 1、R 2、R 3和R 4的选择基团与式I中一致。
在本发明中，所述催化剂优选选自三(2,2'-联吡啶)钌二(六氟磷酸)盐、环金属化铱配合物、三联吡啶氯化钌六水合物、(4,4'-二叔丁基-2,2'-联吡啶)双[(2-吡啶基)苯基]铱(III)六氟磷酸盐、[4,4'-二叔丁基2,2'-联吡啶]二[3,5-二氟-2-(5-三氟甲基-2-吡啶基)苯基]铱(III)六氟磷酸盐、二[2-(2,5-二氟苯基)-5-三氟甲基吡啶]铱二(六氟磷酸)盐、二[2-(2,4-二氟苯基)-5-三氟甲基吡啶][2-2'-联吡啶]铱二(六氟磷酸)盐和[2,2'-联吡啶]二[4,4'-二叔丁基-2,2'-联吡啶]铱(III)六氟磷酸盐中的一种或几种。
在本发明中，所述碱优选选自磷酸钾、磷酸钾三结晶水、磷酸二氢钾、磷酸氢二钾、特戊酸钾、碳酸钾、磷酸钠和四甲基胍中的一种或几种。
在本发明中，将光催化反应所用的溶剂记为第二溶剂；所述第二溶剂优选选自三氟甲苯、乙腈、甲苯、氟苯、氯苯、二氯甲烷、1,4-二氧六环、丙酮和 混合溶剂一种或几种；所述混合溶剂包括：三氟甲苯和叔丁醇；所述三氟甲苯和叔丁醇的体积比优选为(0.8～1.2)：1，更优选为1：1。
在本发明中，所述式VI结构化合物和碱的摩尔比优选为1：(1～2)，更优选为1：(1.3～1.7)，最优选为1：1.5；所述式VI结构化合物和催化剂的摩尔比优选为1：(0.01～0.05)，更优选为1：(0.02～0.04)，最优选为1：0.03。
在本发明中，所述光催化反应优选在密闭和保护性气氛下进行；所述保护性气氛优选选自氮气和/或惰性气体；所述光催化反应过程中的光优选选自蓝光和/或绿光；所述光的功率优选为20～25W，更优选为21～24W，最优选为22～23W；所述光催化反应的温度优选为30～60℃，更优选为40～50℃，最优选为45℃；所述光催化反应的时间优选为6～15小时，更优选为8～12小时，最优选为10小时。
在本发明中，对所述光催化反应的工艺条件进行研究发现，采用不同的催化剂、碱和溶剂制备得到的产物收率不同，采用[Ir(ppy) 2(dtbbpy)]PF 6作为催化剂、K 3PO 4为碱，PhMe为溶剂制备吲哚啉类化合物具有更高的收率。
在本发明中，所述光催化反应完成后优选还包括：
将得到的反应产物减压去除溶剂，对残渣进行柱层析纯化，得到式I结构化合物。
在本发明中，所述式VI结构化合物的制备方法优选包括：
将式V结构化合物、芳基磺酰氯、吡啶和二氯甲烷进行反应，得到式VI结构化合物；
Figure PCTCN2022115450-appb-000007
式V中，R 2、R 3和R 4的选择基团与式I中一致。
在本发明中，所述芳基磺酰氯的结构式为：
Figure PCTCN2022115450-appb-000008
其中，R 1的选择范围与上述式I中R 1的选择范围一致。
在本发明中，所述式V结构化合物、芳基磺酰氯和吡啶的摩尔比优选为1：(1.2～2.5)：(3.0～5.0)，更优选为1：(1.5～2.0)：(3.5～4.5)，最优选为1：(1.6～1.8)：4；所述式V结构化合物在二氯甲烷中的浓度优选为2～4mol/L，更优选为2.5～3.5mol/L，最优选为3mol/L。
在本发明中，所述反应优选在密闭和保护性气氛的条件下进行；所述反应的温度优选为室温。
在本发明中，所述反应完成后优选还包括：
将得到的反应产物进行洗涤、提取、合并有机层洗涤、干燥、过滤、浓度和柱层析，得到式VI结构化合物。
在本发明中，所述洗涤优选采用盐酸溶液进行洗涤；所述盐酸溶液的质量浓度优选为8～12％，更优选为10％；所述提取优选采用乙酸乙酯进行提取；所述合并有机层优选拟采用盐水洗涤；所述干燥优选采用无水硫酸钠干燥；所述柱层析优选为Flash柱层析，所述柱层析过程中优选采用石油醚和乙酸乙酯；所述石油醚和乙酸乙酯的体积比优选为(13～17)：1，更优选为(14～16)：1，最优选为15：1。
在本发明中，所述式V结构化合物的制备方法优选包括：
将式IV结构化合物、对甲苯磺酸在乙腈中进行重排反应，得到式V结构化合物；
Figure PCTCN2022115450-appb-000009
式IV中，R 2、R 3和R 4的选择基团与式I中一致；
未给出的端基为＝CH 2。
在本发明中，所述对甲苯磺酸优选为对甲苯磺酸·结晶水；所述乙腈优选为乙腈水溶液，所述乙腈水溶液中乙腈和水的体积比优选为(35～45)：(3.5～4.5)，更优选为(38～42)：(3.8～4.2)，最优选为40：4。
在本发明中，所述式IV结构化合物和对甲苯磺酸的摩尔比优选为(1～1.2)：(0.1～0.3)，更优选为1.1:0.2；所述式IV结构化合物在乙腈中的浓度优选为2～4mol/L，更优选为3mol/L。在本发明中，所述重排反应优选在密闭和保护性气氛下进行；所述重排反应的温度优选为70～90℃，更优选为75～85℃，最 优选为80℃；所述重排反应的时间优选为过夜。
在本发明中，所述重排反应结束后优选还包括：
将得到的反应产物冷却、洗涤、提取、合并有机层洗涤、干燥、过滤和旋干，得到式V结构化合物。
在本发明中，所述冷却优选为冷却至室温；所述洗涤优选为用水洗涤；所述提取优选为采用乙酸乙酯提取；所述合并有机层洗涤优选为用盐水洗涤；所述干燥优选为采用无水Na 2SO 4干燥。
在本发明中，所述式IV结构化合物的制备方法优选包括：
将式II结构化合物、式III结构化合物和四(三苯基膦)钯在溶剂中进行混合反应，得到式IV结构化合物；
Figure PCTCN2022115450-appb-000010
式II中，R 2的选择基团与式I中一致；
式III中，R 3和R 4的选择基团与式I中一致；
未给出的端基为＝CH 2。
在本发明中，所述式II结构化合物和式III结构化合物的摩尔比优选为1：(1～1.5)，更优选为1：(1.1～1.4)，最优选为1：(1.2～1.3)。
在本发明中，所述式II结构化合物和四(三苯基膦)钯的摩尔比优选为1：(0.02～0.05)，更优选为1:(0.03～0.04)。
在本发明中，将混合反应过程中采用的溶剂记为第一溶剂；所述第一溶剂优选选自四氢呋喃和N,N二甲酰胺的一种或几种。
在本发明中，所述混合反应优选在密闭和保护性气氛下进行；所述混合反应的时间优选为12～24小时，更优选为15～20小时，最优选为16～18小时；所述混合反应的温度优选为25～80℃，更优选为30～70℃，更优选为40～60℃，最优选为50℃；所述混合反应优选在搅拌的条件下进行。
在本发明中，所述混合反应完成后优选还包括：
将得到反应产物进行洗涤、提取、合并有机层洗涤、干燥、过滤、浓缩和纯化，得到式IV结构化合物。
在本发明中，所述洗涤优选采用饱和氯化铵溶液；所述提取优选采用乙酸 乙酯提取；所述合并有机层洗涤优选采用盐水洗涤；所述干燥优选为无水硫酸钠干燥；所述纯化的方法优选为用闪电色谱法，所述闪电色谱法过程中的洗脱液优选包括石油醚和乙酸乙酯；所述石油醚和乙酸乙酯的体积比优选为(55～65)：1，更优选为(58～62)：1，最优选为60：1。
在本发明中，式I结构化合物的合成路线为：
Figure PCTCN2022115450-appb-000011
本发明提供了一种抑制剂，包括：上述技术方案所述的吲哚啉类化合物。
在本发明中，所述抑制剂优选选自calpain-I抑制剂和/或NF-KB抑制剂。
本发明提供了一种治疗青光眼的药物，包括：上述技术方案所述的吲哚啉类化合物。
本发明提供的吲哚啉类化合物具有特定的结构，在可见光催化下得到的产物为噻嗪环稠合的环己二烯，具有对映选择性的产物，能够进一步氧化成苯环。本发明提供的吲哚啉类化合物的制备方法产率高，底物范围大，反应温度低、时间短，金属络合物只需要千分之几的催化量。本发明制备吲哚啉类化合物采用了可见光催化且减少了过渡金属催化和无氧化剂的使用，高效、无害环境；而且条件温和，易获得目标产物。
具体实施方式
下面将对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1
按照以下工艺路线制备得到式1结构化合物：
Figure PCTCN2022115450-appb-000012
具体过程为：
将苯胺(1.82mL,20mmol)、叔丁基-(2-甲基丁基-3-烯-2-基)碳酸酯(5.02g,27mmol)和四(三苯基膦)钯(462.4mg,2mol％)加至四氢呋喃(40mL)和N,N二甲酰胺(2mL，体积比为20：1)溶液中，在惰性气氛下，60℃加热搅拌20h进行反应；
将得到的反应产物冷却并用饱和氯化铵溶液(20mL)洗涤，水层用乙酸乙酯(50mL x2)提取，合并有机层用盐水(30mL)洗涤，无水硫酸钠干燥，过滤，浓缩；用闪速色谱法(洗脱液为石油醚:乙酸乙酯＝60:1)进行纯化，得到纯化的淡黄色固体IV1。
将上述所得的IV1(2.45g,15.2mmol)溶于乙腈：水(40mL:4mL)溶液中，加入对甲苯磺酸·结晶水(289.7mg,1.52mmol,0.1equiv)，在惰性保护下，80℃加热过夜进行反应；
将得到的反应产物冷却至室温后，用水(40mL)清洗，水层用乙酸乙酯(20mL×2)提取，合并有机层用盐水(30mL)洗涤，无水Na 2SO 4干燥，过滤，旋干，得到粗产物V1直接用于下一步，无需进一步纯化。
在惰性气体和室温下，将上述得到V1加至吡啶(5equiv)，再加入对甲苯磺酰氯(1.5equiv)进行反应6h；
将得到的反应产物加入二氯甲烷(50mL)，用10％盐酸溶液(100mL)洗涤，水层用乙酸乙酯(30mL×2)提取，合并有机层用盐水(30mL)洗涤，无水硫酸钠干燥，过滤，浓缩；Flash柱层析(石油醚:乙酸乙酯＝15:1)，得到白色固体VI1。
将化合物VI1(0.2mmol,1.0equiv.)、[Ir(ppy)2(dtbbpy)]PF6(3.83mg,0.004 mmol,2mol％)和磷酸三钾(34.7mg,0.16mmol,0.8equiv.)加入到装有磁搅拌棒的10ml烘干lenk管中；密封、氩气保护，加入甲苯(2.5mL)，反应温度维持在45℃，并在22W蓝色LED下照射6小时进行反应；
待反应结束后，减压去除溶剂，对残渣进行柱层析纯化，得到白色固体。
对本发明实施例1制备的产品进行核磁共振、红外光谱、高分辨质谱、熔点检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.55(d,J＝8.4Hz,1H),7.18–7.11(m,2H),6.94(t,J＝7.4Hz,1H),6.89(t,J＝3.3Hz,1H),5.50(d,J＝1.2Hz,1H),4.26(t,J＝9.6Hz,1H),3.33(s,1H),3.12(dd,J＝15.5,9.0Hz,1H),3.01–2.86(m,1H),2.85–2.65(m,2H),1.78(s,3H),1.10(s,3H),0.78(s,3H)；
13C NMR(151MHz,CDCl 3)δ142.81,135.65,132.81,130.78,128.54,127.80,124.83,122.80,117.42,113.41,71.91,46.42,40.55,30.96,30.68,23.00,22.76,14.28；
FT-IR(thin film,KBr):ν(cm -1):2971,2912,1601,1477,1315,1236,1147,969,919,761,678,622；
HRMS(ESI)[M+Na] +Calculated for C 18H 21NO 2S 338.1185,found 338.1189。
由以上检测结果可知，本发明实施例1提供的方法制备得到了目标产物式1结构化合物：
(11aR,12aS)-2,12,12-trimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为134～138℃(熔点仪检测得到)；收率为84％。
实施例2
按照实施例1的方法采用不同的原料(苯环一侧对位由单甲基取代)制备得到式2结构化合物。
按照实施例1的方法对本发明实施例2制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.55(d,J＝8.4Hz,1H),7.18–7.11(m,2H),6.94(t,J＝7.4Hz,1H),6.89(t,J＝3.3Hz,1H),5.50(d,J＝1.2Hz,1H),4.26(t,J＝9.6Hz,1H),3.33(s,1H),3.12(dd,J＝15.5,9.0Hz,1H),3.01–2.86(m,1H), 2.85–2.65(m,2H),1.78(s,3H),1.10(s,3H),0.78(s,3H)；
13C NMR(151MHz,CDCl 3)δ142.81,135.65,132.81,130.78,128.54,127.80,124.83,122.80,117.42,113.41,71.91,46.42,40.55,30.96,30.68,23.00,22.76,14.28；
FT-IR(thin film,KBr):ν(cm -1):2971,2912,1601,1477,1315,1236,1147,969,919,761,678,622；
HRMS(ESI)[M+Na] +Calculated for C 18H 21NO 2S 338.1185,found 338.1189。
由以上检测结果可知，本发明实施例2提供的方法制备得到了目标产物式2结构化合物：
Figure PCTCN2022115450-appb-000013
(11aR,12aS)-2,9,12,12-tetramethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为132～135℃；收率为88％。
实施例3
按照实施例1的方法采用不同的原料(苯环一侧对位由卤元素F取代)制备得到式3结构化合物。
按照实施例1的方法对本发明实施例3制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.47(dd,J＝8.6,4.5Hz,1H),6.90–6.79(m,3H),5.49(s,1H),4.25(t,J＝9.6Hz,1H),3.31(s,1H),3.08(dd,J＝15.8,8.9Hz,1H),2.98–2.64(m,3H),1.77(s,3.05H),1.08(s,3.10H),0.77(s,3.06H).
13C NMR(151MHz,CDCl 3)δ159.01(d,J＝240.8Hz),138.78,135.47,132.87,131.05,130.58,130.53,117.29,114.14,114.05,113.99,112.36,112.20,77.26,77.05,76.84,72.40,46.40,40.51,30.95,30.65,22.98,22.68,14.29；
FT-IR(thin film,KBr):ν(cm -1):2954,2923,2854,1475,1443,1306,1217,1171,1148,964,913,872,676,629；
HRMS(ESI)[M+H]+Calculated for C 18H 20FNO 2S 334.1272,found 334.1276。
由以上检测结果可知，本发明实施例3提供的方法制备得到了目标产物式3结构化合物：
Figure PCTCN2022115450-appb-000014
(11aR,12aS)-9-fluoro-2,12,12-trimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为127～133℃；收率为76％。
实施例4
按照实施例1的方法采用不同的原料(苯环一侧对位由卤元素Cl取代)制备得到式4结构化合物。
按照实施例1的方法对本发明实施例4制备的产品进行检测，检测结果为：
1H NMR(600MHz,CDCl 3)δ7.45(d,J＝8.3Hz,1H),7.09(d,J＝8.1Hz,2.09H),6.87(dd,J＝4.8,2.0Hz,1.08H),5.48(d,J＝1.0Hz,1H),4.25(t,J＝9.5Hz,1H),3.31(d,J＝1.4Hz,1H),3.08(dd,J＝15.8,9.1Hz,1H),2.96–2.63(m,4H),1.77(s,3H),1.07(s,3H),0.75(s,3H)；
13C NMR(151MHz,CDCl 3)δ141.49,135.43,132.91,131.09,130.56,127.76,127.68,125.05,117.28,114.14,72.09,46.38,40.65,30.95,30.46,22.97,22.63,14.21；
FT-IR(thin film,KBr):ν(cm -1):2970,2916,2873,1467,1319,1230,1176,1148,995,961,828,718,679,624；
HRMS(ESI)[M+H] +Calculated for C 18H 20ClNO 2S 350.0976,found 350.0979。
由以上检测结果可知，本发明实施例4提供的方法制备得到了目标产物式4结构化合物：
Figure PCTCN2022115450-appb-000015
(11aR,12aS)-9-chloro-2,12,12-trimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为125～129℃；收率为74％。
实施例5
按照实施例1的方法采用不同的原料(苯环一侧对位由卤元素Br取代)制备得到式5结构化合物。
按照实施例1的方法对本发明实施例5制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.52–7.30(m,1H),7.26–7.22(m,2H),6.91–6.83(m,1H),5.48(d,J＝1.5Hz,1H),4.26(t,J＝9.5Hz,1H),3.44–3.27(m,1H),3.10(dd,J＝15.8,9.1Hz,1H),2.98–2.58(m,3H),1.77(s,3H),1.08(s,3H),0.75(s,3H)；
13C NMR(151MHz,CDCl 3)δ142.00,135.39,132.93,131.13,130.94,130.62,127.91,117.27,115.16,114.65,71.99,46.36,40.67,30.95,30.41,23.01,22.64,14.22；
FT-IR(thin film,KBr):ν(cm -1):2970,2908,2873,1595,1466,1318,1229,1176,1147,960,825,733,714,679,621；
HRMS(ESI)[M+H]+Calculated for C 18H 20BrNO 2S 394.0471,found 394.0471。
由以上检测结果可知，本发明实施例5提供的方法制备得到了目标产物式5结构化合物：
Figure PCTCN2022115450-appb-000016
(11aR,12aS)-9-bromo-2,12,12-trimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为135～138℃；收率为81％。
实施例6
按照实施例1的方法采用不同的原料(苯环一侧对位由卤元素I取代)制备得到式6结构化合物。
按照实施例1的方法对本发明实施例7制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.46–7.40(m,1.98H),7.34–7.28(m,1.09H),6.93–6.80(m,1.08H),5.55–5.44(m,1H),4.25(t,J＝9.4Hz,1H),3.31 (d,J＝3.7Hz,1H),3.10(dd,J＝15.9,9.1Hz,1H),2.98–2.68(m,3H),1.77(s,3H),1.07(s,3H),0.74(s,3H)；
13C NMR(101MHz,CDCl 3)δ142.82,136.67,135.48,133.72,132.98,131.32,131.12,117.33,115.25,85.28,71.86,46.40,40.72,30.99,30.29,23.02,22.67,14.23；
FT-IR(thin film,KBr):ν(cm -1):2970,2902,1465,1318,1230,1148,960,824,712,679,620；
HRMS(ESI)[M+H] +Calculated for C 18H 20INO 2S 442.0332,found 442.0332。
由以上检测结果可知，本发明实施例6提供的方法制备得到了目标产物式6结构化合物：
Figure PCTCN2022115450-appb-000017
(11aR,12aS)-9-iodo-2,12,12-trimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为130～136℃；收率为72％。
实施例7
按照实施例1的方法采用不同的原料(苯环一侧间位由卤元素Cl取代)制备得到式7结构化合物。
按照实施例1的方法对本发明实施例7制备的产品进行检测，检测结果为：
1H NMR(600MHz,CDCl 3)δ7.42(d,J＝8.1Hz,1H),7.08(t,J＝8.1Hz,1H),6.91(d,J＝8.1Hz,1H),6.89–6.85(m,1H),5.48(d,J＝1.4Hz,1H),4.29(t,J＝9.5Hz,1H),3.32(d,J＝3.5Hz,1H),3.18(dd,J＝16.1,9.3Hz,1.3H),2.93–2.69(m,3.42H),1.77(s,3.39H),1.10(s,3.23H),0.77(s,3H)；
13C NMR(151MHz,CDCl 3)δ143.99,135.43,132.90,131.13,130.74,129.34,127.07,122.75,117.29,111.50,71.45,46.32,40.69,30.95,30.13,22.99,22.60,14.16；
FT-IR(thin film,KBr):ν(cm -1):2916,2855,1595,1448,1328,1244,1152,1052,994,785,686,622；
HRMS(ESI)[M+Na]+Calculated for C 18H 20ClNO 2S 372.0795,found 372.0793。
由以上检测结果可知，本发明实施例7提供的方法制备得到了目标产物式7结构化合物：
Figure PCTCN2022115450-appb-000018
(11aR,12aS)-10-chloro-2,12,12-trimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为126～129℃；收率为72％。
实施例8
按照实施例1的方法采用不同的原料(苯环一侧间位由卤元素Br取代)制备得到式8结构化合物。
按照实施例1的方法对本发明实施例8制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.48(d,J＝7.9Hz,1H),7.14–6.96(m,2H),6.88(s,1H),5.49(s,1H),4.29(t,J＝9.5Hz,1H),3.33(s,1H),3.15(dd,J＝16.2,9.3Hz,1H),2.96–2.64(m,3H),1.78(s,3H),1.11(s,3H),0.78(s,3H)；
13C NMR(151MHz,CDCl 3)δ143.70,135.42,132.90,131.16,129.51,129.22,125.61,119.62,117.29,112.02,71.08,46.31,40.69,32.17,30.95,23.00,22.59,14.17；
FT-IR(thin film,KBr):ν(cm -1):2972,2919,2849,1593,1445,1323,1244,1151,1047,980,767,684,638；
HRMS(ESI)[M+H] +Calculated for C 18H 20BrNO 2S 394.0471,found 394.0473。
由以上检测结果可知，本发明实施例8提供的方法制备得到了目标产物式8结构化合物：
Figure PCTCN2022115450-appb-000019
(11aR,12aS)-10-bromo-2,12,12-trimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为140～144℃；收率为72％。
实施例9
按照实施例1的方法采用不同的原料(苯环一侧由萘环取代)制备得到式9结构化合物。
按照实施例1的方法对本发明实施例9制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.86(d,J＝8.9Hz,1.02H),7.79(d,J＝8.2Hz,1.11H),7.70(d,J＝8.9Hz,1H),7.60(d,J＝8.3Hz,1.09H),7.46(t,J＝7.5Hz,1.09H),7.34(t,J＝7.5Hz,1.14H),6.91(t,J＝3.2Hz,0.98H),5.52(s,1H),4.44(t,J＝9.9Hz,0.98H),3.47(dd,J＝15.5,9.5Hz,1H),3.35(d,J＝17.3Hz,1.11H),3.16(dd,J＝15.5,10.3Hz,1.02H),2.91–2.64(m,2.03H),1.78(s,3H),1.18(s,3.04H),0.81(s,3H)；
13C NMR(101MHz,CDCl 3)δ132.86,130.68,130.31,130.20,128.82,128.70,126.75,124.04,122.77,121.69,117.51,114.41,72.40,46.60,40.76,31.01,29.42,23.04,22.82,14.38；
FT-IR(thin film,KBr):ν(cm -1):2965,2924,1601,1460,1316,1232,1157,1135,973,764,673；
HRMS(ESI)[M+Na]+Calculated for C 22H 23NO 2S 388.1342,found 388.1340。
由以上检测结果可知，本发明实施例9提供的方法制备得到了目标产物式9结构化合物：
Figure PCTCN2022115450-appb-000020
(13aR,14aS)-2,14,14-trimethyl-13,13a,14,14a-tetrahydro-3H-benzo[f]benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为135～138℃；收率为55％。
实施例10
按照实施例1的方法采用不同的原料(苯环一侧对位由乙酸酯基取代)制 备得到式10结构化合物。
按照实施例1的方法对本发明实施例10制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.88–7.85(m,1H),7.81(d,J＝1.1Hz,1H),7.55(d,J＝8.5Hz,0.96H),6.93–6.77(m,0.95H),5.49(d,J＝1.5Hz,1H),4.40–4.35(m,1H),4.32(dd,J＝8.0,6.3Hz,2H),3.35(d,J＝3.7Hz,0.96H),3.18(dd,J＝15.9,9.3Hz,1.03H),3.02–2.68(m,3H),1.88–1.68(s,3H),1.37(t,J＝7.1Hz,3.33H),1.09(s,3.02H),0.74(s,3H)；
13C NMR(151MHz,CDCl 3)δ166.27,146.86,135.35,132.97,131.21,130.36,128.66,126.18,124.83,117.28,112.29,71.96,60.73,46.31,40.97,30.95,30.21,22.98,22.54,14.34,14.06；
FT-IR(thin film,KBr):ν(cm -1):2971,2871,1703,1607,1464,1314,1266,1175,967,769,680,622；
HRMS(ESI)[M+H]+Calculated for C 21H 25NO 4S 388.1577,found 388.1582。
由以上检测结果可知，本发明实施例10提供的方法制备得到了目标产物式10结构化合物：
Figure PCTCN2022115450-appb-000021
ethyl(11aR,12aS)-2,12,12-trimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole-9-carboxylate 5,5-dioxide；
熔点m.p为139～143℃；收率为60％。
实施例11
按照实施例1的方法采用不同的原料(苯环一侧无取代)制备得到式11结构化合物。
按照实施例1的方法对本发明实施例11制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.55(d,J＝8.7Hz,0.96H),7.14(dd,J＝7.2,5.6Hz,2.18H),6.99–6.92(m,1.05H),6.92–6.87(m,0.94H),5.93–5.85(m,1H),5.82–5.75(m,1H),4.28(t,1H),3.41–3.30(m,1H),3.13(dd,J＝15.5,9.0 Hz,1H),3.01–2.83(m,3H),1.10(s,3H),0.83(s,3.05H)；
13C NMR(151MHz,CDCl 3)δ142.83,142.79,135.65,130.67,128.46,127.84,125.33,124.83,123.08,122.84,113.42,71.87,45.37,40.32,30.68,26.34,22.66,14.36；
FT-IR(thin film,KBr):ν(cm -1):2961,2920,2851,1634,1600,1478,1314,1234,1153,1106,967,750,711,638；
HRMS(ESI)[M+Na] +Calculated for C 17H 19NO 2S 324.1029,found 324.1032。
由以上检测结果可知，本发明实施例11提供的方法制备得到了目标产物式11结构化合物：
Figure PCTCN2022115450-appb-000022
(11aR,12aS)-12,12-dimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为136～141℃；收率为80％。
实施例12
按照实施例1的方法采用不同的原料(磺胺一侧由卤元素F取代)制备得到式12结构化合物。
按照实施例1的方法对本发明实施例13制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.53(d,J＝8.4Hz,1H),7.14(dd,J＝7.2,5.0Hz,2.05H),6.96(dd,J＝10.9,4.0Hz,1H),6.88–6.75(m,1H),5.43–5.28(m,1H),4.28(t,J＝9.5Hz,1H),3.66–3.49(m,1H),3.24–2.89(m,4H),1.06(s,3.07H),0.82(s,3.16H)；
13C NMR(101MHz,CDCl 3)δ158.90,156.36(d,J＝256.0Hz),142.53,136.14,136.11,128.54,128.48,128.42,127.97,124.95,123.10,113.42,99.59,99.41,71.68,47.02,46.94,40.84,30.78,27.03,26.73,22.77,14.28；
FT-IR(thin film,KBr):ν(cm -1):2968,2921,1720,1601,1461,1316,1232,1177,1137,962,761,625；
HRMS(ESI)[M+H]+Calculated for C 17H 18FNO 2S 320.1115,found  320.1116。
由以上检测结果可知，本发明实施例12提供的方法制备得到了目标产物式12结构化合物：
Figure PCTCN2022115450-appb-000023
(11aR,12aS)-2-fluoro-12,12-dimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为144～147℃；收率为82％。
实施例13
按照实施例1的方法采用不同的原料(磺胺一侧由卤元素Br取代)制备得到式13结构化合物。
按照实施例1的方法对本发明实施例13制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.53(d,J＝8.6Hz,1H),7.17–7.10(m,2.2H),7.01–6.91(m,1.12H),6.84–6.65(m,1H),6.22–6.12(m,1H),4.27(t,J＝9.5Hz,1.05H),3.54–3.40(m,1.06H),3.37–3.12(m,3.29H),2.96(dd,J＝15.6,9.8Hz,1H),1.12(s,3.1H),0.84(s,3.12H)；
13C NMR(101MHz,CDCl 3)δ142.52,135.17,129.56,128.36,127.99,124.93,124.90,123.12,120.11,113.44,71.45,48.84,40.86,35.36,30.70,22.75,14.62；
FT-IR(thin film,KBr):ν(cm -1):2964,2919,1675,1600,1460,1318,1231,1163,964,762,619；
HRMS(ESI)[M+Na] +Calculated for C 17H 18BrNO 2S 402.0134,found 402.0137。
由以上检测结果可知，本发明实施例13提供的方法制备得到了目标产物式13结构化合物：
Figure PCTCN2022115450-appb-000024
(11aR,12aS)-2-bromo-12,12-dimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6 ][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为135～139℃；收率为85％。
实施例14
按照实施例1的方法采用不同的原料(磺胺一侧由卤元素I取代)制备得到式14结构化合物，与实施例1的区别在于。
按照实施例1的方法对本发明实施例14制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.52(d,J＝8.1Hz,1H),7.19–7.11(m,2.28H),6.99–6.84(m,1.15H),6.64(dd,J＝5.0,1.9Hz,1.01H),6.45(dd,J＝3.5,1.8Hz,1H),4.26(t,J＝9.5Hz,1.06H),3.44–3.24(m,3H),3.14(dd,J＝15.6,9.1Hz,1.16H),2.96(dd,J＝15.6,9.8Hz,1.07H),1.12(s,3H),0.85(s,3H)；
13C NMR(101MHz,CDCl 3)δ142.54,134.90,133.18,130.09,128.33,127.99,124.91,123.10,113.44,93.32,71.32,49.44,40.84,39.30,30.67,22.74,14.68；
FT-IR(thin film,KBr):ν(cm -1):2968,2919,1667,1600,1460,1317,1231,1163,964,761,713,619；
HRMS(ESI)[M+Na]+Calculated for C 17H 18INO 2S 449.9995,found 449.9998。
由以上检测结果可知，本发明实施例14提供的方法制备得到了目标产物式14结构化合物：
Figure PCTCN2022115450-appb-000025
(11aR,12aS)-2-iodo-12,12-dimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为130～135℃；收率为77％。
实施例15
按照实施例1的方法采用不同的原料(磺胺一侧由三氟甲基取代)制备得到式15结构化合物。
按照实施例1的方法对本发明实施例15制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.54(d,J＝8.1Hz,1.09H),7.16(s,2.23H), 7.12–6.79(m,1.29H),6.41(s,1H),4.33(t,J＝9.3Hz,1H),3.52(s,1H),3.29–2.90(m,4H),1.17(s,3H),0.81(s,3.06H)；
13C NMR(151MHz,CDCl 3)δ142.41,135.03,128.44,128.19,127.99,127.72,127.52,127.32,127.11(dd,J＝62.2,31.2Hz),126.24,126.21,126.17,126.14(q,J＝5.5Hz),125.64,123.84,122.03,120.23(q,J＝272.2Hz),124.92,123.16,113.41,71.54,45.71,40.71,30.61,23.72,22.68,14.65；
FT-IR(thin film,KBr):ν(cm -1):2972,2917,1656,1600,1478,1460,1395,1319,1299,1232,1165,1106,969,760,710,622；
HRMS(ESI)[M+H] +Calculated for C 18H 18F 3NO 2S 370.1073,found 370.1073。
由以上检测结果可知，本发明实施例15提供的方法制备得到了目标产物式15结构化合物：
Figure PCTCN2022115450-appb-000026
(11aR,12aS)-12,12-dimethyl-2-(trifluoromethyl)-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为137～139℃；收率为71％。
实施例16
按照实施例1的方法采用不同的原料(磺胺一侧由甲氧基取代)制备得到式16结构化合物。
按照实施例1的方法对本发明实施例16制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.77–7.68(m,1.99H),7.46–7.38(m,0.99H),7.22–7.15(m,1.02H),7.14–7.05(m,4.08H),6.70(s,0.95H),5.05–4.89(m,1H),2.99(d,J＝7.0Hz,2.09H),1.73(d,J＝1.2Hz,3.09H),1.70(s,3H)；
13C NMR(101MHz,CDCl 3)δ153.83,142.77,135.98,129.79,128.62,127.88,124.88,122.89,113.43,89.77,71.89,54.36,46.81,41.14,30.85,28.80,23.00,13.98；
FT-IR(thin film,KBr):ν(cm -1):2970,2902,1719,1682,1477,1318,1219,1152,965,754,625；
HRMS(ESI)[M+Na]+Calculated for C 18H 21NO 2S 354.1134,found 354.1127。
由以上检测结果可知，本发明实施例16提供的方法制备得到了目标产物式16结构化合物：
Figure PCTCN2022115450-appb-000027
(11aR,12aS)-2-methoxy-12,12-dimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为141～146℃；收率为75％。
实施例17
按照实施例1的方法采用不同的原料(磺胺一侧由乙酸酯基取代)制备得到式17结构化合物。
按照实施例1的方法对本发明实施例17制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.58–7.50(m,1H),7.18–7.12(m,2.02H),7.02–6.98(m,0.94H),6.98–6.92(m,1.49H),4.33(t,J＝9.5Hz,1H),3.80(s,3H),3.58–3.50(m,1H),3.20–3.11(m,3.02H),2.96(dd,J＝15.6,9.9Hz,1.05H),1.20(s,3H),0.81(s,3H)；杂质: 1HNMR(400MHz,CDCl 3)δ8.19(d,J＝7.6Hz,0.98H),8.08(dd,J＝8.3,1.6Hz,1.08H),8.01(d,J＝8.3Hz,1H),7.63(d,J＝7.9Hz,0.95H),7.23(d,J＝8.0Hz,1.42H),7.09–7.04(m,1.68H),4.70(t,J＝9.8Hz,1H),4.04–3.93(m,3.32H),3.39(dd,J＝15.8,9.8Hz,1.15H),3.27–3.20(m,1H),1.52(s,3.09H),1.32(s,3.33H)；
混合物: 13C NMR(151MHz,CDCl 3)δ166.07,165.55,145.05,142.53,141.42,140.36,134.43,134.15,133.83,130.26,128.80,128.77,128.36,128.32,128.21,127.96,125.16,124.87,124.33,124.03,123.05,114.46,113.44,71.68,68.15,52.70,52.11,46.80,40.77,39.78,30.90,30.63,29.68,25.92,24.66,24.19,22.79,14.93；
FT-IR(thin film,KBr):ν(cm -1):2919,2850,1717,1460,1317,1263,1164,966,754,655；
HRMS(ESI)[M+H] +Calculated for C 19H 21NO 4S 360.1264,found  360.1269。
由以上检测结果可知，本发明实施例17提供的方法制备得到了目标产物式17结构化合物：
Figure PCTCN2022115450-appb-000028
methyl(11aR,12aS)-12,12-dimethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole-2-carboxylate 5,5-dioxide；
熔点m.p为135～139℃；收率为70％。
实施例18
按照实施例1的方法采用不同的原料(磺胺一侧由苯基取代)制备得到式18结构化合物。
按照实施例1的方法对本发明实施例18制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.58(d,J＝8.3Hz,1H),7.45–7.30(m,5.17H),7.20–7.12(m,2.15H),7.07–7.02(m,1H),6.99–6.90(m,1H),6.16(d,J＝2.0Hz,1H),4.35(t,J＝9.5Hz,1H),3.56(dd,J＝11.3,7.3Hz,0.95H),3.44–3.22(m,2.01H),3.16(dd,J＝15.6,9.1Hz,1.04H),2.98(dd,J＝15.6,10.1Hz,1.11H),1.20(s,3H),0.86(s,3H)；
13C NMR(101MHz,CDCl 3)δ142.79,139.99,135.62,135.34,130.67,128.62,128.49,128.01,127.94,125.32,124.90,122.95,120.06,113.50,71.94,46.92,41.08,30.74,28.69,22.94,14.64；
FT-IR(thin film,KBr):ν(cm -1):2957,2918,2872,1467,1318,1230,1176,1148,961,828,718,679,624；
HRMS(ESI)[M+H]+Calculated for C 23H 23NO 2S 378.1522,found 378.1523。
由以上检测结果可知，本发明实施例18提供的方法制备得到了目标产物式18结构化合物：
Figure PCTCN2022115450-appb-000029
(11aR,12aS)-12,12-dimethyl-2-phenyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide；
熔点m.p为132～135℃；收率为65％。
实施例19
按照实施例1的方法采用不同的原料(烯烃末端由四元环取代)制备得到式19结构化合物。
按照实施例1的方法对本发明实施例19制备的产品进行检测，检测结果为：
1H NMR(600MHz,CDCl 3)δ7.54–7.49(m,1H),7.18(d,J＝7.3Hz,1.05H),7.16–7.09(m,1.26H),6.98–6.92(m,1.05H),6.88(t,J＝3.0Hz,1H),5.79(d,J＝1.3Hz,1.11H),4.32(t,J＝9.5Hz,1.09H),3.39(s,1.07H),3.31(d,J＝9.4Hz,2.04H),2.91(dd,J＝23.4,7.0Hz,1.16H),2.86–2.73(m,1.23H),2.17–2.08(m,1.19H),2.00–1.87(m,2.12H),1.84(s,3H),1.82–1.63(m,3.4H)；
13C NMR(151MHz,CDCl 3)δ142.83,135.15,133.27,130.95,128.61,127.87,124.82,122.87,117.77,113.45,69.76,46.60,43.83,31.59,31.08,24.38,23.14,19.96,14.27；
FT-IR(thin film,KBr):ν(cm -1):2960,2852,1635,1474,1311,1228,1151,993,750,669；
HRMS(ESI)[M+H] +Calculated for C 19H 21NO 2S 328.1366,found 328.1366。
由以上检测结果可知，本发明实施例19提供的方法制备得到了目标产物式19结构化合物：
Figure PCTCN2022115450-appb-000030
(11aR,12aS)-2-methyl-3,11,11a,12a-tetrahydrospiro[benzo[5,6][1,2]thiazino[2,3-a]indole-12,1'-cyclobutane]5,5-dioxide；
熔点m.p为133～138℃；收率为56％。
实施例20
按照实施例1的方法采用不同的原料(烯烃末端被五元环取代)制备得到式20结构化合物。
按照实施例1的方法对本发明实施例20制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.55(d,J＝8.2Hz,1H),7.14(t,J＝7.0Hz,2H),6.94(t,J＝7.4Hz,1H),6.88(s,1H),5.49(s,1H),4.48(t,J＝9.8Hz,1H),3.53(s,1H),3.17(dd,J＝15.3,8.6Hz,1H),3.04–2.67(m,3H),1.97–1.83(m,1H),1.81(s,3H),1.75–1.39(m,7H)；
13C NMR(101MHz,CDCl 3)δ142.95,136.33,132.83,130.83,128.53,127.91,124.77,122.91,118.49,113.64,77.35,77.04,76.72,71.88,52.20,46.18,34.53,31.86,31.12,28.10,27.46,26.59,23.07；
FT-IR(thin film,KBr):ν(cm -1):2956,2863,1601,1478,1317,1235,1153,1001,963,752,677,639；
HRMS(ESI)[M+Na]+Calculated for C 20H 23NO 2S 364.1342,found 364.1333。
由以上检测结果可知，本发明实施例20提供的方法制备得到了目标产物式20结构化合物：
Figure PCTCN2022115450-appb-000031
(11aR,12aS)-2-methyl-3,11,11a,12a-tetrahydrospiro[benzo[5,6][1,2]thiazino[2,3-a]indole-12,1'-cyclopentane]5,5-dioxide；
熔点m.p为130～134℃；收率为60％。
实施例21
按照实施例1的方法采用不同的原料(烯烃链上由单甲基取代)制备得到式21结构化合物。
按照实施例1的方法对本发明实施例21制备的产品进行检测，检测结果为：
1H NMR(400MHz,CDCl 3)δ7.52(d,J＝8.1Hz,1.02H),7.16–7.05(m,2.06H),6.97–6.89(m,1H),6.83(t,J＝2.9Hz,1H),5.49(d,J＝1.5Hz,1H),3.90(d,J＝6.2Hz,1.04H),3.36(s,1.01H),3.29–3.19(m,1.07H),2.88–2.62(m, 2.19H),1.76(s,3.16H),1.40(d,J＝6.8Hz,3H),1.12(s,3.08H),0.67(s,3H)；
13C NMR(151MHz,CDCl 3)δ141.85,135.67,133.85,132.96,129.47,127.92,123.81,122.39,117.39,112.43,78.11,46.43,41.85,37.60,30.82,23.04,22.21,21.93,14.56；
FT-IR(thin film,KBr):ν(cm -1):2968,2921,1598,1477,1460,1319,1232,1150,997,750,688,612；
HRMS(ESI)[M+H] +Calculated for C 19H 23NO 2S 330.1522,found 330.1525。
由以上检测结果可知，本发明实施例21提供的方法制备得到了目标产物式21结构化合物：
Figure PCTCN2022115450-appb-000032
(11aR,12aS)-2,11,12,12-tetramethyl-11,11a,12,12a-tetrahydro-3H-benzo[5,6][1,2]thiazino[2,3-a]indole 5,5-dioxide
熔点m.p为121～126℃；收率为52％。
本发明提供的吲哚啉类化合物具有特定的结构，在可见光催化下得到的产物为噻嗪环稠合的环己二烯，具有对映选择性的产物，能够进一步氧化成苯环。本发明提供的吲哚啉类化合物的制备方法产率高，底物范围大，反应温度低、时间短，金属络合物只需要千分之几的催化量。本发明制备吲哚啉类化合物采用了可见光催化且减少了过渡金属催化和无氧化剂的使用，高效、无害环境；而且条件温和，易获得目标产物。
以上对本发明提供的一种吲哚啉类化合物及其制备方法、应用进行了详细的介绍，本文中应用了具体个例对本发明的原理及实施方式进行了阐述，以上实施例的说明只是用于帮助理解本发明的方法及其核心思想，包括最佳方式，并且也使得本领域的任何技术人员都能够实践本发明，包括制造和使用任何装置或系统，和实施任何结合的方法。应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以对本发明进行若干改进和修饰，这些改进和修饰也落入本发明权利要求的保护范围内。本发明专利保护的范围通过权利要求来限定，并可包括本领域技术人员能够想到的其他实施例。如果 这些其他实施例具有不是不同于权利要求文字表述的结构要素，或者如果它们包括与权利要求的文字表述无实质差异的等同结构要素，那么这些其他实施例也应包含在权利要求的范围内。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。

Claims (10)

  1. 一种吲哚啉类化合物的制备方法，包括：
    在催化剂的作用下，将式VI结构化合物和碱在溶剂中进行光催化反应，得到式I结构化合物；
    Figure PCTCN2022115450-appb-100001
    式VI中，
    R 1选自烷基或取代的烷基、H、卤素原子、羰基或取代的羰基、芳基或取代的芳基；
    R 2选自H、卤素原子、烷基或取代的烷基、芳基或取代的芳基、羰基或取代的羰基；
    R 3选自H、烷基或取代的烷基、与R 4成环；
    R 4选自H、烷基或取代的烷基、与R 3成环。
  2. 根据权利要求1所述的方法，其特征在于，所述催化剂选自三(2,2'-联吡啶)钌二(六氟磷酸)盐、环金属化铱配合物、三联吡啶氯化钌六水合物、(4,4'-二叔丁基-2,2'-联吡啶)双[(2-吡啶基)苯基]铱(III)六氟磷酸盐、[4,4'-二叔丁基2,2'-联吡啶]二[3,5-二氟-2-(5-三氟甲基-2-吡啶基)苯基]铱(III)六氟磷酸盐、二[2-(2,5-二氟苯基)-5-三氟甲基吡啶]铱二(六氟磷酸)盐、二[2-(2,4-二氟苯基)-5-三氟甲基吡啶][2-2'-联吡啶]铱二(六氟磷酸)盐和[2,2'-联吡啶]二[4,4'-二叔丁基-2,2'-联吡啶]铱(III)六氟磷酸盐中的一种或几种。
  3. 根据权利要求1所述的方法，其特征在于，所述碱选自磷酸钾、磷酸钾三结晶水、磷酸二氢钾、磷酸氢二钾、特戊酸钾、碳酸钾、磷酸钠和四甲基胍中的一种或几种。
  4. 根据权利要求1所述的方法，其特征在于，所述溶剂选自三氟甲苯、乙腈、甲苯、氟苯、氯苯、二氯甲烷、1,4二氧六环、丙酮和三氟甲苯/三乙胺中的一种或多种。
  5. 根据权利要求1所述的方法，其特征在于，所述具有式VI结构的化合物与所述碱的摩尔比为1：(1～2.0)；
    所述具有式VI结构的化合物与所述催化剂的摩尔比为1：(0.01～0.05)。
  6. 根据权利要求1所述的方法，其特征在于，所述光催化反应在保护性气氛中进行；所述保护性气氛包括：
    氮气和/或惰性气体。
  7. 根据权利要求1所述的制备方法，其特征在于，所述光催化反应中的光催化剂包括蓝光和/或绿光；
    所述光催化反应的温度30～60℃；
    所述光催化反应的时间为6～15h。
  8. 一种吲哚啉类化合物，具有式I结构：
    Figure PCTCN2022115450-appb-100002
    式I中，R 1选自烷基或取代的烷基、H、卤素原子、羰基或取代的羰基、芳基或取代的芳基；
    R 2选自H、卤素原子、烷基或取代的烷基、芳基或取代的芳基、羰基或取代的羰基；
    R 3选自H、烷基或取代的烷基、与R 4成环；
    R 4选自H、烷基或取代的烷基、与R 3成环。
  9. 根据权利要求8所述的吲哚啉类化合物，其特征在于，所述R 1或R 2中的烷基独立的选自碳原子数为1～5的烷基；取代的烷基独立的选自烷氧基或卤代烷基；
    所述R 1或R 2中的芳基独立的选自苯基；取代的芳基独立的选自烷基取代的芳基、取代的烷基取代的芳基、卤素取代的芳基；
    所述取代的烷基独立的选自烷氧基或卤素取代的烷基。
  10. 根据权利要求8所述的吲哚啉类化合物，其特征在于，所述R 1或R 2中取代的芳基独立的选自4-氟苯基、4-溴苯基、4-碘苯基、4-三氟甲基苯基、4-甲氧基苯基、4-甲苯基、4-氯苯基、5-氯苯基或5-溴苯基；
    所述R 1或R 2中取代的羰基独立的选自烷氧基取代的羰基；
    所述烷氧基取代的羰基中的碳原子数独立的选自2～5。
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