CN116925069A - Synthesis method of iron-catalyzed fused ring [1,2-a ] indole compound - Google Patents

Synthesis method of iron-catalyzed fused ring [1,2-a ] indole compound Download PDF

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CN116925069A
CN116925069A CN202210375094.5A CN202210375094A CN116925069A CN 116925069 A CN116925069 A CN 116925069A CN 202210375094 A CN202210375094 A CN 202210375094A CN 116925069 A CN116925069 A CN 116925069A
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ethyl acetate
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李维双
朱磊
陈舒晗
赵雪
张泽浪
李博解
汪连生
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Hubei Engineering University
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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Abstract

The invention discloses a method for synthesizing an iron-catalyzed fused ring [1,2-a ] indole compound, which comprises the following steps: at room temperature, adding a catalyst A, raw material enaminone, alkali and a solvent into a reaction tube respectively; carrying out reaction under the heating condition, monitoring the reaction progress by TLC, and separating and purifying after the reaction is finished to obtain a condensed ring [1,2-a ] indole compound; wherein catalyst a is a complex of metallic iron/ligand; the reaction temperature is 60 to 120 ℃; separation and purification include, but are not limited to, extraction, column chromatography, recrystallization. The invention takes the commodity with wide sources and low price as the raw material for reaction, synthesizes various substituted condensed ring [1,2-a ] indole compounds under the action of the catalyst of the very cheap iron catalyst, has relatively simple whole reaction condition and convenient post-reaction treatment, and has very good industrialized prospect.

Description

Synthesis method of iron-catalyzed fused ring [1,2-a ] indole compound
Technical Field
The invention relates to a method for synthesizing an iron-catalyzed fused ring [1,2-a ] indole compound, belonging to the field of organic synthesis.
Background
Condensed ring [1,2-a ] indole compounds widely exist in nature and are core skeletons of alkaloid natural products and drug molecules with important biological activity and medicinal value. [ a) J.am.chem.Soc.1981,103,6990.; b) Chem.pharm.bull.1994,42,2546; c) Angew.Chem., int.Ed.2016,55,13529 ]. Fused ring [1,2-a ] indoles are important intermediates in the synthesis of these active pharmaceutical molecules, such as alkaloid natural products Aspidospermidine, quebrachamine, and the like.
Currently, with respect to fused rings [1,2-a ]]The synthesis method of the indole compound mainly comprises the following steps: (1) Classical Fischer indole synthesis involves the prior formation of phenylhydrazones from substituted phenylhydrazine compounds and 2-substituted 1, 3-cyclohexanediones by intramolecular [3,3]Rearranging and removing one molecule of NH 3 To synthesize [ 1) Tetrahedron lett.1964,5,331; 2) Tetrahedron 1992,48,5991; 3) Tetrahedron 1983,39,3657; 4) Heteromyces 2017,95,1245.]The method is not only limited by the electrical property of phenylhydrazine, but also can synthesize the condensed ring [1,2-a ] rich in electrons]Indole compounds; and are limited by regioselectivity, when meta substituents are present on the phenylhydrazine, fused rings [1,2-a ] are generally obtained]Indole mixtures; (2) Transition metal-participated carbon-nitrogen/carbon-carbon coupling reactions to prepare [ 1) org.lett.2019,21,1082; 2) Adv.synth.catalyst.2010, 352, 2667; 3) Tetrahedron 2013,69,4415; 4) Angew.Chem., int.Ed.2012,51,9891; 5) Org.lett.2018,20,6498; 6) Chem.sci.2013,4,29.]. The main problems of these methods are the use of noble metals as catalysts, or the troublesome synthesis of raw materials, etc.
Therefore, there is a need to develop a synthetic method which is efficient in reaction, wide in raw material sources and inexpensive in catalyst.
Disclosure of Invention
In order to solve the problem of noble metal in the prior art, the invention aims to provide a novel method for synthesizing a fused ring [1,2-a ] indole compound by using a cheap metal iron complex, which takes widely available and cheap commodity as a raw material for reaction, synthesizes various substituted fused ring [1,2-a ] indole compounds under the action of a very cheap iron catalyst, has relatively simple whole reaction condition, is convenient for post-reaction treatment and has very good industrialized prospect. The invention provides a simple, convenient and efficient innovative method for constructing the condensed ring [1,2-a ] indole skeleton, and provides a more novel route selection for synthesizing active molecules containing the skeleton.
In order to achieve the above purpose, the technical scheme of the invention is as follows: a method for synthesizing iron-catalyzed fused ring [1,2-a ] indole compounds comprises the following steps:
catalyst A, raw material enaminone, alkali and solvent are respectively added into a reaction tube at room temperature. And (3) carrying out reaction under the heating condition, monitoring the reaction progress by TLC, and separating and purifying after the reaction is finished to obtain the condensed ring [1,2-a ] indole compound. The reaction process is shown in the equation (I):
the condensed ring [1,2-a ] indole compound has a structure shown in an equation (I) C; the starting enaminone has a structure shown in equation (I) B;
wherein R is 1 Optionally the following structure: hydrogen atom, alkyl, cycloalkyl, heteroatom-containing alkyl, fluoro, chloro, bromoalkyl substituted acyl; cyano group; a nitro group; an ester group; an alkyl or aryl substituted amine; alkyl or aryl substituted oxygen; a substituted silicon-based group;
R 2 is alkyl, cycloalkyl, heteroatom-containing alkyl, aryl, heteroaryl or fluoro;
R 1 is mono-substituted or multi-substituted, and forms a ring or does not form a ring;
wherein X is selected from C or N;
wherein Y is selected from Br, I, OTf, OTs, OSO 2 Ph；
Wherein n is taken from 0, 1, 2;
wherein catalyst a is a complex of metallic iron/ligand;
wherein, the metallic iron is a complex formed by divalent or trivalent iron and a ligand, and the molar ratio of the metallic iron to the ligand is 1:1 to 1:3, wherein the metallic iron comprises Fe (acac) z 、Fe(Cl) z 、Fe(Br) z 、FeI 2 、Fe(OAc) z 、Fe(OTf) z Wherein z=2 or 3; the ligands used are optionally of the structure: ethylenediamine and its derivatives, cyclohexanediamine and its derivatives, BINAM and its derivatives, 8-hydroxyquinoline and its derivatives, BINOL and its derivatives, proline;
preference is given to Fe (acac) 2 And 8-hydroxyquinoline in a molar ratio of 1:2, combining;
wherein the reaction solvent is selected from the following solvents or a combination of solvents: n, N-dimethylformamide, N-dimethylacetamide, tetrahydrofuran, toluene, acetonitrile, dimethylsulfoxide;
dimethyl sulfoxide is preferred;
the alkali is selected from KO t Bu、NaO t Bu、K 2 CO 3 、Cs 2 CO 3 、Na 2 CO 3 、K 3 PO 4 、Na 3 PO 4 、K 2 HPO 4 、KH 2 PO 4 、NaOH、KOH；
The mass ratio of the catalyst A, the enaminone B and the alkali is 0.01:1:1 to 0.1:1:3, a step of;
the reaction temperature is 60 to 120 ℃;
separation and purification include, but are not limited to, extraction, column chromatography, recrystallization.
Compared with the prior art, the synthesis method provided by the invention has the following advantages and beneficial effects:
1) The invention is suitable for the synthesis of condensed ring [1,2-a ] indole compounds containing various substituents, has simple reaction operation and less byproducts, and is easy to purify;
2) The invention has wide sources of raw materials, is cheap and easy to obtain, uses cheap metallic iron as the catalyst, effectively reduces the cost of the catalyst, and has good industrial application prospect.
Drawings
FIGS. 1 and 2 show the starting 3- (2-iodoaniline) -2-methylcyclohexenone according to example 1 of the present invention 1 H NMR 13 CNMR spectrogram;
FIGS. 3 and 4 are diagrams showing 10-methyl-7H-8, 9-o [1,2-a ] produced in example 1 of the present invention]Indol-6-ones 1 H NMR 13 CNMR spectra.
Detailed Description
A further understanding of the nature and advantages of the present invention may be realized by the following detailed description. The examples provided are merely illustrative of the methods of the present invention and are not intended to limit the remainder of the disclosure in any way whatsoever.
The reaction conditions for synthesizing the iron-catalyzed fused ring [1,2-a ] indole compounds are researched by taking 3- (2-iodoaniline) -2-methylcyclohexenone as a standard substrate:
wherein, the iron catalyst represents ferrous chloride, ferrous bromide and ferrous acetylacetonate, the ligand is the structure drawn in the table, mol% refers to relative molar quantity, equiv represents equivalent, alkali represents common inorganic alkali, the organic solvent is anhydrous solvent, and the volume is 2mL. Wherein DMSO is dimethyl sulfoxide, DMF is N, N' -dimethylformamide, n.r. represents no reaction. a is the isolation yield.
Example 1
Preparation of 10-methyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 66.1mg of 3- (2-iodoaniline) -2-methylcyclohexenone (0.2 mmol) and 97.5mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, and performing column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 10-methyl-7H-8, 9-o [1,2-a]Indol-6-one (white solid, 35.3 mg), yield: 89%. 1 H NMR(400MHz,CDCl 3 )δ8.47–8.44(m,1H),7.45–7.39(m,1H),7.33–7.24(m,2H),2.89(t,J＝6.2Hz,2H),2.76(t,J＝6.2Hz,2H),2.18(s,3H),2.11–2.03(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.3,134.5,133.3,131.2,124.2,123.8,117.8,116.4,112.3,34.6,21.8,21.3,8.6。
Example 2
1, 10-dimethyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 68.6mg of 3- (2-iodo-3-methylaniline) -2-methylcyclohexenone (0.2 mmol) and 97.3mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, carrying out column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 1, 10-dimethyl-7H-8, 9-o [1,2-a ]]Indol-6-one (white solid, 33.4 mg), yield: 78%. 1 H NMR(400MHz,CDCl 3 )δ8.35(d,J＝8.0Hz,1H),7.18–7.10(m,1H),6.99(d,J＝7.3Hz,1H),2.88(t,J＝6.3Hz,2H),2.77(t,J＝6.5Hz,2H),2.66(s,3H),2.35(s,3H),2.14–2.00(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.2,135.0,133.1,130.3,129.4,125.6,124.3,114.6,113.2,34.7,21.9,21.3,20.3,11.8。
Example 3
2, 10-dimethyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 68.3mg of 3- (2-iodo-4-methylaniline) -2-methylcyclohexenone (0.2 mmol) and 97.9mg of Cs 2 CO 3 (0.3 mmol) and then 1.8mL of dimethyl sulfoxide solvent are added, the whole reaction is placed on a heating module at 120 ℃ for reaction,TLC monitoring, after the reaction, cooling the whole reaction to room temperature, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in turn, extracting with ethyl acetate three times and separating, washing and separating with water twice, washing and separating with saturated saline water finally, washing and separating with saturated saline water, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating, subjecting the crude product to column chromatography separation with petroleum ether and ethyl acetate mixture as eluent (10/1, v/v) and 200-300 mesh silica gel as separating resin to obtain the target product 2, 10-dimethyl-7H-8, 9-o [1, 2-a)]Indol-6-one (white solid, 36.1 mg), yield: 85%. 1 H NMR(400MHz,CDCl 3 )δ8.30(d,J＝8.2Hz,1H),7.21(s,1H),7.11(d,J＝8.4Hz,1H),2.87(t,J＝6.1Hz,2H),2.77–2.67(m,2H),2.45(s,3H),2.15(s,3H),2.13–2.02(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.3,133.3,133.1,132.8,131.5,125.4,118.0,116.1,112.0,34.6,21.7,21.4,21.3,8.7。
Example 4
3, 10-dimethyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 68.7mg of 3- (2-iodo-5-methylaniline) -2-methylcyclohexenone (0.2 mmol) and 97.0mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating, subjecting the crude product to column chromatography separation by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and using 200-300 mesh silica gel as separating resin to obtainTarget product 3, 10-dimethyl-7H-8, 9-o [1,2-a]Indol-6-one (white solid, 35.9 mg), yield: 84%. 1 H NMR(400MHz,CDCl 3 )δ8.28(s,1H),7.31(d,J＝7.8Hz,1H),7.11(d,J＝7.8Hz,1H),2.87(t,J＝6.1Hz,2H),2.75(t,J＝6.1Hz,2H),2.47(s,3H),2.15(s,3H),2.11–2.06(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.5,134.8,134.3,132.6,129.1,125.2,117.6,116.9,112.3,34.5,21.92,21.88,21.4,8.5。
Example 5
2,4, 10-trimethyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 70.1mg of 3- (2-iodo-4, 6-dimethylaniline) -2-methylcyclohexenone (0.2 mmol) and 96.7mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, carrying out column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product 2,4, 10-trimethyl-7H-8, 9-o [1,2-a ]]Indol-6-one (white solid, 38.1 mg), yield: 84%. 1 H NMR(400MHz,CDCl 3 )δ7.04(s,1H),6.90(s,1H),2.89(t,J＝6.3Hz,2H),2.76(t,J＝6.3Hz,2H),2.60(s,3H),2.39(s,3H),2.13(s,3H),2.10–2.01(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ168.6,134.8,133.9,133.4,132.6,129.1,126.5,115.7,112.5,35.4,23.2,22.5,21.4,21.2,8.8。
Example 6
2-fluoro-10-methyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 69.1mg of 3- (2-iodo-4-fluoroaniline) -2-methylcyclohexenone (0.2 mmol) and 96.5mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, carrying out column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product 2-fluoro-10-methyl-7H-8, 9-o [1,2-a ]]Indol-6-one (white solid, 33.0 mg), yield: 76%. 1 H NMR(400MHz,CDCl 3 )δ8.36(dd,J＝9.0,5.0Hz,1H),7.06(dd,J＝9.0,2.5Hz,1H),6.99(td,J＝9.1,2.6Hz,1H),2.90(t,J＝6.0Hz,2H),2.77(t,J＝6.0Hz,2H),2.14(s,3H),2.10–2.03(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.0,160.2(d,J C–F ＝240.3Hz),135.3,132.4(d,J C–F ＝9.7Hz),130.8,117.5(d,J C–F ＝9.2Hz),112.3(d,J C–F ＝3.9Hz),111.4(d,J C–F ＝24.8Hz),103.7(d,J C–F ＝24.0Hz),34.2,21.7,21.3,8.4； 19 F NMR(376MHz,CDCl 3 )δ–119.05。
Example 7
2-chloro-10-methyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 71.8mg of 3- (2-iodo-4-chloroaniline) -2-methylcyclohexenone (0.2 mmol) and 96.3mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, carrying out column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (8/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product 2-chloro-10-methyl-7H-8, 9-o [1,2-a ]]Indol-6-one (white solid, 34.5 mg), yield: 74%. 1 H NMR(400MHz,CDCl 3 )δ8.35(d,J＝8.8Hz,1H),7.37(d,J＝2.1Hz,1H),7.21(dd,J＝8.8,2.1Hz,1H),2.92(t,J＝6.1Hz,2H),2.78(t,J＝6.1Hz,2H),2.14(s,3H),2.11–2.06(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.1,134.9,132.7,132.5,129.4,124.2,117.9,117.4,111.7,34.5,21.8,21.6,8.6。
Example 8
2-bromo-10-methyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 81.0mg of 3- (2-iodo-4-bromoaniline) -2-methylcyclohexenone (0.2 mmol) and 96.8mg of Cs 2 CO 3 (0.3 mmol), and then adding 1.8mL dimethyl sulfoxide solvent, placing the whole reaction on a 120 ℃ heating module for reaction, monitoring by TLC, and after the reaction is finished, adding the whole reactionCooling to room temperature, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing with water and separating sequentially, extracting with ethyl acetate for three times and separating, washing with water and separating again, washing with saturated saline water and separating finally, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating, subjecting the crude product to column chromatography with petroleum ether and ethyl acetate mixture as eluent (8/1, v/v) and 200-300 mesh silica gel as separating resin to obtain the target product 2-bromo-10-methyl-7H-8, 9-o [1,2-a ]]Indol-6-one (white solid, 41.5 mg), yield: 75%. 1 H NMR(400MHz,CDCl 3 )δ8.28(d,J＝8.7Hz,1H),7.54(d,J＝2.0Hz,1H),7.35(dd,J＝8.7,2.0Hz,1H),2.90(t,J＝6.3Hz,2H),2.75(t,J＝6.3Hz,2H),2.14(s,3H),2.12–2.06(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.2,134.6,133.2,133.0,126.8,120.7,117.7,117.1,111.6,34.6,21.8,21.1,8.4。
Example 9
10-methyl-2-trifluoromethyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 79.1mg of 3- (2-iodo-4-trifluoromethylaniline) -2-methylcyclohexenone (0.2 mmol) and 96.8mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, performing column chromatography on the crude product by using petroleum ether and ethyl acetate mixed solution as eluent (5/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain the target product of 10-methyl-2-trifluoromethyl-7H-8, 9-o [1,2-a ]]Indol-6-one (white solid, 36.9 mg), yield: 69%. 1 H NMR(400MHz,CDCl 3 )δ8.30(d,J＝8.6Hz,1H),7.52(d,J＝2.0Hz,1H),7.36(dd,J＝8.6,2.0Hz,1H),2.91(t,J＝6.3Hz,2H),2.76(t,J＝6.3Hz,2H),2.13(s,3H),2.12–2.06(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.2,134.8,133.3,133.0,126.8,120.7,117.7,117.1,111.6,34.4,21.7,21.1,8.4； 19 F NMR(376MHz,CDCl 3 )δ–61.00。
Example 10
10-methyl-2-nitro-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 74.3mg of 3- (2-iodo-4-nitroaniline) -2-methylcyclohexenone (0.2 mmol) and 96.6mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, carrying out column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (5/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 10-methyl-2-nitro-7H-8, 9-o [1,2-a ]]Indol-6-one (yellow solid, 33.4 mg), yield: 69%. 1 H NMR(400MHz,CDCl 3 )δ8.51(d,J＝9.1Hz,1H),8.29(d,J＝2.2Hz,1H),8.14(dd,J＝9.1,2.2Hz,1H),2.97(t,J＝6.3Hz,2H),2.81(t,J＝6.3Hz,2H),2.24(s,3H),2.19–2.07(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.6,144.3,137.8,136.6,131.5,119.7,116.4,114.1,112.7,34.6,21.8,21.0,8.5。
Example 11
5-methyl-6H-7, 8-o [3,2-b ] indolizin-9-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 65.5mg of 3- (3-iodo-2-pyridinamine) -2-methylcyclohexenone (0.2 mmol) and 96.0mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, carrying out column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (1/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 5-methyl-6H-7, 8-o [3,2-b]Indol-9-one (yellow solid, 30.4 mg), yield: 76%. 1 H NMR(400MHz,C 6 D 6 )δ8.51(dd,J＝4.6,1.7Hz,1H),7.26(dd,J＝7.6,1.7Hz,1H),6.83(dd,J＝7.6,4.6Hz,1H),2.17(t,J＝6.2Hz,2H),2.00(t,J＝6.2Hz,2H),1.73(s,3H),1.18–1.04(m,2H)； 13 C NMR(100MHz,C 6 D 6 )δ166.0,148.8,144.6,134.5,125.2,123.6,119.1,108.3,35.1,21.6,20.7,8.0。
Example 12
10-benzyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 80.6mg of 3- (2-iodoaniline) -2-benzylcyclohexenone (0.2 mmol) and 97.0mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, and performing column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 10-benzyl-7H-8, 9-o [1,2-a]Indol-6-one (white solid, 33.6 mg), yield: 61%. 1 H NMR(400MHz,CDCl 3 )δ8.49(d,J＝8.0Hz,1H),7.37(d,J＝8.0Hz,1H),7.31–7.15(m,7H),4.02(s,2H),2.90(t,J＝6.3Hz,2H),2.78(t,J＝6.3Hz,2H),2.16–2.03(m,2H)。
Example 13
10-phenyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 78.1mg of 3- (2-iodoaniline) -2-phenylcyclohexenone (0.2 mmol) and 96.5mg of Cs 2 CO 3 (0.3 mmol) and continuing to add 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing with water and separating in sequence, extracting with ethyl acetate three times and separating, washing with water and separating, washing with saturated saline water and separating, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating, and taking the crude product as a petroleum ether and ethyl acetate mixed solutionEluting agent (10/1, v/v), and separating by column chromatography with 200-300 mesh silica gel as separating resin to obtain target product 10-phenyl-7H-8, 9-benzo [1,2-a ]]Indol-6-one (white solid, 29.2 mg), yield: 56%. 1 H NMR(400MHz,CDCl 3 )δ8.56–8.53(m,1H),7.62–7.59(m,1H),7.52–7.48(m,4H),7.35–7.19(m,3H),3.06(t,J＝6.2Hz,2H),2.85(t,J＝6.2Hz,2H),2.11–2.07(m,2H)。
Example 14
10- (4-trifluoromethyl) -phenyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 91.0mg of 3- (2-iodoaniline) -2- (4-trifluoromethyl) phenylcyclohexenone (0.2 mmol) and 96.7mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, carrying out column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (5/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 10- (4-trifluoromethyl) -phenyl-7H-8, 9-o [1, 2-a)]Indol-6-one (white solid, 39.6 mg), yield: 60%. 1 H NMR(400MHz,CDCl 3 )δ8.57(dd,J＝7.5,0.6Hz,1H),7.76(d,J＝8.0Hz,2H),7.61(d,J＝8.0Hz,2H),7.54(d,J＝7.5Hz,1H),7.38–7.29(m,2H),3.06(t,J＝6.2Hz,2H),2.87(t,J＝6.2Hz,2H),2.15–2.08(m,2H)。
Example 15
10- (4-methoxy) -phenyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 83.4mg of 3- (2-iodoaniline) -2- (4-methoxy) phenylcyclohexenone (0.2 mmol) and 96.2mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, and performing column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (5/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 10- (4-methoxy) -phenyl-7H-8, 9-o [1, 2-a)]Indol-6-one (white solid, 32.6 mg), yield: 56%. 1 H NMR(400MHz,CDCl 3 )δ8.55(d,J＝8.0Hz,1H),7.58(d,J＝7.5Hz,1H),7.44–7.41(m,2H),7.36–7.29(m,2H),7.06–7.03(m,2H),3.89(s,3H),3.03(t,J＝6.4Hz,2H),2.85(t,J＝6.4Hz,2H),2.19–1.99(m,2H)。
Example 16
10-n-butyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 74.0mg of 3- (2-iodoaniline) -2-n-butylcyclohexenone (0.2 mmol) and 96.6mg of Cs 2 CO 3 (0.3 mmol) and then 1.8mL of dimethyl sulfoxide solvent were added, the whole reaction was placed on a 120℃heating module for reaction, and TLC monitoring was performedAfter the reaction is completed, the whole reaction is cooled to room temperature, diluted by ethyl acetate, transferred to a 25mL separating funnel, washed once and separated by water in turn, extracted three times and separated by ethyl acetate, washed twice and separated by water, washed once and separated by saturated saline finally, dried by anhydrous sodium sulfate, filtered and concentrated, the crude product is subjected to column chromatography separation by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and 200-300 mesh silica gel as separating resin to obtain the target product 10-n-butyl-7H-8, 9-o [1,2-a]Indol-6-one (white solid, 30.8 mg), yield: 64%. 1 H NMR(400MHz,CDCl 3 )δ8.46–8.44(m,1H),7.44–7.42(m,1H),7.28–7.24(m,2H),2.88(t,J＝6.4Hz,2H),2.76(t,J＝6.4Hz,2H),2.61(t,J＝7.5Hz,2H),2.08–2.03(m,2H),1.63–1.54(m,2H),1.40–1.31(m,2H),0.93(t,J＝7.3Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ169.5,134.6,133.3,130.7,124.0,123.7,118.2,117.4,116.5,34.7,32.0,23.7,22.6,22.1,21.4,14.0。
Example 17
2- (6, 7,8, 9-Tetrahydropyrido [1,2-a ] indol-6-one) -acetic acid tert-butyl ester
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol 8-hydroxyquinoline), 85.0mg tert-butyl 2- (2- ((2-iodophenyl) amino) -6-oxocyclohex-1-en-1-yl) acetate (0.2 mmol) and 96.9mg Cs 2 CO 3 (0.3 mmol) and continuing to add 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing with water and separating in sequence, extracting with ethyl acetate three times and separating, washing with water and separating, washing with saturated saline water and separating, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating, and separating the crude product with petroleum ether and ethyl acetateThe ethyl acetate mixed solution is used as eluent (5/1, v/v), and 200-300 mesh silica gel is used as separation resin to carry out column chromatography separation to obtain the target product 2- (6, 7,8, 9-tetrahydropyrido [1, 2-a)]Indol-6-one) -acetic acid tert-butyl ester (white solid, 31.1 mg), yield: 52%. 1 H NMR(400MHz,CDCl 3 )δ8.47–8.45(m,1H),7.51–7.48(m,1H),7.32–7.26(m,2H),3.56(s,2H),2.98(t,J＝7.5Hz,2H),2.79(t,J＝7.5Hz,2H),2.11–2.09(m,2H),1.41(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ170.3,169.6,135.5,134.7,130.0,124.5,124.1,118.3,116.5,110.5,34.6,31.8,28.3,22.0,21.1。
Example 18
9-methyl-3H-1, 2-dihydropyrrolo [1,2-a ] indol-3-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 62.8mg of 3- (2-iodoaniline) -2-methylcyclopentenone (0.2 mmol) and 96.7mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, carrying out column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 9-methyl-3H-1, 2-dihydropyrrolo [1,2-a ]]Indol-3-one (white solid, 28.1 mg), yield: 76%. 1 H NMR(400MHz,CDCl 3 )δ8.07–8.05(m,1H),7.51–7.35(m,1H),7.31–7.25(m,2H),3.09(m,4H),2.20(s,3H)； 13 C NMR(100MHz,CDCl 3 )δ171.6,139.3,136.4,130.5,123.8,123.4,118.6,113.7,108.9,35.0,18.6,8.3。
Example 19
10-allyl-7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 70.7mg of 3- (2-iodoaniline) -2-allylcyclohexenone (0.2 mmol) and 96.9mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, carrying out column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 10-allyl-7H-8, 9-o [1,2-a ]]Indol-6-one (white solid, 35.0 mg), yield: 78%. 1 H NMR(400MHz,CDCl 3 )δ8.51–8.41(m,1H),7.50–7.37(m,1H),7.34–7.18(m,2H),5.96–5.91(m,1H),5.24–4.87(m,2H),3.39(d,J＝6.0Hz,2H),2.88(t,J＝6.0Hz,2H),2.76(t,J＝6.4Hz,2H),2.07(p,J＝6.4Hz,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.5,135.7,134.6,134.0,130.3,124.2,123.7,118.3,116.5,115.6,114.3,34.5,28.3,21.8,21.1。
Example 20
10-cinnamyl-7H-8, 9-o [1,2-a ] indol-6-one
To the reaction tube previously dried, 0.2mL of metallic iron was added to complex eachDMSO solution of the substance (containing 0.02mmol Fe (acac)) 2 And 0.04mmol of 8-hydroxyquinoline), 85.4mg of 3- (2-iodoaniline) -2-cinnamyl cyclohexenone (0.2 mmol) and 96.3mg of Cs 2 CO 3 (0.3 mmol) and then adding 1.8mL of dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished, diluting with ethyl acetate, transferring to a 25mL separating funnel, washing and separating with water in sequence, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water finally and separating, drying an organic phase with anhydrous sodium sulfate, filtering and concentrating, and performing column chromatography separation on a crude product by using petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and using 200-300 mesh silica gel as separating resin to obtain a target product of 10-cinnamyl-7H-8, 9-o [1,2-a]Indol-6-one (yellow oily liquid, 37.9 mg), yield: 63%. 1 H NMR(400MHz,CDCl 3 )δ8.54–8.46(m,1H),7.50(dd,J＝7.3,1.6Hz,1H),7.37–7.29(m,6H),7.26–7.18(m,1H),6.51–6.44(m,1H),6.40–6.28(m,1H),3.60(dd,J＝6.1,1.5Hz,2H),2.98(t,J＝6.3Hz,2H),2.80(t,J＝6.3Hz,2H),2.16–2.10(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ169.5,137.4,134.7,134.3,130.7,130.3,128.7,127.4,127.3,126.1,124.5,123.8,118.2,116.5,114.5,34.6,27.6,22.1,21.2。
Example 21
10- (3-methyl-2-butenyl) -7H-8, 9-o [1,2-a ] indol-6-one
To the previously dried reaction tubes, 0.2mL of DMSO solution of metallic iron complex (containing 0.02mmol of Fe (acac)) was added, respectively 2 And 0.04mmol of 8-hydroxyquinoline), 76.0mg of 3- (2-iodoaniline) -2- (3-methyl-2-butenyl) cyclohexenone (0.2 mmol) and 96.6mg of Cs 2 CO 3 (0.3 mmol), then adding 1.8mL dimethyl sulfoxide solvent, placing the whole reaction on a heating module at 120 ℃ for reaction, monitoring by TLC, cooling the whole reaction to room temperature after the reaction is finished,diluting with ethyl acetate, transferring to 25mL separating funnel, sequentially washing with water and separating, extracting with ethyl acetate three times and separating, washing with water twice and separating, washing with saturated saline water and separating, drying the organic phase with anhydrous sodium sulfate, filtering and concentrating, subjecting the crude product to column chromatography with petroleum ether and ethyl acetate mixed solution as eluent (10/1, v/v) and 200-300 mesh silica gel as separating resin to obtain target product 10- (3-methyl-2-butenyl) -7H-8, 9-o [1, 2-a)]Indol-6-one (white solid, 38.1 mg), yield: 75%. 1 HNMR(400MHz,CDCl 3 )δ8.41–8.32(m,1H),7.41–7.31(m,1H),7.26–7.13(m,2H),5.18–5.13(m,1H),3.26(d,J＝7.0Hz,2H),2.90–2.78(m,2H),2.75–2.62(m,2H),2.03–1.98(m,2H),1.74(s,3H),1.67–1.60(m,3H)； 13 C NMR(100MHz,CDCl 3 )δ169.5,134.8,133.3,132.3,130.6,124.3,123.9,122.0,118.4,116.4,116.3,34.6,25.9,23.0,21.9,21.2,18.0。
The above-described embodiments of the present invention do not limit the scope of the present invention. Any other corresponding changes and modifications made in accordance with the technical idea of the present invention shall be included in the scope of the claims of the present invention.

Claims (2)

1. Condensed ring [1,2-a ] indole compounds of the formula:
wherein R is 1 Optionally the following structure: hydrogen atom, alkyl, cycloalkyl, heteroatom-containing alkyl, fluoro, chloro, bromoalkyl substituted acyl; cyano group; a nitro group; an ester group; an alkyl or aryl substituted amine; alkyl or aryl substituted oxygen; a substituted silicon-based group;
R 2 is alkyl, cycloalkyl, heteroatom-containing alkyl, aryl, heteroaryl or fluoro;
R 1 is mono-substituted or multi-substituted, and forms a ring or does not form a ring;
wherein X is selected from C or N;
wherein n is taken from 0, 1, 2.
2. A method for synthesizing an iron-catalyzed fused ring [1,2-a ] indole compound is characterized by comprising the following steps:
at room temperature, adding a catalyst A, raw material enaminone, alkali and a solvent into a reaction tube respectively;
carrying out reaction under the heating condition, monitoring the reaction progress by TLC, and separating and purifying after the reaction is finished to obtain a condensed ring [1,2-a ] indole compound;
the reaction equation is shown below:
wherein R is 1 Optionally the following structure: hydrogen atom, alkyl, cycloalkyl, heteroatom-containing alkyl, fluoro, chloro, bromoalkyl substituted acyl; cyano group; a nitro group; an ester group; an alkyl or aryl substituted amine; alkyl or aryl substituted oxygen; a substituted silicon-based group; r is R 2 Is alkyl, cycloalkyl, heteroatom-containing alkyl, aryl, heteroaryl or fluoro; r is R 1 Is mono-substituted or multi-substituted, and forms a ring or does not form a ring;
wherein X is selected from C or N;
wherein Y is selected from Br, I, OTf, OTs, OSO 2 Ph；
Wherein n is taken from 0, 1, 2;
wherein catalyst a is a complex of metallic iron/ligand;
wherein, the metallic iron is a complex formed by divalent or trivalent iron and a ligand, and the molar ratio of the metallic iron to the ligand is 1:1 to 1:3, metallic iron includes Fe (acac) z 、Fe(Cl) z 、Fe(Br) z 、FeI 2 、Fe(OAc) z 、Fe(OTf) z Wherein z=2 or 3;
the ligands used are optionally of the structure: ethylenediamine and its derivatives, cyclohexanediamine and its derivatives, BINAM and its derivatives, 8-hydroxyquinoline and its derivatives, BINOL and its derivatives, proline;
preference is given to Fe (acac) 2 And 8-hydroxyquinoline in a molar ratio of 1:2, combining;
wherein the reaction solvent is selected from the following solvents or a combination of solvents: n, N-dimethylformamide, N-dimethylacetamide, tetrahydrofuran, toluene, acetonitrile, dimethylsulfoxide;
dimethyl sulfoxide is preferred;
the alkali is selected from KO t Bu、NaO t Bu、K 2 CO 3 、Cs 2 CO 3 、Na 2 CO 3 、K 3 PO 4 、Na 3 PO 4 、K 2 HPO 4 、KH 2 PO 4 、NaOH、KOH；
The mass ratio of the catalyst A, the enaminone B and the alkali is 0.01:1:1 to 0.1:1:3, a step of;
the reaction temperature is 60 to 120 ℃;
separation and purification include, but are not limited to, extraction, column chromatography, recrystallization.
CN202210375094.5A 2022-04-11 2022-04-11 Synthesis method of iron-catalyzed fused ring [1,2-a ] indole compound Pending CN116925069A (en)

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