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Method for preparing chiral 3-nitroindole compound through nickel-catalyzed asymmetric nitration reaction

A technology of nitroindole and nitration reaction, which is applied in the field of preparation of chiral 3-nitroindole compounds, can solve the problems of uncontrollable reaction system, unstable nitration reagent, and low reaction efficiency, and reach the scope of application of substrates Wide range of effects, high reaction stereoselectivity, and low catalyst cost

Pending Publication Date: 2021-11-19
SHANDONG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0010] Aiming at the deficiencies of the prior art, the present invention provides a method for preparing chiral 3-nitroindole compounds through a nickel-catalyzed asymmetric nitration reaction, which solves the problems of unstable nitration reagents and low reaction selectivity in the existing nitration reactions , the reaction system is uncontrollable, the reaction efficiency is low, the post-reaction treatment is complex and the lack of single-configuration products cannot be obtained

Method used

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  • Method for preparing chiral 3-nitroindole compound through nickel-catalyzed asymmetric nitration reaction
  • Method for preparing chiral 3-nitroindole compound through nickel-catalyzed asymmetric nitration reaction
  • Method for preparing chiral 3-nitroindole compound through nickel-catalyzed asymmetric nitration reaction

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Embodiment 1

[0039] A method for preparing chiral 3-nitroindole compounds (Ⅲa) through nickel-catalyzed asymmetric nitration reaction, the reaction scheme is as follows:

[0040]

[0041] Concrete preparation steps are as follows: add indol-2-ketone compound (being raw material Ia, 62mg, 0.2mmol) in 5mL round bottom flask, tert-butyl nitrite (being raw material II, 31mg, 0.3mmol), nickel catalyst ( NiCl 2 DME, 3.3mg, 0.015mmol), Box ligand (7mg, 0.016mmol), tert-butanol (15mg, 0.2mmol), 100 mg of molecular sieve and 1 mL of dichloromethane were then stirred and reacted in an oxygen atmosphere at 0° C., and the reaction progress was detected by TLC until the raw material Ia disappeared (reaction time was 12 h). After the reaction was completed, the solvent was removed from the resulting reaction solution, and the resulting crude product was separated and purified by column chromatography (eluent: ethyl acetate:petroleum ether=1:50~1:20, v / v) to obtain 34 mg of the target product. The y...

Embodiment 2

[0047] A method for preparing chiral 3-nitroindole compound (Ⅲb) through nickel-catalyzed asymmetric nitration reaction, the reaction scheme is as follows:

[0048]

[0049] The specific preparation steps are as follows: in the 5mL round bottom flask, add indol-2-ketone compound (i.e. raw material Ib, 65mg, 0.2mmol), tert-butyl nitrite (i.e. raw material II, 31mg, 0.3mmol), nickel catalyst ( NiCl 2 DME, 3.3mg, 0.015mmol), Box ligand (7mg, 0.016mmol), tert-butanol (15mg, 0.2mmol), 100 mg of molecular sieve and 1 mL of dichloromethane were then stirred and reacted in an oxygen atmosphere at 0° C., and the reaction progress was detected by TLC until the raw materials disappeared (reaction time was 12 h). After the reaction was completed, the solvent was removed from the resulting reaction solution, and the resulting crude product was separated and purified by column chromatography (eluent: ethyl acetate:petroleum ether=1:50~1:20, v / v) to obtain 39 mg of the target product. T...

Embodiment 3

[0055] A method for preparing chiral 3-nitroindole compound (Ⅲc) through nickel-catalyzed asymmetric nitration reaction, the reaction scheme is as follows:

[0056]

[0057] Concrete preparation steps are as follows: in the 5mL round-bottomed flask, add indol-2-ketone compound (being raw material Ic, 84mg, 0.2mmol), tert-butyl nitrite (being raw material II, 31mg, 0.3mmol), nickel catalyst ( NiCl 2 DME, 3.3mg, 0.015mmol), Box ligand (7mg, 0.016mmol), tert-butanol (15mg, 0.2mmol), 100 mg of molecular sieve and 1 mL of dichloromethane were then stirred and reacted in an oxygen atmosphere at 0° C., and the reaction progress was detected by TLC until the raw materials disappeared (reaction time was 12 h). After the reaction was completed, the resulting reaction solution was removed from the solvent, and the resulting crude product was separated and purified by column chromatography (eluent: ethyl acetate:petroleum ether=1:50~1:20, v / v) to obtain 65 mg of the target product, w...

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Abstract

The invention provides a method for preparing a chiral 3-nitroindole compound through a nickel-catalyzed asymmetric nitration reaction. The method comprises the following steps: in a solvent, under the action of an additive, a nickel catalyst and a ligand, carrying out an asymmetric nitration reaction on an indole-2-one compound I and tert-butyl nitrite II to obtain the chiral 3-nitroindole compound III. According to the invention, chiral 3-nitroindole is constructed through a nickel-catalyzed asymmetric nitration reaction, and the method has the advantages of low catalyst cost, convenience in operation, wide substrate application range, cheap and easily available reaction raw materials and the like.

Description

technical field [0001] The invention relates to a method for preparing chiral 3-nitroindole compounds through a nickel-catalyzed asymmetric nitration reaction, belonging to the technical field of organic synthesis. Background technique [0002] The nitro group is considered to be a widely used and unique functional group in medicinal chemistry. Because it can be used as a hydrogen bond acceptor, and has the characteristics of strong electron-withdrawing ability and reduction potential, it plays an important role in various drugs. different effects (K. Nepali, H.Y. Lee, J.P. Liou, J. Med. Chem. 2019, 62, 2851-2893.). On the other hand, as a precursor that can undergo various functional group transformations, nitro groups are also of great significance in organic synthesis. Traditional nitrification reactions often have limitations such as harsh reaction conditions, low regioselectivity, and difficult post-treatment. Therefore, how to introduce nitro groups gently and effici...

Claims

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Application Information

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IPC IPC(8): C07D209/34C07B53/00B01J31/22
CPCC07D209/34C07B53/00B01J31/1815C07B2200/07B01J2531/0244B01J2231/4283B01J2531/847Y02P20/55
Inventor 李孝训吕明君
Owner SHANDONG UNIV
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