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Method for asymmetric synthesis of 3,3-disubstituted-2-oxindole compound

A technology of indole compound and oxindole, applied in the direction of asymmetric synthesis, organic chemical methods, chemical instruments and methods, etc., to achieve the effect of low price, wide sources and less pollution

Inactive Publication Date: 2012-09-12
EAST CHINA NORMAL UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, there are not many methods for efficiently constructing 3,3-disubstituted-2-oxindole compounds disclosed in the prior art

Method used

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  • Method for asymmetric synthesis of 3,3-disubstituted-2-oxindole compound
  • Method for asymmetric synthesis of 3,3-disubstituted-2-oxindole compound
  • Method for asymmetric synthesis of 3,3-disubstituted-2-oxindole compound

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Experimental program
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Effect test

Embodiment 1

[0026]

[0027] In reaction vial A, substrate 2a (16 mg, 0.10 mmol) was dissolved in 0.1 mL DCM and stirred for 10 min. Meanwhile, in Reaction Vial B, Oxindole Substrate 1 (37 mg, 0.12 mmol) and Catalyst I (4.1 mg, 0.01 mmol) were dissolved in 0.5 mL DCM and stirred at room temperature. Then, the reaction liquid in the reaction bottle A was added dropwise into the reaction bottle B, and reacted for 3 hours. The progress of the reaction was detected by TLC. After the reaction was completed, water was added and extracted with ethyl acetate. The organic phases were combined, washed once with water and once with saturated brine, and dried over anhydrous magnesium sulfate. Finally, the target product 3a was purified and isolated by flash column chromatography, 38.6 mg, with a yield of 83% and ee=64%. 1 H NMR (500MHz, CDCl 3 ): δ8.04(dd, J=1.5, 7.5Hz, 1H), 8.00(d, J=8.0Hz, 1H), 7.96(dd, J=1.5, 7.5Hz, 1H), 7.74-7.67(m, 2H), 7.43-7.36(m, 6H), 7.19(m, 1H), 7.13(dd, J=1.0, 7.5Hz,...

Embodiment 2

[0029]

[0030] In reaction vial A, substrate 2a (16 mg, 0.10 mmol) was dissolved in 0.1 mL of DCM and stirred for 10 minutes. Meanwhile, in reaction vial B, oxindole substrate 1 (37 mg, 0.12 mmol) and catalyst II (6.0 mg, 0.01 mmol) were dissolved in 0.5 mL of DCM and stirred at room temperature. Then, the reaction liquid in the reaction bottle A was added dropwise into the reaction bottle B, and reacted for 3 hours. The progress of the reaction was detected by TLC. After the reaction was completed, water was added and extracted with ethyl acetate. The organic phases were combined, washed once with water and once with saturated brine, and dried over anhydrous magnesium sulfate. Finally, the target product 3a was purified and isolated by flash column chromatography, 30 mg, with a yield of 65% and ee=62%. The product was detected as compound 3a by spectrogram.

Embodiment 3

[0032]

[0033] In reaction vial A, substrate 2a (16 mg, 0.10 mmol) was dissolved in 0.1 mL DCM and stirred for 10 min. Meanwhile, in reaction vial B, oxindole substrate 1 (37 mg, 0.12 mmol) and catalyst III (4.9 mg, 0.01 mmol) were dissolved in 0.5 mL DCM and stirred at room temperature. Then, the reaction liquid in the reaction bottle A was added dropwise into the reaction bottle B, and reacted for 3 hours. The progress of the reaction was detected by TLC. After the reaction was completed, water was added and extracted with ethyl acetate. The organic phases were combined, washed once with water and once with saturated brine, and dried over anhydrous magnesium sulfate. Finally, the target product 3a was purified and isolated by flash column chromatography, 39.5 mg in yellow solid, with a yield of 85%, ee=75%. The product was detected as compound 3a by spectrogram.

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Abstract

The invention discloses a method for asymmetric synthesis of a 3,3-disubstituted-2-oxindole compound. The method is characterized in that a 3-monosubstituted-2-oxindole compound and a 1,4-naphthoquinone compound as reaction raw materials undergo a reaction in the presence of chiral organic catalysts in air to produce the 3,3-disubstituted-2-oxindole compound. The method has mild reaction conditions and adopts easily available raw materials. The 3,3-disubstituted-2-oxindole compound obtained by the method has a very high ee value, provides a key skeleton structure for the synthesis of many natural products and drugs, and can be widely used for large-scale industrial production.

Description

technical field [0001] The invention specifically relates to an asymmetric synthesis method of 3,3-disubstituted-2-oxindole compounds, which belongs to the technical field of organic compound technology application. Background technique [0002] The 3,3-disubstituted-2-oxindole skeleton is a very important pharmaceutical and chemical intermediate with very high application value. Because these compounds have very good pharmaceutical activity, they have attracted more and more researchers' attention in recent years. This core skeleton exists in many natural products and drug molecules, such as: Surugatoxin, (-)-Paraherquamide A, Physostigmine, Ag-041R, Horsfiline, Coemlescine, (+)-elacomine, anti-cancer agent (Hoffmann-La Roche), etc., as follows: [0003] [0004] However, there are not many methods for efficiently constructing 3,3-disubstituted-2-oxindole compounds disclosed in the prior art. Asymmetric conjugated addition as shown in formula (II), Aldol reaction, Mor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07B53/00C07D209/34C07D401/04
Inventor 姜雪峰汪舰刘会李文军
Owner EAST CHINA NORMAL UNIV
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