Chiral pyrrolidine functionalized imidazolium salt, and preparation method and application thereof

A pyrrolidine and functionalization technology is applied in the synthesis field of chiral compounds to achieve the effects of high diastereoselectivity and enantioselectivity, readily available raw materials and convenient preparation

Inactive Publication Date: 2014-02-12
SHANXI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the currently developed organic small molecule catalytic systems still have certain limitations in terms of scope of application and versatility. Therefore, the development of organic small molecule catalysts with novel structures, high efficiency, and high selectivity is still an asymmetric Michael addition reaction. Research Hotspots

Method used

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  • Chiral pyrrolidine functionalized imidazolium salt, and preparation method and application thereof
  • Chiral pyrrolidine functionalized imidazolium salt, and preparation method and application thereof
  • Chiral pyrrolidine functionalized imidazolium salt, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Preparation of 1-[2-(S)-(pyrrolidinyl)methyl]-3-phenacyl imidazolium bromide hydrobromide

[0026] (1) In a 1L reaction flask, add 23g (0.2mol) L-proline and 400mL dichloromethane, start stirring, cool to 0°C with an ice-water bath, then add 26.3g (0.26mol) triethylamine, Then add 61g (0.28mol) Boc in batches 2 O, control the feed rate to keep the temperature of the reaction system at 0±2°C, and keep the reaction at 0°C for 2.5 hours after the addition is complete. The reaction solution was washed with saturated aqueous citric acid solution, the organic phase was separated, the solvent was removed under reduced pressure, and recrystallized with a mixed solvent of ethyl acetate and petroleum ether to obtain 39.5 g of Boc-L-proline with a yield of 92%.

[0027] (2) In a 500mL reaction flask, add 6.08g (0.16mol) sodium borohydride and 90mL isopropyl acetate, start stirring, cool to -5°C with an ice-water bath, then add 21.5g (0.1mol) Boc-L - Proline, after the addition, ...

Embodiment 2

[0038] Preparation of 1-[2-(S)-(pyrrolidinyl)methyl]-3-phenacyl imidazolium bromide hydrobromide

[0039] (1) The preparation of Boc-L-proline is the same as in Example 1;

[0040] (2) The preparation of Boc-L-prolinol is the same as in Example 1;

[0041] (3) The preparation of (S)-2-(p-toluenesulfonyloxymethyl)pyrrolidine-1-carboxylic acid tert-butyl ester is the same as in Example 1;

[0042] (4) The preparation of (S)-2-(1-imidazolylmethyl)pyrrolidine-1-carboxylic acid tert-butyl ester is the same as in Example 1;

[0043] (5) In a 250mL reaction flask, add 100mL toluene and 5.02g (20mmol) (S)-2-(1-imidazolylmethyl)pyrrolidine-1-carboxylic acid tert-butyl ester, start stirring, then add 4.78g (24 mmol) α-bromoacetophenone, heated to reflux for 10 hours. Cool, remove toluene under reduced pressure, and separate by column to obtain N-Boc-protected chiral pyrrolidine functionalized imidazolium salt. Dissolve it in 80 mL of anhydrous methanol, add 11.7 mL of 40% hydrobromic...

Embodiment 3

[0045] Preparation of 1-[2-(S)-(pyrrolidinyl)methyl]-3-phenacyl imidazolium bromide hydrobromide

[0046] (1) The preparation of Boc-L-proline is the same as in Example 1;

[0047] (2) The preparation of Boc-L-prolinol is the same as in Example 1;

[0048] (3) The preparation of (S)-2-(p-toluenesulfonyloxymethyl)pyrrolidine-1-carboxylic acid tert-butyl ester is the same as in Example 1;

[0049] (4) The preparation of (S)-2-(1-imidazolylmethyl)pyrrolidine-1-carboxylic acid tert-butyl ester is the same as in Example 1;

[0050] (5) In a 250mL reaction flask, add 100mL toluene and 5.02g (20mmol) (S)-2-(1-imidazolylmethyl)pyrrolidine-1-carboxylic acid tert-butyl ester, start stirring, then add 5.97g (30mmol) α-bromoacetophenone, heated to reflux for 12 hours. Cool, remove toluene under reduced pressure, and separate by column to obtain N-Boc-protected chiral pyrrolidine functionalized imidazolium salt, dissolve it in 80 mL of anhydrous methanol, add 14.7 mL of 40% hydrobromic ...

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Abstract

The invention provides a chiral pyrrolidine functionalized imidazolium salt, and a preparation method and an application thereof. The chiral pyrrolidine functionalized imidazolium salt is bromized 1-[2-(S)-(pyrrolidyl)methyl]-3-benzoyl methyl imidazole hydrobromide. The preparation method of the chiral pyrrolidine functionalized imidazolium salt comprises the following steps of: by taking natural amino acid L-proline as the starting raw material, obtaining the chiral pyrrolidine functionalized imidazolium salt through a plurality of conventional organic synthetic reactions such as Boc acylation, carboxylic acid reduction, hydroxyl sulfonylation, nucleophilic substitution of imidazole anions, quaternization of halohydrocarbon and de-Boc protection. The chiral pyrrolidine functionalized imidazolium salt provided by the invention is capable of catalyzing asymmetric Michael addition reaction of cyclohexanone and nitroolefin, and has extremely high diastereoselectivity and enantioselectivity.

Description

technical field [0001] The invention belongs to the technical field of synthesis of chiral compounds, in particular to a preparation method of chiral pyrrolidine functionalized imidazolium salt and its application in asymmetric Michael addition reaction. Background technique [0002] Small organic molecule catalysis is the third effective catalytic method after enzyme catalysis and organometallic catalysis. It plays a huge role in organic synthesis and pharmaceutical industry, and provides broad prospects for the development of medicine, chemistry, materials and biology. . In recent years, organic small molecule catalysis has been widely used in asymmetric catalytic reactions due to its easy operation and "green" advantages. [0003] The Michael addition reaction is one of the classic reactions for constructing carbon-carbon bonds in organic synthesis, and it is also one of the important methods for constructing new functional organic molecules. In recent years, with the r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/06B01J31/02C07C205/45C07C201/12
CPCB01J31/0235B01J2231/482C07C201/12C07D403/06C07C205/45
Inventor 张永斌魏学红郝俊生郭志强钞建宾刘滇生
Owner SHANXI UNIV
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