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Method for achieving asymmetrical alpha-benzoylation through phase-transfer catalysis of beta-keto ester

A technology of phase transfer catalysis and phase transfer catalyst, which is applied in the directions of organic chemistry methods, chemical instruments and methods, carboxylate preparation, etc., to achieve the effect of easy separation and good catalytic effect.

Active Publication Date: 2018-02-23
XINXIANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] It is worth noting that the methods for asymmetric oxidation of the α-position of β-ketoesters are mostly limited to hydroxylation, and asymmetric benzoylation of the α-position of β-ketoesters can introduce An active benzoyl group, which has potential application value, but there are few reports in the literature
In 2015, Luo Sanzhong's research group reported for the first time the asymmetric α-benzoylation of β-ketoesters catalyzed by chiral primary amines, with the highest ee value of 98%, but this method requires the addition of trifluoromethanesulfonic acid And butylated hydroxybenzene is used as a reaction aid, and the substrates are mostly linear and non-aromatic cyclic β-ketoester compounds, and the β-ketoester compounds derived from indanone and tetralone are not involved ( Organic letters 2015,17,576-579)

Method used

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  • Method for achieving asymmetrical alpha-benzoylation through phase-transfer catalysis of beta-keto ester
  • Method for achieving asymmetrical alpha-benzoylation through phase-transfer catalysis of beta-keto ester
  • Method for achieving asymmetrical alpha-benzoylation through phase-transfer catalysis of beta-keto ester

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Experimental program
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Effect test

Embodiment 1

[0024] Preparation of (S)-2-benzoyl-1-indanone-2-carboxylic acid methyl ester IIIb-1

[0025]

[0026] Weigh 0.1mmol 1-indanone-2-carboxylate adamantyl IIIa-1, add 5mol% phase transfer catalyst Ia-1, 0.15mol benzoyl peroxide (mass fraction 70%), put it into a 20mL single-port reaction tube, add K at a mass concentration of 30% 2 CO 3 Aqueous solution 0.5mL, 4mL toluene, stirred reaction at 25°C. After reacting for 24 hours, the mixture was extracted three times with ethyl acetate, washed three times with water, dried over anhydrous sodium sulfate, filtered, and spin-dried. The crude product was separated by column chromatography (petroleum ether: ethyl acetate = 25:1) to obtain the asymmetric benzoylated product IIIb-1 (31 mg, yield 72%, 43% ee); [α] D 25 110.6 (c 0.62, CHCl 3 ) 1 H NMR (400MHz, Chloroform-d) δ8.21–8.08(m,2H),7.88(d,J=7.6Hz,1H),7.73–7.66(m,1H),7.60(d,J=7.4Hz, 1H), 7.54–7.42(m, 4H), 4.14(d, J=17.4Hz, 1H), 3.47(d, J=17.4Hz, 1H), 2.17–2.09(m, 3H), 2.08...

Embodiment 66

[0071] Preparation of (S)-2-benzoyl-1-indanone-2-formic acid methyl ester IIIb-1 (phase transfer catalyst recycling)

[0072]

[0073] Weigh 2.5mmol 1-indanone-2-carboxylate adamantyl IIIa-1, add 2.5mol% phase transfer catalyst II-b, 3.8mmol benzoyl peroxide (mass fraction 70%), put into a 500mL reaction bottle, add K at a mass concentration of 30% 2 CO 3 Aqueous solution 25mL, 250mL toluene, stirred and reacted at 15 ℃, after reacting for 24 hours, the mixed liquid was separated into layers, the phase transfer catalyst was insoluble in the organic layer, suspended in the water layer, collected the organic layer and spin-dried the organic solvent, and separated by column chromatography ( Petroleum ether: ethyl acetate = 25:1) to obtain the asymmetric benzoylated product IIIb-1. Add 2.5mmol 1-indanone-2-carboxylate adamantyl IIIa-1, 3.8mmol benzoyl peroxide (mass fraction 70%), and 250mL toluene to the aqueous layer containing the phase transfer catalyst again, and continu...

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Abstract

The invention discloses a method for achieving asymmetrical alpha-benzoylation through phase-transfer catalysis of beta-keto ester and belongs to the technical field of synthesis of alpha-oxo-beta-keto ester compounds having optical activity. According to the technical scheme, the method is characterized in that a beta-keto ester compound, a phase transfer catalyst, benzoyl peroxide and an alkaline solution perform stirring reaction in a solvent at the temperature of -78 to 60 DEG C to prepare a chiral alpha-benzoyl-beta-keto ester compound, and a reaction equation in the preparation process is shown in the description. The effectiveness of the method is achieved by using cheap cinchona alkaloid quaternary ammonium salt easy to obtain, asymmetrical alpha-benzoylation of the beta-keto estercompound and the benzoyl peroxide is successfully achieved by adopting the method for the first time, and a novel and effective way is provided for synthesis of the alpha-oxo-beta-keto ester compounds having optical activity.

Description

technical field [0001] The invention belongs to the technical field of synthesis of optically active α-oxo-β-ketoester compounds, and in particular relates to a method for phase transfer catalyzed asymmetric α-benzoylation of β-ketoesters. Background technique [0002] Optically active α-oxo-β-ketoester compounds are a very important structural unit that widely exist in natural products, chiral pharmaceuticals and pesticide intermediates. Davis first reported the method (Tetrahedron Lett.1981,22,4385-4388) of using Davis reagent to obtain chiral α-oxo-β-ketoesters in 1981, but the method is cumbersome to operate and the reaction conditions are relatively harsh , the use of chemical doses of chiral oxidants is expensive and not suitable for production applications. [0003] In recent years, researchers have reported a large number of methods for the asymmetric synthesis of chiral α-oxo-β-ketoester compounds, which can be divided into two categories: a) metal complexes / active...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C69/78C07C67/00C07C67/56
CPCC07B2200/07C07C67/00C07C67/56C07C69/78
Inventor 王亚坤孟庆伟白素平高庆贺房立真李国伟
Owner XINXIANG MEDICAL UNIV
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