Phase-transfer-catalyzed asymmetric α-benzoylation of β-keto esters

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

Active Publication Date: 2020-09-22
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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  • Phase-transfer-catalyzed asymmetric α-benzoylation of β-keto esters
  • Phase-transfer-catalyzed asymmetric α-benzoylation of β-keto esters
  • Phase-transfer-catalyzed asymmetric α-benzoylation of β-keto esters

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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 amantadine 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 with a mass concentration of 30% 2 CO 3 The aqueous solution was 0.5 mL, 4 mL toluene, and the reaction was stirred at 25°C. After reacting for 24 hours, the mixed solution was extracted 3 times with ethyl acetate, washed 3 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 benzoylation product IIIb-1 (31mg, 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....

Embodiment 66

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

[0072]

[0073] Weigh 2.5mmol 1-indanone-2-carboxylate IIIa-1, add 2.5mol% phase transfer catalyst II-b, 3.8mmol benzoyl peroxide (mass fraction 70%), put it into a 500mL reaction flask, add K with a mass concentration of 30% 2 CO 3 25mL of aqueous solution, 250mL of toluene, stirred at 15°C for reaction. After 24 hours of reaction, the mixture was separated into layers. The phase transfer catalyst was insoluble in the organic layer and suspended in the aqueous layer. The organic layer was collected and spin-dried to dry the organic solvent. Petroleum ether: ethyl acetate=25:1) to obtain the asymmetric benzoylation product IIIb-1. Add 2.5mmol 1-indanone-2-adamantyl carboxylate IIIa-1, 3.8mmol benzoyl peroxide (mass fraction 70%), 250mL toluene to the water layer containing the phase transfer catalyst again, continue to stir the reaction, after the reaction is...

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Abstract

The invention discloses a phase-transfer catalyzed asymmetric α-benzoylation method of β-ketoester, and belongs to the technical field of synthesis of optically active α-oxo-β-ketoester compounds. The main points of the technical scheme of the present invention are: stirring and reacting β-keto ester compounds, phase transfer catalysts, benzoyl peroxide and alkaline solution in a solvent at -78-60°C to prepare chiral α-benzoyl- β-keto ester compounds, the reaction equation in the preparation process is: the effectiveness of the present invention is reflected in the use of cheap and easy-to-get cinchona base quaternary ammonium salts, and the first successful realization of β-ketone by the method of phase transfer catalysis The asymmetric α-benzoylation of ester compounds with benzoyl peroxide provides a novel and effective approach for the preparation of optically active α-oxo-β-ketoester compounds.

Description

Technical field [0001] The invention belongs to the technical field of synthesis of optically active α-oxo-β-keto acid ester compounds, and specifically relates to a method for phase transfer catalyzed asymmetric α-benzoylation of β-keto acid esters. Background technique [0002] Optically active α-oxo-β-keto acid ester compounds are a very important structural unit, which is widely present in natural products, chiral medicines and pesticide intermediates. Davis first reported the use of Davis reagent to obtain chiral α-oxo-β-ketoester compounds in 1981 (Tetrahedron Lett. 1981, 22, 4385-4388), but the method is complicated to operate and the reaction conditions are relatively harsh , The use of chemical doses of chiral oxidants has a high cost and is not suitable for production applications. [0003] In recent years, researchers have reported a large number of methods for asymmetric synthesis of chiral α-oxo-β-ketoester compounds. These methods can be divided into two categories: ...

Claims

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Application Information

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Patent Type & Authority Patents(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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