Economic and efficient method for asymmetric synthesis of R-configuration aromatic alcohol through copper salt catalysis

A technology for asymmetric and aromatic alcohols, which is applied in the field of catalytic asymmetric hydrosilylation to prepare optically active alcohols, can solve the problems of limited wide application and low stability, and achieve easy availability of raw materials, high yield and enantioselectivity, and reaction The effect of mild conditions

Inactive Publication Date: 2015-03-11
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, a common problem in the asymmetric hydrosilylation reaction of catalyzed ketones is that the reaction system is not stable in the air, requiring the protection of an inert gas and the reaction at a lower temperature, which greatly limits the wide range of applications

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] At room temperature, 0.006g of catalyst precursor Cu(OAc) 2 ·H 2 O. 0.003g chiral bisphosphine ligand (R)-BINAP was stirred and mixed with 3mL toluene for coordination reaction for 0.5h; 180μL polymethylhydrogensiloxane was added dropwise, and stirring was continued for 30min to generate catalytically active substances in situ; Add 117 μL of substrate acetophenone, react at 55°C for 4 hours, and monitor the reaction by thin-layer chromatography; after the reaction, add methanol and sodium hydroxide solution, stir vigorously, and obtain a mixture of chiral aromatic alcohol crude products after hydrolysis.

[0013] The mixed solution obtained after hydrolysis was extracted and separated with dichloromethane, and the organic layer was collected. The organic layer was washed with water and dried over anhydrous sodium sulfate. After drying, the solvent was distilled off under reduced pressure to obtain a crude product concentrate, which was further separated and purified b...

Embodiment 2

[0015] At room temperature, 0.006g of catalyst precursor Cu(OAc) 2 ·H 2 O. 0.006g chiral bisphosphine ligand (R)-BINAP was stirred and mixed with 3mL toluene for coordination reaction for 1h; 180μL polymethylhydrogensiloxane was added dropwise, and stirring was continued for 30min to generate catalytically active substances in situ; 130 μL of the substrate 2-chloroacetophenone was placed at 25°C for 4 hours, and the reaction was monitored by thin-layer chromatography; after the reaction was completed, methanol and sodium hydroxide solution were added, vigorously stirred, and a mixture of crude chiral aromatic alcohols was obtained after hydrolysis .

[0016] The mixed solution obtained after hydrolysis was extracted and separated with dichloromethane, and the organic layer was collected. The organic layer was washed with water and dried over anhydrous sodium sulfate. After drying, the solvent was distilled off under reduced pressure to obtain a crude product concentrate, wh...

Embodiment 3

[0018] At room temperature, 0.002g catalyst precursor Cu(OAc) 2 ·H 2O. 0.010g chiral bisphosphine ligand (R)-BINAP was stirred and mixed with 3mL dihydrofuran for coordination reaction for 1h; 570μL triethoxysilane was added dropwise, and stirring was continued for 30min to generate catalytically active substances in situ; 130 μL of the substrate 4-chloroacetophenone, reacted at 25°C for 10 hours, and monitored the reaction by thin-layer chromatography; after the reaction, add methanol and sodium hydroxide solution, stir vigorously, and obtain a mixture of chiral aromatic alcohol crude products after hydrolysis .

[0019] The mixed solution obtained after hydrolysis was extracted and separated with dichloromethane, and the organic layer was collected. The organic layer was washed with water and dried over anhydrous sodium sulfate. After drying, the solvent was distilled off under reduced pressure to obtain a crude product concentrate, which was further separated and purifie...

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Abstract

The invention relates to an economic and efficient method for asymmetric synthesis of R-configuration aromatic alcohol through copper salt catalysis, and belongs to the technical field of preparing optically active alcohol through catalysis asymmetric hydrosilation. According to the method, Cu salt and chiral bisphosphine ligand form a clathrate with a certain spatial configuration, and a substance with catalytic activity is formed by in-situ reaction under the action of stoichiometric hydrogenous silane and is used for preparing the R-configuration aromatic alcohol with asymmetric catalysis hydrosilation reduction aromatic ketone. According to the method, a non-noble metal catalyst is adopted, raw materials are easy to get, nitrogen protection is not needed, reaction condition is mild, operation is simple, use of hazardous articles, such as hydrogen, can be avoided, the method is safe, reliable and environmental-friendly, atom economy is good, substrate conversion rate is up to 99%, an enantiomer excess value of the product of the R-configuration aromatic alcohol is up to 93%, the simple, direct and efficient new method is provided for preparing chiral aromatic alcohol, and the method has an important industrial application value.

Description

technical field [0001] The invention relates to an economical and efficient copper salt catalyzed asymmetric synthesis method of R-configuration aromatic alcohol, which belongs to the technical field of catalytic asymmetric hydrosilylation preparation of optically active alcohol. Background technique [0002] Chiral aromatic alcohols are key chiral building blocks for the synthesis of many chiral drugs (such as R-atomoxetine, S-propranolol, S-albuterol, S-fluoxetine, etc.). From the perspectives of reaction efficiency, environmental friendliness, and atom economy, the asymmetric reduction of prochiral ketones with different structures is one of the most direct and effective methods for the synthesis of such chiral aromatic alcohols. The method of chemically catalyzing the asymmetric reduction of aromatic ketones to prepare chiral aromatic alcohols has the advantages of fast and efficient, and is usually divided into asymmetric hydrogenation hydrogenation, asymmetric transfer...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07B41/02C07C29/143C07C33/22C07C33/46C07C201/12C07C205/19C07C41/26C07C43/23C07C33/20
Inventor 刘湘梁敏婷夏晓峰
Owner JIANGNAN UNIV
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