Method for asymmetrically synthesizing chiral olefinic acid ester

A synthesis method and alkenoate technology, applied in the field of medicine, can solve the problems of few synthesis methods and the like

Inactive Publication Date: 2019-11-22
CHINA AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In summary, the research on the synthesis of chiral enoates is still in its infancy, and few synthetic methods

Method used

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  • Method for asymmetrically synthesizing chiral olefinic acid ester
  • Method for asymmetrically synthesizing chiral olefinic acid ester
  • Method for asymmetrically synthesizing chiral olefinic acid ester

Examples

Experimental program
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Effect test

Embodiment 1

[0019] Synthesis of (S)-2,4-dimethyl-3-pentenoic acid benzyl ester 3a

[0020] Add anhydrous CoCl to a dry Shrek reaction flask 2 (6.5mg, 0.05mmol), pass through argon, dry in vacuum for 2h, add bis The oxazoline chiral ligand L1 (37.6mg, 0.06mmol) and anhydrous THF (3mL), stirred at room temperature for 2h, then lowered the reaction temperature to -40°C, added benzyl 2-bromopropionate (60.8mg, 0.25 mmol), slowly dropwise added 2-methyl-1-propenylmagnesium bromide (2.7mL, 0.37M tetrahydrofuran solution, 1.0mmol), continued to stir the reaction at -40°C for 5h, added saturated aqueous ammonium chloride solution (3mL) Quenches the reaction. Separate the layers, extract the aqueous layer with diethyl ether (10mL×4), combine the organic layers, wash with saturated aqueous sodium chloride (10mL), dry over anhydrous sodium sulfate, concentrate under reduced pressure and purify by silica gel column chromatography (n-hexane / ethyl acetate 80:1), to obtain pale yellow oil 3a (43.7mg...

Embodiment 2

[0022] Synthesis of (S)-2-methyl-3-butene benzyl ester 4a

[0023] Add anhydrous LiI (26.8 mg, 0.2 mmol) and CoCl to a dry Shrek reaction flask 2 (13.0mg, 0.1mmol), pass through argon, dry in vacuum for 2h, add bis The oxazoline chiral ligand L2 (56.7 mg, 0.12 mmol) and anhydrous THF (3 mL) were stirred at room temperature for 2 h. The reaction temperature was lowered to -20°C, benzyl 2-bromopropionate (60.8mg, 0.25mmol) was added, vinylmagnesium bromide (2.1mL, 0.6M solution in tetrahydrofuran, 1.25mmol) was slowly added dropwise with stirring, and in- The stirring reaction was continued at 20°C for 24h. Add saturated aqueous ammonium chloride solution (3mL) to quench the reaction, separate the layers, extract the aqueous layer with ether (10mL×4), combine the organic layers, wash with saturated aqueous sodium chloride solution (10mL), dry over anhydrous sodium sulfate, and concentrate under reduced pressure Afterwards, it was purified by silica gel column chromatography ...

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Abstract

The invention discloses a novel method for asymmetric catalytic synthesis of chiral olefinic acid ester. According to the method, an asymmetric Kumada cross-coupling reaction between racemic 2-halogenated carboxylic ester and a an alkenyl Grignard reagent, which is catalyzed by a bisoxazoline chiral ligand and cobalt, is utilized to directly introduce alkenyl to an alpha site of the ester to synthesize the olefinic acid ester. The method provided by the invention has the advantages of mild reaction conditions, environmental friendliness, good reaction yield (up to 80% yield), high optical product purity (up to 93%ee), and the like.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a new method for asymmetrically catalyzing the synthesis of chiral enoate. Background technique [0002] Chiral enoate (formula 1) is an important skeleton and synthetic raw material of some natural products and chiral pesticides, and has an important position in the field of asymmetric synthesis (Hesse, M.J.; Butts, C.P.; Willis, C.L.; Aggarwal, V.K.Angew . Chem., Int. Ed. 2012, 51, 12444-12448. Fehr, C.; Chaptal-Gradoz, N.; Galindo, J. Chem.-Eur. J. 2002, 8, 853-858.). In addition, chiral enoate contains two functional groups of alkenyl and ester, which can be converted into various compounds. For example, chiral carboxylic acid is synthesized by hydrolysis reaction, chiral alkyl ester is obtained by reduction reaction, long-chain chiral enoate is synthesized by olefin metathesis reaction, and chiral hydroxylactone is synthesized by asymmetric dihydroxylation reaction ( Den ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C67/343C07C69/533C07C69/65C07C69/593C07C69/618
CPCC07B53/00C07B2200/07C07C67/343C07C69/533C07C69/65C07C69/593C07C69/618
Inventor 边庆花周云钟江春袁谷城王李锋王敏
Owner CHINA AGRI UNIV
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