Method for synthesizing cis-beta-hydroxy ketone through ruthenium catalytic transfer hydrogenation desymmetry

A technology of transfer hydrogenation and desymmetry, applied in organic chemistry methods, chemical instruments and methods, formation/introduction of hydroxyl groups, etc., can solve problems such as limited examples

Active Publication Date: 2021-09-14
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, the desymmetrization reduction reaction of chain 1,3-diketone and 1,3-cyclohexanedione has relatively good development, and the desymmetry reduction reaction of 1,3-cyclopentadione limited examples

Method used

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  • Method for synthesizing cis-beta-hydroxy ketone through ruthenium catalytic transfer hydrogenation desymmetry
  • Method for synthesizing cis-beta-hydroxy ketone through ruthenium catalytic transfer hydrogenation desymmetry
  • Method for synthesizing cis-beta-hydroxy ketone through ruthenium catalytic transfer hydrogenation desymmetry

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-8

[0023] Optimization of hydrogenation reaction conditions

[0024] Under nitrogen atmosphere, drop into the chiral diamine complex catalyst of ruthenium (5mol% of substrate consumption) formic acid / triethylamine azeotrope (HCO 2 H / Et 3 N, the molar ratio of formic acid and triethylamine is 5:2), stirred and reacted at 50°C for 6 hours. Then, stop the reaction, add aqueous solution, extract with EA, combine the organic layers, remove the extraction solvent under reduced pressure, and separate by column chromatography to obtain pure product. The reaction formula and catalyst structure are as follows:

[0025]

[0026] The yield is the conversion rate, and the enantiomeric excess of the product is determined by chiral liquid chromatography, and the type of organic solvent in the process is changed, see Table 1 for details.

[0027] Table 1. Optimization of desymmetrization conditions for 1,3-diketone hydrogenation a

[0028]

[0029]

Embodiment 9-23

[0031] 2,2-Disubstituted-1,3-cyclopentanedione 1 Hydrogenation Desymmetry Synthesis of cis β-Hydroxyketone Derivative 2

[0032] Under nitrogen atmosphere, drop into the chiral diamine complex catalyst of ruthenium (5mol% of substrate consumption) and formic acid / triethylamine azeotrope 1.00mL (HCO 2 H / Et 3 N, the molar ratio of formic acid and triethylamine is 5:2), stirred and reacted at 50°C for 6 hours. Then, stop the reaction, remove the solvent under reduced pressure, add water, extract with EA, combine the organic layers, remove the solvent under reduced pressure, separate the pure product by column chromatography, change the type of reaction substrate, see the reaction formula for specific reaction conditions and parameters And Table 2, the reaction formula is as follows:

[0033]

[0034] Table 2.1,3-diketone hydrogenation desymmetrization substrate expansion

[0035]

[0036]

[0037] [a]Conditions:1(0.25mmol),(R,R)-Teth-Tsdpen-RuCl(5mol%),HCO 2 H / Et 3N...

Embodiment 24-29

[0040] 2,2-Disubstituted-1,3-cyclopentanedione 1 Hydrogenation Desymmetry Synthesis of cis β-Hydroxyketone Derivative 2

[0041] Under nitrogen atmosphere, drop into the chiral diamine complex catalyst of ruthenium (5mol% of substrate consumption) and formic acid / triethylamine azeotrope 1.00mL (HCO 2 H / Et 3 N, the molar ratio of formic acid and triethylamine is 5:2), stirred and reacted at 50°C for 6 hours. Then, stop the reaction, remove the solvent under reduced pressure, add water, extract with EA, combine the organic layers, remove the solvent under reduced pressure, separate the pure product by column chromatography, change the type of reaction substrate, see the reaction formula for specific reaction conditions and parameters , the reaction is as follows

[0042]

[0043] [a] Protected with p-bromobenzoyl chloride.

[0044] The yield is an isolated yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography.

[0045] (+)-(2R,3R)...

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Abstract

The invention provides a method for synthesizing cis-beta-hydroxy ketone through ruthenium catalytic transfer hydrogenation desymmetry. A formic acid-triethylamine (5: 2) azeotrope is used as a hydrogen source, and transfer hydrogenation desymmetry of 2, 2-disubstituted-1, 3-cyclopentanedione can be realized in a solvent-free system. An important synthetic intermediate beta-hydroxy ketone is obtained through the reaction, and the enantiomeric excess of the beta-hydroxy ketone can reach 99.9% at most. The method has the characteristics of simplicity and convenience in operation, high yield, environment friendliness, commercially available catalyst and mild reaction conditions, and has potential practical application value.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing cis-β- The Hydroxyketone Method. Background technique [0002] Cis-β-hydroxyketone derivatives are versatile synthetic building blocks that can be applied in the synthesis of pharmaceutical molecules and natural active substances. (Reference 1: (a) Asakawa, Y. Genjida, F. Hayashi, S. Matsuura, T. Tetrahedron Lett. 1969, 38, 3235; (b) Kawagishi, H. Fukumoto, Y. Hatakeyama, M. He, P. Arimoto, H. Matsuzawa, T. Arimoto, Y. Suganuma, H. Inakuma, T. Sugiyama, K. J. Agric. Food Chem. 2001, 49, 2215; (c) Kim, O. K. Murakami, A. Nakamura, Y. Takeda, N. Yoshizumi, H. Ohigashi, H. J. Agric. Food Chem. 2000, 48, 1557; (d) Kim, O. K. Murakami, A. Takahashi, D. Nakamura, Y. Torika, K. Kim, H. W. Ohigashi, H Biosci. Biotechnol. Biochem. 2000, 64, 2504.). Such as (+)-estrone (estrone) is a kind of estrogen secreted by humans and animals. And curcumalact...

Claims

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Application Information

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IPC IPC(8): C07C45/65C07C49/747C07C49/755C07C49/83C07C69/76C07B41/02
CPCC07C45/65C07C67/08C07B41/02C07B2200/07C07C2601/08C07C2602/08C07C49/747C07C49/755C07C49/83C07C69/76Y02P20/584
Inventor 周永贵王晗余长斌赵洋孙蕾
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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