Zirconium catalyst and method for preparing chiral alpha-hydroxy-beta-keto ester compound by use of zirconium catalyst

A compound and ketoester technology, applied in the field of asymmetric catalytic synthesis, can solve the problems of complex structure and limited application, and achieve the effects of simple operation, low price and mild reaction conditions

Active Publication Date: 2016-04-27
DALIAN UNIV OF TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the oxidants used in these methods are generally aziridines with complex structures
These factors limit the application of the above two types of methods

Method used

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  • Zirconium catalyst and method for preparing chiral alpha-hydroxy-beta-keto ester compound by use of zirconium catalyst
  • Zirconium catalyst and method for preparing chiral alpha-hydroxy-beta-keto ester compound by use of zirconium catalyst
  • Zirconium catalyst and method for preparing chiral alpha-hydroxy-beta-keto ester compound by use of zirconium catalyst

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Preparation of (1S, 2S)-1,2-bis((4,6-diphenyl)phenol-2-methylamino)-cyclohexane (formula IIa, R 5 , R 6 for phenyl)

[0044] Weigh 2.28g (20mmol) of (1S,2S)-1,2-cyclohexanediamine and dissolve it in 100mL of methanol, and dissolve 10.96g (40mmol) of 2-hydroxy-3,5-diphenyl-benzaldehyde in 50mL of THF After slowly adding dropwise to the system at room temperature, the system was added to reflux for 3 hours, and the system turned into a yellow solution. Subsequently, the system was cooled to room temperature, and 3.08 g (80 mmol) of sodium borohydride was added in portions, followed by reaction at room temperature for 1 hour. Add 50 mL of water and 100 mL of dichloromethane to the system, separate the layers, extract the aqueous layer with 30 mL of dichloromethane x 2, wash the combined dichloromethane with water and 50 mL of saturated brine, and dry over anhydrous sodium sulfate. After filtration, the solvent was removed by rotary evaporation under reduced pr...

Embodiment 2

[0045] Example 2 Preparation of (1S, 2S)-1,2-bis((4,6-bis(1-naphthyl))phenol-2-methylamino)-cyclohexane (formula IIa, R 5 , R 6 for 1-naphthyl)

[0046] Weigh 1.71g (15mmol) of (1S,2S)-1,2-cyclohexanediamine and dissolve it in 100mL of methanol, and dissolve 11.22g (30mmol) of 2-hydroxy-3,5-diphenyl-benzaldehyde in 50mL of THF After slowly adding dropwise to the system at room temperature, the system was added to reflux for 3 hours, and the system turned into a yellow solution. Subsequently, the system was cooled to room temperature, and 2.31 g (60 mmol) of sodium borohydride was added in portions, followed by reaction at room temperature for 1 hour. Add 50 mL of water and 100 mL of dichloromethane to the system, separate the layers, extract the aqueous layer with 30 mL of dichloromethane x 2, wash the combined dichloromethane with water and 50 mL of saturated brine, and dry over anhydrous sodium sulfate. After filtration, the solvent was removed by rotary evaporation under...

Embodiment 3

[0047] Example 3 Preparation of (1S,2S)-2-((3,5-di-tert-butyl-2-hydroxybenzylidene)amino)cyclohexane-1-amine hydrochloride

[0048] Weigh 5.7g (50mmol) of (1S,2S)-1,2-cyclohexanediamine and dissolve it in 100mL of methanol, measure 4.17mL (50mmol) of concentrated hydrochloric acid with a pipette, and slowly add it dropwise in an ice bath, Stirring was continued for 30 minutes after the dropwise addition was complete. Subsequently, weigh 11.7g (50mmol) of 3,5-di-tert-butyl-2-hydroxy-benzaldehyde and dissolve it in 50mLTHF, and slowly add it dropwise in an ice bath (not less than 50 minutes), and then the system rises to room temperature The reaction was stopped after 35 minutes of reaction. The solvent was removed under reduced pressure, 50 mL of methanol was added to the residue, and suction filtration was performed under reduced pressure. After drying in vacuo, 17.9 g of a yellow solid was obtained, with a yield of 98%.

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Abstract

The invention relates to a method for preparing a chiral alpha-hydroxy-beta-keto ester compound by the application of a zirconium catalyst with a chiral diaminocyclohexane derivative as a ligand. The method comprises the following process: in the presence of a zirconium complex with a diaminocyclohexane derivative as a ligand, a beta-keto ester compound and an oxidizing agent are contacted with each other in an inert solvent, wherein dosage of a catalyst is 0.5-50 mol% of dosage of the beta-keto ester compound; dosage of the oxidizing agent is 100-2000 mol% of dosage of the beta-keto ester compound; and reaction temperature is 0-100 DEG C. yield of the alpha-hydroxy-beta-keto ester compound reaches up to 99%, and ee value reaches up to 98%. According to the invention, the zirconium catalyst with the diaminocyclohexane derivative as a ligand that is easy to synthesize, is low-cost and has stable performance is used, and then the alpha-hydroxy-beta-keto ester compound can be effectively prepared. By the method, very high yield and good enantioselectivity can be gained. The method of the invention is simple to operate, is low-cost and is suitable for industrialization.

Description

technical field [0001] The invention belongs to the technical field of asymmetric catalytic synthesis, and relates to a chiral (1S, 2S)-cyclohexanedi-(2-hydroxy-arylmethyl)amine derivative as a ligand and a zirconium complex as a catalyst to prepare α -Hydroxy-beta-keto ester compound method. technical background [0002] Some optically active α-hydroxy-β-ketoester compounds are important structural units, which widely exist in natural products and are used as intermediates in the preparation of drugs, pesticides and fine chemicals. The most ideal, simple and quick way to prepare chiral α-hydroxy-β-keto ester compounds is enantioselective catalytic oxidation of β-keto ester compounds. Davis first reported the method of using Davis reagent to obtain chiral α-hydroxyl-β-dicarbonyl compound in 1981 (Tetrahedron Lett.1981, 22, 4385-4388), but the method is cumbersome to operate, the reaction conditions are relatively harsh, and excessive use of Chiral oxidizing agent has high ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01J31/22C07C67/31C07C69/757
CPCB01J31/182B01J31/2217B01J2231/70B01J2531/0266B01J2531/48C07C67/31C07C69/757C07C2602/08
Inventor 孟庆伟杨帆刘广志王亚坤赵静喃
Owner DALIAN UNIV OF TECH
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