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Method for synthesizing alpha-acyloxylated cycloketone compounds with high diastereoselectivity

An acyl-oxidation cyclic ketone and diastereomeric technology is applied in the field of synthesizing α-acyl-oxidation cyclic ketone compounds with high diastereoselectivity, which can solve the problem of not involving stereoselectivity and the like, and achieve controllable reaction products and avoidance of Metal residue and toxicity, high chemoselectivity effect

Active Publication Date: 2018-08-03
GUANGDONG UNIV OF TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these studies were limited to the α-acyl oxidation of cyclic ketones, and did not involve the study of their stereoselectivity

Method used

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  • Method for synthesizing alpha-acyloxylated cycloketone compounds with high diastereoselectivity
  • Method for synthesizing alpha-acyloxylated cycloketone compounds with high diastereoselectivity
  • Method for synthesizing alpha-acyloxylated cycloketone compounds with high diastereoselectivity

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038]

[0039] Dissolve 87.1mg (0.50mmol) of p-phenylcyclohexanone and 241.6mg (0.75mmol) of iodobenzenediacetic acid in 1.0mL of acetic acid, then add 185.1μL (3.00mmol) of boron trifluoride diethyl ether dropwise into the reaction system , after reacting at room temperature for 24 h, the reaction was quenched with 20 mL of saturated sodium bicarbonate and 5 mL of sodium thiosulfate (0.1 g / mL), extracted three times with dichloromethane, and the combined organic phases were concentrated under reduced pressure to obtain the crude product 1 . The crude product 1 was separated and purified by silica gel column chromatography (acetone:n-hexane=1:30) to obtain a white solid product 1 with a yield of 67%, dr=11.8:1.

[0040] Its characterization data are as follows:

[0041] Cis isomer, melting point: 90.1-95.1°C;

[0042] 1 H NMR (400MHz, CDCl 3 ):δ=7.35-7.23(m,5H),5.38(dd,J=12.8Hz,J=6.4Hz,1H),3.23(t,J=12.4Hz,1H),2.62-2.59(m,2H) ,2.49-2.44(m,1H),2.27-2.24(m,1H),2.17(s,3H)...

Embodiment 2

[0047]

[0048] Dissolve 87.1mg (0.50mmol) m-phenylcyclohexanone and 241.6mg (0.75mmol) iodobenzenediacetic acid in 1.0mL acetic acid, then add 185.1μL (3.00mmol) boron trifluoride diethyl ether dropwise into the reaction system , after reacting at room temperature for 48 h, the reaction was quenched with 20 mL of saturated sodium bicarbonate and 5 mL of sodium thiosulfate (0.1 g / mL), extracted three times with dichloromethane, and the combined organic phases were concentrated under reduced pressure to obtain the crude product 2 . The crude product 2 was separated and purified by silica gel column chromatography (acetone:n-hexane=1:30) to obtain a white solid product 2 with a yield of 47%, dr=6.1:1.

[0049] Its characterization data are as follows:

[0050] Trans isomer, melting point: 71.9-74.8°C;

[0051] 1 H NMR (400MHz, CDCl 3 ):δ=7.35-7.31(m,2H),7.25-7.20(m,3H),5.29(dd,J=6.4Hz,J=12.8Hz,1H),3.02-2.94(m,1H),2.70- 2.62(m,2H),2.40-2.35(m,1H),2.18(s,3H),2.14(m,1H),2.0...

Embodiment 3

[0056]

[0057] Dissolve 77.1 mg (0.50 mmol) of p-tert-butylcyclohexanone and 241.6 mg (0.75 mmol) of iodobenzenediacetic acid in 1.0 mL of acetic acid, then add 185.1 μL (3.00 mmol) of boron trifluoride diethyl ether dropwise into the reaction system, After reacting at room temperature for 24 h, the reaction was quenched with 20 mL of saturated sodium bicarbonate and 5 mL of sodium thiosulfate (0.1 g / mL), extracted three times with dichloromethane, and the combined organic phases were concentrated under reduced pressure to obtain crude product 3. The crude product 3 was separated and purified by silica gel column chromatography (acetone:n-hexane=1:30) to obtain a colorless and transparent liquid product 3 with a yield of 57%, dr=11.1:1.

[0058] Its characterization data are as follows:

[0059] cis isomer;

[0060] 1 H NMR (400MHz, CDCl 3 ):δ=5.23-5.18(m,1H),2.52-2.47(m,1H),2.43-2.34(m,1H),2.33-2.27(m,1H),2.15(s,3H),2.13-2.07 (m,1H),1.74-1.66(m,1H),1.57(q,J=12.4Hz,1H)...

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Abstract

The application belongs to the technical field of synthetic chemistry, and particularly relates to a method for synthesizing alpha-acyloxylated cycloketone compounds with high diastereoselectivity. The synthesis method provided by the invention comprises the following step: under the oxidation catalysis effect of a hypervalent iodine reagent, cycloketone compound, Lewis acid and an acyloxylating reagent react in a reaction solvent. The reaction condition of the method is mild and controllable, operation is simple and optimized, only one product exists, diastereoselectivity is high, and the method is applicable to a variety of cycloketone compounds. Compared with the prior art, the advantages of the method are as follows: the diastereoisomer selectivity of the product prepared by the methodis up to 12:1, and the method is applicable to the preparation of alpha-acyloxylated cycloketone drug intermediates and fine chemicals with specific spatial configurations.

Description

technical field [0001] The invention belongs to the technical field of synthetic chemistry, and in particular relates to a method for synthesizing alpha-acyloxycyclic ketone compounds with high diastereoselectivity. Background technique [0002] The α-acyl oxidation of cyclic ketones, especially the construction of α-substituted cyclic ketones with different conformations, plays a very important role in the construction of new compounds and pharmaceutical intermediates. For organic chemistry, it is a very important task and task to study synthetic methods with good stereoselectivity to construct these compounds. [0003] The traditional synthesis of α-acyloxycyclic ketones is usually obtained by using electrophilic reagents to attack enol or enol compound intermediates, and these methods usually require relatively high reducing and alkaline conditions. The steps of the traditional synthetic method are relatively complicated, and the intermediate of enol must be synthesized ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C67/00C07C69/157C07C69/24C07C69/14C07F7/08
CPCC07C67/00C07F7/083C07B2200/07C07C2601/14C07C2602/28C07C69/157C07C69/24C07C69/14
Inventor 刘艳朱伟钦谭嘉燊徐伟平柯翠连丸岡啓二
Owner GUANGDONG UNIV OF TECH
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