Method for synthesizing highly diastereoselective α-acyloxycyclic ketones

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 problems such as no stereoselectivity involved, and achieve controllable reaction products and chemical chemistry. High selectivity, easy separation and purification

Active Publication Date: 2022-04-19
GUANGDONG UNIV OF TECH
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for synthesizing highly diastereoselective α-acyloxycyclic ketones
  • Method for synthesizing highly diastereoselective α-acyloxycyclic ketones
  • Method for synthesizing highly diastereoselective α-acyloxycyclic ketones

Examples

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)...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The application belongs to the technical field of synthetic chemistry, and in particular relates to a method for synthesizing highly diastereoselective α-acyloxycyclic ketone compounds. The synthesis method provided by the invention comprises: reacting cyclic ketone compounds, Lewis acids and acyl oxidation reagents in a reaction solvent under the catalytic oxidation of hypervalent iodine reagents. The method has mild and controllable reaction conditions, simple and optimized operation, single product and high diastereoselectivity, and is applicable to various cyclic ketone compounds. Compared with the prior art, the present invention has the advantage that the product prepared by the above method has a diastereoisomer selectivity as high as 12:1, which is suitable for the preparation of α-acyl in specific stereoconfiguration in laboratories and factories. Oxycyclic ketone drug intermediates and fine chemicals.

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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(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
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap