Method for synthesizing chiral benzosultam via palladium-catalytic asymmetric hydrogenation

A benzosultam, asymmetric technology, applied in the field of cyclic sulfonamide compounds, achieves the effects of complete reaction, convenient preparation, high reactivity and enantioselectivity

Inactive Publication Date: 2012-10-03
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For benzo penta-sultam compounds and benzo hexa-sultam compounds with ester groups outside the ring, there is no effective method to obtain

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 chiral benzosultam via palladium-catalytic asymmetric hydrogenation
  • Method for synthesizing chiral benzosultam via palladium-catalytic asymmetric hydrogenation
  • Method for synthesizing chiral benzosultam via palladium-catalytic asymmetric hydrogenation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Embodiment 1: optimization of conditions

[0030] Put palladium trifluoroacetate (0.0025 mmol, 0.85 mg) and chiral ligand (0.003 mmol) into the reaction bottle, add 1 ml of acetone after nitrogen replacement, and stir at room temperature for 1 hour. Then concentrate in vacuo, add 2.5 milliliters of 2,2,2-trifluoroethanol under nitrogen, transfer this solution to the reaction kettle with substrate 1a (34 mg, 0.125 mmol) in advance, and feed hydrogen gas for 28 or 40 Atmospheric pressure, 50 or 70°C for 15 hours. Slowly release hydrogen, remove the solvent, and directly separate the pure product by column chromatography. The reaction formula and ligand structure are as follows:

[0031]

[0032] The conversion rate was determined by proton nuclear magnetic resonance spectroscopy, and the enantiomeric excess of the product was determined by chiral liquid chromatography, as shown in Table 1.

[0033] Table 1. Asymmetric hydrogenation of benzo six-membered cyclic sulfen...

Embodiment 2

[0042] Example 2: Synthesis of various chiral benzosultams by palladium-catalyzed asymmetric hydrogenation 2

[0043] Drop into palladium trifluoroacetate (0.85 mg, 0.0025 mmol) and (R, S p )-JosiPhos (1.9 mg, 0.003 mmol) or (R, R p)-WalPhos (2.8 mg, 0.003 mmol), after nitrogen replacement, 1 ml of acetone was added, and stirred at room temperature for 1 hour. Then concentrate in vacuo, add 2.5 milliliters of 2,2,2-trifluoroethanol under nitrogen, transfer this solution to a reaction kettle with substrate (0.125 mmol) in advance, feed hydrogen to 28 atmospheres, and react at room temperature for 15 - 24 hours, slowly releasing hydrogen. After removing solvent, direct column chromatography separates and obtains pure product, and reaction formula is as follows:

[0044]

[0045] The enantiomeric excess of the product was determined by chiral liquid chromatography, see Table 2.

[0046] Table 2. Palladium-catalyzed asymmetric hydrogenation for the synthesis of various chir...

Embodiment 3

[0049] Example 3: Synthesis of various chiral benzopenta-sultams 4 by palladium-catalyzed asymmetric hydrogenation

[0050] Palladium trifluoroacetate (0.85 mg, 0.0025 mol) and (S,S)-f-Binaphane (2.4 mg, 0.003 mmol) were put into the reaction flask, 1 ml of acetone was added after nitrogen replacement, and stirred at room temperature for 1 hour. Then concentrate in vacuo, add 2.5 milliliters of 2,2,2-trifluoroethanol under nitrogen, transfer this solution to a reaction kettle with substrate (0.125 mmol) in advance, feed hydrogen to 40 atmospheres, and react at room temperature for 15 Hours, slowly release hydrogen. After removing solvent, direct column chromatography separates and obtains pure product, and reaction formula is as follows:

[0051]

[0052] R 1 is H or methyl, R 3 is methyl, ethyl or tert-butyl.

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 invention discloses a method for synthesizing chiral benzosultam via palladium-catalytic asymmetric hydrogenation, comprising the following reaction conditions that: the temperature is 25-70DEG C; a solvent is 2,2,2-trifluoroethanol; the pressure is 28-40atm; the proportion of a substrate to a catalyst is 50 / 1; the catalyst is a complex of palladium trifluoroacetate and diphosphine ligand; the benzo six-membered ring shaped sulfonyl enamine of the benzo is hydrogenated to obtain the corresponding chiral benzo six-membered sultam with an enantiomeric excess up to 98%; and the benzo five-membered ring shaped sulfonyl enamine is hydrogenated to obtain the corresponding chiral benzo five-membered sultam with an enantiomeric excess up to 94%. The method disclosed by the invention is simple, convenient and practical for operation, high in enantioselectivity, good in yield and environmentally friendly, and has green atom economy for the reaction.

Description

technical field [0001] The invention relates to cyclic sulfonamide compounds, in particular to a method for synthesizing chiral benzosultams through the highly enantioselective catalytic hydrogenation of benzocyclic sulfenamides using a palladium homogeneous system. Background technique [0002] Cyclic sulfonamide (sulfonamide) compounds are widely used in the design and research of peptidomimetic, antibacterial, antiviral, antitumor and other drugs due to their stable conformation. Chiral sultams are also important chiral auxiliary reagents and chiral reagents in organic synthesis. [0003] For the synthesis of optically active benzo five-membered sulphonyl lactam compound, mainly adopt cycloaddition reaction at present, Friedel-Crafts reaction or hydrogenation of benzo five-membered cyclic sulfonimide obtain (document 1: (a) Zhou, A.H. ; Hanson, P.R.Org.Lett.2008.10, 2951. (b) Ahn, K.H.; Ham, C.; D.C.Org.Lett.1999, 1, 841.(d) Liu, P.-N.; Gu, P.-M.; Deng, J.-G.; Tu, Y.-Q....

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): C07D279/02
Inventor 周永贵余长斌高凯
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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