Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A method for palladium catalyzed asymmetric hydrogenolysis and racemization of oxaziridine to synthesize chiral amines

An oxaziridine and asymmetric technology is applied in the field of synthesizing chiral sulfonamide by catalytic hydrogenolysis and racemization of oxaziridine to achieve the effects of high reactivity and enantioselectivity, convenient preparation and convenient separation

Active Publication Date: 2018-08-24
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, expanding the substrate scope of asymmetric hydrogenolysis reactions remains a challenge due to the fragility and variability of substrates in the hydrogenolysis environment.

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
  • A method for palladium catalyzed asymmetric hydrogenolysis and racemization of oxaziridine to synthesize chiral amines
  • A method for palladium catalyzed asymmetric hydrogenolysis and racemization of oxaziridine to synthesize chiral amines
  • A method for palladium catalyzed asymmetric hydrogenolysis and racemization of oxaziridine to synthesize chiral amines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1: optimization of conditions

[0033] Put palladium trifluoroacetate (3 mol% of the substrate amount) and chiral phosphine ligand (3.3 mol% of the substrate amount) into the reaction bottle, add 1 ml of acetone after nitrogen replacement, and stir at room temperature for 1 hour. Concentrate in vacuo then, add 3 milliliters of dichloromethane under nitrogen, this solution is transferred in the reaction kettle that has put substrate 1a (51.8 mg, 0.2 mmol) and camphorsulfonic acid (10mol% of substrate consumption) in advance, pass Inject hydrogen gas at 600psi, and react at 50°C for 20 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:

[0034]

[0035] The yield was determined from the reaction crude product with 1,3,5-trimethoxybenzene as the internal standard 1 H NMR to determine, the enantiomeric excess of the product was determin...

Embodiment 2

[0040] Example 2: Synthesis of various chiral sulfonamides by palladium catalyzed asymmetric hydrogenolysis 2

[0041] Drop into palladium trifluoroacetate (3 mol% of substrate consumption) and (S, S, R, R)-TangPhos (3.3mol% of substrate consumption) in reaction bottle, add 1 milliliter of acetone after nitrogen displacement, room temperature stirs 1 Hour. Concentrate in vacuo then, add 3 milliliters of dichloromethane under nitrogen, this solution is transferred to the reaction kettle that has put substrate (0.2 mmol) and L-CSA (10mol% of substrate consumption) in advance, feeds hydrogen to 600psi , React at 50°C for 15-24 hours, and slowly release hydrogen. After removing solvent, direct column chromatography separates and obtains pure product, and reaction formula is as follows:

[0042]

[0043] The yield is the separation yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography, see Table 2.

[0044]Table 2. Palladium-catalyzed...

Embodiment 3

[0048] Example 3: Synthesis of various chiral sulfonamides by palladium-catalyzed asymmetric hydrogenolysis 4

[0049] Drop into palladium trifluoroacetate (3 mol% of substrate consumption) and (S, S, R, R)-TangPhos (3.3mol% of substrate consumption) in reaction bottle, add 1 milliliter of acetone after nitrogen displacement, room temperature stirs 1 Hour. Concentrate in vacuo then, add 3 milliliters of dichloromethane under nitrogen, this solution is transferred to the reaction kettle that puts substrate (0.2 mmol) and L-CSA (10mol% of substrate consumption) in advance, feeds hydrogen to 1000psi , React at 70°C for 15-24 hours, slowly release hydrogen. After removing solvent, direct column chromatography separates and obtains pure product, and reaction formula is as follows:

[0050]

[0051] The yield is the isolated yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography, see Table 3.

[0052] Table 3. Synthesis of various chira...

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 palladium-catalyzed asymmetric hydrogenolysis and racemization-substituted oxaziridine method for synthesizing chiral sulfonamides. The catalytic system used in the method is palladium chiral bisphosphine complexes. Hydrogenolysis of racemic substituted oxaziridines can afford the corresponding chiral sulfonamides with an enantiomeric excess of 99%. The invention is simple and practical to operate, the catalyst is commercially available, and the reaction conditions are mild. In addition, the synthesis of chiral sulfonamides by asymmetric hydrogenolysis has high enantioselectivity and good yield, and the reaction is environmentally friendly with green atom economy.

Description

technical field [0001] The invention relates to a method for synthesizing chiral sulfonamide by using palladium homogeneous system to catalyze hydrogenolysis and racemization to replace oxaziridine with high enantioselectivity. Background technique [0002] Hydrogenolysis occupies a very important position in organic synthesis and industrial applications (references one: (a) Arnold, M.R.Chem.Eng.Rev.1956,48,1629. (b) Martin, A.; Armbruster, U. ; Gandarias, I.; Arias, P.L. Eur. J. Lipid Sci. Technol. 2013, 115, 9. (c) Chaudhari, Raghunath V.; Torres, A.; Jin, X. Ind. Eng. Chem. Res. 2013, 52, 15226.). Most hydrogenolysis reactions are mainly used to synthesize racemic or achiral compounds, and there are very few examples of asymmetric hydrogenolysis so far. Early explorations of asymmetric hydrogenolysis focused on the desymmetrization of symmetrical epoxides and geminal dihalides (Reference 2: (a) Chan, A.S.C.; Coleman, J.P.J.Chem.Soc.Chem.Commun.1991, 535. (b) Bakos, J.;...

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): C07D275/02C07D275/06
Inventor 周永贵宋波余长斌黄文学陈木旺
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com