Copper/iridium synergistically catalyzed asymmetric allylation/2-aza-cope rearrangement and its application

A technology of allylation and synergistic catalysis, which is applied in the field of chemical medicine to achieve the effect of high yield, great value and prospect of drug synthesis, and good enantioselectivity

Active Publication Date: 2022-04-01
WUHAN UNIV
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, no research group has reported the use of asymmetric catalysis to synthesize chiral amines using methyleneamine ylides ((a) Nugent, T.C. Chiral Amine Synthesis: Methods, Developments and Applications, Wiley-VCH, 2010. (b) Puentes , C.O.Kouznetsov, V.J.Heterocycl.Chem.2002,39,595; (c) Przheval'skii, N.M.Grandberg, I.I.Usp.Khim.1987,56,814; (d) Kobayashi, S.; Mori, Y.; Fossey, J.S; Salter , M.M.Chem.Rev.2011,111,2626; (e) Yus, M.; González-Gómez, J.C.; Foubelo, F.Chem.Rev.2011,111, 7774; (f) Yus, M.; Gómez, J.C.; Foubelo, F. Chem. Rev. 2013, 113, 5595.)

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
  • Copper/iridium synergistically catalyzed asymmetric allylation/2-aza-cope rearrangement and its application
  • Copper/iridium synergistically catalyzed asymmetric allylation/2-aza-cope rearrangement and its application
  • Copper/iridium synergistically catalyzed asymmetric allylation/2-aza-cope rearrangement and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] preparation

[0056] Add 0.003mmol [Ir(COD)Cl] to a 25mL reaction tube 2 , 0.006 mmol (S, S, S)-L1, 0.5 mL of deoxygenated THF and 0.5 mL of deoxygenated n-propylamine, react at 50° C. for 30 minutes and then evaporate the solvent under reduced pressure to obtain an iridium complex. In another 25mL reaction tube, add 0.01mmol Cu(CH 3 EN) 4 BF 4 With 0.011 mmol DPEphos, under nitrogen protection, 1 mL of dichloromethane was added, and the mixture was stirred at room temperature for half an hour. Then at 25°C, 0.30 mmol of methyl 2-(p-chlorobenzylideneamino)isovalerate, 0.20 mmol of methyl cinnamyl carbonate, 0.3 mmol of cesium carbonate and iridium complex were added in sequence, and after stirring for 24 h, Add 0.5mL 2N hydrochloric acid for 0.5h, add 1.0mL 2NNaoH aqueous solution and 0.4mmol Boc 2 O was reacted for 3h, the solvent was evaporated, and the product was subjected to silica gel column chromatography (petroleum ether / ethyl acetate 10:1) to obtain a wh...

Embodiment 2

[0058] preparation

[0059] Add 0.003mmol [Ir(COD)Cl] to a 25mL reaction tube 2 , 0.006 mmol (S, S, S)-L1, 0.5 mL of deoxygenated THF and 0.5 mL of deoxygenated n-propylamine, react at 50° C. for 30 minutes and then evaporate the solvent under reduced pressure to obtain an iridium complex. In another 25mL reaction tube, add 0.01mmol Cu(CH 3 EN) 4 BF 4 With 0.011 mmol DPEphos, under nitrogen protection, 1 mL of dichloromethane was added, and the mixture was stirred at room temperature for half an hour. Then at 25°C, 0.30 mmol of methyl 2-(p-chlorobenzylideneamino)isovalerate, 0.20 mmol of methyl 3-p-tolylallyl carbonate, 0.3 mmol of cesium carbonate and iridium complex were added in sequence After stirring for 24 h, 0.5 mL of 2N hydrochloric acid was added to react for 0.5 h, and 1.0 mL of 2N aqueous NaOH solution and 0.4 mmol Boc were added. 2 O was reacted for 3h, the solvent was evaporated, the product was subjected to silica gel column chromatography (petroleum ether...

Embodiment 3

[0061] preparation

[0062] Add 0.003mmol [Ir(COD)Cl] to a 25mL reaction tube 2 , 0.006 mmol (S, S, S)-L1, 0.5 mL of deoxygenated THF and 0.5 mL of deoxygenated n-propylamine, react at 50° C. for 30 minutes and then evaporate the solvent under reduced pressure to obtain an iridium complex. In another 25mL reaction tube, add 0.01mmol Cu(CH 3 EN) 4 BF 4 With 0.011 mmol DPEphos, under nitrogen protection, 1 mL of dichloromethane was added, and the mixture was stirred at room temperature for half an hour. Then at 25°C, 0.30 mmol 2-(p-chlorobenzylideneamino)isovalerate methyl ester, 0.20 mmol 3-m-tolylallyl methyl carbonate, 0.3 mmol cesium carbonate and iridium complex were added in sequence , after stirring for 24h, add 0.5mL 2N hydrochloric acid for 0.5h, add 1.0mL 2N NaoH aqueous solution and 0.4mmol Boc 2 O was reacted for 3h, the solvent was evaporated, and the product was subjected to silica gel column chromatography (petroleum ether / ethyl acetate 10:1) to obtain a wh...

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 novel copper / iridium synergistically catalyzed allylation / 2-aza-Cope rearrangement reaction involving the participation of methyleneamine ylides to synthesize chiral multi-substituted homoallylamine derivatives. The method is as follows: in an organic solvent, under the protection of an inert gas, using allyl carbonate and amino acid-derived imine as raw materials, using copper complex and iridium complex as co-catalysts, adding cesium carbonate, at 25 ° C React at high temperature for 12-24 hours, add a high boiling point solvent at 25-100°C and continue to react for 4-24 hours, after hydrolysis, protection and other post-treatments, the target compound is obtained by column chromatography.

Description

technical field [0001] The invention belongs to the field of chemical medicine, and in particular relates to a copper / iridium synergistic catalyzed asymmetric allylation / 2-aza-Cope rearrangement reaction to synthesize terminally substituted homoallylamine derivatives and a preparation method and application thereof. Background technique [0002] Chiral amine building blocks are widely found in compounds with important biological activities (such as marketed drugs) and transition metal ligands. Therefore, efficient, universal, and easy-to-use chiral amine synthesis methods have always been a hot research field in synthetic chemistry. Methyleneamine ylide, as a common synthetic intermediate, is cheap and easy to obtain, and is widely used in the synthesis of nitrogen-containing heterocycles and unnatural amino acid derivatives. However, so far, no research group has reported the use of asymmetric catalysis to synthesize chiral amines using methyleneamine ylides ((a) Nugent, T...

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): C07D207/10C07C209/00C07C211/28C07C269/00C07C271/14C07C271/16C07D307/52C07D333/20C07D213/40C07D213/64C07D215/12C07C271/12C07D209/14
CPCC07D207/10C07C211/28C07C271/14C07C271/16C07D307/52C07D333/20C07D213/40C07D213/64C07D215/12C07C271/12C07D209/14C07B2200/07C07C2601/14
Inventor 王春江卫亮
Owner WUHAN UNIV
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