Download PDF
Synthesis 2002(12): 1663-1668
DOI: 10.1055/s-2002-33655
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Isoxazolines and Isoxazoles Using Poly(ethylene glycol)
as Support

Yong-Jia Shang, Yan-Guang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
Fax: +86(571)87951512; e-Mail: orgwyg@css.zju.edu.cn;
Further Information

Publication History

Received 1 April 2002
Publication Date:
05 September 2002 (online)

    Permissions and Reprints All articles of this category

Abstract

A general method for the liquid-phase syntheses of isoxazoles and isoxazolines through a 1,3-dipolar cycloaddition is described. The poly(ethylene glycol) (PEG)-supported alkyne 2 or alkene 6 reacted with nitrile oxides generated in situ from aldoximes 3, followed by cleavage from the PEG, to give isoxazoles or isoxazolines in good yield and purity.

Key words

poly(ethylene glycol) - isoxazolines - isoxazoles - cycloaddition - liquid-phase

    References

  • 1a Früchtel JS. Jung G. Angew. Chem., Int. Ed. Engl.  1996,  35:  17 
    CrossrefPubMedGoogle Scholar
  • 1b Thompson LA. Ellman JA. Chem. Rev.  1996,  96:  555 
    CrossrefPubMedGoogle Scholar
  • 2 Han H. Wolfe MM. Brenner S. Janda KD. Proc. Natl. Acad. Sci. U.S.A.  1995,  92:  6419 
    CrossrefGoogle Scholar
  • 3a Wentworth J. Janda KD. Chem. Commun.  1999,  1917 
    Google Scholar
  • 3b Gekeler KE. Adv. Polym. Sci.  1995,  121:  31 
    Google Scholar
  • Reviews on liquid-phase organic synthesis (LPOS):
  • 4a Gravert DJ. Janda KD. Chem. Rev.  1997,  97:  489 
    Google Scholar
  • 4b Harwig CW. Gravert DJ. Janda KD. Chemtracts: Org. Chem.  1999,  12:  1 
    Google Scholar
  • 4c Gravert DJ. Janda KD. In Molecular Diversity and Combinatorial Synthesis: Libraries and Drug Discovery, ACS Symposium Series   Chaiken IM. Janda KD. American Chemical Society; Washington DC: 1996.  p.118-127  
    Google Scholar
  • 4d Vandersteen AM. Han H. Janda KD. Mol. Diversity  1996,  2:  89 
    Google Scholar
  • 4e For a recent example of LPOS, see: Annunziata R. Benaglia M. Cinquini M. Cozzi F. Chem.-Eur. J.  2000,  6:  133 
    Google Scholar
  • 5 MeOPEG is not soluble in THF or CH2Cl2 at -78 °C. To circumvent this problem Janda et al. have successfully used noncross-linked chloromethylated polystyrene (NCPS) as a soluble polymer support: Chen S. Janda KD. J. Am. Chem. Soc.  1997,  119:  8724 
    CrossrefGoogle Scholar
  • 6 Zhao XY. Metz WA. Sieber F. Janda KD. Tetrahedron Lett.  1998,  39:  8433 
    CrossrefGoogle Scholar
  • 7 Zhu J. Hegedus LS. J. Org. Chem.  1995,  60:  5831 
    Google Scholar
  • 8 Blaskovich MA. Kahn M. J. Org. Chem.  1998,  63:  1119 
    CrossrefGoogle Scholar
  • 10 The first example of a liquid-phase 1,3-dipolar cycloaddition reaction was reported by Norris et al.: Moore M. Norris P. Tetrahedron Lett.  1998,  39:  7027 
    CrossrefGoogle Scholar
  • 11a Shankar BB. Yang DY. Girton S. Ganguly AK. Tetrahedron Lett.  1998,  39:  2447 
    CrossrefGoogle Scholar
  • 11b Batra S. Rastogi SK. Kundu B. Patra A. Bhaduri AP. Tetrahedron Lett.  2000,  41:  5971 
    CrossrefGoogle Scholar
  • 12 Luca LD. Giacomelli G. Riu A. J. Org. Chem.  2001,  66:  6823 
    CrossrefGoogle Scholar
  • 13 Kantorowski EJ. Kurth MJ. J. Org. Chem.  1997,  62:  6797 
    CrossrefGoogle Scholar
9

A search in MDDR (MDL data base) revealed the presence of more than 250 structures based on the isoxazole scaffold and endowed with several pharmacological activities used for analgesia, inflammation, immunology and CNS diseases (such as anxiety, memory impairment, depression, Parkinson’s and stroke).