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
1b Thompson LA.
Ellman JA.
Chem.
Rev.
1996,
96:
555
2 Han H.
Wolfe MM.
Brenner S.
Janda KD.
Proc. Natl. Acad. Sci. U.S.A.
1995,
92:
6419
3a Wentworth J.
Janda KD.
Chem.
Commun.
1999,
1917
3b Gekeler KE.
Adv. Polym. Sci.
1995,
121:
31
4a Gravert DJ.
Janda KD.
Chem.
Rev.
1997,
97:
489
4b Harwig CW.
Gravert DJ.
Janda KD.
Chemtracts: Org. Chem.
1999,
12:
1
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
4d Vandersteen AM.
Han H.
Janda KD.
Mol. Diversity
1996,
2:
89
4e Annunziata R.
Benaglia M.
Cinquini M.
Cozzi F.
Chem.-Eur. J.
2000,
6:
133
5 2 Cl2 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
6 Zhao XY.
Metz WA.
Sieber F.
Janda KD.
Tetrahedron Lett.
1998,
39:
8433
7 Zhu J.
Hegedus LS.
J. Org. Chem.
1995,
60:
5831
8 Blaskovich MA.
Kahn M.
J. Org. Chem.
1998,
63:
1119
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).
10 Moore M.
Norris P.
Tetrahedron
Lett.
1998,
39:
7027
11a Shankar BB.
Yang DY.
Girton S.
Ganguly AK.
Tetrahedron Lett.
1998,
39:
2447
11b Batra S.
Rastogi SK.
Kundu B.
Patra A.
Bhaduri AP.
Tetrahedron
Lett.
2000,
41:
5971
12 Luca LD.
Giacomelli G.
Riu A.
J.
Org. Chem.
2001,
66:
6823
13 Kantorowski EJ.
Kurth MJ.
J. Org. Chem.
1997,
62:
6797
