Studies on the synthetic compatibility of aryloxime linkers in the solid-phase synthesis of 3-aminobenzisoxazoles.
J Org Chem
; 65(10): 2924-32, 2000 May 19.
Article
en En
| MEDLINE
| ID: mdl-10814179
ABSTRACT
Further exploration of the scope of our solid-phase method for the synthesis of 3-aminobenzisoxazoles (using the Kaiser oxime resin 1) is described. The effects of base, leaving group, and solvent on the nucleophilic aromatic substitution based resin-loading reaction are discussed. Representative aryloxime intermediates were subjected to a variety of acidic conditions commonly used in protecting group removal to establish the acid stability profile of this linker. Regioselectivity was evaluated with various di- and trifluorobenzonitriles, which gave single benzisoxazole products after loading and cyclorelease reactions. Substituent effects observed in the course of the acid stability and regioselectivity studies suggest that the nitrile plays a critical role in the oxime hydrolysis mechanism. Finally, to establish the compatibility of the aryloxime linker with a variety of useful on-resin synthetic transformations, functionalized substrates were loaded onto resin 1, and carbon-nitrogen, carbon-oxygen, and carbon-carbon bond-forming reactions were successfully executed.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Isoxazoles
Idioma:
En
Revista:
J Org Chem
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos