Synthesis of 2-Isoxazolines: Enantioselective and Racemic Methods Based on Conjugate Additions of Oximes

Tutkimustuotos: Lehtiartikkeli

Tutkijat

  • Antti Pohjakallio
  • Petri M. Pihko
  • Ulla M. Laitinen

Organisaatiot

  • University of Jyväskylä

Kuvaus

The formation of 3-unsubstituted 2-isoxazolines by means of condensation reactions between alpha,beta-unsaturated aldehydes and oximes proceeds readily in the presence of catalytic amounts of anilinium salts. Mechanistically, the process involves a fast conjugate addition of the oxime and a slower intramolecular oxime-transfer reaction. The rate of oxime transfer was found to correlate with the acidity of the catalyst. This finding enabled us to discover an enantioselective process in which the fragile conjugate-addition product generated in the first stage is rapidly cyclized into the stable isoxazoline under acidic conditions, with conservation of enantiomeric excess. In summary, herein we describe synthetically useful protocols for accessing 3-unsubstituted 2-isoxazolines in both the enantioselective and racemic manner. The mechanism of the condensation reaction catalyzed by the anilinium salt was also investigated by NMR spectroscopy experiments in which the effect of differently substituted aldehydes and oximes as well as water on the reaction rate was studied. The results point to the rate-limiting elimination of water from the 3-hydroxy-2-isoxazolidine intermediate.

Yksityiskohdat

AlkuperäiskieliEnglanti
Sivut11325-11339
Sivumäärä15
JulkaisuCHEMISTRY: A EUROPEAN JOURNAL
Vuosikerta16
Numero37
TilaJulkaistu - 2010
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

ID: 14102243