6533b7d6fe1ef96bd12670bf
RESEARCH PRODUCT
Synthesis of 2-isoxazolines: enantioselective and racemic methods based on conjugate additions of oximes.
Antti PohjakallioUlla M. LaitinenPetri M. Pihkosubject
Organic ChemistryEnantioselective synthesisGeneral ChemistryNuclear magnetic resonance spectroscopyOximeCondensation reactionCatalysisCatalysisReaction ratechemistry.chemical_compoundchemistryIntramolecular forceOrganic chemistryEnantiomeric excessdescription
The formation of 3-unsubstituted 2-isoxazolines by means of condensation reactions between α,β-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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-08-19 | Chemistry (Weinheim an der Bergstrasse, Germany) |