Oxonium ion-mediated synthesis of 4-substituted spiro-isoxazolines

The stereoselective synthesis of 4-bromo-spiro-isoxazolines was achieved in one step through the bromination of various isoxazoles that contain a pendant alcohol or carboxylic acid functional group. Isoxazole bromination leads to a bromonium ion intermediate, which opens either by neighboring oxygen lone pair electrons or by intramolecular nucleophilic attack. Single X-ray crystal data provide evidence that the two contiguous stereocenters of the spiro-isoxazoline are formed by the anti intramolecular attack of the nucleophile relative to bromine, since there is an anti stereochemical relationship between the spirocyclic ring oxygen and the bromine atom.