An atom-economical, catalytic, and regioselective synthesis of 3,4,5-trisubstituted isoxazoles has been successfully developed. Treatment of O-arylmethyl alkynyl oxime ethers with 5 mol % of Cu(OTf)(2) in chlorobenzene at reflux gave 4-arylmethylisoxazoles in good to excellent yields via the sequential intramolecular addition of the oxime moiety to the alkyne with subsequent 1,3-migration of the arylmethyl group.