Synthesis of Halomethyl Isoxazoles/Cyclic Nitrones via Cascade Sequence: 1,2-Halogen Radical Shift as a Key Link

A novel iminoxyl radical-promoted dichotomous regioselective 5-exo-trig cyclization onto vinylic halogen/1,2-halogen radical shift sequence is developed for the synthesis of halomethyl isoxazoles/cyclic nitrones using beta-halo -beta,gamma- and gamma-halo-gamma,delta-unsaturated ketoximes as the sub- strates and PhI(OAc)(2)/TEMPO as the oxidation system. DFT calculations reveal that a halogen-bridged three-membered ring transition state is involved in the 1,2-C1-/Br-atom shift, while the 1,2-I atom migration can be taken into account with an elimination/readdition mechanism. The migration ability was indicated to be ranked in the following order: I > Br > Cl.