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Synthesis of Halomethyl Isoxazoles/Cyclic Nitrones via Cascade Sequence: 1,2-Halogen Radical Shift as a Key Link
Hong-Lei Chen1, Dian Wei1, Jian-Wu Zhang1
1State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering , Lanzhou University , Lanzhou , 730000 , People's Republic of China.
Abstract:
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 β-halo-β,γ- and γ-halo-γ,δ-unsaturated ketoximes as the substrates 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-Cl-/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.
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