Organic Letters
Letter
position of the tethered alkenes. When the halogen atom is Cl
or Br, intermediates II−O and II−N are generated in the
cyclization step, from which the C-centered radicals III−O and
III−N are formed, as a result of the 1,2-halogen radical
migration. Finally, TEMPO-promoted aromatization of III−O
occurs to give isoxazole 2, while cyclic nitrone 4 is generated
from III−N via radical trapping by TEMPO. When the halogen
atom is iodine, on the other hand, radical I experiences a
concerted O-atom/N-atom 5-exo-trig cyclization/I atom
elimination process to deliver intermediates IV−O and IV−N
directly. The latter species then react with TEMPO to afford
isoxazole 2 and cyclic nitrone 4, respectively.
In summary, a novel, efficient, and metal-free approach has
been developed for the synthesis of halomethyl isoxazoles/
cyclic nitrones by using vinylic halogen-tethered ketoximes as
the substrates and PhI(OAc)2/TEMPO as the oxidation
system. The reaction involves the initiation of iminoxyl radicals
from the oxidation of β-halo-β,γ- and γ-halo-γ,δ-unsaturated
ketoximes by PhI(OAc)2, followed by a cascade regioselective
radical cyclization/1,2-halogen shift/aromatization or TEMPO-
trapping sequence. DFT calculations reveal that the Cl- and Br-
atom shift passes through a transition state of halogen-bridged
three-membered ring, but the I atom migration follows an
elimination/readdition process. The migration ability was
found to be in the order of I > Br > Cl. Further studies on
new 1,2-halogen radical shift-involved reactions, for synthetic
purposes, are ongoing in our laboratory.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
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S
Detailed experimental procedures and spectral data for
Accession Codes
supplementary crystallographic data for this paper. These data
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, U.K.; fax: +44
1223 336033.
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank the National Natural Science Foundation of China
(Nos. 21422205 and 21632001), the “111” Project, the
Program for Changjiang Scholars and Innovative Research
Team in University (IRT-15R28), the Fundamental Research
Funds for the Central Universities (Nos. lzujbky-2016-ct02 and
lzujbky-2016-ct08) for financial support.
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