Communication
ChemComm
Conflicts of interest
The authors declare no competing financial interest.
Notes and references
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Scheme 6 Mechanism studies.
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Scheme 7 Proposed mechanism.
To clarify the reaction mechanism, some control experi-
ments were performed (Scheme 6). Treatment of 1a with 1.2
equiv. of CuCl2 delivered the product 2a in 76% yield. This
indicates that the halogen source comes from the copper–
halogen intermediate. The addition of 1.0 equiv. of TEMPO to
the reaction of 1a and MgCl2 reduced the yield of 2a to 10%,
along with TEMPO-adduct 13 in a 33% yield. Moreover, the
yield of 2a was also decreased to 57% when radical inhibitor
BHT (1.0 equiv.) was added. Both the results support a radical
pathway for this reaction.
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Based on the above observations, a proposed mechanism is
depicted in Scheme 7.9,12 First, anion exchange of Cu(OAc)2
with HX (aq) forms the Cu(II)X species, which delivers the key
Cu(I)X species through disproportionation.13 Single-electron
reduction of 1a by Cu(I)X affords the cycloalkoxy radical A,
which undergoes b-scission to give the keto-alkyl radical inter-
mediate B. Radical B is trapped by Cu(II)X and undergoes
subsequent halogen atom transfer (from copper(II)X species to
B) to provide the target products 2a–4a and regenerate the
Cu(I)OH species. The HX is necessary to facilitate regeneration
of the Cu(I)X from the Cu(I)OH species.
In summary, we have developed a simple and efficient
copper-catalyzed radical ring-opening halogenation with HX
(aq). It is shown that HX (aq) can also be used as an efficient
source of radical halogenation. This protocol provided an
economic, environmentally benign, and practical synthetic
approach to the important distally halogenated alkyl ketones
and halogenated alkyl nitriles.
We thank the Natural Science Foundation of China (No.
21971201), and Natural Science Basic Research Plan in Shaanxi
Province of China (2021JM-003), and the China Postdoctoral
Science Foundation Funded Project (2019M663659) is greatly
appreciated. We also thank Mr Zhang, Miss Feng and Miss Bai
at the Center for Instrumental Analysis of Xi’an Jiaotong
University for their assistance with NMR and HRMS analysis.
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Chem. Commun.
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