Communication
Organic & Biomolecular Chemistry
According to a reported study24 and our experiments, we
proposed the reaction mechanism for the intramolecular cycli-
zation and intermolecular cyclocondensation reactions
(Scheme 4). First, the fluoroiodane 1 is activated by a Lewis
acid to form intermediate A, in which the fluorine is co-
ordinated to the Lewis acid. Then, substrate N-acetyl enamine
2 enters and engages in a metathesis reaction with A and leads
to the formation of intermediate B. An intramolecular nucleo-
philic attack occurs to form a five-membered ring intermediate
D and release the iodine E. Finally, deprotonation and elimin-
ation of HF give the product 3. If the substrate is enamine 4,
in which the C–C double bond is much less electron-rich than
that in substrate 2, the formation of an iodonium ion F
instead of a metathesis reaction is observed. The intermediate
F undergoes an intermolecular nucleophilic attack by CH3CN
to generate intermediate G, the elimination of E and the Lewis
acid to form H and then after intramolecular cyclization and
elimination of the acetyl group to give imidazole product 5.
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Conclusions
In summary, we have developed intramolecular cyclization of
N-acetyl enamines and intermolecular cyclocondensation reac-
tion of enamines and nitriles by using hypervalent fluoroio-
dane reagent 1. The reaction was performed under mild con-
ditions and afforded the oxazole and imidazole products in
moderate to excellent yields. A variety of functional groups
could be tolerated well under the reaction conditions. The
reaction mechanism was proposed and the selectivity of the
intra- or intermolecular reaction could be controlled by the
molecular properties of substrates.
Conflicts of interest
9 A. Yoshimura and V. V. Zhdankin, Chem. Rev., 2016, 116,
3328–3435.
There are no conflicts to declare.
10 (a) S. V. Kohlhepp and T. Gulder, Chem. Soc. Rev., 2016, 45,
6270–6288; (b) A. M. Arnold, A. Ulmer and T. Gulder, Chem.
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Acknowledgements
Financial support from the National Natural Science
Foundation of China (NSFC 81602952), the Natural Science
Foundation of Jiangsu Province (BK20160748), the Project
Program of Jiangsu Key Laboratory of Drug Design and
Optimization, and the China Pharmaceutical University
(2018KFKT-3) is acknowledged.
˜
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Notes and references
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