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RSC Advances
Page 3 of 4
DOI: 10.1039/C5RA07320K
Journal Name
COMMUNICATION
imidate or thioamidium. An attractive concept for the
synthesis of imidazoles is the utilization of the ring strain and
chemical reactivity of 2H-azirines. Aldehyde groups and halide
substituents were compatible with the developed reaction
conditions, thus providing convenient handles for further
functionalization.
Acknowledgement
This project was supported from the National Natural
Science Foundation of China (No. 81273356 and 81473074),
National Science & Technology Major Projects for "Major New
Figure 1. X-Ray crystal structure of 3g
Drugs
Innovation
and
Development"
of
China
(2014ZX09304002-007), the Program for Zhejiang Leading
Team of S&T Innovation Team (2011R50014), and Arthritis &
Chronic Pain Research Institute, USA, to Y. Yu; National Natural
Science Foundation of China (No. 81402778) and the
Fundamental Research Funds for the Central Universities (No.
2015QNA7029) to W. Chen; the China Postdoctoral Science
Foundation Funded Project (2015M570520) to J. Shao.
Based on the results of the study, we supposed that the reaction
may proceed through 2H-azirines involving tandem cyclization. To
this end, we prepared the 2H-aziridine (A) [10] by thermolysis of vinyl
azide 1a. [11] To our expectation, the reaction of 2H-aziridine (A)
with ethoxyimidate proceeded well at room temperature to give
the desired product 3a. (Scheme 1) This result finally supported our
hypothesis.
Notes and references
1
For the biological application of imidazoles, see: (a) G. J.
Atwell, J. Fan, K. Tan, W. A. Denny, J. Med. Chem., 1998, 41
,
4744; (b) P. B. Koswatta, C. H. Lovely, Nat. Prod. Rep., 2011,
28, 511; (c) F. V. Lali, A. E. Hunt, S. J. Turner, B. M. J. Foxwell,
J. Biol. Chem., 2000, 275, 7395; (d ) R. R. Wexler, W. J.
Greenlee, J. D. Irvin, M. R. Goldberg, K. Prendergast, R. D.
Smith, P. B. M. W. M. Timmermans, J. Med. Chem., 1996, 39
625; (e) S. Riduan, Y. Zhang, Chem. Soc. Rev., 2013, 42, 9055.
,
2
For publications on imidazole coordination chemistry, see:
(a) Y. Sunatsuki, Y. Motoda, N. Matsumoto, Coord. Chem.
Rev., 2002, 226, 199; (b) Y. Sunatsuki, R. Kawamoto, K. Fujita,
H. Maruyama, T. Suzuki, H. Ishida, M. Kojima, S. Iijima, N.
Matsumoto, Coord. Chem. Rev., 2010, 254, 1871; (c) K. M.
Lancaster, J. B. Gerken, A. C. Durrell, J. H. Palmer, H. B. Gray,
Coord. Chem. Rev., 2010, 254, 1803.
Scheme 1. Control experiments
Accordingly, we proposed
a mechanism for this tandem
cyclization as shown in Scheme 2. Firstly, vinyl azides 1 can be
transformed to the corresponding 2H-aziridines in situ by thermal
[10]
elimination of N2.
The reaction may proceed through the
3
4
5
(a) T. Iwamura, S. Nakamura, Polymer, 2013, 54, 4161; (b) S.
Yuan, Y. Deng, D. Sun, Chem.-Eur. J., 2014, 20, 1.
C. Sӓmann, E. Coya, P. Knochel, Angew. Chem. Int. Ed. 2014,
53, 1430.
(a) R. V. A. Orru, V. G. Nenajdenko, Isocyanide Chemistry;
Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany,
2012, 109. (b) A. V. Lygin, A. de Meijere, Angew. Chem., Int.
Ed. 2010, 49, 9094. (c) A. V. Gulevich, A. G. Zhdanko, R. V. A.
Orru, V. G. Nenajdenko, Chem. Rev. 2010, 110, 5235. (d) U.
Schöllkopf, Angew. Chem., Int. Ed. Engl. 1977, 16, 339.
addition of activated imines 2 to the imino carbon of 2H-aziridine,
following by the intramolecular nucleophilic attack following with
the ring opening of the strained three-membered ring to obtain the
imidazole 3.
6
7
(a)H. Bredereck, R. Gompper, D. Hayer, Chem.Ber., 1959, 92,
338. (b)T.J. Donohoe, M.A. Kabeshov, A.H. Rathi, I.E.D. Smith,
Org. Biomol. Chem., 2012, 10, 1093. (c)T.Kumar, D. Verma,
R.F.S. Menna-Barreto, W.O. Valenca, E.N. da Silva
Jú
nior ,I.N.N. Namboothiri, Org. Biomol. Chem. 2015, 13
,
1996.
(a) S. Liu, W. Chen, J. Luo, Y. Yu, Chem. Commun., 2014, 50
Scheme 2. Proposed reaction mechanism for the construction of
poly-functionalized imidazoles 3
,
8539; (b) W. Chen, M. Hu, J. Wu, H. Zou, Y. Yu, Org. Lett.,
2010, 12, 3863; (c) J. Shao, W. Yu, Z. Shao, Y. Yu, Chem.
Commun., 2012, 48, 2785; (d) G. Zhang, H. Ni, W. Chen, J.
Shao, H. Liu, B. Chen, Y. Yu, Org. Lett., 2013, 15, 5967;
selected references: (e) L. Xiang, Y. Niu, X. Pang, X. Yang, R.
In summary, we have developed a concise approach for the
synthesis of poly-functionalized imidazoles by tandem
annulation of vinyl azides and activated imines, such as
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