Please do not adjust margins
Page 3 of 4
ChemComm
Journal Name
COMMUNICATION
azide‐alkene
1,3‐dipolar
cycloaddition/ring
DOI: 10.1039/C5CC06487B
migration/denitrogenation, followed by copper‐catalyzed aerobic
oxidative dehydrogenative cyclization of the resulting imines. The
use of naturally abundant air as an oxidant as well as an oxygen
source, easily available starting materials including the copper
catalyst, and an experimentally convenient catalytic process are the
added advantages of the present protocol. Further investigations on
the synthetic applications of this reaction are ongoing in our
laboratory.
We would like to thank the Ministry of Education of China
(IRT1225), National Natural Science Foundation of China (21362002,
41465009 and 81260472), State Key Laboratory Cultivation Base for
the Chemistry and Molecular Engineering of Medicinal Resources,
Ministry of Science and Technology of China (CMEMR2014‐A02 and
CMEMR2012‐A20), and Bagui Scholar Program of Guangxi for
financial support.
A plausible mechanism for this cascade reaction is shown in
Scheme 1. The first step is the regioselective 1,3‐dipolar
cycloaddition of benzyl azide 2a with styrene 1a to form the
triazoline intermediate A. Subsequently, A decomposes to the
zwitterionic species B, which undergoes 1,2 H‐shift with the loss of
nitrogen to give the imine C.8 Then, one‐electron oxidation of C by
the higher‐oxidation‐state CuII species generated from CuICl with
molecular oxygen2f, 9 yields a radical intermediate D, and D could
then be envisaged reacting with molecular oxygen to give peroxy
radical E. The latter could then undergo a 1,5‐hydrogen atom
abstraction2f, 5d, 10 to afford intermediate F with regeneration of the
CuII species. Finally, intramolecular radical coupling would afford
the 4,5‐dihydrooxazole intermediate G, which could be easily
oxidized by air to the final oxazole product 3a.3d, 5d
Notes and references
1 For some reviews, see: (a) P. Wipf, Chem. Rev., 1995, 95, 2115; (b)
Y. Hamada and T. Shioiri, Chem. Rev., 2005, 105, 4441; (c) Z. Jin,
Nat. Prod. Rep., 2006, 23, 464; (d) Z. Jin, Nat. Prod. Rep., 2009, 26,
382; (e) Z. Jin, Nat. Prod. Rep., 2011, 28, 1143; (f) C. T. Walsh, S. J.
Malcolmson and T. S. Young, ACS Chem. Biol., 2012, 7, 429; (g) Z.
Jin, Nat. Prod. Rep., 2013, 30, 869.
ESI/MS experiments were performed to gain evidence for the
possible intermediates in the proposed mechanism. Under an argon
atmosphere, a mixture of 1a (0.5 mmol), 2a (0.6 mmol) and CuCl
(0.05 mmol) in toluene (3.0 mL) was reacted at 80 oC for 8 h and 50
μL of the mixture was used for the ESI analysis in CH3OH. The
ESI/MS analyses showed a peak at m/z 210.1270, which was
identified as an imine species (see the Supporting Information).
Although the unstable imine C underwent decomposition during
the column chromatography, this result supported the generation
of the imine intermediate C.
2 (a) E. Merkul and T. J. J. Muller, Chem. Commun., 2006, 4817; (b) C.
Verrier, T. Martin, C. Hoarau and F. Marsais, J. Org. Chem., 2008,
73, 7383; (c) Y. Pan, F. Zheng, H. Lin and Z. Zhan, J. Org. Chem.,
2009, 74, 3148; (d) H. Jiang, H. Huang, H. Cao and C. Qi, Org. Lett.,
2010, 12, 5561; (e) C. Wan, J. Zhang, S. Wang, J. Fan and Z. Wang,
Org. Lett., 2010, 12, 2338; (f) Y.‐F. Wang, H. Chen, X. Zhu and S.
Chiba, J. Am. Chem. Soc., 2012, 134, 11980.
3 (a) A. I. Meyers and F. X. Tavares, J. Org. Chem., 1996, 61, 8207; (b)
D. R. Williams, D. P. Lowder, G.‐Y. Gu and D. A. Brooks,
Tetrahedron Lett., 1997, 38, 331; (c) A. J. Phillips, Y. Uto, P. Wipf,
M. J. Reno and D. R. Williams, Org. Lett., 2000, 2, 1165; (d) Y.
Huang, L. Ni, F. Gan, Y. He, J. Xu, X. Wu and H. Yao, Tetrahedron,
2011, 67, 2066.
4 (a) E. F. Flegeau, M. E. Popkin and M. F. Greaney, Org. Lett., 2006,
8, 2495; (b) F. Derridj, S. Djebbar, O. Benali‐Baitich and H. Doucet,
J. Organomet. Chem., 2008, 693, 135; (c) K. Lee, C. M. Counceller
and J. P. Stambuli, Org. Lett., 2009, 11, 1457; (d) D. R. Williams
and L. F. Fu, Org. Lett., 2010, 12, 808.
5 (a) T. H. Graham, Org. Lett., 2010, 12, 3614; (b) W. He, C. Li and L.
Zhang, J. Am. Chem. Soc., 2011, 133, 8482; (c) I. Cano, E. Álvarez,
M. C. Nicasio and P. J. Pérez, J. Am. Chem. Soc., 2011, 133, 191; (d)
Z. Xu, C. Zhang and N. Jiao, Angew. Chem., Int. Ed., 2012, 51,
11367; (e) X. Li, L. Huang, H. Chen, W. Wu, H. Huang and H. Jiang,
Chem. Sci., 2012, 3, 3463; (f) A. Saito, A. Taniguchi, Y. Kambara
and Y. Hanzawa, Org. Lett., 2013, 15, 2672; (g) Y. Odabachian, S.
Tong, Q. Wang, M.‐X. Wang and J. Zhu, Angew. Chem., Int. Ed.,
2013, 52, 10878; (h) T. Selvi and K. Srinivasan, Chem. Commun.,
2014, 50, 10845; (i) L. Zhang and X. Zhao, Org. Lett., 2015, 17, 184.
Scheme 1 A plausible mechanism for the cascade reaction of terminal
alkenes and azides.
In summary, we have demonstrated a novel approach for the
synthesis of 2,5‐disubstituted oxazoles that operates via sequential
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 3
Please do not adjust margins