4
Tetrahedron
Macro Lett. 2013, 2, 317–321; (c) Mahuteau-Betzer, F.; Piguel, S.
Tetrahedron Lett. 2013, 54, 3188–3193.
presence of the chlorine atom, and the reaction proceeded
selectively at the C-Br bond.
3. Chinchilla, R.; Nájera, C, Chem. Soc. Rev. 2011, 40, 5084–5121,
and referenes cited therein.
Unfortunately, the possibility of employing an ester group or a
trialkylsilyl group to protect C-2 revealed to be impracticable. In
fact, when ethyl 1-methyl-1H-imidazole-2-carboxylate (1f) or 2-
(tert-butyldimethylsilyl)-1-methyl-1H-imidazole (1g) were used,
the halogenation step provided an almost equimolar mixture of
two mono-brominated products (4- and 5-bromo derivatives).
Moreover, during the attempted alkynylation step partial
decarboxylation or desilylation occurred.
4. Selected examples of Sonogashira alkynylation involving halogen-
substituted azoles: (a) Yamauchi, T.; Shibahara, F.; Murai, T. J.
Org. Chem. 2014, 79, 7185–7192; (b) Gao, Y.; Yin, M.; Wu, W.;
Huang, H.; Jiang, H. Adv. Synth. Cat. 2013, 355, 2263–2273; (c)
Neilde, K.; Crozet, M. D.; Terme, T.; Vanelle, P. Synthesis 2013,
45, 1349–1356; (d) Shibahara, F.; Dohke, Y.; Murai, T. J. Org.
Chem. 2012, 77, 5381–5388; (e) Li, J.; Kaoud, T. S.; Laroche, C.;
Dalby, K. N.; Kerwin, S. M. Bioorg. Med. Chem. Lett. 2009, 19,
6293–6297; (f) Zhao, Z.; Peacock, J. G.; Gubler, D. A.; Peterson,
M. A. Tetrahedron Lett. 2005, 46, 1373–1375; (g) Xhao, Z.; Peng,
Y.; Dalley, N. K.; Cannon, J. F.; Peterson, M. A. Tetrahedron
Lett. 2004, 45, 3621–3624; (h) Kim, G.; Kang, S.; Ryu, Y.; Keum,
G.; Joon Seo, M. Synth. Commun. 1999, 29, 507–512.
5. (a) Wu, W.; Jiang, H. Acc. Chem. Res. 2014, 47, 2483–2504; (b)
Dudnik, S.A.; Gevorgyan, V. Angew. Chem. Int. Ed. 2010, 49,
2096–2098.
Figure 1. Chemical structure of imidazoles 1f and 1g
6. Selected recent examples of oxidative alkynylation of azoles: (a)
Jie, X.; Shang, Y.; Hu, P.; Su, W. Angew. Chem. Int. Ed. 2013, 52,
3630–3633; (b) Shihabara, F.; Dohke, Y.; Murai, T. J. Org. Chem.
2012, 77, 5381–5388; (c) Yang, L.; Zhao, L.; Li, C-J. Chem
Commun. 2010, 46, 4184–4186; (d) Matsuyama, N.; Kitahara, M.;
Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2010, 12, 2538–2361.
7. (a) Bellina, F.; Guazzelli, N.; Lessi. M.; Manzini, C. Tetrahedron
2015,71, 2298–2305; (b) Bellina, F.; Lessi, M.; Manzini, C. Eur.
J. Org. Lett. 2013, 5621–5630; (c) Bellina, F.; Rossi, R.
Tetrahedron 2009, 65, 10269–10310, and references therein cited.
8. (a) Prampolini, G.; Bellina, F.; Biczysko, M.; Cappelli, C.; Carta,
L.; Lessi, M.; Pucci, A.; Ruggeri, G.; Barone, V. Chem. Eur. J.
2013, 19, 1996–2004; (b) Platonova, I.; Branchi, A.; Lessi, M.;
Ruggeri, G.; Bellina, F.; Pucci, A. Dyes and Pigments 2014, 110,
249–255; (c) Lessi, M.; Manzini, C.; Minei, P.; Perego, L. A.;
Bloino, J.; Egidi, F.; Barone, V.; Pucci, A.; Bellina, F.
ChemPlusChem 2014, 79, 366–370.
3. Conclusions
In summary, an effective one-pot strategy for the direct
alkynylation of imidazoles with alkynes has been developed.
Through a careful choice of the reaction conditions, we were able
to obtain the regioselective C-5 monobromination of 2-
substituted imidazoles, including 2-chloroimidazole, and to
successfully pair this reaction with an effective Sonogashira
coupling with functionalized alkynes, allowing us to obtain
several 2-substituted 5-alkynylimidazoles in high yields. In the
next future, we are planning to apply this unprecedented one-pot
procedure to the synthesis of new classes of imidazole-based
organic dyes.
9. For an example of a one-pot sequential halogenation-cross-
coupling of arenes, see: Do, H.-Q.; Daugulis, O. Chem. Commun.
2009, 6433–6435.
Acknowledgments
10. Grimmett, M. R. Adv. Het. Chem. 1993, 57, 291–411.
11. Rao, A. K. S. B.; Rao, C. G.; Singh, B. B. J. Org. Chem. 1992 57,
3240–3242.
This study was supported by the Università di Pisa under PRA
2015 (project no. 2015_0038) and by MIUR-FIRB
(RBFR122HFZ).
12. Chelucci, G.; Figus, S. J. Mol. Cat. A 2014, 393, 191–209.
13. Whittle, C. P. Aust. J. Chem. 1980, 33, 1545–1551.
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