2776 J. Org. Chem. 2010, 75, 2776–2784 Published on Web 11/18/2009 DOI: 10.1021/jo9022815 r 2009 American Chemical Society pubs.acs.org/joc Tandem [8 þ 2] Cycloaddition-[2 þ 6 þ 2] Dehydrogenation Reactions Involving Imidazo[1,2-a]pyridines and Imidazo[1,2-a]pyrimidines Maialen Aginagalde, † Yosu Vara, ‡ Ana Arrieta, † Ronen Zangi, †,§ Vicente L. Cebolla, ^ Arantzazu Delgado-Cam on, ^ and Fernando P. Cossı´o* ,† † Kimika Organikoa I Saila, Universidad del Paı´s Vasco-Euskal Herriko Unibertsitatea (UPV-EHU), P. K. 1072, 20018 San Sebasti  an-Donostia, Spain, ‡ Ikerchem Ltd., Tolosa Etorbidea 72, 20018 San Sebasti  an-Donostia, Spain, § Ikerbasque, Basque Foundation for Science 48011 Bilbao, Spain, and ^ Instituto de Carboquı´mica, Consejo Superior de Investigaciones Cientı´ficas (CSIC), Miguel Luesma Cast  an 4, 50018 Zaragoza, Spain fp.cossio@ehu.es Received November 4, 2009 The reaction between benzynes and imidazo[1,2-a]pyridines (pyrimidines) to form benzo[a]imidazo- [5,1,2-cd]indolizines and 2,3,9c-triazocyclopenta[j,k]fluorenes has been studied computationally and experimentally. It is found that these reactions take place via tandem [ π 8 s þ π 2 s ] and [ σ 2 s þ π 6 s þ σ 2 s ] processes. The [8 þ 2] cycloaddition steps are essentially barrierless, and the aromatization steps occur via highly synchronous aromatic transition structures. From an experimental standpoint, the reaction is feasible under microwave irradiation and using 2-(trimethylsilyl)phenyl triflates as benzyne precursors. Depending on the substitution pattern in the starting triflate a complete regiocontrol of the reaction can be achieved. The tetracyclic compounds thus prepared emitted blue light when excited at 365 nm and exhibited interesting photophysical properties. Introduction The Woodward-Hoffmann rules for thermal cycloaddi- tions predict that allowed supra-supra reactions require 4n þ 2π-electrons in the reacting system. 1 Whereas thermal cycload- ditions with n = 1 have been extensively studied, the extension to n = 2 has been explored into a much lesser extent. 2 Several [ π 8 s þ π 2 s ] thermal cycloadditions have been studied, most of them involving 7-methylenecyclohepta-1,3,5-triene 3 and heteroanalogous 5,7-dimethylenecyclohepta-1,3-diene 4 and indolizines. 5,6 In many cases, aromatized products are ob- tained. 5,6 This aromatization step is related to thermally allowed cycloadditions involving hydrogen and aromatic hydrocarbons and heterocycles, a process that has attracted the interest of different research groups. 7 Recently, our group has published 8 the preparation of 1H- indoles, imidazo[1,2-a]pyridines, and imidazo[1,2a]pyrimidines. (1) Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969, 8, 781–853. (2) (a) Nair, V.; Abhilash, K. G. Synlett 2008, 301–312. (b) Sankararaman, S. Pericyclic Reactions -A Textbook; Wiley-VCH: Weinheim, 2005; pp 193-196. (3) (a) Doering, W. v. E.; Wiley, D. W. Tetrahedron 1960, 11, 183–198. (b) Rigby, J. H.; Ahmed, G.; Ferguson, M. D. Tetrahedron Lett. 1993, 34, 5397–5400. (c) Rigby, J. H.; Pigge, F.-C.; Ferguson, M. D. Tetrahedron Lett. 1994, 35, 8131–8132. (d) Machiguchi, T.; Yamabe, S. Tetrahedron Lett. 1990, 31, 4169–4172. (e) Ito, K.; Saito, K.; Takahashi, K. Bull. Chem. Soc. Jpn. 1992, 65, 812–816. (f) Nair, V.; Abhilash, K. G. Tetrahedron Lett. 2006, 47, 8707–8709. (4) Farrant, G. C.; Feldman, R. Tetrahedron Lett. 1970, 11, 4979–4982. (5) See, for example: (a) Galbraith, A.; Small, T.; Barnes, R. A.; Bockelheide, V. J. Am. Chem. Soc. 1961, 83, 453–456. (b) Kuznetsov, A. G.; Bush, A. K.; Babaev, E. V. Tetrahedron 2008, 64, 749–756. (6) (a) Mitsumori, T.; Benoikov, M.; Dautel, O.; Wudl, F.; Shioya, T.; Sato, H.; Sato, Y. J. Am. Chem. Soc. 2004, 126, 16793–16803. (b) Shen, Y.-M.; Grampp, G.; Leesakul, N. L.; Hu, H.-W.; Xu, J.-H. Eur. J. Org. Chem. 2007, 3718–3726. (7) (a) Hayden, A. E.; Houk, K. N. J. Am. Chem. Soc. 2009, 131, 4084– 4089. (b) Zhong, G.; Chan, B.; Radom, L. J. Am. Chem. Soc. 2007, 129, 924– 933. (8) Vara, Y.; Aldaba, E.; Arrieta, A.; Pizarro, J. L.; Arriortua, M. I.; Cossio, F. P. Org. Biomol. Chem. 2008, 6, 1763–1772.