Regioselective Synthesis of 3-Alkynyl-5-bromo-2-pyrones via Pd-Catalyzed Couplings on 3,5-Dibromo-2-pyrone Jin-Hee Lee, Jung-Sang Park, and Cheon-Gyu Cho* Department of Chemistry, Hanyang UniVersity, Seoul 133-791, Korea ccho@hanyang.ac.kr Received January 24, 2002 ABSTRACT 3,5-Dibromo-2-pyrone underwent facile Pd(0)-catalyzed coupling reactions with various alkynes to give rise to the corresponding 3-alkynyl- 5-bromo-2-pyrones with good to excellent chemical yields and regioselectivity. As structural subunits present in a variety of biologically active natural products 1 and as versatile synthetic building blocks, 2 2-pyrones have gained much interest over the past few decades. There have been a number of reports in the literature on their chemical behaviors toward dienophiles, nucleophiles, and electrophiles in addition to their prepara- tions. 3 Halogenated 2-pyrones are of particular interest, in that they would offer a convergent approach to the com- pounds containing 2-pyrone units. Halogenated 2-pyrones have been either used directly for transition metal catalyzed coupling reactions with aryltin and arylboronic acids or converted into tin-, boron-, zinc-, and copper-based orga- nometallic reagents for couplings with electrophilic partners. 4 We have recently reported a convenient synthetic method 5 for 3,5-dibromo-2-pyrone as well as its potency as an ambident diene. 6 Its 13 C NMR spectrum indicated that the two carbon centers with bromine atoms attached (C3 and C5 of 3,5-dibromo-2-pyrone) differ in their chemical shifts, implying that oxidative addition of Pd(0) could occur preferably at one carbon center (presumably the C3 position), leading to regioselective coupling reactions. 7 Second coupling reactions with other functionalities onto the remaining bromine group would thus provide, in principle, an easy (1) (a) Schlingmann, G.; Milne, L.; Carter, G. T. Tetrahedron 1998, 54, 13013. (b) Shi, X.; Leal, W. S.; Liu, Z.; Schrader, E.; Meinwald, J. Tetrahedron Lett. 1995, 36, 71. (c) Barrero, A. F.; Oltra, J. E.; Herrador, M. M.; Sanchez, J. F.; Quilez, J. F.; Rojas, F. J.; Reyes, J. F. Tetrahedron 1993, 49, 141. (2) For representative examples, see: (a) Okamura, H.; Shimizu, H.; Iwagawa, T.; Nakatani, M. Tetrahedron Lett. 2000, 41, 4147. (b) Posner, G. H.; Lee, J. K.; White, M. W.; Hutchings, R. H.; Dai, H.; Kachinski, J. L.; Dolan, P.; Kensler, T. W. J. Org. Chem. 1997, 62, 3299 and references cited therein. (c) Posner, G. H.; Cho, C.-G.; Anjeh, T. E. N.; Johnson, N.; Horst, R. L.; Kobayashi, T.; Okano, T.; Tsugawa, N. J. Org. Chem. 1995, 60, 4617. (d) Nicolaou, K. C.; Yang, Z.; Liu, J. J.; Ueno, H. et al. Nature, 1994, 367, 630. (3) (a) Afarinkia, K.; Vinader, V.; Nelson, T. D.; Posner, G. H. Tetrahedron 1992, 48, 9111. (b) Kvita, V.; Fischer, W. Chimia 1993, 47, 3. (c) Afarinkia, K.; Berna-Canovas, J. Tetrahedron Lett. 2000, 41, 4955. (d) Okamura, H.; Shimizu, H.; Nakamura, Y.; Iwagawa, T.; Nakatani, M. Tetrahedron Lett. 2000, 41, 4147. (e) Yao, S.; Roberson, M.; Reichel, F.; Hazell, R. G.; Jorgensen, K. A. J. Org. Chem. 1999, 64, 6677. (f) Stigers, K. D.; Mar-Tang, R.; Bartlett, P. A. J. Org. Chem. 1999, 64, 8409. (g) Kotretsou, S. I.; Georgiadis, M. P. Org. Prep. Proced. Int. 2000, 32, 161. (h) Larock, R. C.; Doty, M. J.; Han, X. J. Org. Chem. 1999, 64, 8770. (i) Bodwell, G.; Pi, Z.; Potti, I. R. Synlett 1999, 4, 477. (j) Liebeskind, L. S.; Wang, J. Tetrahedron 1993, 49, 5461. (4) (a) Danieli, B.; Lesma, G.; Martinelli, M.; Passarella, D.; Peretto, I.; Silvani, A. Tetrahedron 1998, 54, 14081. (b) Liu, Z.; Meinwald, J. J. Org. Chem. 1996, 61, 6693. (c) Cerezo, S.; Moreno-Manas, M.; Pleixats, R. Tetrahedron 1998, 54, 7813. (d) Bellina, F.; Biagetti, M.; Carpita, A.; Rossi, R. Tetrahedron Lett. 2001, 42, 2859. (e) Posner, G.; Harrison, W.; Wettlaufer, D. J. Org. Chem. 1985, 50, 5014. (5) Cho, C.-G.; Park, J.-S.; Kim, Y.-W.; Lee, H. Tetrahedron Lett. 2001, 42, 1065. (6) (a) Cho, C.-G.; Kim, Y.-W.; Lim, Y.-K.; Park, J.-S.; Lee, H.; Koo, S. J. Org. Chem. 2002, 67, 290. (b) Cho, C.-G.; Kim, Y.-W.; Kim, W.-K. Tetrahedron Lett. 2001, 42, 8193. ORGANIC LETTERS 2002 Vol. 4, No. 7 1171-1173 10.1021/ol025613q CCC: $22.00 © 2002 American Chemical Society Published on Web 03/08/2002