10.1021/ol301212j r 2012 American Chemical Society Published on Web 06/05/2012 ORGANIC LETTERS 2012 Vol. 14, No. 12 2956–2959 Cyclization of 1,6-Enynes Catalyzed by Gold Nanoparticles Supported on TiO 2 : Significant Changes in Selectivity and Mechanism, as Compared to Homogeneous Au-Catalysis Charis Gryparis, Christina Efe, Christos Raptis, Ioannis N. Lykakis, † and Manolis Stratakis* Department of Chemistry, University of Crete, Voutes 71003 Iraklion, Greece stratakis@chemistry.uoc.gr Received April 5, 2012 ABSTRACT Gold nanoparticles supported on TiO 2 (1.2 mol %) catalyze, for the first time under heterogeneous conditions, the cycloisomerization of a series of 1,6-enynes in high yields. In several cases, the product selectivity differs significantly as compared to homogeneous Au(I)-catalysis. Based on product analysis and stereoisotopic studies it is proposed that the major or exclusive pathway involves a 5-exo cyclization mode to form stereoselectively gold cyclopropyl carbenes that undergo a single cleavage pathway, in contrast to homogeneous Au-catalysis where the double cleavage pathway operates substantially. The homogeneous Au(I)-catalyzed cyclization of 1,6- enynes has been extensively studied during the past decade, revealing a variety of unprecedented modes of skeletal rearrangements. 1 The puzzling mechanistic peculiarity of cycloisomerizations and the discussions over the nature of the intermediates (carbenes or carbocations) continue to fascinate. 2 Under heterogenized conditions the reaction has been marginally studied. A specific example was recently presented using a gold(I) complex covalently bound on a polystyrene resin that provides the typical product selectivity of homogeneous Au(I) catalysts. 3 The identification of stabilized ionic gold species on metal oxide supported gold nanoparticles (Au NPs), 4 and the fact that epoxides 5 and silanes 6 are readily activated by Au NPs on titania (Au/TiO 2 ), 7 let us recently examine its catalytic † Current address: Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. (1) Recent review articles: (a) Zhang, L.; Sun, J.; Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271. (b) Jimenez-Nunez, E.; Echavarren, A. M. Chem. Commun. 2007, 333. (c) Furstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410. (d) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395. (e) Michelet, V.; Toullec, P. Y.; Genet, J.-P. Angew. Chem., Int. Ed. 2008, 47, 4268. (f) Echavarren, A. M.; Jimenez-Nunez, E. Chem. Rev. 2008, 108, 3326. (g) Soriano, E.; Marco-Contelles, J. Acc. Chem. Res. 2009, 42, 1026. (h) Belmont, P.; Parker, E. Eur. J. Org. Chem. 2009, 6075. (i) Shapiro, N. D.; Toste, F. D. Synlett 2010, 675. (j) Echavarren, A. M.; Jimenez-Nunez, E. Top. Catal. 2010, 53, 924. (2) (a) Nieto-Oberhuber, C.; Lopez, S.; Jimenez-Nunez, E.; Echavarren, A. M. Chem.;Eur. J. 2006, 12, 5916. (b) Cabello, N.; Jimenez-Nunez, E.; Bunuel, E.; Cardenas, D. J.; Echavarren, A. M. Eur. J. Org. Chem. 2007, 4217. (c) Furstner, A.; Morency, L. Angew. Chem., Int. Ed. 2008, 47, 5030. (d) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2008, 47, 6754. (e) Seidel, G.; Mynott, R.; Furstner, A. Angew. Chem., Int. Ed. 2009, 48, 2510. (f) Perez-Galan, P.; Herrero-Gomez, E.; Hog, D. T.; Martin, N. J. A.; Maseras, F.; Echavarren, A. M. Chem. Sci. 2011, 2, 141. (g) Perez-Galan, P.; Martin, N. J. A.; Campana, A. G.; Cardenas, D. J.; Echavarren, A. M. Chem.;Asian J. 2011, 6, 482. (3) Cao, W.; Yu, B. Adv. Synth. Catal. 2011, 353, 1903. (4) (a) Carrettin, S.; Blanco, M. C.; Corma, A.; Hashmi, A. S. K. Adv. Synth. Catal. 2006, 348, 1283. (b) Fierro-Gonzaleza, J. C.; Gates, B. C. Chem. Soc. Rev. 2008, 37, 2127. (c) Boronat, M.; Concepcion, P.; Corma, A. J. Phys. Chem. C 2009, 113, 16772. (d) Naya, K.; Ishikawa, R.; Fukui, K.-I. J. Phys. Chem. C 2009, 113, 10726. (e) Brown, M. A.; Fujimori, Y.; Ringleb, F.; Shao, X.; Stavale, F.; Nilius, N.; Sterrer, M.; Freund, H.-J. J. Am. Chem. Soc. 2011, 133, 10668. (5) Raptis, C.; Garcia, H.; Stratakis, M. Angew. Chem., Int. Ed. 2009, 48, 3133. (6) Lykakis, I. N.; Psyllaki, A.; Stratakis, M. J. Am. Chem. Soc. 2011, 133, 10426. (7) Au/TiO 2 (∼1 wt % in Au) is commercially available.