General Papers ARKIVOC 2007 (i) 205-212 ISSN 1424-6376 Page 205 © ARKAT USA, Inc. Synthesis of novel conjugated enynes: a reaction of lithium acetylenides with β-dimethylaminovinyl ketones Marcos A. P. Martins,* Marcelo Rossatto, Fernanda A. Rosa, Pablo Machado, Nilo Zanatta, and Helio G. Bonacorso Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil E-mail: mmartins@base.ufsm.br Abstract The reaction of lithium acetylenide (R–C≡CLi, where R = Ph, Pentyl) with β-dimethylamino vinyl ketones [X-4-Ph-C(O)CH=CH-NMe 2 , where X = F, Cl, Br, NO 2 ] in the presence of BF 3 •OEt 2 is described. The regiospecific formation of (E)-1-aryl-2-alken-4-yn-1-ones, the 1,4- addition products, was observed in moderate to good yields. Keywords: Enynes, acetylenes, enaminones, organolithium Introduction Conjugated enynes are fundamental building blocks in organic synthesis. 1 These moieties are found to be integral parts of highly potent antitumor, 2 and antifungal agents, 3 and first line components of antiretroviral therapy. 4 Terbinafine (Lamisil™) 3 is one example of an enyne derivative in clinical use. In addition, in many systems rigidification has been an efficient method used to increase the activity of a drug or to reduce its side-effects. This strategy locks the drug molecule into a more rigid conformation such that it cannot take up other shapes or conformations. One such method is to incorporate a rigid functional group such as an alkyne in the drug candidates. 5 The synthesis of enynes has received special attention during recent decades, and new methods for their preparation have been developed. The most employed protocol for the synthesis of such compounds has been the palladium-catalysed cross-coupling reactions between vinyl halides and terminal acetylenes. 6 On the other hand, the reactions of acetylenes with α,β-unsaturated ketones have been scarcely reported. With regards to β-dimethylaminovinyl ketones, Mellor et al. 7 demonstrated the reaction of 4-dimethylamino-1,1,1-trifluoro-3-buten-2-one with alkyl(aryl)acetylenes based on Grignard and organolithium reagents. In these reactions only a single example in moderate