3-Aryl-2-isoxazolines and 3-arylisoxazoles from reaction of arylnitrile oxides and enolates: synthesis and reactivity

Isoxazoles and isoxazolines are five-membered heterocycles widely used as versatile building blocks in preparative organic chemistry, due to the easy cleavage of their N-O bond [1]. They are masked forms of dicarbonyl compounds and are useful in the synthesis of other heterocycles. Moreover, these heterocycles are components of a wide number of pharmaceutical products and biologically active molecules [2], such as herbicides, fungicides, analgesics, GABA-antagonists, anti-viral, antibacterial and anti-inflammatory drugs [3]. The synthesis of functionalized 3-arylisoxazoles and 3-aryl-2-isoxazolines, from reaction of arylnitrile oxides and enolates [4] will be reported in this presentation. The regioselectivity and the synthetic versatility, due to the use of enolates intermediates, will be discussed with particular attention to the methodologies useful for the preparation of pharmacologically active heterocycles [5]. References [1] (a) J. C. Badenock, "Topics in Heterocyclic Chemistry", Springer-Verlag Berlin Heidelberg, 2012, (G. W. Gribble, ed.), vol 26, p. 261; (b) P. Grünanger, P. Vita-Finzi, J. E. Dowling, (eds.) Isoxazoles. Part 2, Vol. 170. In: The Chemistry of Heterocyclic Compounds, John Wiley & Sons, 2009. [2] (a) T. M. V. D. Pinho e Melo, Curr. Org. Chem. 2005, 9, 925; (b) P. Pevarello, R. Amici, M. G. Brasca, M. Villa, M. Varasi Targets in Heterocyclic Systems 1999, 3, 301-339. [3] J.J. Talley, D.L. Brown, J.S. Carter, M.J. Graneto, C.M. Koboldt, J.L. Masferrer, W.E. Perkins, R.S. Rogers, A.F. Shaffer, Y.Y. Zhang, B.S. Zweifel, K. Seibert, J. Med. Chem. 2000, 43, 775. [4] P. Vitale, A. Scilimati Curr. Org. Chem. 2013, 17, 1986-2000; (b) P. Vitale, A. Scilimati In: Advances in Heterocyclic Chemistry, Eric F. V. Scriven and Christopher A. Ramsden (eds.) 2016, vol. 122, 1-41; (c) P. Vitale, A. Scilimati, Synthesis (Germany) 2013, 45, 2940-2948. [5] L. Di Nunno, P. Vitale, A. Scilimati, S. Tacconelli, and P. Patrignani, J. Med. Chem. 2004, 47, 4881; (b) P. Vitale, S. Tacconelli, M. G. Perrone, P. Malerba, L. Simone, A. Scilimati, A. Lavecchia, M. Dovizio, E. Marcantoni, A. Bruno, P. Patrignani J. Med. Chem. 2013, 56, 4277