ИСТИНА

The indole core is one of the most important structural fragments of modern drugs and natural products [1]. In particular, 3-vinylindoles are an important class of functionalized indoles. These molecules have been used as building blocks for the synthesis of a number of significant biologically active compounds [2-5]. Incorporation of fluorine into the molecule is one of the fundamental tools in the development of new drugs and materials. This work is devoted to the synthesis of novel 3-(2-fluoroalkyl) indoles. We developed a one-pot method that involves Michael addition of β-fluoro-β-nitrostyrenes to indoles in neat and catalysts-free conditions and a subsequent elimination of HNO2 using DBU as a base. (Scheme 1). The starting β-fluoro-β-nitrostyrenes were prepared according to the previously developed method (Scheme 2), based on the radical nitration of 2-bromo-2-fluorostyrenes. [5] 2-Bromo-2-fluorostyrenes, in turn, were obtained by the reaction of catalytic olefination from the corresponding aromatic aldehydes. [6] This method opens up a direct way to valuable 3- (2-fluoroalkenyl) indoles, which in turn can be used as precursors for the synthesis of various fluorine-substituted biologically active compounds. This work was supported by the Russian Science Foundation (RSF) (Grant No. 17-73-10358). This work was partially supported by the Russian Federation President Grant for leading scientific schools № 4687.2018.3. References [1] M. J. Naim, O. Alam, M. J. Alam, F. Bano, P. Alam, N. Shrivastava. International Journal of Pharma Sciences and Research (IJPSR), 2016, 7 (2), 51-62 [2] B. Tan, G. Hernández-Torres, C. F. Barbas.J. Am. Chem. Soc. 2011, 133, 12354–12357 [3] Y. Liu, M. Nappi, E. C. Escudero-Adan, P. Melchiorre. Org. Lett., 2012, 14 (5), 1310–1313 [4] C. Zhang, L.-X. Zhang, Y. Qiu, B. Xu, Y. Zong, Q.-X. Guo., RSC Adv. 2014, 4, 6916–6919 [5] V. A. Motornov, V. M. Muzalevskiy, A. A. Tabolin, R. A. Novikov, Yu. V. Nelyubina, V.G. Nenajdenko, S. L. Ioffe, J. Org. Chem. 2017, 82, 5274–5284. [6] A. V. Shastin, V. M. Muzalevsky, E. S. Balenkova, V. G. Nenajdenko, Mendeleev Commun. 2006, 16, 178−180