2-Substituted 4-fluoroquinolines 3 are obtained by the reaction of 2-(trifluoromethyl)aniline (1) with lithium enolates 2 derived from methyl ketones. A similar reaction of 1 with lithium enolate of acetaldehyde produces 4-fluoroquinoline. l-Fluoro-3-phenyl-4,6-phenanthroline ( 18) is obtained by treatment of lithium enolate of acetophenone with 4-(trifluoromethyl)quinolin-3-amine (17). By contrast, (Z)-W-[2-(l-fluoroalkenyl)phenyl]carboxamides 10 and 12 are the products of the reaction of 1 with the respective enolate ions derived from 3-pentanone and isobutyl phenyl ketone. A unified mechanism for the formation of quinolines and carboxamides is proposed.The trifluoromethyl group in 2-(trifluoromethy)aniline(1), its para isomer, and heteroaromatic analogs exhibits unusual reactivity under basic conditions that cause ionization of the amino function.* 1'2 The CF3 group in such substrates is easily hydrolyzed to a carboxylate group in the presence of hydroxide base and transformed into a carbonitrile function in an amide ion mediated reaction.1•2 Recently, the anionically activated CF3 group has emerged as a valuable synthon for substituted dihydro-LH-imidazoles,3 1,4,5,6-tetrahydropyrimidines,3-5 acyclic amidines,4 benzothiazoles,6 benzoxazoles,6 and alkenes.7Ketimines derived from 1 are efficiently cyclized to quinolines in base-mediated reactions.4•5•8-10 The quinolines obtained in the presence of lithium alkylamide or dialkylamide reagents contain an amino function in the C-4 position. A similar approach has been used in a novel synthesis of quinazolin-4-amines11 from 1. This chemistry permits a facile preparation of amino-substituted heterobiaryls which, depending on structure, bind selectively to different types of nucleic acids.10•12-15 Several RNA binding agents of this class of compounds show promise for development as anti-HIV-1 drugs.9•10•15 Some cationic heterobiaryls are DNA triple-helix specific intercalators, and they are currently being developed as
Several trifluoromethyl‐substituted aromatic and heteroaromatic amines have been obtained by the reactions of the corresponding amines with the title reagent system. Computational results provide rationalization for the observed regioselectivities and support a mechanism in which the electrophilic trifluoromethyl radicals interact with the aromatic ring at the sites with the greatest electron density of the HOMO orbitals, and then the resultant adducts are oxidized to cations. The products obtained are potential building blocks for a number of heterocyclic systems.
New Triple-Helix DNA Stabilizing Agents. -All compounds show triple-helix stabilizing activity. Compounds (I) also show strong duplex stabilizing activity with compound (Ic) being the most selective towards duplex DNA. Compounds (II) do not stabilize duplex DNA, they are completely triple-helix selective. -(STREKOWSKI*, L.; HOJJAT, M.; WOLINSKA, E.; PARKER, A. N.; PALIAKOV, E.; GORECKI, T.; TANIOUS, F. A.; WILSON, W. D.; Bioorg. Med. Chem. Lett. 15 (2005) 4,
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