L. Strekowski,, Shouwang Lin, John Nguyen
1995
Citations
0
Influential Citations
11
Citations
Journal
Heterocyclic Communications
Abstract
A reaction of trifluoromethyl-substituted anilines 1-3 with dianions derived from oximes of 3-pentanon and cyclohexanone provides a facile entry into the corrresponding isoxazoles 4-7. Triazines 8,9 are obtained upon treatment of a monoanion derived from benzamidine with the respective substrates 1, 2. Anions derived from 4-(trifluoromethyl)aniline 1 s its ortho isomer 2, substituted derivatives such as 3 (Scheme 1) and analogs containing other ionizable groups at ortho or para position to the trifluoromethyl function undergo elimination of fluoride to generate the corresponding intermediate products illustrated by 11 in Scheme 2. The meta isomers are stable under basic conditions. The early chemistry of the anionically activated trifluoromethyl group has been reviewed (1) and another recent review describes synthetic applications of the chemistry of trifluoromethyl-substituted substrates (2). The most recent developments not yet reviewed include one-pot synthesis of 2-(1-alkenyl)anilines (3), naphthalenes (4), fluoro heteroaromatic compounds (5,6), benzothiazoles (7), benzoxazoles (7), and additional examples of 4-aminoquinolines (8) obtained by the chemistry already described (2). A strong selective stabilization of the triplex DNA structure in the presence of duplex DNA has been found for certain 4-aminoquinoline products (9-11) derived from 2. The synthetic importance of the chemistry of the activated trifluoromethyl group, thus, is growing rapidly. A large number of substrates including 1-3 are available commercially, and others can easily be prepared by a trifluoromethylation reaction of electron-rich aromatic and heteroaromatic amines (12). In this paper, as part of our fundamental studies on the chemistry ο the anionically activated trifluoromethyl group, we describe a novel one-pot preparation of isoxazoles (13) and 1,3,5triazines (14) (Scheme 1). Isoxazoles 4-6 are obtained by the reaction of dianton derived from 3-pentanone oxime with the respective trifluoromethyl-substituted anilines 1-3. The cyclization involves the C F 3 group, the carbon atom of which becomes C-5 01 the isoxazole system. In a typical experiment a solution of LDA (20 mmol) and n-BuLi (20 mmol) prepared by the addition of n-BuLi (40 mmol, 2 Μ in cyclohexane) to a solution of diisopropylamine (20 mmol) in THF (20 mL) is treated dropwise at -75 °C under a nitrogen atmosphere with 3-pentanone oxime (20 mmol) (15,16). The mixture is stirred at +23 °C for 30 mir cooled to -75 °C and then treated with a solution of 1-3 (4 mmol) in THF (2 mL). The mixture is stirred at -75 °C for 30 min and then at +23 °C for 2 h. A standard workup is followed by chromatography on silica gel with pentanes/ether (1:1) as an eluent to give the corresponding isoxazole 4-6. A similar treatment of dianion of cyclohexanone oxime with 2 gave the