No abstract

No abstract

The yields of the title reaction are greatly affected by the electronic effect of the substituent on the benzene ring. Good yields are obtained with imidoyl chlorides bearing no or electron-donating substituents. The utility of the indole products is demonstrated by conversion of indole (IIb) into heterotauxin derivative (III). -(GE, F.; WANG, Z.; WAN, W.; HAO*, J.; Synlett 2007, 3, 447-450; Dep. Chem., Shanghai Univ., Shanghai 201800, Peop. Rep. China; Eng.) -Klein 25-113

Key indicators: single-crystal X-ray study; T = 273 K; mean (C-C) = 0.003 Å; R factor = 0.035; wR factor = 0.090; data-to-parameter ratio = 13.8.The title compound, C 21 H 15 ClF 3 OP, was obtained by a convenient and efficient one-pot synthesis. The length of the C C bond indicates a large enolic contribution to the structure. Intra-and intermolecular C-HÁ Á ÁO hydrogen bonds are present in the crystal structure.

2-Fluoroalkyl-substituted indole derivatives were simply prepared via the Grignard cyclization reaction (GCR) of corresponding fluorinated N-aryl imidoyl chlorides in good yields. This approach provides a novel and facile access to the biologically important 2-fluoroalkylindole derivatives.Due to the many potential bioactivities, fluorine-containing heterocycles have long received wide attention from either synthetic chemists or pharmaceutical scientists. As one of the important heterocycles, indole ring systems are found in many pharmaceuticals, for instance, indomethacin, oxypertine, and sumatriptan. Even today, the synthesis and applications of various indole derivatives are key subjects of considerable efforts. 1,2 However, indole ring systems bearing a fluoroalkyl group, especially 2-or 3-fluoroalkyl-substituted systems, have not been well-investigated due to the lack of efficient approaches to access the systems. Recently, Konno and his co-workers reported the palladium(0)-catalyzed regioselective annulation of fluorine-containing internal alkynes with o-iodoanilines, which provided a direct access to both 2-and 3-fluoroalkyl-substituted indole derivatives with good yields. 3 However, the application of this method is still somewhat limited due to the use of valuable palladium catalyst and the starting material source. Some other methods were also developed, but most of them suffered from either poor yields or the limitation of starting materials. 4 The development of novel and simple approach to synthesize the fluorine-containing indole derivatives from commercially or rapidly available materials still remains a challenge.Our interest in the synthesis of 2-fluoroalkyl-substituted indoles arose from ongoing research projects for the synthesis of 2-trifluoromethyl-substituted indole 3-carbinol and indomethacin derivatives, which all contain the indole ring systems. In this letter, we wish to report and share our preliminary results from the synthesis of 2-fluoroalkyl indole derivatives via Grignard cyclization reaction (GCR) of the corresponding N-aryl imidoyl chlorides, which were readily prepared from commercially available o-alkylanilines and fluorine-containing carboxylic acids, This approach provides a novel and facile access to various 2-fluoroalkyl-subsituted indole derivatives specifically (Scheme 1).The 2-fluoroalkyl-substituted indole derivatives 3 were successfully prepared through the GCR of either fluorinated N-(2-bromoalkyl)phenyl imidoyl chlorides 2 under normal Grignard reaction condition in moderate to good yields. 5