Indolo quinolines indoles

The Graebe-Ullman carbazole synthesis has been enmloyed in the preparation of substituted carbolines, as well as indolo[2,3-i] quinolines, which are often difficult to synthesize via other approaches, for example, the Fischer indole process. 

Other indoles that have been prepared using the Sonogashira coupling and cyclization sequence include 5,7-difluoroindole and 5,6,7-trifluoroindole [219], 4-, 5-, and 7-methoxyindoles and 5-, 6-, and 7-(triisopropylsilyl)oxyindoles [220], the 5,6-dichloroindole SB 242784, a compound in development for the treatment of osteoporosis [221], 5-azaindoles [222], 7-azaindoles [160], 2,2-biindolyls [223,176], 2-octylindole for use in a synthesis of carazostatin [224], chiral indole precursors for syntheses of carbazoquinocins A and D [225], a series of 5,7-disubstituted indoles [226], a pyrrolo[2,3-eJindole [226], an indolo[7,6-g]indole [227], pyrrolo[3,2,l-y]quinolines from 4-arylamino-8-iodoquinolines [228], optically active indol-2-ylarylcarbinols [229], 2-alkynylindoles [176], 7-substituted indoles via the lithiation of the intermediate 2-alkynylaniline derivative [230], and a variety of 2,5,6-trisubstituted indoles [231], This latter study employs tetrabutylammonium fluoride, instead of Cul or alkoxide, to effect the final cyclization of 215 to indoles 216 as summarized here. 

The nitrene from compound (139) attacks the indole position 3 to give the rearranged product (140 34%). When heated above its melting point (186 °C) this extrudes sulfur to yield the indolo[3,2-6]quinoline (141). The isomer (142) of (139) also reacts and rearranges with triethyl phosphite. The nitrene inserts at C-2 to give the indolothiazine (143 70%) (75CC911). 

Intramolecular Diels-Alder reaction (with high periselectivity and good yields) of conjugated carbodiimides, catalyzed by Lewis acids, affords a simple procedure for the construction of pyrido[2,3-h]indole and indolo[2,3-ft]quinoline ring systems (equation 176)631. This procedure is superior to the often mixed reactions that occur in the absence of the Lewis acid632-635. It is interesting to note that Lewis acids also improve yields and selectivity in intermolecular reactions of this type636. 

Formation of indole derivative by the reaction of 2-ethynylaniline, aryl halide and CO is known [53]. Cacchi extended the reaction to the synthesis of indolo[3.2-c]quinoline. Reaction of 2-(2 -aminophenylethynyl)trifluoroacetanilide 122, 4-iodoanisole and CO occurred as shown by 123 to provide 124 and then the 3-aroylindole 125. Treatment of 125 with a base gave the indoloquinoline 126 in 70% overall yield [54]. 

Myriad examples are known of oxindoles reacting to form indoles without prior carbonyl activation. Given (he vast scope of this subject, only a few early examples will be cited in addition to recent studies. Several groups have annulated oxindoles to access fused-indole heterocycles. Ila, Junjappa, and coworkers prepared pyrido[2,3-( ]indoles [61, 62] and 67/-indolo[2,3-fc]quinolines [63] using this approach (Scheme 9, equation 1). Adib and colleagues reported a simple synthesis of 9/7-pyrimido[4,5-Z ]indoles from oxindoles (eqnation 2) [64], and Bazgir and coworkers described a four-component one-pot a-carboUne synthesis... 

Parvatkar et al. [47] developed a facile one-pot synthetic methodology of substituted linear and angular indoloquinoline derivatives 19 by the reaction of indole-3-carboxaldehyde and substituted anilines in the presence of iodine as a catalyst (Scheme 10.13). Some indolo[2,3-Z)]quinolines were tested against human hepatocellular carcinoma HepG2 and human breast carcinoma MCF-7 cells. In an antiproliferative assay against human hepatocellular carcinoma HepG2 and human breast carcinoma MCF-7 cells, methyl-substituted 6//-indolo[2,3-(>]quinoline was found to be most active. 

Indole-2-carboxylic acids, 121, 252, 254 Indole-3-carboxylic acids, 253, 254 Indolenines, 84, 167, 169 dichloromethyl-, 68 quatemization of, 39 quinolines from, 69-71 ring expansion of, 69-71 Indolizmes, formylation of, 73 Indolo[l,2-a]pyrazinone, 119 Indolo[2,3-a]quinolizinium salts, synthesis of, 178... 

Molina P, Alajarin M, Vidal A (1990) New methodology for the preparation of pyrrole and indole derivatives via iminophosphoranes synthesis of pyrrolo[l,2-fl]quinoxalines, indolo[3,2-c] quinolines and indolo[l,2-c]quinazolines. Tetrahedron 46(3) 1063-1078. doi 10.1016/80040-4020(01)81384-3... 

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