Pyrido indole synthesis

Pyrido[ 1, 2 1,2]imidazo[4,5-b]quinoxaline nomenclature, 1, 22 2,2 -Pyridoin synthesis, 2, 337 Pyrido[ 1,2-6]indazoles synthesis, 5, 335 E ridoindoles rearrangement, 4, 508 Pyrido[a]indoles synthesis, 4, 233 Pyrido[6]indoles nomenclature, 4, 498 Pyridooxadiazolones ring contraction, 4, 149... 

This indole synthesis has been extended to P-tetrahydrocarbolines (300) [371], azaketotetrahydrocarbazoles [372], carbolines, carbazoles, and pyrido[l,2-a]benzimidazoles [373]. Examples of the former two reaction types are illustrated. An early Heck cyclization of 2-carboxy-2 -iododiphenylamine to 1-carbazolecarboxylie acid (73% yield) [374] has been generally overlooked by subsequent investigators. 

Carbodiimide, N-benzyl-AT-lithio-, 56, 210 Carbodiimides, o-styryl-, generation, electrocyclization, 57, 36 Carbodiimides, N-io-styryD-A -t/S-styryl)-, o-carbolines from, 57, 50 Carbodiimides, vinyl-, generation, uses in synthesis, 57, 36, 49 Carbolines, see entries under the appropriate Pyrido-indole names Carbon, as pivotal atom in... 

A NEW GENERAL SYNTHESIS OF SUBSTITUTED AND ANNULATED PYRIDO[2,3-6]INDOLES... 

This indole C-7 Heck cyclization strategy was employed by Shao and Cai in a synthesis of anhydrolycorine-7-one from the requisite N-aroylindoline [275], by Miki in syntheses of pratosine and hippadine from substrates like 262 [276], and by Rigby to synthesize anhydrodehydrolycorine from an N-benzylhydroindolone [277, 278]. Thai and co-workers constructed examples of the new ring systems, pyrido[2 ,3-d ]pyridazino[2,3-a]indole (264) and pyrido[2 ,3 -Heck cyclizations on the appropriate 2-bromopyridine precursors (e.g., 263) at C-2 or C-7, respectively [279, 280]. Compound 264 undergoes oxidative-addition with methyl acrylate at the C-3 position. This resulting product (not shown) can also be obtained from 263 in a tandem Heck sequence with methyl acrylate (62% yield). 

A versatile and convenient method for the synthesis of substituted benzo[o]carbazoles and pyrido[2,3-a]carbazoles has recently been developed [59]. Treatment of 2-(o-tolyl)- or 2-(3-methyl-2-pyridyl)-substituted indole-3-carbaldehydes (obtained by Suzuki reaction) with potassium tert-butoxide in DMF at 70-80 °C under irradiation by a 400 W high-pressure mercury lamp afforded benzo[a] carbazoles and pyrido] 2,3-o] carbazoles, respectively, in good yields (Eq. (30)). 

As shown in Equation (23), the condensation of w-diacetylbenzene with two equivalents of 8-hydrazinoquinoline gives the bis(pyrido[3,2-<7]indole) (48) in a Fischer synthesis upon cyclization of the intermediate bis(quinolinylhydrazone) with ppa (93JA872). 

The extension of the above regioselective 6-endo cyclization to appropriately substituted substrates provided a novel synthetic entry to the pyrido[4,3-b]carbazole skeleton of the indole alkaloid olivacine, which resulted in a concise total synthesis of its tetrahydro derivative ( )-guatambuine <6 IT 160 67CJC89>. 

Methyl-lf/-indol-l-yl)butanoic acid 135 easily prepared from 3-methylindole and dihydro-2(3//)-furanone, was used in the synthesis of natural 12//-pyrido[l,2- 7 3,4-/ ]diindoles which have antimicrobial activity and are cytotoxic against L-1210 mouse leukemia (Equation 25) <1996TL5207>. 

Archer and co-workers (84) have used the original Stillwell ellipticine synthesis (87), as later exploited by Gouyette et al. (88) to prepare the simple 9-hydroxy-6//-pyrido[4,3-fe]carbazole (158) (Scheme 27). V-Benzyl-4-piperidone was converted via enamine 154 to the enone 155. Hydrogenation gave a mixture of cis- and trawj-ketones 156 which were separately converted to indole 157 by Fischer indolization. Some of the nonlinear pyrido[3,4-c]carbazole (17%) was formed from the cis-ketone. Dehydrogenation and demethylation gave the desired 158. 

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