Attachment of a Carbocyclic Fragment to an Indole Nucleus

The cyclization of 4-cyanomethyl or 4-carbethoxymethyl-substituted 3-indolylpropionic acids 187 by the action of sodium hydride in tetrahy-drofuran leads to 5-substituted l,3,5-trihydrobenzo[c / indoles 188a,b 

The initial indole derivatives 185 and 187 are synthesized from ortho-nitrotoluenes 191 (57CB1980 60CB2024 79JOC4003). Indolylcarboxylic 

The interaction of 1,2-dimethyIindoles 194 (R = H, OMe) with pro-piolactone gives rise to 3-indolylpropionic acids 195 (R = H, OMe) and, on treatment with a mixture of sulfuric and phosphoric acids, only the 5-methoxy-derivative for this series can be transformed into 1,3,4-trihydrobenzo[crf]indole-5-one 196, whereas in the absence of an activating substituent (195, R = H), the cyclization does not take place [53CI(L)823 80LA971]. 

The intramolecular C-acylation into position 4 becomes possible after hydrogenation of the C2—C3 bond in the indole nucleus. Thus, by the action of aluminum chloride, l-benzoyI-2,3-dihydroindo ylpropionyl chloride 197 is converted into pentahydrobenzo[crf]indolone 198 (54J A5256 56JA3087). Intramolecular electrophilic substitution is favored also by conjugation between a carbonyl or a nitrile group at the /3-substituent containing three carbon atoms and the indole nucleus. 

Interaction of 1,2-dimethylindole with malonyl chloride or diketene gives 1,2,5-tri-substituted benzo[c /]indole-3-ones 199 (78S685 80LA971). 

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