A One‐Pot Pseudo Three‐Component Domino Strategy for the Synthesis of Structurally Distinct Cycloocta[ <i>f</i> ]‐ and [ <i>e</i> ]‐Fused Indole Hybrids

ABSTRACT A facile one‐pot pseudo three‐component domino strategy has been developed for the construction of structurally scarce cycloocta[ f ]indole and cycloocta[ e ]indole hybrids. The transformation involves 2‐amino‐4‐arylbenzo[ a ]cyclooctene‐1,3‐dicarbonitriles and two equivalents of ethyl/methyl bromoacetate under mild basic conditions, proceeding through a domino N ‐alkylation, Thorpe–Ziegler‐type cyclization, and tautomerization sequence. The optimized protocol enables the efficient synthesis of a library of thirty‐four novel cycloocta[ f ]‐ and [ e ]‐indole derivatives in good yields. Comprehensive spectroscopic analyses were employed for structural elucidation. Given the prominence of indole‐based scaffolds in medicinal chemistry, the present methodology provides a valuable synthetic entry to architecturally complex cycloocta‐indole frameworks of potential biological relevance.