Cascade Reactions of Enone-Tethered Ketones and Aldehydes with Indoles: Substrate-Controlled Divergent Synthesis of Indenes and Indanes

A cascade strategy involving the reactions of enone-tethered ketones with indoles for the synthesis of indenes is outlined in the presence of iodine as a catalyst. Halogen bonding between molecular iodine and enones activates substrates to undergo Michael addition with indoles, resulting in the formation of enolates. These enolates in situ are transformed into indenes via an intramolecular aldol condensation. Enone-tethered aldehydes, however, react with two molecules of indoles to give indanes through a reaction sequence that involves chemoselective Michael addition followed by intramolecular aldol, and nucleophilic substitution. The substrate-controlled diversity-oriented synthesis has been realized to readily access indenes and indanes bearing indole moieties under benign metal-free conditions. The compatibility of these reactions has also been tested with a scale-up reaction for practical applications.