3,4-Annulated Indoles via Tandem Cyclopropane Ring-Opening/Conia-ene and Michael Addition/Conia-ene Reactions

The indole moiety is ubiquitous in natural products, and as such their reactions and syntheses are a high priority for organic chemists. The use of tandem reactions is an excellent strategy to optimize the efficiency of chemical processes. This thesis details the process of designing and implementing of strategies for the syntheses of 3,4-annulated indoles from 4-ethynylindoles via tandem cyclopropane ring-opening/Conia-ene and Michael addition/Conia-ene reactions. It was discovered through optimization experiments that the reactions are highest yielding using superstoichiometric amounts of Lewis acidic zinc halides. The cyclopropane variant of the reaction was applied to successfully synthesize 23 new 3,4-cycloheptannoindoles products. The Michael addition variant was used to synthesize 14 new 3,4-cyclohexannoindoles. Both reactions tolerated electron withdrawing and electron donating aryl groups on the electrophilic substrates. Yields were generally higher using cyclopropane substrates compared to Michael-acceptors. In both cases 4-ethynyl-1-methylindole performed significantly better than unprotected 4-ethynylindole