Master of Science
Kerr, Michael A.
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.
Summary for Lay Audience
A vast number of pharmaceuticals are derived from molecules obtained from natural sources like plants and fungi. Some of these natural products can be efficiently harvested and used directly, however many cannot be obtained in significant amounts. For these cases, synthetic organic chemists are employed to replicate the natural products and similar molecules so that they can eventually be used for treatment of ailments. It is important to note that not all synthetic organic chemists focus directly on the synthesis of drugs or natural products; this type of research is known as target-oriented synthesis. Many chemists focus on the development and optimization of different chemical reactions (this type of research is known as methodology-oriented synthesis) which increases the collective knowledge of organic chemists. While methodology-oriented synthesis typically does not produce potentially useful compounds, it creates a plethora of new options for target-oriented researchers to use.
Cochrane, Shane R., "3,4-Annulated Indoles via Tandem Cyclopropane Ring-Opening/Conia-ene and Michael Addition/Conia-ene Reactions" (2022). Electronic Thesis and Dissertation Repository. 8548.
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