Electronic Thesis and Dissertation Repository


Doctor of Philosophy




M. A. Kerr


Part one of this thesis focuses on the synthesis of pyrrolo[1,2-a]indoles from nitrones and 1,1-cyclopropanediesters, by way of tetrahydro-1,2-oxazines. A five step synthetic sequence through tetrahydro-1,2-oxazine synthesis, intramolecular Heck reaction, Krapcho dealkoxycarbonylation, reductive N-O bond cleavage, and acid catalyzed transannular alcohol displacement, is developed to access the desired pyrrolo[1,2-a]indoles. Part two of this thesis details the functionalization of indoles by installation of a malonate moiety, by means of copper catalyzed carbenoid reactivity. A wide range of malonyl indoles with varying substitution patterns is shown to be accessible through the developed method. The final chapter focuses on the application of this reaction in a biomimetic approach towards the total synthesis of the indole alkaloid arboflorine. This reaction provided access to an advanced intermediate which allowed for the study of a key Mannich ring closure step that was proposed in the postulated biogenesis of the natural product. The current synthetic sequence includes the copper catalyzed malonyl carbenoid insertion, reduction of a pyridinium salt, reductive ammination, and a Polonovski-Potier reaction to install and mask an iminium motif. As of yet, the proposed Mannich reaction has been unsuccessful in securing the required azepane ring.