Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Chemistry

Supervisor

Dr. M. Kerr

Abstract

The development and utility of cyclopropanes is an ever-growing field within organic chemistry. In particular, donor-acceptor cyclopropanes have been used in a vast array of methods to access a variety of different hetero and carbocyclic molecular scaffolds. Recently, we have developed a Zn(NTf2)2 catalyzed tandem reaction consisting of a nucleophilic ringopening of 1,1-cyclopropanediesters by 2-alkynyl indoles followed by a Conia-ene ring closure, resulting in the efficient one-step synthesis of tetrahydrocarbazoles. These adducts may be further elaborated to carbazoles. The scope and limitations of this method were determined along with a mechanistic study into the function of the zinc catalyst. In an expansion of our work with 1,1-cyclopropanediesters, we have explored the reactivity and utilization of hemimalonate cyclopropanes. To this end, we have developed two unique methods exploring the self-activating nature of these cyclopropanes under catalyst free conditions. Cyclopropane hemimalonates, when treated with sodium azide, undergo a tandem ring-opening decarboxylation to produce γ-azidobutyric acids in good yields. These adducts were hydrogenated to form γ-aminobutyric acid (GABA) methyl esters. Additionally, cyclopropane hemimalonates have led to the facile synthesis of γ-substituted butanolides. Under microwave irradiation, cyclopropane hemimalonates undergo rapid conversion to butanolides in the presence of inorganic salts with an unprecedented retention of stereochemistry. This unique process, in conjunction with a newly developed crossmetathesis method, has been applied to the total synthesis of the naturally occurring, (R)- dodecan-4-olide. Finally, recent efforts to develop a unified approach to piperidine-containing indole natural products have shown great promise. A preliminary investigation into the prospect of a common synthetic intermediate for the synthesis of a variety of indole alkaloids has led to a synthesis of substituted piperidinones and the corresponding piperidines. These common natural product cores are accessed via a reductive amination/lactamization sequence of dimethyl 3-ethyl-3-formylpimelate. The synthetic utility of this initial study has been displayed in the formal synthesis of (+/-)-quebrachamine.

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