Indolizidine alkaloids and asymmetric synthesis of carbocycles

Abstract

The first chapter of this thesis describes the development of an asymmetric route to the core structure of the indolizidine alkaloids and its application to the total synthesis of (+)-ipalbidine, a member of this compound class. The initial approach was designed to use the intramolecular conjugate displacement (ICD) reaction developed in this group as the method to form the bicyclic core structure of these compounds. Some limitations of this useful method were uncovered under these circumstances, and a different approach was required to carry out the synthesis. The indolizidine structure was formed by use of a conjugate addition and the total synthesis of (+)-ipalbidine was completed. The second chapter describes the expansion of the all-carbon ICD reaction previously developed by this group for carbocyclic ring formation. The goal was to install a pendant chain in an asymmetric fashion onto the carbocycle precursors and then form the rings using the ICD reaction. The strategically placed pendant chain could then be manipulated and utilized as a handle to elaborate the carbocyclic intermediates into more complex structures. This chapter describes (a) the use of the Myers asymmetric alkylation reaction as an installation method for the pendant chain, (b) the production of the asymmetrically substituted carbocycles via the ICD reaction and (c) our efforts to elaborate these intermediates into more complex compounds.