1. Synthesis of a complex polycycle via olefin metathesis. 2. New methodological approaches towards the synthesis of nakadomarin A

This dissertation describes two independent research projects. The first section describes a cascade metathesis approach towards the synthesis of polyheterocycles. The incorporation oxanorbornene moieties in an oligomer consisting of terminal olefins has provided an expedient access to intricate polyheterocycles via an olefin metathesis cascade. Ring-opening/ring-closing metathesis was the method of choice in the preparation of these polyheterocycles due to the preservation of stereochemical complexity derived from their precursors. The monomeric oxanorbornenes are prepared from simple, ready available starting materials and their stereochemistry is established by utilizing the Diels-Alder reaction. Studies in the preparation of a pentacycle (where n = 0) lacking the amide carbonyl are described in this section utilizing the cascade metathesis approach, as efforts towards the preparation of the analogous pentacycle containing an 8-membered lactam was unsuccessful.* The second project describes a novel approach to Nakadomarin A. A tandem radical cyclization approach was studied where the B/D rings of Nakadomarin A could be concomitantly formed via an α-acylamino radical. Due to the complexity of the radical precursor required to synthesize Nakadomarin A, studies were conducted on simpler substrates that would lead to the construction of the BCD-core of the natural product. Two methods of generating the requisite α-acylamino radical are described and their cyclization results are reported.* A second approach towards the core of Nakadomarin A was investigated where formation of the B/D rings would occur via an intramolecular formal [4+1] cycloaddition between an isocyanide and a functionalized 1,3-butadiene system. Preliminary studies on the proposed cyclization in an intermolecular fashion utilizing 2-furan-3-yl-cyclohex-2-enone and methyl isocyanide led to an unexpected 1:2 annulated adduct. Through this unanticipated result, a novel methodology was developed by examination of other diene substrates that resulted in the synthesis of polycyclic structures. Studies illustrating the scope and limitations of the novel cyclization reaction are presented. *Please refer to dissertation for diagrams