Development of Dearomatization Chemistry for the Total Syntheses of Sesquiterpene Natural Products

The synthesis of biologically active molecules derived from natural sources is of primary interest to national health. Furthermore, numerous families of these natural products contain common structural motifs that would greatly benefit from the use of general methods for their construction. A large number of these compounds are derived from or contain aromatic functionality. Due to the large feedstock of aromatic materials that are commercially available and their structural similarity to interesting natural products, our group has focused on the development of methods for the dearomatization and/or functionalization of aromatic motifs. The structurally complex materials derived from these manipulations are further elaborated to provide practical routes to several natural products.;The first part of this dissertation focuses on the development of a synthetic route to verify the biosynthesis of the eight-membered ethereal ring in the helianane family. Our attempts to provide a biomimetic approach ultimately led to the discovery of a structural misassignment and complete repudiation of the helianane family. A new procedure for the generation and consumption of ortho-quinone methides was developed to avoid side-reactions that plagued specific aromatic substrates.;The second part describes the development of an oxidative dearomatization-induced [5 + 2] cycloaddition reaction and its application to the synthesis of three natural products. The creation of this novel cascade reaction allowed for construction of the densely functionalized tricyclic skeleton of the cedrenoid family from a simple aromatic precursor.