Abstract: The research described herein focuses on the development of novel methods and synthetic sequences to solve problems in organic synthesis. Chapter 1 details our work on an operationally simple method to synthesize furans and pyrroles in high yield from keto-oxetanes, a non-obvious, easily accessible 1,4-dicarbonyl surrogate.
Chapter 2 moves away from synthetic methodologies and is focused on the dihydro-β-agarofuran family of sesquiterpenoid natural products. This chapter begins by detailing the structural features that make this family unique and the diverse array of biological activity that has generated considerable interest in their study. It concludes by discussing the significant amount of synthetic efforts towards the agarofurans, focusing mainly on the most recent examples. Chapter 3 details four strategies towards the synthesis of an easily diversifiable core that could be used to synthesize several agarofurans and related analogs. Key contributions include the first use of an ester chiral auxiliary in a diastereoselective Birch reduction/alkylation reaction of substituted benzenes, an expedient route towards a fully oxidized A-ring fragment, and the synthesis of the AB-core of the agarofurans using an intramolecular 1,3-dipolar cycloaddition reaction.
Chapter 4 describes the history of the diastereoselective Birch reduction/alkylation reaction and its use in the synthesis of natural products. Chapter 5 details the development of using ester chiral auxiliaries to effect a diastereoselective Birch reduction/alkylation reaction. This method generates quaternary carbons directly from salicylic acid derivatives with good diastereoselectivity using an easily removable (−)-8-phenylmenthol chiral auxiliary.