The Development of New Methods Toward Guaiane Natural Products: the Use of Irontricarbonyl Cyclobutadiene in Total Synthesis

Guaiane natural products are complex architectures that contain multiple stereogenic centers, ring junctures, and functionalities that render their synthesis difficult without an efficient and effective methodology. Herein, a new method for generating these natural products will be discussed. In particular, highly strained intermediates, generated through an intramolecular cyclobutadiene cycloaddition, will be studied and utilized. The following are a summary of the chapters: Chapter 1: Tricyclo[3.2.0.02,4]heptanes are unique scaffolds that possess many interesting chemistries. A review of both their synthesis and chemistry is covered. Chapter 2: Syn-tethered tetracyclo[5.3.0.01,5.02,4]decanes are strained systems obtained through a cyclobutadiene cycloaddition-intramolecular cyclopropanation sequence. Studies related to these systems will be covered. Chapters 3 & 4: An intramolecular cyclobutadiene cycloaddition-cyclopropanation-thermal fragmentation methodology is utilized for the asymmetric total synthesis of two guaiane natural products. In addition, the methodology is further expanded upon to access multiple guaianes from a single intermediate.