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 and 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.