UCLA

This dissertation describes the application of strained cyclic allene methodology to the total synthesis of lissodendoric acid A, the further exploration of cyclic allene reactivity, and developments in chemical education. Strained cyclic allenes are fleeting intermediates and valuable synthetic building blocks due to their ability to undergo strain-driven reactions. In particular, heterocyclic allenes can be used to rapidly construct valuable motifs containing nitrogen or oxygen. Herein, the use of a strained azacyclic allene in a stereoselective Diels–Alder cycloaddition that enables the total synthesis of lissodendoric acid A is described. Synthetic strategies toward the natural product and computational studies of the key cycloaddition are also detailed. Moreover, a methodology study of the Diels–Alder cycloadditions of strained oxacyclic allenes and pyrones is described. Finally, the development of an organic chemistry summer camp for children called Chem Kids is detailed, highlighting an important initiative in STEM outreach. Chapter one offers a perspective on the field of strained cyclic alkynes and allenes. Despite their validation over fifty years ago, strained cyclic alkynes and allenes have become valuable building blocks for the synthesis of complex small molecules. This chapter highlights recent methodologies and syntheses using strained arynes, allenes, and alkynes to generate complex products bearing stereodefined quaternary centers or generate products with multiple fused rings in high enantioenrichment. Chapters two and three describe the total synthesis of lissodendoric acid A, highlighting the use of a key Diels–Alder cycloaddition between a strained azacyclic allene and a pyrone to stereoselectively construct the azadecalin core of the natural product. Chapter two focuses on the optimized asymmetric synthesis of the natural product, which had previously never been synthesized. The synthesis of an enantioenriched silyl bromide allows for a stereoretentive cycloaddition of the resultant allene, which provides the core of the natural product stereoselectively. An efficient synthetic endgame then provides (–)-lissodendoric acid A. Chapter three provides a full account of the total synthesis study. Model system studies are detailed, providing insights into reaction design. Several earlier generation strategies and synthetic routes are also described, showing key challenges and the corresponding solutions developed. In addition, experimental and computational investigations of the key cycloaddition are detailed, revealing substituent effects and interesting selectivity trends. Chapter four describes the development of Diels–Alder cycloadditions of oxacyclic allenes and pyrones. The results arising from the use of alkyl-substituted oxacyclic allenes and various pyrones are detailed, showing trends in regioselectivity and a panel of highly functionalized bicyclic products. Next, the reactions of ester-substituted and ester- and methyl-di-substituted oxacyclic allenes provide insight into the effects of allene substitution on reaction outcome. Competition studies between pyrone and furan trapping partners then suggest relative rates of reaction between oxacyclic allenes and different trapping partners. Finally, the use of an enantioenriched oxacyclic allene precursor is described, wherein the cycloaddition proceeds with high stereospecificity and gives rise to a complex, enantioenriched scaffold. Chapter five details the development of Chem Kids, an organic chemistry summer camp for children. The motivations and objectives behind the program are discussed, as well as descriptions of daily activities. Finally, key takeaways and future directions are highlighted.