UCLA

This dissertation describes the development of methodologies that engage strained cyclic allene intermediates in complexity-generating reactions. One major effort involves palladium-catalyzed interception of strained cyclic allenes for the synthesis of saturated polycyclic products. Additionally, a novel mode of reactivity of cyclic allenes is reported involving the interception of 1,2-cyclohexadiene with a nitroxyl radical. The ability of strained cyclic allenes to engage with exocyclic alkenes in [2+2] cycloadditions is also described, pushing the limits of complexity in products formed from cyclic allene reactivity. Finally, the development of silyl tosylates as strained intermediate precursors is reported.Chapter one offers a current perspective on the field of strained cyclic alkynes and allenes. Despite being validated 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 enantioenriched products with multiple fused rings. Chapters two and three are related to the development of palladium-catalyzed reactions of strained cyclic allenes. Chapter two describes the development of a modular annulation reaction of strained allenes. This methodology employs aryl halides and cyclic allene precursors to generate fused heterocyclic products via the formation of two new bonds and a new stereocenter; moreover, an asymmetric variant of the transformation is employed. Chapter three details the engagement of strained cyclic allenes with pi-allylpalladium species to afford complex polycyclic products. Through judicious choice of the ligand used in the transformation, either of two isomeric products can be accessed with high selectivity. The development of these metal-catalyzed reactions demonstrates that despite their high reactivity and short lifetimes, strained cyclic intermediates can be efficiently engaged in catalysis, to access complex products with control of abstolute stereochemistry. Chapter four details the study of a novel mode of monoradical reactivity with strained cyclic allenes. Use of the nitroxyl radical TEMPO allows for the interception of 1,2-cyclohexadiene, affording a ketone product. The transformation demonstrates the viability of engaging cyclic allenes in one electron chemistry. Chapter five describes the investigation of [2+2] cycloadditions between strained cyclic allenes and exocyclic alkenes to afford highly substituted cyclobutanes, providing an alternative strategy to photochemical methods. Under mild reaction conditions, scope studies demonstrate that a variety of alkene trapping partners can engage with cyclic allenes with a high degree of selectivity. Furthermore, the cyclobutanes accessed via this methodology contain many features indicative of structurally complexity such as spiro centers, multiple contiguous stereocenters, and vicinal quaternary centers. The strained alkylidene cyclobutanes that are accessed can undergo thermal isomerization. Cycloadducts are also further elaborated, demonstrating the utility of the transformation in providing rapid access to structurally complex scaffolds. Chapter six illustrates the development of an alternative precursor toward strained cyclic allenes and alkynes. Our studies of strained cyclic allenes revealed that, in some cases, silyl triflate precursors were inaccessible. This study shows that silyl tosylates can serve as alternative precursors to strained cyclic allenes and alkynes.