Gold-Catalyzed Asymmetric Synthesis of Cyclic Ethers and Copper-Catalyzed Hydrofunctionalization of Alkynes

Thesis (Ph.D.)--University of Washington, 2015Gold-catalyzed cyclization of enantioenriched trisubstituted allenols to form enantioenriched α-tetrasubstituted cyclic ethers has been developed. This structural motif can be found in many natural products that have useful biological properties. The cyclization reaction is compatible with multiple functional groups and can be used to prepare enantioenriched furans, pyrans, and chromans all containing an α-tetrasubstituted stereocenter. The reaction development, scope, and a preliminary mechanistic study are discussed. In addition, a method to synthesize the required enantioenriched trisubstituted allenols based on copper-catalyzed cross coupling of enantioenriched propargylic phosphates and organoboron reagents has been developed. This allows the overall sequence to be practical and convergent. Copper-catalyzed hydrobromination and hydroalkylation of alkynes have been developed. The reactions are compatible with many functional groups and can be used to prepare functionalized alkenes in high yield and as one regio- and diastereoisomer. The reaction development, scope, and preliminary mechanism studies are discussed for both reactions. The development of copper-catalyzed hydrobromination and hydroalkylation of alkynes demonstrates that copper-catalyzed hydrofunctionalization of alkynes is a general approach to the synthesis of different types of functionalized alkenes