Development of Stereoselective Iridium-Catalyzed Allylic Alkylation Methods

Citation

Shockley, Samantha Elizabeth (2018) Development of Stereoselective Iridium-Catalyzed Allylic Alkylation Methods. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/S93J-6P85. https://resolver.caltech.edu/CaltechTHESIS:05302018-124410879

Abstract

The Stoltz group, and moreover the synthetic community at large, has long been interested in the development of methods for the synthesis of enantioenriched all-carbon quaternary stereocenters. Historically, our group’s interest has centered on palladium-catalyzed allylic alkylation, though recently effort has moved to include the study of iridium catalysts. This thesis presents four related projects, all unified by the use of enantioselective iridium-catalyzed allylic alkylation to construct highly-congested C–C bonds.

First, the development of the first diastereo-, enantio-, and regioselective iridium-catalyzed allylic alkylation reaction of prochiral enolates to form vicinal tertiary and all-carbon quaternary stereodyads with alkyl-substituted allylic electrophiles is described. Next, the first enantioselective iridium-catalyzed allylic alkylation reaction of a masked acyl cyanide (MAC) nucleophile is presented, representing a rare example of umpolung strategy in iridium-catalyzed allylic alkylation. Additionally, the application of a MAC reagent in the first highly enantioselective iridium-catalyzed allylic alkylation to provide access to products bearing an allylic all-carbon quaternary stereocenter is detailed. The use of the MAC nucleophile enables the one-pot preparation of α-quaternary carboxylic acids, esters, and amides with a high degree of enantioselectivity. Finally, the first enantioselective transition metal-catalyzed allylic alkylation providing access to acyclic products bearing vicinal all-carbon quaternary centers is presented.

Thesis Files