Synthesis of Enantioenriched 1,5-Dienes and 1,5-Enynes by a Palladium-Catalyzed 3,3'-Reductive Elimination

Abstract

This dissertation details the development, application and study of new palladium-catalyzed carbon-carbon bond forming strategies that generate synthetically useful enantioenriched small molecules. Controlled by a bidentate phosphine ligand, these transformations are thought to operate through a unique 3,3'-reductive elimination that leads to high regio- and stereoselectivity. Specifically, Chapter 1 introduces background on prior work that led to the first allyl-allyl coupling to deliver branched 1,5-dienes, and presents new computational studies on the origins of regioselectivity with mono- and bidentate ligands. Building on these studies, Chapter 2 describes the development of a diastereoselective allyl-allyl coupling of substituted allylboron reagents with allylic chloride electrophiles. To extend the scope of allyl-allyl coupling, Chapter 3 details further reaction optimization and mechanistic studies that have allowed for increasingly congested bond formations. In Chapter 4, a related allyl-propargyl coupling to give enantioenriched 1,5-enynes through stereospecific reactions and kinetic resolution is presented. These developments are accompanied by laboratory and computational data that provide a deeper understanding of reaction mechanisms and the origins of regio- and stereoselectivity.