UC Irvine

Metal hydride hydrogen atom transfer (HAT) has emerged as a highly chemoselective method for the hydrofunctionalization of alkenes. This methodology has enabled practitioners to incorporate a wide range of functional groups into complex molecules. Despite the significant advances in the selectivity of the HAT event, there are still limitations. The work presented in this dissertation will bridge this gap in methodology by utilizing alcohols and amines as directing groups for iron hydride HAT to alkenes. Chapter 1 will provide an overview of metal hydride HAT processes including the general mechanism and the variety of functional groups that can be installed. Select examples of the application of metal hydride HAT in synthesis will be provided to highlight the utility of these reactions. The gaps in current methodology will then be outlined to explain the motivation of the work presented in this dissertation. Chapter 2 will discuss the development and application of an alcohol-directed iron hydride HAT for the site-selective hydrofunctionalization of hydroxypolyenes. Early studies demonstrated the importance of solvent effects to realize the directing effect of alcohols. Factors that affect selectivity and the relevant mechanistic considerations will be discussed. This work culminates in a demonstration of the utility of the method with the site-selective reaction of hydroxypolyenes for the preparation of aminoalcohols. Chapter 3 will discuss the development and application of an amine-directed iron hydride HAT for the selective hydrofunctionalization of various enamines. Critical to the success of this method is the discovery that amines stabilize iron hydrides, which has implications for the transition state of the HAT event. This work also represents the first catalytic iron hydride HAT initiated hydroaminoxylation. The directed reaction enables the site-selective hydrofunctionalization of aminopolyenes and the regioselective hydrofunctionalization of cis, trans, and tetrasubstituted alkenes. The chapter concludes with a discussion of the putative reaction mechanism, which is supported by experimentation.