UC Berkeley

The following dissertation discusses the development of novel methodology for the catalytic borylation of C-H bonds and includes in-depth studies on the mechanism and selectivity of these synthetic transformations. These methods include the borylation of heteroaryl C-H bonds, the selective borylation of benzylic C-H bonds, and the directed and undirected borylation of unactivated alkyl C-H bonds.

Chapter 1 contains a comprehensive review of C-H borylation methodology. This review focuses on the initial development of catalytic C-H borylation and on the state-of- the-art of methodology for the undirected and directed borylation of aryl, benzylic, and alkyl C-H bonds. Additionally, this review highlights knowledge gaps and unsolved challenges. Furthermore, this review provides the author’s opinion on future directions for research on the borylation of C-H bonds.

Chapter 2 describes the study of the iridium-catalyzed borylation of heteroaryl C- H bonds. Contained is an examination of the scope of the borylation of heterocycles containing more than one heteroatom and rules for predicting the site-selectivity of this reaction. Also included are experimental and computational studies that reveal the mechanism of this reaction and the origins of the observed regioselectivity.

Chapter 3 discusses the development of the selective borylation of the primary benzylic C-H bonds of methylarenes. Key to this development was the discovery that the combination of a novel iridium catalyst and a silylborane allows for the selective borylation of benzylic C-H bonds over aryl C-H bonds. Experimental and computational studies that investigate the origins of this selectivity are also discussed.

Chapter 4 discusses the development of the iridium-catalyzed, hydrosilyl-directed borylation of alkyl C-H bonds. This methodology allows for the diastereoselective borylation of secondary alkyl C-H bonds under relatively mild conditions.

Chapter 5 explores the effect of ligand structure on the rates of alkyl C-H borylation catalyzed by Ir-phenanthroline complexes. Experimental and computational studies reveal that in addition to the relative electron-donating ability of phenanthrolines, weak interactions involving the phenanthroline in the transition state of the turnover- limiting step for the borylation of alkyl C-H bonds can have a large impact on the relative rates of alkyl C-H borylation catalyzed by various Ir-phenanthroline complexes.