UC Berkeley

The following dissertation discussed the development of new catalytic systems for the silylation and borylation of C–H bonds. These reactions involve iridium complexes that catalyze the cleavage of a C–H bond in either aryl of alkyl substrates and the subsequent formation of C–B or C–Si bond with high chemo- and regioselectivity. The development of a new catalytic system has increased the reliability of the C–H borylation in both large- and small-scale reactions. The development of a new catalytic system has expanded the scope of substrates that can undergo C–H silylation.

Chapter 1 is a comprehensive review of the applications C–H silylation and C–H borylation reactions in the synthesis and functionalization of complex molecules. Advances in both undirected and directed methods for the transition metal-catalyzed silylation and borylation of C–H bonds have led to their widespread adoption in the early-, mid-, and late-stage synthesis of complex molecules. This chapter outlines the state of the art of the transition-metal catalyzed silylation and borylation of C–H bonds and identifies reaction types within these areas that are prospects for future progress.

Chapter 2 describes the development of an iridium-catalyzed, stereoselective conversion of secondary alcohols or ketones to anti-1,3-diols by the silylation of secondary C–H bonds to oxygen and oxidation of the resulting oxasilolane. The silylation of secondary C–H bonds in secondary silyl ethers derived from alcohols or ketones is enabled by a catalyst formed from a simple bisamidine ligand. The silylation occurs with high selectivity at a secondary C–H bond to oxygen over distal primary or proximal secondary C–H bonds. Initial mechanistic investigations suggest the source of the newly achieved reactivity is a long catalyst lifetime resulting from the high binding constant of the strongly electron-donating bisamidine ligand.

Chapter 3 describes the development of a new, single-component iridium precatalyst for the borylation of aryl C–H bonds. The new precatalyst is air-stable and catalyzes the borylation of C–H bonds at comparable rates to the commonly used two-component system, which employs an air-sensitive precatalyst. The air-stable precatalyst shares the capabilities of the two-component system with respect to regioselectivity and substrate scope of C–H borylation. The air-stability of the precatalyst improves the batch-to-batch reproducibility of the yield of the borylation of C–H bonds and is being used for the borylation of C–H bonds on nanomole-scale at AbbVie.