Project Summary The goal of our proposed research program is the design of new catalytic methodology for the synthesis of complex organic building blocks via site-selective activation of carbon-hydrogen bonds in simple organic molecules. Our approach makes use of a class of dipyridylarylmethanes as supporting ligands in iridium-catalyzed sp3 C-H borylation catalysis. This family of ligands was recently identified in our laboratory and is designed to borrow features of previous diimine and pentamethylcyclopentadienyl ligands for the same transformation while offering the advantage of modular synthetic routes for their preparation. Our initial studies on this ligand class identified one of the best catalysts for sp3 C-H borylation yet known, which has led us to design a research program that takes advantage of the improved functional group tolerance of this system to expand the scope of suitable substrates. Our proposed work will address challenges presented by the need for selectivity in sp3 C-H borylation, and in so doing will provide access to functionalized alkylboronic ester products with functional groups that were previously inaccessible through C-H activation. Further applications to the synthesis of linker molecules and biologically relevant cyclic boronate esters are proposed. We will also explore applications of dipyridylarylmethane ligands to C-H silylation catalysis, a class of chemical reactions that is substantially underdeveloped by comparison to C-H borylation. In total this program provides enabling technologies in the form of chemical methodology for the synthesis of complex building blocks from simple precursors. These methods will empower synthetic chemists in the synthesis of drug candidates and biological probes by providing tools to address the necessary complexity of molecules that interface with biological systems.