PROJECT SUMMARY/ABSTRACT Many of the medicines, materials, and agrochemicals important to modern society are constructed using synthetic organic chemistry. Throughout the past 50 years, transition metal-catalyzed cross-coupling methodologies have become indispensable to the practice of organic chemistry due to their general and predictable ability to construct carbon-carbon and carbon-heteroatom bonds. C?H bonds represent an ideal latent nucleophile in this context due to their abundance as well as the atom- and step-economy of direct C?H functionalization. Aim 1 of this proposal describes how the combination of polyoxometalate catalysis and transition metal catalysis would enable the generation of alkyl radicals from strong, neutral alkyl C?H bonds that can be intercepted by transition metal catalysts to forge carbon-carbon bonds. Aim 2 of this proposal focuses on the selective photoredox-mediated C?H amination of native tyrosine residues in peptides and proteins. Such conjugated products are of high value in drug development, medical imaging, hybrid material engineering, biochemistry, and chemical biology. The ability to use light as a mild driving force coupled with the use of C?H bonds as ideal coupling partners would improve the means by which a variety of important chemical scaffolds are accessed.