The topological complexity of sp3-rich scaffolds imparts specific beneficial properties into organic small molecules and enables refined tuning of a molecule’s properties. However, this complexity amplifies both reactivity and selectivity challenges, making the development of versatile methods to construct and diversify these structures difficult. By combining fundamental advances in transition metal catalysis with organic synthesis, we aim to discover new reactions to solve unmet challenges in the construction of functional sp3-rich organic scaffolds. In one area, we have found that identifying “unconventional” ligand platforms for palladium catalysis leads to new reactivity and selectivity in olefin heteroannulation reactions. In another area, we have found that copper complexes can promote a range of oxidative radical addition reactions.