Author Description

Accessing novel sp3-rich structures to improve physicochemical properties remains a challenge in drug discovery. By increasing sp3 character in pharmacologically relevant molecules, medicinal chemists could direct structure−activity relationship (SAR) away from the “aryl flatland” to a more desirable property space, which offers new vectors for innovative molecular design. To this end, C(sp3)−H activation provides an efficient way to access many functionalities from prevalent C−H bonds. In my PhD thesis, I focus on creating novel methodologies for sp3-rich scaffolds by transforming unactivated C(sp3)−H bonds into various C−C, C−O, C−N, and C−X bonds using palladium catalysts. The key to the success of activating elusive and challenging C(sp3)−H bonds relies upon the design and discovery of novel ligands. Based on experimental data we gained through the years, our research group developed a fundamental understanding of the ligand-palladium-substrate ternary complex at the transition state that translated into a molecular model to guide our ligand design.