The Doyle lab conducts research at the interface of organic, organometallic, physical organic, and computational chemistry. Our goal is to address unsolved problems in organic synthesis through the development of catalysts, catalytic reactions, and synthetic methods. This lecture will describe some of our recent reaction discovery efforts in the area of Ni-catalyzed cross coupling, Ni/photoredox catalysis and photoredox catalysis aimed at the conversion of abundant feedstock chemicals to value-added products in a selective manner. We apply mechanistic and computer-assisted techniques to the analysis of these reactions in order to uncover general principles that can guide the design of improved ligands, catalysts and the discovery of new reactions. These studies have included the development of machine learning tools for reaction optimization, prediction and mechanistic inference.