The future of synthetic organic chemistry depends on the development of low-cost, robust, environmentally friendly transformations. Our laboratory seeks to develop new reactions that enable the efficient synthesis of biologically relevant small molecules. These reaction manifolds provide novel modes of bond formation in an environmentally sustainable fashion. By examining known mechanistic data, we identify gaps in understanding that can be exploited to create entirely new reaction pathways. Further mechanistic refinement in our laboratory leads to a better understanding of these catalytic processes at a level of conceptual depth that permit the design of new reactions in a rational and systematic fashion. The seminar will describe our recent mechanistic insights and their application to expand cross-coupling reactions to Csp3 centers.