PROJECT SUMMARY/ABSTRACT The overall goals of this research program are to develop analyses, tools, and methods to achieve new, more effective catalysts and reactions. New synthetic methods greatly increase access to untapped chemical space, leading to materials and pharmaceuticals that benefit society. To achieve these goal, investigations will focus on obtaining an improved understanding of reactivity and selectivity. The fundamental hallmark of this program is the ability to access new reaction patterns to construct important organic structures in an efficient and rational manner. Reaction models and mechanistic understanding gives us the tools to solve problems and posit hypotheses. High throughput microscale experimentation permits rational hypotheses to be interrogated broadly and to develop new models to understand reaction space. One set of goals will be state-of-the-art computational and machine learning methods combined with new high throughput experimentation methods and large datasets to understand stereoselectivity, chemoselectivity, and reactivity at the molecular level with the aim of designing new, more effective catalysts and reactions.. The control of selectivity and reactivity are essential features of efficient synthesis, yet our molecular level understanding of how fundamental interactions perturb these aspects is only rudimentary. Another set of goals will be oxidative coupling of fragments via C-C and C-O bond formation by means of C– H activation. The development of new oxidative coupling chemistry is a particular focus due to increases in efficiency from lower step counts and smaller waste streams. The challenge in this area is selectivity in any given transformation due the numerous C–H bonds present in a typical organic molecule. Use of biomimetic processes leads to bioactive natural products and natural product-like cores, desirable entities in medicinal chemistry. The focus will be on transformations that are currently inaccessible include cross selective couplings, coupling at unactivated positions, and couplings with substrates resistant to direct oxidation. New strategies that will be implemented include the use of templating groups and alternate protocols to generate oxidized equivalents. Catalyst libraries will be deployed in a high-throughput microscale format to discover new reactivity. Invaluable training, largely absent outside of industrial settings, will be afforded to graduate students and other coworkers.