Project Summary Research and training in organic synthesis impacts all fields of science that require the design and construction of molecular architecture. This project will advance catalytic methods, including hydroacylation and hydroamination, as attractive and powerful tools for chemical synthesis. The coupling methods proposed are modern and innovative because they rely on common functional groups (e.g., aldehydes, amines) to generate new carbon-carbon and carbon-nitrogen bonds from unsaturated partners (e.g., styrenes, dienes, cyclopropenes), with high selectivity and atom economy. Through experimental and theoretical studies, this project will yield fundamental insights into the mechanism of various transition metal catalysts, including rhodium, cobalt, and copper. Beyond catalysis and mechanistic studies, we plan to build chemical motifs of high significance to the field of drug discovery. We target privileged motifs (e.g., chiral nitrogen-containing heterocycles) and explore chemical space (e.g., tricyclic cages bearing high sp3 character). Through partnerships with experts in other fields, we address exciting challenges in fluorescent microscopy, NMR spectroscopy, and cancer immunotherapy by designing functional molecules. This project demonstrates innovation in making molecules at the interface of catalysis, medicinal chemistry, and biology.