TITLE New Methods for the Synthesis and Study of Bioactive Nitrogen-Containing Molecules PROJECT SUMMARY/ABSTRACT The ubiquitous presence of nitrogen atom in small-molecule probes and drugs highlights the significance of nitrogen-containing molecules in biomedical research and drug discovery. Rapid and efficient synthesis of structurally diverse nitrogen-containing skeletons is of the utmost importance, as is the ability to understand their biology, pharmacology and potential as chemical probes and drug candidates. Thus, developing new methods for the synthesis and study of novel nitrogen-containing molecules is significant and necessary to advance our understanding of human disease and the discovery of new therapies. The broad availability of drugs is directly dependent on the existence of cost-efficient methods that can reliably build such novel molecular structures and uncover their biological activity and therapeutic promise. The long-term goal of our research is to establish a chemical platform that expedite the synthesis and development of novel small- molecule probes and tools toward advancing the understanding and treatment of human disease. The objective of this project is to develop new catalytic selective alkene aminofunctionalization methods that enable rapid and efficient access to structurally complex and richly functionalized novel nitrogen-containing molecules from readily available alkene as starting materials. Toward this, this application will exploit the electrophilic amination strategy based on the unique and diverse reactivity of heteroatom-nitrogen bonds––readily available yet traditionally underutilized nitrogen precursors––to design new C–N bond formation reactions that are different but complementary to existing methods. Successful implementation of these studies will greatly facilitate the synthesis and study of a wide range of nitrogen-containing molecules that are difficult or impossible to access with current technologies. Lessons learned in reaction engineering for efficacy and selectivity will be applicable to the invention and development of useful chemical processes, beyond amination chemistry. Overall, these new abilities are highly valuable and important in organic synthesis, medicinal chemistry, biomedical research, and drug discovery, by greatly contributing to the expansion of novel chemical space and diversity of N-containing molecules as well as the discovery of new lead compounds and small- molecule probes.