New Amination Methods and Strategies for Chemical Synthesis

Title: New Amination Methods and Strategies for Chemical Synthesis 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. 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. 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. Our research program aims to establish a chemical platform that expedite the synthesis and development of novel nitrogen-containing molecule as new probes and leads toward advancing the understanding and treatment of human disease. Toward this, we will develop new catalytic selective amination methods and aminofunctionalization cascades that can streamline the creation of structurally complex and richly functionalized novel nitrogen-containing molecules from readily available starting materials, such as alkenes, dienes, cyclopropanes, and functional molecules. We will focus on 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.