This project is focused on the development of a series of practical and mechanistically defined allylic amination and etherification processes with amines, ammonia, ammonia equivalents, phenols and aliphatic alcohols, including reactions to form oxygen and nitrogen heterocycles by intramolecular allylic amination and etherification and intermolecular amination and etherification followed by ring-closing metathesis. These reactions will be explored, in part, with new phosphoramidites containing less stereochemical complexity and fewer electron-donating substituents. To uncover the origin of regio- and enantioselectivity, allyl complexes that are intermediates in the catalytic process will be isolated and structurally characterized. The mechanism of the reactions will be probed, exploring whether rearrangements of diastereomeric allyl complexes or attack of nucleophiles on the allyl intermediates is faster.
This award from the Organic and Macromolecular Chemistry Program supports the research of Professor John F. Hartwig, of the Department of Chemistry at Yale University. Professor Hartwig is developing new methods for the synthesis of molecules containing nitrogen and oxygen. Such molecules are ubiquitous in natural products and in pharmaceutical candidates, and the development of effective methods for their formation with high control of three-dimensional structure is essential. By pursuing a fundamental, molecular-level understanding of the reactions forming such molecules, Professor Hartig's research is expected to lead to important advances in the design of new and effective catalysts with high selectivity, fast rates, low catalyst loadings, and broad scope.
