Principal Investigator/Program Director (Last, First, Middle): Rovis, Tomislav Asymmetric Synthesis of Nitrogen Heterocycles Abstract Nitrogen is ubiquitously found in biologically active molecules and pharmaceuticals, the fourth most common element after carbon, hydrogen and oxygen. Its presence impacts interactions with biological targets, pharmacokinetics and pharmacodynamics, as well as myriad physical properties. Given the increased importance of saturation in drug-like molecules, carbon-nitrogen bonds are increasingly stereogenic and thus, methods to incorporate nitrogen should likewise address doing so in stereocontrolled fashion. We have long been interested in constructing saturated nitrogen heterocycles from commonly available feedstocks to address synthetic challenges associates with the most common rings such as piperidines and pyrrolidines. With this competitive renewal, we seek support to address problems associated with acyclic nitrogen containing molecules. Herein we propose a multi-pronged approach to synthesize complex structures containing nitrogen substitution from simple precursors. We focus on using the most commonly available starting materials such as alkenes and dienes, and forge a union to a modestly activated nitrogen coupling partner. Ideal among the latter is the dioxazolone moiety, trivially assembled from carboxylic acids, hydroxylamine and a phosgene equivalent. Importantly, after C-N bond formation, the product is the amide, thereby avoiding subsequent derivatization. We further illustrate that this union can be conducted in an exceedingly complex setting. PHS 398/2590 (Rev. 09/04) Page Continuation Format Page