Project Summary/Abstract Functionalized diaziridines are privileged scaffolds due to the multitude of reactivity profiles that can lead to the production of complex N,N-containing heterocyclic pharmacophores. Among these, diazepines and benzodiazepines stand out as one of the most pharmacologically relevant drug families. Thus, the chemical synthesis field has focused its attention on the development of novel methods for the synthesis of such highly complex heterocycles. This proposal aims to study the enantioselective rearrangement reactions of divinyldiaziridines under a series of reaction conditions for the systematic synthesis of optically pure diazepines and benzodiazepines. This proposal consists of 3 Aims. Aim 1: Enantioselective Synthesis of 1,2-, 1,3- and 1,4-Diazepines via the Stereoselective Rearrangement Reactions of Substituted Diaziridines. Aim 2: Enantioselective Rearrangement Reactions of Substituted Diaziridines for the Synthesis of Benzodiazepines. Aim 3: Diaza-Claisen Rearrangement for the Synthesis of Relevant Drug Scaffolds and Complex Heterocycles. The Moura-Letts laboratory has developed a strong research platform for the development of methods for the synthesis of heterocyclic scaffolds. This combination of skills and trained students would facilitate the successful implementation of the aims described in this proposal. The Claisen rearrangement reactions of divinyldiaziridines have never been reported. However, the knowledge acquired from diaziridine synthesis and their cycloadditions has served as a cornerstone for the design and rationalization of the proposed reactions. This work will allow efficient and systematic access to a large variety of unprecedented complex diazepines and benzodiazepines and thus help further elucidate their pharmacological profiles. The GML group is highly interested in developing organic methodologies for the synthesis and transformation of small heterocycles into more complex pharmacologically-relevant scaffolds. The success of this project would allow for the potential discovery of an unprecedented diaza-[3,3]-Claisen rearrangement and ring expansion pathways through the reaction of easily accessible vinyl and divinyldiaziridines. The impact of this project is also expanded by its ability to develop state-of-the-art organic chemistry skills in undergraduate students, high school students and returning veterans. These students have the potential to acquire a level of organic expertise that will qualify them to compete at the highest academic and industrial levels. 1