Synthetic Versatility of N-O Bond Rearrangements

University Of Illinois At Chicago, Chicago IL

Investigators

Abstract

With this award, the Chemical Synthesis Program is supporting the research of Professor Laura L. Anderson of the Department of Chemistry at the University of Illinois at Chicago to explore the design and application of new N-O bond rearrangements for the efficient and stereoselective synthesis of new and challenging organic molecules. The Anderson group has previously established the proof of concept for the value and versatility of these types of transformations and will advance these synthetic tools toward the efficient preparation of new potentially "privileged" structures, chiral non-racemic compounds, and key four-carbon synthons. These advances will have a broad impact on the elucidation of new pathways to important pharmaceuticals and materials. Furthermore, the compounds generated in this study will be submitted to the chemical library at the UICentre for Drug Discovery to be screened against new biological targets. The mechanistic approach to this research program will expose graduate and undergraduate student co-workers to elements of both synthetic and physical organic chemistry. The PI will continue here efforts to broaden participation, particularly by working with women and undergraduate students to encourage them to consider career paths in STEM. There is also a high school outreach component designed to introduce students to data analysis of chemical reactions. This project will expand the use of N-alkenyl nitrones and O-alkenyl oximes as key intermediates in the rapid and efficient synthesis of complex organic molecules. Specifically, the following goals will be pursued: 1) asymmetric hydrogen-bond-donor catalysis will be used to convert mixtures of N-alkenyl nitrones and allenes to enantioenriched indole-based heterocycles through a cascade process whose selectivity can be controlled through a balance of solvent effects; 2) conditions for the electrocyclization and [4+2]-cycloaddition of N-alkenyl nitrones will be optimized for the synthesis of new morpholine-based heterocycles and 3) methods for the modular and stereoselective synthesis of 1,4-iminoketones will be explored through a copper-mediated coupling and rearrangement approach. In addition, mechanistic studies will be used to elucidate the origin of the chemoselectivity of the Chan-Lam reaction for the synthesis of N-alkenyl nitrones and O-alkenyl oximes to facilitate access to a wider variety of modular substrates for rearrangement. Completion of these goals will advance synthetic chemistry by providing new tools for retrosynthetic analysis and expanding chemical space through access to new structural motifs.