RUI: Accessing Asymmetric Carbon Atoms by Samarium(II)-Water Allylic Benzoate Reductions

Western Washington University, Bellingham WA

Investigators

Abstract

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Gregory O'Neil. Professor O'Neil is a faculty member in the Department of Chemistry at Western Washington University. He is developing new reactions that allow access to one mirror image of a carbon atom over another. Many important molecules (e.g. medicinal natural products) and materials exist as a single mirror image with their activity directly related to that specific mirror image. Hence, methods to control which mirror image of a carbon atom is formed are essential for the construction of molecules that have the correct biological activity. Accordingly, Professor O-Neil and his group are harnessing the unique chemistry of samarium(II)-water complexes to achieve this goal. The reactions were chosen because samarium(II) is readily available, and the ability to perform the reactions in water obviates special handling or equipment requirements. Thus, the chemistry is readily adoptable by others, well suited for research at a primarily undergraduate institution, and compatible with incorporation into an Introductory Organic Laboratory course. In addition, student participants are learning a variety of research methods including organic synthesis and advanced analytical techniques. They become integrated into the scientific community through attendance at professional meetings and dissemination of results using both standard (e.g. scientific papers and posters) and less traditional outlets (e.g. podcasts, videos, magazine articles). Professor O'Neil's group is well positioned to provide this experience for students underrepresented in science. The ability to generate stereogenic carbons with absolute stereocontrol is a requirement for many compelling synthetic targets. The goal of this project is to investigate the use of SmI2(H2O)n for allylic benzoate reductions. The combination leads a highly versatile and accessible method for the synthesis of asymmetric carbon atoms. The reactions are potentially powerful because they provide a solution to an existing challenge that does not require the use of specialized reagents, is easy to execute, and has a broad substrate scope and functional group tolerance. The methods are capable of generating asymmetric carbon atoms that can be difficult to construct with other methods, they consistently and predictably lead to stereoselectivities that are controllable by starting substrate structure and independent of the groups attached to the newly formed stereogenic carbon, they are straightforward to conduct using readily available reagents/substrates and with water (thereby allowing for functional groups (e.g. -OH) often not tolerated), and they are controlled by a stereo-differentiating group that can either be incorporated into the final target or be recycled as a chiral auxiliary. Broader impacts and educational components of the project include the development and implementation of a 4-day undergraduate laboratory experiment that teaches concepts related to stereochemistry and the methods needed for isomer ratio determination. This work will also create a repository with optical activity data for various chiral aldehydes available for use by other groups. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.