In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Tarek Sammakia of the Department of Chemistry and Biochemistry at The University of Colorado will explore the development of methods for the stereoselective formation of hindered carbon-carbon bonds, including all-carbon quaternary and tertiary centers. The general reaction to be developed proceeds by a cascade of cycloaddition and rearrangement reactions. This reaction is mechanistically novel, and as such studies are proposed to further elucidate the mechanism and to render it asymmetric using stoichiometric methods.
While some methods exist for the synthesis of quaternary carbons, they are limited in scope and this new method allows for the preparation of structural motifs that are not available by existing methods. The overall transformation is the equivalent of an oxidative cross-coupling of two enolates, thereby preparing 1,4-dicarbonyl compounds. There are currently no methods that directly accomplish this transformation in a stereoselective fashion bearing such hindered carbons and the major aim of this work is to provide a new and more efficient method for the preparation of this class of molecules. This will lead to a significant reduction in step-count for the synthesis of this structural motif, and the greater efficiency means less waste and fewer by-products. Successful development of this method will have an impact on many synthesis activities including the synthesis of pharmaceutical agents and new materials that bear this motif. In addition, this project will provide excellent training of undergraduate and graduate students, including those from groups historically underrepresented in the sciences. Finally, the incorporation of these methods into undergraduate organic chemistry laboratories will be considered as this reaction is facile and cycloadditions and sigmatropic rearrangements are not commonly encountered by undergraduates.
