In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Robert J. Hinkle of the College of William & Mary will explore the stereochemical preferences for attack of highly-reactive nucleophiles on cyclic oxocarbenium ions. Although formation of C-glycosides via oxocarbenium ions has been utilized in a number of total syntheses, the factors governing facial selectivity are not clear and significant erosion of selectivity occurs with highly-reactive enol ether and ketene silyl acetal nucleophiles. Studies on electronically biased, fully-substituted oxocarbenium carbon atoms will be undertaken to determine if the reactions are occurring via SN1-like, or SN2-like mechanisms. The broader impacts primarily involve training students while broadening participation through the inclusion of numerous undergraduate and Master's researchers on the project. The activities herein will continue to foster a strong, inclusive, predominantly undergraduate program at the College of William & Mary.
Establishing the factors which govern facial selectivity in the approach of nucleophiles on cyclic oxocarbenium ions could lead to greater, and more predictable, stereocontrol in the synthesis of valuable C-glycosides. These ring structures are common elements in a vast number of compounds possessing anti-cancer, antibiotic and other biological activities. The skills developed in this research will be applicable to a wide variety of chemical endeavors such as those relating to the pharmaceutical and agricultural industries as well as research to improve catalysts and develop biological probes; all of these activities require the controlled syntheses of organic molecules. Finally, this project will provide excellent mechanistic and synthetic training for undergraduate and Master's students, including those from groups historically underrepresented in the physical sciences.
