In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Gerald B. Hammond of the Department of Chemistry at the University of Louisville will investigate fluorine-gold activation processes that can mediate tandem sequences leading to novel metal-mediated nucleophilic addition/coupling/fluorination reactions, which, in turn, should lead to efficient synthesis of organofluoro compounds. Even though fluorine has a unique ability to modify the physico-chemical properties of a compound, its introduction on small molecules is usually cumbersome. Indeed, the syntheses of fluorinated aliphatic and cyclic systems require tedious reagents or synthetic procedures that rely on a small pool of commercial fluorine-containing building blocks. The mechanism-based approach of this research will enable the synthesis of aliphatic organofluoro compounds, such as fluoroketones and fluoroheterocycles in a medicinal chemistry-friendly manner, utilizing cationic metal species capable of metal-mediated fluorinations, oxidations or couplings, and readily available alkynes or alkenes as starting materials. Ultimately, the work proposed on fluorine-engendered cationic species will yield substantial insights on the interaction of fluorine and transition metals.
The broader impact of this project is that its well-defined modules are suitable for training a younger generation of students and postdoctoral fellows in organofluorine chemistry, a research area that is performed by a handful of scientists in the U.S., compared to other industrialized nations, despite the ever-increasing importance of fluorine in the medicinal or agrochemical fields. This project will impact the manufacturing field broadly defined because it will give ready access to fluorinated compounds in a diversified manner and with fewer synthetic steps.