Transition metal assisted fluorinations

University Of Louisville Research Foundation Inc, Louisville KY

Investigators

Abstract

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.