Fluorine in organic chemistry is an important topic across the synthetic pharmaceutical, agrochemical and materials areas because switching out hydrogen atoms selectivity for this element allows chemists to tune the reactivity of specific groups within a given molecule.
Now, chemists in Switzerland have turned to fluorine to help them make specific carbon-carbon bonds. The formation of C-C bonds is one of the most important steps in organic chemistry for the construction of complex molecules from simpler sub-units. Perhaps most important among the tools for building C-C bonds is the Friedel-Crafts reaction. It involves an attack on a carbocation-type substrate generated by a Lewis acid by the electron-rich pi-clouds of aromatic rings leading to an alkylated or acylated version of the aromatic ring.
A complete field within organometallic chemistry has emerged to support the Friedel-Crafts C-C endeavor. However, the instability of the phenyl ion means that coupling aromatic group to aromatic group using this chemistry has until now required a range of metal-mediated approaches. Jay Siegel and his colleagues at the University of Zürich hoped to simplify the schemes and avoid the need to use often expensive metal catalysts.
They have used Lewis acid activation of aryl fluorides to make biaryls intramolecularly. The Lewis acids are silicon cations generated by catalytic super acid, he told Chemistry Views. In a synthetic methods paper published in Science, Siegel and colleagues build on research published in Angewandte Chemie in which they revealed the C-F activation and work also published in Angewandte and JACS on the structure and properties of the silicon cations.
Siegel explains that this is a, “physical-organic success story of looking at a fundamental reactive intermediate and ending up with a new synthetic methodology.” He adds that, “Given that people put CF bonds into molecules to make them more inert, it is special that our method targets exactly these sites.”
Allemann, O., Duttwyler, S., Romanato, P., Baldridge, K., & Siegel, J. (2011). Proton-Catalyzed, Silane-Fueled Friedel-Crafts Coupling of Fluoroarenes Science, 332 (6029), 574-577 DOI: 10.1126/science.1202432