New method for aromatic coupling

28 April 2011

Chemists in Switzerland have developed a way to couple aromatic rings through the Friedel-Crafts mechanism - something many people would have believed impossible. Furthermore, the method involves activating the highly stable bond between an aromatic carbon and a fluorine. So far the method only works for aromatic sites in the same molecule, but the team believes that the underlying concept could allow for couplings between discrete molecules.

The Friedel-Crafts reaction enables alkyl or acyl groups to be attached to an aromatic ring via the generation of a carbocation that attacks the ring's electron-rich pi clouds. Coupling two aromatic rings in this way has been problematic because of the instability of the phenyl cation. Instead, aromatic coupling - a hugely important reaction in the fine chemical and pharmaceutical industries - is usually carried out via palladium catalysts.

Aromatic rings can be coupled with the help of a silyl cation

Now, Jay Siegel's team at the University of Zurich has shown that an aryl halide can be coaxed to participate as an electophile in Friedel-Crafts reactions. The precursor molecule for the reaction is a polyaromatic containing a strong C-F bond. However, the bond between silicon and fluorine is even stronger. The researchers showed that when the C-F bond is exposed to a silyl cation - R3Si+ - the fluorine hops off the ring to join with the silicon. This would leave an aryl cation, were it not captured by its neighbouring ring, thus coupling the two rings. The proton that is released is then reacts with a silane to regenerate the silyl cation and repeat the cycle.

Siegel says that the technique could be used to make finely tuned fragments of graphene - sheets of carbon one atom thick. Large numbers of fluorinated polyaromatic precursor molecules could be bolted together by conventional methods, then the new method used to knit-up the 'loose ends'. 'If you bring many molecules together you end up with effectively a tattered sail, says Siegel. 'We can knit this together to make a single contiguous sheet of very specific geometry.' Fluorine is useful in this context, rather than the other halogens, because it is much smaller and so more suited to a sterically congested environment where fine control over molecular geometries is being sought.

The team is now looking into the possibility of coupling aromatic sites from separate molecules. To carry out this reaction the various intermediate species need to survive long enough for the relevant collisions to occur. 'We have some ideas of how we might tackle this,' says Siegel.

Scott Denmark at the University of Illinois in the US, is impressed and describes the approach as 'ingenious', adding that 'the accomplishment is particularly remarkable because it engages the least reactive of all the aryl halides, namely aryl fluorides. This new transformation allows ready access to important polyarene structures and opens vistas for exploration of novel chemical reactivity.'

Simon Hadlington


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