Heteroaromatic compounds are widely used in the pharmaceutical industry, so flexible and regioselective approaches for forming them from commercially available starting materials are particularly important. Alkene cross-metathesis, using ruthenium-based catalysts, in principle offers just that: a method for combining two alkene fragments to give an intermediate that can undergo cyclization to give aromatic compounds. This approach, however, is limited because alkene cross-metathesis generates trans-alkenes, and these must be isomerized in a separate step to produce the cis-isomers that can be cycloaromatized.

Now, Tim Donohoe and John Bower from the University of Oxford have developed1 a tandem catalytic process for the generation of highly substituted furans by alkene cross-metathesis. This was achieved by the use of a Brønsted acid co-catalyst alongside the Grubbs–Hoveyda catalyst in the reaction of an allylic alcohol and an enone. The initially formed trans-alkene was isomerized in situ by the acid, giving the cis-alkene which could cyclize to give the disubstituted furan in one step.

The formation of trisubstituted alkenes by cross-metathesis, however, is more challenging for ruthenium catalysts and so Donohoe and Bower used a different approach to generate trisubstituted furans. A Heck reaction was used in a second step, rather than the acid catalyst, to invert the alkene geometry and to add the extra substituent. The overall approach allows functionalized furans to be made easily from simple precursors and has the potential to be used to make other complex heteroaromatic compounds without the need for additional steps.