The metathesis reaction has recently emerged as one of the most powerful methodologies for producing alkenes. Despite the extensive use of metathesis in organic synthesis, there are remarkably few examples of the reaction being used to form aromatic compounds. Thus, the group commenced investigations into the application of the RCM reaction to provide intermediates at the correct oxidation state to prepare fully aromatic compounds.
Initials studies focused on the synthesis of furans, and we planned to utilise the RCM reaction to form a dihydrofuran unit that is equipped with a leaving group (OR). This intermediate could subsequently undergo an acid catalysed elimination to furnish the corresponding furan.
A range of functionalised allylic alcohols were prepared, which could be transformed into unsymmetrical mixed acetals using a palladium (II) catalysed reaction with methoxyallene. Following successful synthesis of these precursors, the RCM and acid catalysed aromatisation proceeded smoothly to provide the corresponding furans. Using this methodology a range of mono- and disubstituted furans were generated. The same sequence could be applied to the synthesis of pyrroles by use of an allylic amine, providing a route to 2- and 3-substituted derivatives.
The strategy was extended to the synthesis of linked biaryl compounds using a double coupling, RCM and aromatisation protocol. This approach provides a rapid and high yielding route to polyaryl compounds.
The synthesis of deoxypukalide, a compound obtained through deoxygenation of the natural product pukalide, is currently in progress within the group. The route employs the RCM/aromatisation protocol as the key step to construct the furan unit embedded within the macrocyclic product.