Unexpected migration of benzoyl group in the synthesis of 3-benzoyl-2-phenylbenzofurans under Wittig conditions

3-Aroyl[b]benzofurans represent the structural cores of a large number of bioactive molecules in current pharmaceutical use or development. As a result, numerous approaches towards the synthesis of 3-acylbenzofurans have been disclosed in the literatura.

The Wittig reaction, is an easy procedure to the benzofuran ring system. In a previous paper Hercouet and Le Corre reported that the intramolecular condensation of o-acyloxybenzylidenetriphenylphosphoranes leads to the benzofuran in aprotic medium (toluene) or to acylated product in protic medium (t-BuOH).

We recently found that the reaction of the triphenylphosphonium salt and aroyl chlorides leads together with the expected benzofurans, also to 3-benzoyl-2-phenylbenzo[b]furans via ylide acylation under Wittig conditions. We hypothesised that the key intermediate that leads to the 3-benzoyl derivatives was the o-[(benzoyloxy)benzyl]-triphenyl-phosphoranes. It was therefore prepared starting from o-cresol, and reacted with benzoyl chloride using Et₃N in aprotic solvent i.e. toluene. In contrast with Hercouet and Le Corre findings, we obtained the 3-benzoyl derivatives, thus confirming our hypothesis. However, when the o-(benzoyloxy)benzyl)-triphenyl-phosphonium salt was reacted with 4-nitrobenzoyl chloride, we unexpectedly observed the formation of two 3-acyl isomers, thus suggesting that the regioselective benzoyl group migration occurred in some extent.

Our results are of considerable interest not only because they get insights into the reactivity of o-acyloxybenzylidenetriphenylphosphoranes, but also because they allowed to discover a versatile and general approach to functionalized 3-benzoyl-2-phenylbenzo[b]furans.