Revisiting Duff reaction: New experimental insights

The formylation of aromatic substrates is an important reaction in organic chemistry. Indeed, several protocols have been published to afford aromatic aldehydes, which are important precursors in materials and medicinal chemistry. One useful, nevertheless poorly described formylation protocol is the Duff reaction, which is normally carried out in acetic or trifluoroacetic acids. In the quest for a suitable and reproducible protocol to introduce a formyl group within the 7-hydroxy-4-methylcoumarin, we have found that the reaction can be carried out in the presence of zinc (II) acetate in dimethylformamide to yield the 8-formylcoumarin, conditions that have not been previously described. Furthermore, this methodology was used to obtain 1H-indole-3-carboxaldeyde, which, to the best of our knowledge, is not a common substrate for Duff reaction, it makes us believe that Duff reaction may still have some surprises within the field of organic synthesis.