Linked pyrroles and chalcones are ubiquitous structural motifs in biological and medicinal chemistry. Surprisingly however, β,β'-linked bispyrrolyl chalcones seem to be completely absent from the literature. Chalcones are typically straightforward to prepare by the Claisen-Schmidt condensation, but this approach fails to deliver β,β'-linked bispyrrolyl chalcones, presumably due to the acidity of the pyrrole nitrogen.
To address this knowledge gap and to make new scaffolds available for future applications in biological and medicinal chemistry, we have developed the first synthesis of β,β'-linked bispyrrolyl chalcones. The method employs the Doebner modification of the Knoevenagel condensation followed by a second Friedel-Crafts acylation. The method is high-yielding, requires no column chromatography, and delivers bispyrroles that are orthogonally substituted to allow subsequent elaboration into diverse targets.