Clicking Pyrroles Into Place

The synthetic tools known as click reactions, which assemble molecules with high efficiency, selectivity, and yield, help chemists construct compounds. In addition to their application in organic synthesis, they’ve been used for medicinal chemistry, surface science, polymer chemistry, and bioconjugation applications. Now, chemists in China are introducing a new click reaction to the toolbox (Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201302604). A team led by Aiwen Lei of Wuhan University found that Ag₂CO₃ can catalyze cycloaddition of terminal alkynes and isocyanides to generate pyrroles (shown). Pyrroles are common structural motifs in natural products, biologically active alkaloids, pharmaceuticals, and agrochemicals. The reaction works best in N-methyl-2-pyrrolidone at 80 °C and can generate a variety of substituted structures. Interestingly, Ag₂CO₃ proved to be a key component to the reaction, whereas other silver salts, such as Ag₂O and AgNO₃, were ineffective. “From a synthetic point of view, this protocol represents an extremely simple, efficient, and atom-economic way to construct substituted pyrroles in good yields with high selectivity,” the researchers note.