A unified approach for the synthesis of heteroaromatics by combining decatungstate photocatalysis and Paal-Knorr reaction in flow

Heteroaromatics are coveted scaffolds in pharmaceuticals, agrochemicals and material science: their expedite synthesis is therefore of prime importance. A privileged access point to these precious motifs is the Paal-Knorr approach, especially for the synthesis of five- and six-membered heterocyclic compounds including furans, thiophenes, pyrroles and pyridazines. This approach demands for the wide availability of 1,4 diketones. Consequently, substantial efforts have been directed towards to developing efficient methodologies for preparation of such compounds. A very convenient method consists in the decatungstate (DT) photocatalyzed hydrogen atom transfer (HAT) acylation of electrophilic olefins, which starts from readily available raw materials such as aldehyde and α,β-unsaturated carbonyl compounds. In this study, we present a unified strategy for a streamlined two-step synthesis of heteroaromatics, combining decatungstate photocatalysis and the Paal-Knorr reaction in flow conditions. The first photocatalytic step involves the reaction between an aldehyde and a vinyl ketone to obtain 1,4-diketone via DT-photocatalyzed HAT, which occurs in 5 minutes. Without isolating the intermediate, the diketone enters a second reactor and is reacted with amines, Bronsted acid, Lawesson's reagent, and hydrazine to afford pyrroles, furans, thiophenes and pyridazines, respectively.