A UNIFIED APPROACH FOR THE SYNTHESIS OF 5-MEMBERED 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 (Figure 1). 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 and Lawesson's reagent to afford pyrroles, furans and thiophenes, respectively. This approach stands as a straightforward and scalable route to these commercially important scaffolds.