A unified approach for the synthesis of 5-membered heteroaromatics by combining decatungstate photocatalysis and Paal-Knorr reaction in flow

Heteroaromatic compounds are highly sought after in pharmaceuticals, agrochemicals, and materials science, making the rapid synthesis of these molecules crucial. A key approach to accessing these valuable motifs is the Paal-Knorr method, particularly for synthesizing five-membered heterocyclic compounds such as furans, thiophenes, pyrroles. This method relies on the availability of 1,4-diketones. As a result, considerable efforts have been made to develop efficient strategies for preparing such compounds[1,2]. One particularly convenient approach is the tetrabutylammonium decatungstate (TBADT)-photocatalyzed hydrogen atom transfer (HAT) acylation of electrophilic olefins, which starts from readily available starting materials like aldehydes and α,β-unsaturated carbonyl compounds[3]. In this study, we present a unified strategy for a streamlined two-step synthesis of heteroaromatics, combining decatungstate photocatalysis and the Paal-Knorr reaction under flow conditions (Figure 1). The first step is a photocatalytic one that involves the reaction between an aldehyde and a vinyl ketone to form a 1,4-diketone via TBADT photocatalyzed HAT reaction. The second step is a cyclization one using amines, Brønsted acids, Lawesson's reagent to yield pyrroles, furans, thiophenes, respectively. This approach stands as a straightforward and scalable route to these commercially important scaffolds.