Visible-light-driven electrophilic chalcogen species: integration of sustainable synthesis, green metrics, and computational discovery of antioxidants

Abstract

The emergence of green chemistry principles has driven researchers to develop more sustainable methods for organic synthesis. However, despite this emphasis on environmentally friendly transformations, the green chemistry metrics are often overlooked when assessing the true environmental impact of a reaction, making it difficult to objectively compare new methods with traditional approaches or to determine their true sustainability. With this in mind, this work presents an approach for synthesizing chalcogenylbenzo[b]furans through the visible light-driven generation of electrophilic chalcogen species and further evaluates the sustainability of the developed protocol using various traditional and emerging green chemistry metrics to effectively assess reagent utilization, waste generation and toxicity, and material recovery. The synthetic methodology utilizes the combination of diaryldichalcogenides and carbon tetrabromide to promote the oxidative cyclization of 2-alkynylanisoles, leading to the formation of both selenylbenzo[b]furans and thiobenzo[b]furans in satisfactory yields. The study demonstrates the effectiveness and versatility of the method by employing a range of substrates. Furthermore, the obtained chalcogenylbenzo[b]furans were subjected to in silico screening to evaluate their antioxidant potential through molecular docking, assessing their interaction with xanthine oxidase and NADPH oxidase enzymes, as well as predicting their ADME/T profiles. Visible-light-driven synthesis of chalcogenylbenzo[b]furans combines green metrics evaluation with in silico screening and ADME/T profiles, providing an efficient route to biologically relevant heterocycles.