Lipase-Catalyzed Cyclization of β-Ketothioamides with β-Nitrostyrene for the Synthesis of Tetrasubstituted Dihydrothiophenes.

Tetrasubstituted dihydrothiophenes represent a class of heterocyclic compounds with significant potential in various fields, particularly in medicinal chemistry and materials science. In this work, we have developed an eco-friendly and efficient method for synthesizing such compounds, using porcine pancreatic lipase (PPL) as a biocatalyst to promote the cyclization reaction between β-ketothioamides and β-nitrostyrenes. Through this approach, sixteen tetrasubstituted dihydrothiophenes were successfully synthesized, and all of them achieved high yields, ranging from 80% to 96%. This research not only expands the application scope of lipase in organic synthesis, demonstrating its versatility beyond traditional hydrolytic reactions, but also provides a new environmentally friendly pathway for the production of tetrasubstituted dihydrothiophenes, which is of great significance for advancing related fields of chemical synthesis.