Merging Electrosynthesis and Biocatalysis to Access Sulfur-Based Chiral α-Fluorinated Carboxylic Acids

Abstract

We describe a sustainable process to synthesize chiral sulfur-based organofluorine compounds by integrating electrosynthesis and biocatalysis within a single vessel while using water as a solvent. In this context, differently substituted 2-fluoro-3-mercaptopropionic acids have been synthesized in good isolated yields using thiophenols and fluorine-containing α,β-unsaturated alkenes. In addition, molecular docking and control experiments were carried out that suggest the formation of radical species during the electrolysis and participation of the lipase active site during the biocatalysis. The scalability and applicability of the developed protocol have been illustrated through the synthesis of a key intermediate of the MMP-3 inhibitor and by performing a gram-scale reaction. Further, the compatibility of the lipase enzyme with electricity highlights the promising potential of enzymatic electrosynthesis in advancing environmentally friendly organic transformations.