FWF - Alpha-Sulfurylation - Chemo- and Stereoselective Alpha-Sulfurylation of Amides

The late-stage functionalization of small molecules aiming for the formation of bioactive compounds has become an increasingly valuable tool in modern drug discovery. Despite the high abundance of the amide motif in pharmaceuticals, the modification of peptide bonds in the presence of other chemically related moieties is rather challenging, limiting the scope of chemical reagents. For this purpose, a general chemo- and stereoselective α-sulfurylation of amides is proposed, which allows the step-economical formation of a central subclass of small molecules with expected bioactive potency under essentially neutral conditions. Based on an intramolecular rearrangement as key transformation with the possibility for the installation of different sulfur-substituents, this strategy will not only overcome the limitations of other methods, but also enlarges the diversity of modifications by another important factor.