Catalytic Enantioselective Synthesis of Pyridyl Sulfoximines

With unique chemical and biological activity, sulfoximines have attracted enormous attention in the past decades, whereas limited reports exist for their synthesis via asymmetric catalysis. We report the synthesis of chiral sulfoximines through the desymmetrizing N-oxidation of pyridyl sulfoximines using an aspartic acid-containing peptide catalyst. Various mono- and bis-pyridyl sulfoximine oxides are obtained with up to 99:1 er. The directing group introduced on the substrate highly enhances the enantioinduction and could be easily removed to give the free N-H sulfoximines. Additionally, peptides with methyl ester and the methyl amide C-terminal protecting group give the opposite enantiomers of the product. A binding model is proposed to explain this phenomenon.

Automated summary

This study reports the synthesis of chiral sulfoximines through desymmetrizing N-oxidation, with the introduction of a directing group to enhance enantioinduction. Peptides with different C-terminal protecting groups were found to give opposite enantiomers of the product, suggesting a potential binding model to explain this phenomenon.