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.