Asymmetric Synthesis of Chiral Sulfimides through the O-Alkylation of Enantioenriched Sulfinamides and Addition of Carbon Nucleophiles

Chiral sulfimides, the aza-analogues of sulfoxides, are valuable compounds in organic synthesis and medicinal chemistry. Herein, we report an efficient method for preparing chiral sulfimides from easily available enantioenriched sulfinamides. The key step of this method is a stereospecific oxygen-selective alkylation of enantioenriched sulfinamides, which is accomplished by using isopropyl iodide, K2CO3, and DMPU. The resulting chiral sulfinimidate esters are transformed to chiral sulfimides by the nucleophilic addition of the Grignard reagents under simple conditions. This transformation enables access to the enantioenriched diaryl or dialkyl sulfimides bearing two similar carbon substituents, which are difficult to synthesize by previous methods.

Automated summary

In this study, an efficient method for preparing chiral sulfimides from easily available enantioenriched sulfinamides was reported. The key step involves a stereospecific oxygen-selective alkylation of enantioenriched sulfinamides using isopropyl iodide, K2CO3, and DMPU. The resulting chiral sulfinimidate esters are transformed to chiral sulfimides through nucleophilic addition of Grignard reagents under simple conditions. This method allows access to enantioenriched diaryl or dialkyl sulfimides bearing two similar carbon substituents, which are difficult to synthesize using previous methods.