Redox-Neutral Synthesis of Sulfilimines through the S-Alkylation of Sulfenamides

Sulfilimines are a class of bioisosteres with immense potential in medicinal chemistry, characterized by the presence of a tetravalent sulfur atom bearing one nitrogen and two distinct carbon substitutes. The conventional methods for synthesizing sulfilimines, relying on metal-catalyzed oxidative thioesters, suffer from a poor atomic economy and wastage of resources. To this end, we present a metal-free and redox-neutral approach for the first selective S-alkylation of sulfenamides under basic conditions to obtain sulfilimines. Our sustainable and efficient strategy involves sulfur-selective alkylation of easily accessible sulfenamides and commercially available halogenated hydrocarbons, leading to the successful synthesis of 60 sulfimides with high yields (36–99%) in a short reaction time. This novel approach not only offers a promising alternative to traditional methods but also expands the synthetic toolbox for the preparation of sulfilimines in medicinal chemistry.