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

Abstract

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.

Metal-Free Chemoselective S-Arylation of Sulfenamides To Access Sulfilimines

“…In 2017, Zhao and co-workers disclosed a bioinspired approach to orth-sulfiliminyl phenols via the [2,3] sigmatropic rearrangement of oxyacetamides with an electrophilic sulfenlyation reagent . Recently, elegant methodologies based on sulfenamides were successfully established to provide sulfilimines. − For example, Ellman’s group reported the catalytic enantioselective sulfur alkylation of sulfenamides with diazo compounds in the presence of a chiral rhodium catalyst . Later, Kozlowski, Jia, and co-workers developed a copper-catalyzed Chan–Lam-type coupling strategy to access S -aryl sulfilimines using sulfenamides with arylboronic acids .…”

Copper-Catalyzed Aerobic S-Amination of Sulfenamides for the Synthesis of Sulfinamidines

“…Possessing excellent sulfur nucleophilicity, these compounds have recently become the subject of extensive research among chemists. For instance, Ellman achieved S-alkylation of carbenes with sulfenamides using a Rh­(II) catalyst, while Li and our group accomplished S-alkylation under metal-free conditions. Moreover, we have recently reported on S -arylation and S -esterification reactions involving sulfenamides.…”

Base-Promoted S-Arylation of Sulfenamides for the Synthesis of Sulfilimines

“…In our work, we found that a mild reaction condition using a weaker and moisture-stable base combined with suitable solvents can give the desired sulfilimines in high yields with exclusive chemoselectivity. In addition, in all of the abovementioned sulfur alkylation and arylation reaction of sulfenamides, ,, only the N -acyl sulfenamides were used or found to be suitable substrates. In this work, we demonstrated that both N -acyl sulfenamides and several N -aryl sulfenamides were compatible in the reaction conditions.…”