Sulfur-Phenolate Exchange as a Mild, Fast, and High-Yielding Method toward the Synthesis of Sulfonamides

Abstract

Sulfonamides have many important biological applications, yet their synthesis often involves long reaction times under dry and non-ambient conditions. Here we report the synthesis of a large range of sulfonamides at room temperature using 4-nitrophenyl benzylsulfonate as a starting material. Sulfonamides were prepared from a wide range of aliphatic, linear, and cyclic amines, anilines, and N -methylanilines. The yields and reaction times observed here were comparable to or better than those reported previously, establishing sulfur-phenolate exchange as a viable alternative.

Synthesis of Large Macrocycles with Chiral Sulfur Centers via Enantiospecific SuFEx and SuPhenEx Click Reactions

“…In this, we noted the potential of enantiospecific S­(VI) exchange reactions . Such reactions, like the sulfur–fluorine exchange (SuFEx) and sulfur–phenolate exchange (Su­Phen­Ex) click reactions, have become widely popular tools in synthetic chemistry for the synthesis of both small molecules, , biologically relevant molecules, , and new functional organic materials . Importantly, these reactions are highly efficient, resulting in high yields of the desired product, and they are often performed under mild conditions.…”

“…Importantly, these reactions are highly efficient, resulting in high yields of the desired product, and they are often performed under mild conditions. Our research group has shown a keen interest in the area of sulfur­(VI) exchange reactions, specifically as a tool to introduce intrinsically chiral click chemistries. , Using the enantiospecificity observed for small-molecule SuFEx and SuPhenEx reactions of chiral sulfonimidoyl fluorides and phenolates, , our group synthesized, for example, configurationally chiral polymers using disulfonimidoyl fluorides (further: di-SFs) and diphenols (Figure ). Interestingly, in nearly all polymerization reactions byproducts were observed in low yields (typically <5%) with a distinct mass that could be directly related to the structure of the di-SFs and diphenolates used.…”