Abstract

Sulfur-fluoride exchange (SuFEx) chemistry is emerging as a promising synthetic tool in chemical biology, material science, and synthetic chemistry. In synthesis, sulfur (VI) fluorides show unique promise as synthons in organic chemistry due to their stability versus other sulfur (VI) halogen analogues. The key to adopting SuFEx chemistry is the development of efficient modes to synthesize and react to sulfur (VI) fluorides. Research initiatives employing Lewis acids, and transition-metal chemistry toward synthesizing sulfonyl fluorides will be described. New SuFEx methods that react a broad set of S(VI) fluorides with carbon, oxygen, and nitrogen-based nucleophiles towards structurally diverse S(VI) compounds will also be presented. Our study introduces a novel SuFEx reaction that synthesizes nitrogen-based sulfonylated compounds from a variety of S(VI) fluorides, mediated via a Lewis acidic calcium salt. This reaction, conducted under a unified set of reaction conditions, allows for the coupling of sulfonyl fluorides, fluorosulfates, and sulfamoyl fluorides with various amines. The result is the synthesis of a wide array of aryl and alkyl sulfonamides, sulfamides, and sulfamates in good to excellent yield. We will also discuss computational and NMR kinetic studies that aim to elucidate the mechanism of Ca-activation, as well as the lessons learned from these mechanistic studies that have led to new catalytic SuFEx reactions that work across an array of Lewis acids.