Sulfur fluoride exchange with carbon pronucleophiles

Abstract

Aryl alkyl sulfones are an important class of compounds in drug discovery; thus, new methods toward their synthesis are desirable. A general sulfur fluoride exchange (SuFEx) method to couple aryl sulfonyl fluorides with alkyl carbon pronucleophiles to make aryl alkyl sulfones is described. The reaction was applied to a diverse set of pronucleophiles, including esters, amides, heteroarenes, nitriles, sulfones, sulfoxides, and sulfonamides, at room temperature under mild conditions. We highlight the application of this transformation in parallel medicinal chemistry for the high-throughput generation of a broad array of aryl alkyl sulfones. Lastly, we apply this method to the late-state SuFEx derivatization of a complex sulfonyl fluoride template.