Synthesis of Quinoline Silyloxymethylsulfones as Intermediates to Sulfonyl Derivatives

Heterocyclic sulfones, sulfonamides, and sulfonyl fluorides constitute an important structural motif in medicinal chemistry. Methods to make six-membered heteroaromatic sulfonyl compounds, however, remain challenging, and most efforts rely on commercial sulfonyl chlorides. We report herein the reaction of sodium tert-butyldimethyl silyloxymethylsulfinate with quinoline N-oxides to selectively furnish C2-substituted sulfones. The silyloxymethylsulfinate can be deprotected to then form sulfonyl fluorides, sulfonamides, and sulfones. This transformation is scalable and has broad applicability to a wide array of quinoline and isoquinoline functionality.