A Broad‐Spectrum, Catalytic Amidation of Sulfonyl Fluorides and Fluorosulfates

A broad-spectrum, catalytic method has been developed for the synthesis of sulfonamides and sulfamates. With the activation by the combination of a catalytic amount of 1-hydroxybenzotriazole (HOBt) and silicon additives, amidations of sulfonyl fluorides and fluorosulfates proceeded smoothly and excellent yields were generally obtained (87%-99%). Noticeably, this protocol is particularly efficient for sterically hindered substrates. Catalyst loading is generally low and only 0.02 mol% of catalyst is required for the multidecagram-scale synthesis of an amantadine derivative. In addition, the potential of this method in medicinal chemistry has been demonstrated by the synthesis of the marketed drug Fedratinib via a key intermediate sulfonyl fluoride 13 . Since a large number of amines are commercially available, this route provides a facile entry to access Fedratinib analogues for biological screening.