Copper-Mediated Radical Fluorine-Atom Transfer to Sulfonyl Radical: A Dramatic 4-Methoxypyridine 1-Oxide Ligand Effect

Although the transition metal-catalyzed radical fluorine atom transfer (FAT) strategy has emerged as a powerful tool for the construction of C-F bonds, to our knowledge, this approach has rarely been applied to the formation of S-F bonds. Here, we report that 4-methoxypyridine 1-oxide can serve as an inexpensive and simple yet effective ligand and thus promote the transformation of the copper-mediated challengeable radical FAT to sulfonyl radicals, paving the way for the assembly of an FSO2 group. Based on this concept, three Cu(I)-catalyzed protocols involving site-selective intra- and intermolecular fluorosulfonylation of inert C(sp(3))-H bonds and 1,2-aminofluorosulfonylation of inactivated alkenes have been developed, enabling the preparation of C(sp(3))-rich aliphatic sulfonyl fluorides that cannot be easily synthesized by known methods. These practical and operationally simple methods result in high functional group tolerance under mild conditions and can be applied to the modification of bioactive derivatives and preparation of highly valued molecules. Detailed mechanistic studies indicate the unique role of the 4-methoxypyridine 1-oxide ligand in facilitating the formation of such rare radical FATs via an outer-sphere pathway.