Epimerization of Tertiary Carbon Centers via Reversible Radical Cleavage of Unactivated C(sp3)–H Bonds

Reversible cleavage of C­(sp3)–H bonds can enable racemization or epimerization, offering a valuable tool to edit the stereochemistry of organic compounds. While epimerization reactions operating via cleavage of acidic C­(sp3)–H bonds, such as the Cα–H of carbonyl compounds, have been widely used in organic synthesis and enzyme-catalyzed biosynthesis, epimerization of tertiary carbons bearing a nonacidic C­(sp3)–H bond is much more challenging with few practical methods available. Herein, we report the first synthetically useful protocol for the epimerization of tertiary carbons via reversible radical cleavage of unactivated C­(sp3)–H bonds with hypervalent iodine reagent benziodoxole azide and H2O under mild conditions. These reactions exhibit excellent reactivity and selectivity for unactivated 3° C–H bonds of various cycloalkanes and offer a powerful strategy for editing the stereochemical configurations of carbon scaffolds intractable to conventional methods. Mechanistic study suggests that the unique ability of N3• to serve as a catalytic H atom shuttle is critical to reversibly break and reform 3° C–H bonds with high efficiency and selectivity.