A General Strategy for C(sp3)–H Functionalization with Nucleophiles Using Methyl Radical as a Hydrogen Atom Abstractor

We have developed a photocatalytic method that employs widely available, low-cost nucleophiles and a readily accessible HAT precursor for C(sp³)–H fluorination, chlorination, etherification, thioetherification, azidation, and carbon–carbon bond formation. Mechanistic studies are consistent with methyl radical-mediated HAT and linear free-energy relationships suggest that radical oxidation influences site-selectivity. Furthermore, this approach was highly effective for the construction of multi-halogenated scaffolds and the late-stage functionalization of several bioactive molecules and pharmaceuticals with tunable regioselectivity.