Distinct Hydrogen Atom Transfer and Radical Capture Reactivity of Copper(III) OH/F Complexes Enables Site-Selective C(sp3)-H 18F-Fluorination

High-valent metal intermediates play a key role in C(sp3)-H functionalization reactions in both enzymatic catalysis and organometallic chemistry. Despite its generality, this strategy often requires a single metal complex to efficiently mediate both hydrogen atom transfer and radical capture—a combination challenging to achieve. To overcome this limitation, we propose a decoupled approach, where separate high-valent metal complexes independently perform HAT and RC. As a proof of concept, we leveraged the complementary reactivity of copper(III) hydroxide (efficient for hydrogen atom transfer) and copper(III) fluoride (efficient for radical capture) to develop a decoupled 18F-fluorination protocol. The distinct reactivity of copper(III) hydroxide and copper(III) fluoride not only enables precise control over the C-H activation process but also preserves the valuable [¹⁸F]fluoride for radical capture, preventing its consumption during HAT. With this mechanistic insight, we achieved the selective fluorination of α-ethereal, benzylic, and allylic C-H bonds, facilitating the synthesis of a series of 18F-labeled organic molecules.