# Distinct hydrogen atom transfer and radical capture reactivity of copper(iii) OH/F complexes enables site-selective C(sp3)–H 18F-fluorination

## TL;DR

A new method uses copper complexes to selectively fluorinate specific carbon-hydrogen bonds in organic molecules.

## Contribution

A decoupled approach using copper(III) hydroxide and fluoride enables site-selective C(sp3)–H fluorination.

## Key findings

- Copper(III) hydroxide efficiently performs hydrogen atom transfer.
- Copper(III) fluoride effectively captures radicals for fluorination.
- The method enables selective fluorination of α-ethereal, benzylic, and allylic C–H bonds.

## Abstract

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 hydrogen atom transfer (HAT) and radical capture (RC). As a proof of concept, we leveraged the complementary reactivity of copper(iii) hydroxide (efficient for HAT) and copper(iii) fluoride (efficient for RC) 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.

A decoupled HAT and radical capture strategy using formal copper(iii) complexes enables selective C–H 18F-fluorination. The distinct selectivity arises from asynchronicity PCET, contrasting the conventional C–H activation selectivity based on BDFE.