The Fluorination of C−H Bonds: Developments and Perspectives

This Review summarizes advances in fluorination by C(sp2)−H and C(sp3)−H activation. Transition‐metal‐catalyzed approaches championed by palladium have allowed the installation of a fluorine substituent at C(sp2) and C(sp3) sites, exploiting the reactivity of high‐oxidation‐state transition‐metal fl...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-10, Vol.58 (42), p.14824-14848
Main Authors: Szpera, Robert, Moseley, Daniel F. J., Smith, Lewis B., Sterling, Alistair J., Gouverneur, Véronique
Format: Article
Language:English
Subjects:
Control methods
Coordination compounds
C−H activation
Fluorides
Fluorination
Fluorine
Intermediates
Metal fluorides
Metals
Oxidation
Palladium
radical chemistry
radiochemistry
Reagents
Stereoselectivity
transition-metal catalysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This Review summarizes advances in fluorination by C(sp2)−H and C(sp3)−H activation. Transition‐metal‐catalyzed approaches championed by palladium have allowed the installation of a fluorine substituent at C(sp2) and C(sp3) sites, exploiting the reactivity of high‐oxidation‐state transition‐metal fluoride complexes combined with the use of directing groups (some transient) to control site and stereoselectivity. The large majority of known methods employ electrophilic fluorination reagents, but methods combining a nucleophilic fluoride source with an oxidant have appeared. External ligands have proven to be effective for C(sp3)−H fluorination directed by weakly coordinating auxiliaries, thereby enabling control over reactivity. Methods relying on the formation of radical intermediates are complementary to transition‐metal‐catalyzed processes as they allow for undirected C(sp3)−H fluorination. To date, radical C−H fluorinations mainly employ electrophilic N−F fluorination reagents but a unique MnIII‐catalyzed oxidative C−H fluorination using fluoride has been developed. Overall, the field of late‐stage nucleophilic C−H fluorination has progressed much more slowly, a state of play explaining why C−H 18F‐fluorination is still in its infancy. The direct fluorination of C−H bonds has emerged as a powerful method for accessing functional molecules such as pharmaceuticals or PET radiotracers. This Review provides an overview of the state of play of this field with an emphasis on the advantages and limitations of the main activation modes exploited to date. The discussion brings to light the importance of the fluorination reagent, and the challenges associated with nucleophilic C−H fluorination methods.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201814457