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The Fluorination of C−H Bonds: Developments and Perspectives
Author(s) -
Szpera Robert,
Moseley Daniel F. J.,
Smith Lewis B.,
Sterling Alistair J.,
Gouverneur Véronique
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201814457
Subject(s) - bond , chemistry , business , finance
This Review summarizes advances in fluorination by C(sp 2 )−H and C(sp 3 )−H activation. Transition‐metal‐catalyzed approaches championed by palladium have allowed the installation of a fluorine substituent at C(sp 2 ) and C(sp 3 ) 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(sp 3 )−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(sp 3 )−H fluorination. To date, radical C−H fluorinations mainly employ electrophilic N−F fluorination reagents but a unique Mn III ‐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 18 F‐fluorination is still in its infancy.