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Abstract

The number and diversity of methods for installing carbon–fluorine bonds have substantially expanded over the past two decades, enabling enantioselective fluorinations, reactions with complex substrates, and the use of ever simpler reaction precursors. Fluorination chemistry was long held back by unreactive alkali fluoride salts and highly reactive electrophilic fluorine sources, such as molecular fluorine and cobalt(III) fluoride. The introduction of fluorination reagents with controlled reactivity has been a key driving force in harnessing the reactivity of fluoride, as has the strategic use of transition metals. These approaches enable predictable and functional-group-tolerant carbon–fluorine bond formation. Herein, transition-metal-catalyzed and transition-metal-mediated syntheses of aromatic, heteroaromatic, and alkyl fluorides are reviewed. In addition, methods for allylic fluorination, benzylic fluorination, and fluorination α to carbonyl groups are presented. The influence of these reactions on the synthesis of complex fluorinated molecules and the preparation of ¹⁸F-PET probes are described, and experimental procedures for illustrative examples are included.