Carbon–Fluorine Reductive Elimination from a High–Valent Palladium Fluoride

We have observed two high-valent arylpalladiumfluoride complexes that afford carbon−fluorine bond formation upon thermolysis.Chemistry and Chemical Biolog

Palladium-Mediated Fluorination of Arylboronic Acids

Saving the best for last: Novel palladium complexes allow mild, two-step fluorination of aryl boronic acids (see scheme). The reaction is regiospecific, functional-group tolerant, has a broad substrate scope, and is ideally suited for the introduction of fluorine substituents at a late stage for aryl fluoride synthesis.Chemistry and Chemical Biolog

Silver-Mediated Fluorination of Functionalized Aryl Stannanes

We report a regiospecific silver-mediated fluorination of aryl stannanes. The presented reaction can afford complex fluoroarenes from readily available phenols in three steps. The operational simplicity and the broad substrate scope of the fluorination should render this reaction a useful tool for the synthesis of milligram to gram quantities of functionalized aryl fluorides. Silver-mediated oxidative transformations of aryl nucleophiles that proceed via bimetallic redox processes are a new avenue to develop carbon−heteroatom bond formations.Chemistry and Chemical Biolog

Carbon–Fluorine Bond Formation

We present a selection of carbon–fluorine bond formations that have been developed in the recent past. An overview of the most common fluorination reagents is followed by fluorination reactions organized by reactivity. We have distinguished between nucleophilic and electrophilic fluorinations as well as aliphatic and aromatic fluorinations. Each section is divided into more specific reaction classes and examples for syntheses of pharmaceuticals, $^{18}$F-radiolabeling, and mechanistic investigations are provided.Chemistry and Chemical Biolog

Mechanism of C−F Reductive Elimination from Palladium(IV) Fluorides

The first systematic mechanism study of C−F reductive elimination from a transition metal complex is described. C−F bond formation from three different Pd(IV) fluoride complexes was mechanistically evaluated. The experimental data suggest that reductive elimination occurs from cationic Pd(IV) fluoride complexes via a dissociative mechanism. The ancillary pyridyl-sulfonamide ligand plays a crucial role for C−F reductive elimination, likely due to a κ^3 coordination mode, in which an oxygen atom of the sulfonyl group coordinates to Pd. The pyridyl-sulfonamide can support Pd(IV) and has the appropriate geometry and electronic structure to induce reductive elimination

A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging

The unnatural isotope fluorine-18 $(^{18}F)$ is used as a positron emitter in molecular imaging. Currently, many potentially useful $^{18}F$-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of $^{18}F$ requires rapid syntheses for which $[^{18}F]$fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment. However, conventional $[^{18}F]$fluoride chemistry has been limited to nucleophilic fluorination reactions. We report the development of a palladium-based electrophilic fluorination reagent derived from fluoride and its application to the synthesis of aromatic $^{18}F$-labeled molecules via late-stage fluorination. Late-stage fluorination enables the synthesis of conventionally unavailable positron emission tomography (PET) tracers for anticipated applications in pharmaceutical development as well as preclinical and clinical PET imaging.Chemistry and Chemical Biolog

Mechanism of C−F Reductive Elimination from Palladium(IV) Fluorides

The first systematic mechanism study of C−F reductive elimination from a transition metal complex is described. C−F bond formation from three different Pd(IV) fluoride complexes was mechanistically evaluated. The experimental data suggest that reductive elimination occurs from cationic Pd(IV) fluoride complexes via a dissociative mechanism. The ancillary pyridyl-sulfonamide ligand plays a crucial role for C−F reductive elimination, likely due to a κ3 coordination mode, in which an oxygen atom of the sulfonyl group coordinates to Pd. The pyridyl-sulfonamide can support Pd(IV) and has the appropriate geometry and electronic structure to induce reductive elimination.Chemistry and Chemical Biolog

Carbon-fluorine bond formation for the synthesis of aryl fluorides

A selection of carbon-fluorine bond-forming reactions is presented with particular focus on transition-metal-mediated fluorination. A brief summary of conventional fluorination reactions is followed by a discussion of fluorination reactions mediated by palladium and silver. Investigations into the mechanism as well as the conceptual difficulty associated with transition-metal-mediated carbon-fluorine bond formation are presented. 1 Introduction 2 Nucleophilic Fluorination 3 Electrophilic Fluorination 4 Balz-Schiemann Reaction 5 Palladium-Mediated C-X Bond Formation 6 Palladium-Mediated Nucleophilic Fluorination 7 Palladium-Mediated Directed Electrophilic Fluorination 8 Palladium-Mediated Electrophilic Fluorination 9 Silver-Mediated Fluorination 10 Conclusion