Transition metal catalyzed transformations using fluorinating reagents have been developed extensively for the preparation of synthetically valuable fluorinated targets. This is a topic of critical importance to facilitate laboratory and industrial chemical synthesis of fluorine containing pharmaceuticals and agrochemicals. Translation to (18)F-radiochemistry is also emerging as a vibrant research field because functional imaging based on Positron Emission Tomography (PET) is increasingly used for both diagnosis and pharmaceutical development. This review summarizes how fluoride sources have been used for the catalytic nucleophilic fluorination of various substrates inclusive of aryl triflates, alkynes, allylic halides, allylic esters, allylic trichloroacetimidates, benzylic halides, tertiary alkyl halides and epoxides. Until recently, progress in this field of research has been slow in part because of the challenges associated with the dual reactivity profile of fluoride (nucleophile or base). Despite these difficulties, some remarkable breakthroughs have emerged. This includes the demonstration that Pd(0)/Pd(II)-catalyzed nucleophilic fluorination to access fluoroarenes from aryl triflates is feasible, and the first examples of Tsuji-Trost allylic alkylation with fluoride using either allyl chlorides or allyl precursors bearing O-leaving groups. More recently, allylic fluorides were also made accessible under iridium catalysis. Another reaction, which has been greatly improved based on careful mechanistic work, is the catalytic asymmetric hydrofluorination of meso epoxides. Notably, each individual transition metal catalyzed nucleophilic fluorination reported to date employs a different F-reagent, an observation indicating that this area of research will benefit from a larger pool of nucleophilic fluoride sources. In this context, a striking recent development is the successful design, synthesis and applications of a fluoride-derived electrophilic late stage fluorination reagent. This new class of reagents could greatly benefit preclinical and clinical PET imaging.

Mild and rapid: The title reaction is presented and its applicability to 18F radiolabeling is demonstrated (see scheme; TBAF=tetra‐n‐butylammonium fluoride, THF=tetrahydrofuran, dba=dibenzylideneacetone). The use of p‐nitrobenzoate as the leaving group is significant to the success of this catalytic organometallic fluorination process. A range of allylic fluorides were synthesized by this method.

This paper describes a new catalytic method for the regio-and stereocontrolled fluorination of allylic carbonates. This transformation uses TBAF$4tBuOH as the fluoride source and [Ir(COD)Cl] 2 as the catalyst; the most commonly used [Ir(COD)Cl] 2 /phosphoramidite system is ineffective. Synthetically, this reaction is characterized by a high degree of structural conservation in going from substrates to the products. The fluorination of (E)-allylic carbonates leading to linear (E)-allylic fluorides (l : b > 20 : 1, E : Z > 20 : 1) is unprecedented and a unique feature of fluoride as the nucleophile. The first examples of transition metal catalyzed fluorination affording (Z)-allyl fluorides (Z : E ratio >20 : 1) are disclosed along with the successful fluorination of branched, linear (E)-and (Z)-allyl carbonates with [ 18 F] fluoride in the presence of [Ir(COD)Cl] 2 . 18 O-Labeling of the reactant reveals internal return during the allylic ionization step, and pathways for effective intra-and intermolecular isotope exchange.

Allyl fluorides are reactive toward Pt-catalyzed alkylation with malonate and likewise toward N-and Onucleophiles under mild conditions. The reactivity of fluoride as a leaving group equals or exceeds that of the esters and carbonates commonly employed in allylic alkylation. The order of leaving-group ability with Pt catalysts was found to be F ≥ OCO 2 Me ≫ OBz ≥ OAc. This discouraged the application of platinum catalysts for the reverse reaction, fluorination of allylic substrates. Fluoride displacement involves predominant or complete retention of configuration in all the observed cases, and this was confirmed as a general feature of Pt catalysis, the stereochemical integrity being as high or higher as in Pd catalysis for the examples chosen.

Schnell und mild: Die Titelreaktion, die eine Fülle von Allylfluoriden zugänglich macht, beruht auf dem Einsatz der p‐Nitrobenzoat‐Abgangsgruppe (siehe Schema; TBAF=Tetra‐n‐butylammoniumfluorid, THF=Tetrahydrofuran, dba=Dibenzylidenaceton). Das katalytische metallorganische Fluorierungsverfahren eignet sich für radioaktive Markierungen mit 18F.