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Herein, we report that α-fluorocarboxylic acids undergo manganese-mediated oxidative 18 F-fluorodecarboxylation with [ 18 F]fluoride affording biologically relevant 18 F-difluoromethyl(ene)-containing molecules. This no-carrier added process provides a solution to a known challenge in radiochemistry and expands the radiochemical space available for positron emission tomography (PET) ligand discovery. Scalability on a fully automated radiosynthetic platform is exemplified with the production of [ 18 F]4,4-difluoropiperidine that, we demonstrate, is amenable to postlabeling functionalization including N -heteroarylation and amide as well as sulfonamide bond formation.

Protein-carbohydrate interactions are implicated in many biochemical/biological processes that are fundamental to life and to human health. Fluorinated carbohydrate analogues play an important role in the study of these interactions and find application as probes in chemical biology and as drugs/diagnostics in medicine. The availability and/or efficient synthesis of a wide variety of fluorinated carbohydrates is thus of great interest. Here, we report a detailed study on the synthesis of monosaccharides in which the hydroxy groups at their 4- and 6-positions are replaced by all possible mono- and difluorinated motifs. Minimization of protecting group use was a key aim. It was found that introducing electronegative substituents, either as protecting groups or as deoxygenation intermediates, was generally beneficial for increasing deoxyfluorination yields. A detailed structural study of this set of analogues demonstrated that dideoxygenation/fluorination at the 4,6-positions caused very little distortion both in the solid state and in aqueous solution. Unexpected trends in α/β anomeric ratios were identified. Increasing fluorine content always increased the α/β ratio, with very little difference between regio- or stereoisomers, except when 4,6-difluorinated.

Herein, we report a highly effective protocol for the cross-coupling of (hetero)aryl bromides with fluorinated alcohols using the commercially available precatalyst t BuBrettPhos Pd G3 and Cs 2 CO 3 in toluene. This Pd-catalyzed coupling features a short reaction time, excellent functional group tolerance, and compatibility with electron-rich and -poor (hetero)arenes. The method provides access to 18 F-labeled trifluoroethyl ethers by cross-coupling with [ 18 F]trifluoroethanol.

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., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The diastereoselective synthesis of fluorinated building blocks that contain chiral fluorine substituents is of interest. Here we describe optimisation efforts in the synthesis of anti -2,3-difluorobutane-1,4-diol, as well as the synthesis of the corresponding syn -diastereomer. Both targets were synthesised using an epoxide opening strategy.