F-Difluoromethyl(ene) Motifs via Oxidative Fluorodecarboxylation with [F]Fluoride.

Herein, we report that α-fluorocarboxylic acids undergo manganese-mediated oxidative F-fluorodecarboxylation with [F]fluoride affording biologically relevant 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 [F]4,4-difluoropiperidine that, we demonstrate, is amenable to postlabeling functionalization including -heteroarylation and amide as well as sulfonamide bond formation.

Synthesis and Structural Characteristics of all Mono- and Difluorinated 4,6-Dideoxy-d--hexopyranoses.

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.

Synthesis of Fluorinated Alkyl Aryl Ethers by Palladium-Catalyzed C-O Cross-Coupling.

Herein, we report a highly effective protocol for the cross-coupling of (hetero)aryl bromides with fluorinated alcohols using the commercially available precatalyst BuBrettPhos Pd G3 and CsCO 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 F-labeled trifluoroethyl ethers by cross-coupling with [F]trifluoroethanol.

The Fluorination of C-H Bonds: Developments and Perspectives.

This Review summarizes advances in fluorination by C(sp )-H and C(sp )-H activation. Transition-metal-catalyzed approaches championed by palladium have allowed the installation of a fluorine substituent at C(sp ) and C(sp ) 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.

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers.

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