Appel halogenation reactions are widely used to convert alcohols to alkyl halides but are not suitable to prepare alkyl fluorides because fluoride is sequestered as a difluorophosphorane. In this work...

Herein, we report a Ni-mediated 18F,D2-monofluoromethylation of (hetero)arenes from (pseudo)halide coupling partners. This new approach offers key advantages compared to traditional radiochemistry based on SN2-type reactivity with [18F]fluoride. These include increased precursor stability and availability, obviating bespoke precursor syntheses, broad functional group tolerance, and the late-stage introduction of deuterium and fluorine-18 in a single step, all features facilitating early access to PET ligands for discovery campaigns. This novel protocol is applied to over 30 diverse substrates, including complex bioactive molecules, and is amenable to scale-up via a semiautomated protocol on a commercial platform, illustrated by isolation of a 18F,D2-labeled PARP radiotracer.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants, some associated with detrimental impacts on human health upon chronic exposure. Many processes have been reported to...

Synergistic catalysis whereby both the nucleophile and the electrophile can be simultaneously activated by two distinct catalysts can rescue otherwise unattainable chemical transformations, as well as...

Knowledge on how fluoride interacts with peptides is currently limited to in silico studies. Here, we report an experimental investigation on the ability of peptidic scaffolds to bind fluoride using TBAF·3H2O or CsF. For CsF, in-depth NMR and GOAT-DFT studies shed light on peptides acting as chelators to both fluoride and cesium ions. This finding led to the development of the first peptide-catalyzed fluorination reactions. These advances open a new avenue to investigate fluorination chemistry with peptide-based catalysts that are considered as the possible ancestors to enzymes.

A general Ni-mediated (C)sp2–(C)sp3 cross-coupling expedites access to 18F-radiopharmaceuticals, essential for positron emission tomography imaging and drug discovery. This late-stage diversification...