This article describes a sequential Ir/Cu-mediated process for the meta-selective C−H radiofluorination of (hetero)arene substrates. In the first step, Ir-catalyzed C(sp 2 )−H borylation affords (hetero)aryl pinacolboronate (BPin) esters. The intermediate organoboronates are then directly subjected to coppermediated radiofluorination with [ 18 F]tetrabutylammonium fluoride to afford fluorine-18 labeled (hetero)arenes in high radiochemical yield and radiochemical purity. This entire process is performed on a benchtop without Schlenk or glovebox techniques and circumvents the need to isolate (hetero)aryl boronate esters. The reaction was automated on a TracerLab FX FN module with 1,3dimethoxybenzene and a meta-tyrosine derivative. The products, [ 18 F]1-fluoro-3,5-dimethoxybenzene and an 18 F-labeled meta-tyrosine derivative, were obtained in 37 ± 5% isolated radiochemical yield and >99% radiochemical purity and 25% isolated radiochemical yield and 99% radiochemical purity, and 0.52 Ci/μmol (19.24 GBq/μmol) molar activity (A m ), respectively.
Radiocyanation is an attractive strategy
for incorporating
carbon-11
into radiotracer targets, particularly given the broad scope of acyl
moieties accessible from nitriles. Most existing methods for aromatic
radiocyanation require elevated temperatures (Cu-mediated reactions
of aryl halides or organometallics) or involve expensive and toxic
palladium complexes (Pd-mediated reactions of aryl halides). The current
report discloses a complementary approach that leverages the capture
of aryl radical intermediates by a Cu–11CN complex
to achieve rapid and mild (5 min, room temperature) radiocyanation.
In a first example, aryl radicals are generated via the reaction of
a CuI mediator with an aryldiazonium salt (a Sandmeyer-type
reaction) followed by radiocyanation with Cu–11CN.
In a second example, aryl radicals are formed from aryl iodides via
visible-light photocatalysis and then captured by a Cu–11CN species to achieve aryl–11CN coupling.
This approach provides access to radiocyanated products that are challenging
to access using other methods (e.g., ortho-disubstituted aryl nitriles).
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