Search

We present a photo- and Cu-mediated 11 C cyanation of bench-stable (hetero)aryl thianthrenium salts via an aryl radical addition pathway. The thianthrenium substrates can be readily accessed via C-H functionalization, and the radiocyanation protocol proceeds under mild conditions (<50 °C, 5 min) and can be automated using open-source, readily accessible augmentations to existing radiochemistry equipment.

Nucleophilic aromatic fluorination (S N Ar) is among the most common methods for the formation of C(sp 2 )-F bonds. Despite many recent advances, a long-standing limitation of these transformations is the requirement for rigorously dry, aprotic conditions to maintain the nucleophilicity of fluoride and suppress the generation of side products. This report addresses this challenge by leveraging tetramethylammonium fluoride alcohol adducts (Me 4 NF·ROH) as fluoride sources for S N Ar fluorination. Through systematic tuning of the alcohol substituent (R), tetramethylammonium fluoride tert- amyl alcohol (Me 4 NF· t- AmylOH) was identified as an inexpensive, practical, and bench-stable reagent for S N Ar fluorination under mild and convenient conditions (80 °C in DMSO, without the requirement for drying of reagents or solvent). A substrate scope of more than 50 (hetero) aryl halides and nitroarene electrophiles is demonstrated.

A copper-mediated method for the transformation of diverse arylboron compounds and arylstannanes to aryl-[ 11 C]-nitriles is reported. This method is operationally simple, uses commercially available reagents, and is compatible with a wide variety of substituted aryl- and heteroaryl substrates. This method is applied to the automated synthesis of high specific activity [ 11 C]perampanel in 10% nondecay-corrected radiochemical yield (RCY).

This communication describes a method for the nucleophilic radiofluorination of electron-rich arenes. The reaction involves the initial C(sp 2 )-H functionalization of an electron-rich arene with MesI(OH)OTs to form a (mesityl)(aryl)iodonium salt. This salt is then used in situ in a Cu-mediated radiofluorination with [ 18 F]KF. This approach leverages the stability and availability of electron-rich arene starting materials to enable mild late-stage radiofluorination of toluene, anisole, aniline, pyrrole, and thiophene derivatives. The radiofluorination has been automated to access a 41 mCi dose of an 18 F-labeled nimesulide derivative in high (2800 ± 700 Ci/mmol) specific activity.

A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [ 18 F]KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [ 18 F]F-phenylalanine and [ 18 F]F-DOPA. In addition, an automated synthesis of [ 18 F]MPPF is demonstrated that delivers a clinically validated dose of 200 ± 20 mCi with a high specific activity of 2400 ± 900 Ci/mmol.

A copper-mediated radiofluorination of aryl- and vinylboronic acids with K(18)F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [(18)F]FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors.