SAr Radiofluorination with In Situ Generated [F]Tetramethylammonium Fluoride.

This report describes a method for the nucleophilic radiofluorination of (hetero)aryl chlorides, (hetero)aryl triflates, and nitroarenes using a combination of [F]KF·K and MeNHCO for the in situ formation of a strongly nucleophilic fluorinating reagent (proposed to be [F]MeNF). This method is applied to 24 substrates bearing diverse functional groups, and it generates [F](hetero)aryl fluoride products in good to excellent radiochemical yields in the presence of ambient air/moisture. The reaction is applied to the preparation of F-labeled HQ-415 for potential (pre)clinical use.

Tetramethylammonium Fluoride Alcohol Adducts for SAr Fluorination.

Nucleophilic aromatic fluorination (SAr) is among the most common methods for the formation of C(sp)-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 (MeNF·ROH) as fluoride sources for SAr fluorination.

Development of SAr Nucleophilic Fluorination: A Fruitful Academia-Industry Collaboration.

The identification of reliable, general, and high yielding methods for the formation of C(sp)-fluorine bonds remains a major challenge for synthetic organic chemists. A very common approach involves nucleophilic aromatic fluorination (SAr fluorination) reactions of aryl chlorides or nitroarenes. Despite being known for more than a century, traditional SAr fluorination reactions suffer from significant limitations, particularly on a process scale.