Room-Temperature Copper-Mediated Radiocyanation of Aryldiazonium Salts and Aryl Iodides via Aryl Radical Intermediates.

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-CN complex to achieve rapid and mild (5 min, room temperature) radiocyanation. In a first example, aryl radicals are generated via the reaction of a Cu mediator with an aryldiazonium salt (a Sandmeyer-type reaction) followed by radiocyanation with Cu-CN. In a second example, aryl radicals are formed from aryl iodides via visible-light photocatalysis and then captured by a Cu-CN species to achieve aryl-CN coupling. This approach provides access to radiocyanated products that are challenging to access using other methods (e.g., ortho-disubstituted aryl nitriles).