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-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., orthodisubstituted aryl nitriles).

Automated summary

Radiocyanation is an attractive and complementary strategy for incorporating carbon-11 into radiotracer targets. This approach utilizes a Cu-11CN complex to capture aryl radical intermediates, enabling rapid and mild radiocyanation. Examples include the reaction of CuI with aryldiazonium salt and visible-light photocatalysis of aryl iodides, both followed by coupling with Cu-11CN to access challenging radiocyanated products.