Room-Temperature Copper-Mediated Radiocyanation of Aryldiazonium Salts and Aryl Iodides via Aryl Radical Intermediates
Eric Webb, Kevin Cheng, Jay S. Wright, Jocelyn Cha, Xia Shao, Melanie S. Sanford, Peter J. H. Scott
Abstract
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– 11 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 I mediator with an aryldiazonium salt (a Sandmeyer-type reaction) followed by radiocyanation with Cu– 11 CN. In a second example, aryl radicals are formed from aryl iodides via visible-light photocatalysis and then captured by a Cu– 11 CN species to achieve aryl– 11 CN coupling. This approach provides access to radiocyanated products that are challenging to access using other methods (e.g., ortho-disubstituted aryl nitriles).