Department of Radiology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, Michigan 48109, United States.
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
J Am Chem Soc. 2023 Mar 29;145(12):6921-6926. doi: 10.1021/jacs.3c00422. Epub 2023 Mar 14.
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).
放射性氰化是将碳-11 掺入放射性示踪剂靶标中的一种有吸引力的策略，特别是考虑到可以从腈类中获得广泛的酰基部分。大多数现有的芳香族放射性氰化方法需要高温（Cu 介导的芳基卤化物或有机金属反应）或涉及昂贵且有毒的钯配合物（Pd 介导的芳基卤化物反应）。本报告披露了一种互补的方法，该方法利用 Cu-CN 配合物捕获芳基自由基中间体来实现快速和温和（5 分钟，室温）的放射性氰化。在第一个例子中，芳基自由基通过 Cu 介导剂与芳基重氮盐（桑德迈尔型反应）反应生成，然后用 Cu-CN 进行放射性氰化。在第二个例子中，芳基自由基通过可见光光催化从芳基碘化物形成，然后被 Cu-CN 物种捕获，以实现芳基-CN 偶联。这种方法提供了对使用其他方法难以获得的放射性氰化产物的访问（例如，邻位取代的芳基腈）。
