Iron-Catalyzed α-C-H Cyanation of Simple and Complex Tertiary Amines

This manuscript details the development of a general and mild protocol for the alpha-C-H cyanation of tertiary amines and its application in late-stage functionalization. Suitable substrates include tertiary aliphatic, benzylic, and aniline-type substrates and complex substrates. Functional groups tolerated under the reaction conditions include various heterocycles and ketones, amides, olefins, and alkynes. This broad substrate scope is remarkable, as comparable reaction protocols for alpha-C-H cyanation frequently occur via free radical mechanisms and are thus fundamentally limited in their functional group tolerance. In contrast, the presented catalyst system tolerates functional groups that typically react with free radicals, suggesting an alternative reaction pathway. All components of the described catalyst system are readily available, allowing implementation of the presented methodology without the need for lengthy catalyst synthesis.

Automated summary

This study details the development of a mild protocol for the alpha-C-H cyanation of tertiary amines and its successful application in late-stage functionalization. The method is not only applicable to a variety of substrates, but also tolerates numerous functional groups, demonstrating a broad substrate scope and high practicality.