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

Abstract

This manuscript details the development of a general and mild protocol for the α-C-H cyanation of tertiary amines as well as its application in late stage functionalization. Suitable substrates include tertiary aliphatic, benzylic, and aniline-type substrates as well as complex substrates. Functional groups tolerated under the reaction conditions include various heterocycles, as well as ketones, amides, olefins, and alkynes. This broad substrate scope is remarkable, as comparable reaction protocols for α-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 system are readily available, allowing implementation of the presented methodology without the need for lengthy catalyst synthesis.Recent mechanistic work in the Fe catalyzed α-C-H oxidation of tertiary amines has uncovered a radical rebound ASSOCIATED CONTENT Supporting Information. Reaction optimization details, synthetic procedures, characterization for new and known compounds.