Cooperative Fe/Co-Catalyzed Remote Desaturation for the Synthesis of Unsaturated Amide Derivatives.

Unsaturated amides represent common functional groups found in natural products and bioactive molecules and serve as versatile synthetic building blocks. Here, we report an iron(II)/cobalt(II) dual catalytic system for the syntheses of distally unsaturated amide derivatives. The transformation proceeds through an iron nitrenoid-mediated 1,5-hydrogen atom transfer (1,5-HAT) mechanism. Subsequently, the radical intermediate undergoes hydrogen atom abstraction from vicinal methylene by a cobaloxime catalyst, efficiently yielding β,γ- or γ,δ-unsaturated amide derivatives under mild conditions. The efficiency of Co-mediated HAT can be tuned by varying different auxiliaries, highlighting the generality of this protocol. Remarkably, this desaturation protocol is also amenable to practical scalability, enabling the synthesis of unsaturated carbamates and ureas, which can be readily converted into various valuable molecules.