Iron-Catalyzed Deoxynitrogenation of Carboxylic Acids with Cyanamides to Access Nitriles

Abstract

Efficient strategies to access nitriles from common organic functionalities are highly important, given their significance in synthetic and medicinal chemistry. Although the direct transformation of carboxylic acids to nitriles have been explored for decades, there is few general and practical protocol to access nitriles from carboxylic acid precursors. Herein, an iron-catalyzed deoxynitrogenaton strategy to convert carboxylic acids into nitriles is described. This method utilizes a cyanamide as the recyclable nitrogen donor and deoxygenating reagent, operates broadly across aryl, alkenyl, and alkyl carboxylic acids, and features an easy setup without inert gas protection. The synthetic value of this method is demonstrated by application in late-stage modification of drug molecules, synthesis of a pharmaceutical structure, and scaleup reactions and downstream derivatizations.

Keywords: carboxylic acid; cyanamide; deoxynitrogenation; iron catalysis; nitrile.