Assembly of α-(Hetero)aryl Nitriles via Copper-Catalyzed Coupling Reactions with (Hetero)aryl Chlorides and Bromides

alpha-(Hetero)aryl nitriles are important structural motifs for pharmaceutical design. The known methods for direct synthesis of these compounds via coupling with (hetero)aryl halides suffer from narrow reaction scope. Herein, we report that the combination of copper salts and oxalic diamides enables the coupling of a variety of (hetero)aryl halides (Cl, Br) and ethyl cyanoacetate under mild conditions, affording alpha-(hetero)arylacetonitriles via one-pot decarboxylation. Additionally, the CuBr/oxalic diamide catalyzed coupling of (hetero)aryl bromides with alpha-alkyl-substituted ethyl cyanoacetates proceeds smoothly at 60 degrees C, leading to the formation of alpha-alkyl (hetero)arylacetonitriles after decarboxylation. The method features a general substrate scope and is compatible with various functionalities and heteroaryls.

Automated summary

The combination of copper salts and oxalic diamides enables the synthesis of α-(hetero)aryl nitriles via one-pot decarboxylation under mild conditions. The method demonstrates a broad substrate scope and compatibility with various functionalities and heteroaryls.