Assembly of α‐(Hetero)aryl Nitriles via Copper‐Catalyzed Coupling Reactions with (Hetero)aryl Chlorides and Bromides. (17th February 2021)

• Record Type: Journal Article
• Authors: Chen, Ying; Xu, Lanting; Jiang, Yongwen; Ma, Dawei
• Is Part Of: Angewandte Chemie. Volume 133:Number 13(2021)
• Page Start: 7158
• Page End: 7162
• Publication Date: 2021-02-17
• Subjects: anti-inflammatory drugs -- C−C cross-coupling -- copper -- oxalamide ligands -- α-(hetero)aryl nitriles; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202014638
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: α‐(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 α‐(hetero)arylacetonitriles via one‐pot decarboxylation. Additionally, the CuBr/oxalic diamide catalyzed coupling of (hetero)aryl bromides with α‐alkyl‐substituted ethyl cyanoacetates proceeds smoothly at 60 °C, leading to the formation of α‐alkyl (hetero)arylacetonitriles after decarboxylation. The method features a general substrate scope and is compatible with various functionalities and heteroaryls. Abstract : Cu‐catalyzed formation of α‐(hetero)aryl nitriles from (hetero)aryl halides proceeds with a broad reaction scope by using two pyridine‐embodied oxalamide ligands.