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Assembly of α‐(Hetero)aryl Nitriles via Copper‐Catalyzed Coupling Reactions with (Hetero)aryl Chlorides and Bromides
Author(s) -
Chen Ying,
Xu Lanting,
Jiang Yongwen,
Ma Dawei
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202014638
Subject(s) - aryl , chemistry , decarboxylation , alkyl , catalysis , halide , oxalic acid , combinatorial chemistry , substrate (aquarium) , organic chemistry , copper , coupling reaction , oceanography , geology
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.