General Method for the Amination of Aryl Halides with Primary and Secondary Alkyl Amines via Nickel Photocatalysis

The Buchwald-Hartwig C-N coupling reaction has been ranked as one of the 20 most frequently used reactions in medicinal chemistry. Owing to its much lower cost and higher reactivity toward less reactive aryl chlorides than palladium, the C- N coupling reaction catalyzed by Ni-based catalysts has received a great deal of attention. However, there appear to be no universal, practical Ni catalytic systems so far that could enable the coupling of electron-rich and electron-poor aryl halides with both primary and secondary alkyl amines. In this study, it is reported that a Ni(II)-bipyridine complex catalyzes efficient C-N coupling of aryl chlorides and bromides with various primary and secondary alkyl amines under direct excitation with light. Intramolecular C-N coupling is also demonstrated. The feasibility and applicability of the protocol in organic synthesis is attested by more than 200 examples.

Automated summary

The Buchwald-Hartwig C-N coupling reaction is widely used in medicinal chemistry. Ni-based catalysts have attracted great attention due to their lower cost and higher reactivity towards less reactive aryl chlorides. However, there is currently no universal Ni catalytic system available for the coupling of electron-rich and electron-poor aryl halides with primary and secondary alkyl amines. In this study, a Ni(II)-bipyridine complex is reported to catalyze efficient C-N coupling of aryl chlorides and bromides with various primary and secondary alkyl amines under direct excitation with light. The feasibility and applicability of this protocol in organic synthesis are demonstrated with over 200 examples.