Mapping Dual‐Base‐Enabled Nickel‐Catalyzed Aryl Amidations: Application in the Synthesis of 4‐Quinolones

The C−N cross‐coupling of (hetero)aryl (pseudo)halides with NH substrates employing nickel catalysts and organic amine bases represents an emergent strategy for the sustainable synthesis of (hetero)anilines. However, unlike protocols that rely on photoredox/electrochemical/reductant methods within N...

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Bibliographic Details
Published in:Angewandte Chemie 2022-03, Vol.134 (13), p.n/a
Main Authors: McGuire, Ryan T., Lundrigan, Travis, MacMillan, Joshua W. M., Robertson, Katherine N., Yadav, Arun A., Stradiotto, Mark
Format: Article
Language:English
Subjects:
4-Quinolones
Amidation
Amides
Aniline
Aromatic compounds
Bisphosphine
Camps Cyclization
Catalysts
Chemistry
Couplings
Cross coupling
Electrochemistry
Halides
N-(ketoaryl)-amides
Nickel
Quinolones
Reducing agents
Substrates
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Summary:The C−N cross‐coupling of (hetero)aryl (pseudo)halides with NH substrates employing nickel catalysts and organic amine bases represents an emergent strategy for the sustainable synthesis of (hetero)anilines. However, unlike protocols that rely on photoredox/electrochemical/reductant methods within NiI/III cycles, the reaction steps that comprise a putative Ni0/II C−N cross‐coupling cycle for a thermally promoted catalyst system using organic amine base have not been elucidated. Here we disclose an efficient new nickel‐catalyzed protocol for the C−N cross‐coupling of amides and 2′‐(pseudo)halide‐substituted acetophenones, for the first time where the (pseudo)halide is chloride or sulfonate, which makes use of the commercial bisphosphine ligand PAd2‐DalPhos (L4) in combination with an organic amine base/halide scavenger, leading to 4‐quinolones. Room‐temperature stoichiometric experiments involving isolated Ni0, I, and II species support a Ni0/II pathway, where the combined action of DBU/NaTFA allows for room‐temperature amide cross‐couplings. A nickel‐catalyzed C−N cross‐coupling of amides with 2′‐(pseudo)halide‐substituted acetophenones enabled the synthesis of sought‐after 4‐quinolones. The use of a new pre‐catalyst supported by PAd2‐DalPhos in combination with a DBU/NaTFA dual‐base system, along with a thorough mechanistic investigation led to a successful demonstration of room‐temperature amide cross‐couplings.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202200352