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

McGuire, Ryan T.; Lundrigan, Travis; MacMillan, Joshua W. M.; Robertson, Katherine N.; Yadav, Arun A.; Stradiotto, Mark

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.

ARYL halides; NICKEL catalysts; ORGANIC bases; ACETOPHENONE; HALIDES; ANILINE

Angewandte Chemie, 2022, Vol 134, Issue 13, p1

0044-8249

Academic Journal

10.1002/ange.202200352