Premium
Negishi Cross‐Coupling Reactions Catalyzed by an Aminophosphine‐Based Nickel System: A Reliable and General Applicable Reaction Protocol for the High‐Yielding Synthesis of Biaryls
Author(s) -
Gerber Roman,
Frech Christian M.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201101037
Subject(s) - catalysis , aryl , negishi coupling , chemistry , nickel , steric effects , reagent , halide , combinatorial chemistry , trifluoromethyl , coupling reaction , medicinal chemistry , organic chemistry , alkyl
Treatment of NMP solutions of NiCl 2 with 1,1′,1′′‐(phosphanetriyl)tripiperidine (≈2.05 equiv), dissolved in THF, in air at 25 °C forms a highly active catalytic system for the cross‐coupling of a large variety of electronically activated, non‐activated, deactivated, and ortho ‐substituted, heterocyclic, and functionalized aryl bromides and aryl chlorides with diarylzinc reagents. Very high levels of conversion and yields were obtained within 2 h at 60 °C in the presence of only 0.1 mol % of catalyst (based on nickel) and thus at catalyst loadings far lower than typically reported for nickel‐catalyzed versions of the Negishi reaction. Various aryl halides—which may contain trifluoromethyl groups, fluorides, or other functional groups such as acetals, ketones, ethers, esters, lactones, amides, imines, anilines, alkenes, pyridines, quinolines, and pyrimidines—were successfully converted into the corresponding biaryls. Electronic and steric variations are tolerated in both reaction partners. Experimental observations indicate that a molecular (Ni I /Ni III ) mechanism is operative.