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A General and Practical Palladium‐Catalyzed Direct α‐Arylation of Amides with Aryl Halides
Author(s) -
Zheng Bing,
Jia Tiezheng,
Walsh Patrick J.
Publication year - 2014
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201300851
Subject(s) - chemistry , aryl , catalysis , palladium , halide , phosphine , acetamide , indole test , ligand (biochemistry) , stoichiometry , yield (engineering) , intermolecular force , combinatorial chemistry , organic chemistry , amide , medicinal chemistry , alkyl , molecule , biochemistry , receptor , materials science , metallurgy
An efficient system for the direct catalytic intermolecular α‐arylation of acetamide derivatives with aryl bromides and chlorides is presented. The palladium catalyst is supported by Kwong’s indole‐based phosphine ligand and provides monoarylated amides in up to 95% yield. Excellent chemoselectivities (>10:1) in the mono‐ and diarylation with aryl bromides were achieved by careful selection of bases, solvents, and stoichiometry. Under the coupling conditions, the weakly acidic α‐protons of amides (p K a up to 35) were reversibly depotonated by lithium tert ‐butoxide (LiO‐ t‐ Bu), sodium tert ‐butoxide (NaO‐ t‐ Bu) or sodium bis(trimethylsilyl)amide [NaN(SiMe 3 ) 2 ].