A General and Practical Palladium-Catalyzed Direct α-Arylation of Amides with Aryl Halides.
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 (pKaup to 35) were reversibly depotonated by LiOtBu, NaOtBu, or NaN(SiMe3)2.
Department of Applied Chemistry, China Agricultural University, Beijing 100193, P. R. China. ; Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
Bing
B
Zheng
Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
Tiezheng
T
Jia
Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
Patrick J
PJ
Walsh
C-C bond formation; amides; aryl halides; chemoselectivity; cross-coupling; palladium