Ligand-Enabled, Palladium-Catalyzed Beta-C (sp3)–H Arylation of Weinreb Amides
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We report the development of Pd(II)-catalyzed C(sp3)–H arylation of Weinreb amides. A pyridinesulfonic acid ligand is designed to accommodate the weak, neutral coordinating property of Weinreb amides via preserving the cationic character of Pd center through zwitterionic assembly of Pd/ligand complexes. DFT studies of the C–H cleavage step indicate that the superior reactivity of 3-pyridinesulfonic acid ligand compared to pyridine, Ac-Gly-OH, and ligandless conditions originates from the stabilization of overall substrate-bound Pd species.