Ligand-Enabled, Palladium-Catalyzed β‑C(sp3)–H Arylation of Weinreb Amides
journal contributionposted on 05.09.2018, 00:00 by Hojoon Park, Nikita Chekshin, Peng-Xiang Shen, Jin-Quan Yu
We report the development of Pd(II)-catalyzed C(sp3)–H arylation of Weinreb amides. Both the inductive effect and the potential bidentate coordination mode of the Weinreb amides pose a unique challenge for this reaction development. A pyridinesulfonic acid ligand is designed to accommodate the weak, neutral-coordinating property of Weinreb amides by preserving the cationic character of Pd center through zwitterionic assembly of Pd/ligand complexes. Density functional theory (DFT) studies of the C–H cleavage step indicate that the superior reactivity of 3-pyridinesulfonic acid ligand, compared to Ac-Gly-OH and ligandless conditions, originates from the stabilization of overall substrate-bound Pd species.