Surpassing the Limited Coordination Affinity of Native Amides by Introducing Pyridone-Pd-AgOAc Clusters to Promote Distal γ-C (sp3)–H Arylation

摘要: The utilization of weak coordination in promoting site-selective C(sp3)–H functionalization is of immense importance. Herein, we report a Pd-catalyzed distal γ-C(sp3)–H arylation that harnesses the weak coordination affinity of keto groups with the native noncoordinating amide moiety. The current protocol overcomes one of the major challenges associated with the diversification of synthetic modular frameworks of quaternary centers: controlling the mono- vs difunctionalization of chemically equivalent C–H bonds. The developed condition overrides the interference of the acidic α-hydrogen for possible side reactions of amides and delivers the exclusive formation of the γ-monoarylated product. The association of 2-hydroxy pyridine ligands bearing electron-withdrawing substituents demonstrated the best partnership with the Pd–Ag hetero-bimetallic complex to achieve this distal γ-C(sp3)–H activation of a range of …