A Three‐Component Arene Difunctionalization: Merger of C(sp 3 )/(sp 2 )−H Bond Addition
Résumé
Abstract A tandem three‐component C−H bond addition involving the activation of an inert C(sp 3 )−H bond is reported. The process enables the direct regioselective synthesis of 1,2‐difunctionalized arenes with the formation of C(sp 3 )− and C(sp 2 )−C(arene) bonds. 2‐Iodobenzoic acid derivatives behave as masked bifunctional reagent (BFR) and react with 2‐pyridyl‐methyl sulfoximine (MPyS) protected aliphatic acids bearing α,α‐disubstituted groups, and alkenes to produce β‐aryl‐δ‐alkenyl amide derivatives in a single operation. The transformation involves Pd(II)/Pd(IV) and Pd(II)/Pd(0) catalytic systems. Detailed mechanistic studies, including density functional theory (DFT) calculations, reveal the formation of large T‐shaped palladacycles and the onset of a 1,2‐palladium migration via decarboxylation.