Palladium(II)-Catalyzed Annulative Difunctionalization of Two Inert C(sp3)–H Bonds by a Bifunctional Reagent

Illustrated herein is a Pd­(II)-catalyzed direct difunctionalization of two C­(sp3)–H bonds of aliphatic carboxylic acid derivatives by bifunctional reagents (BFRs) of the 2-iodobenzoic acid series. The methyl 2-pyridyl sulfoximine (MPyS) bidentate directing group (DG), 2-chloro-5-trifluoromethylpyridine ligand, AgOAc as a base, and NaBrO3 as a co-oxidant help the concerted metalation deprotonation (CMD) of inert C­(sp3)–H bonds, as well as the reductive elimination; density functional theory (DFT) studies shed light on these crucial steps. This process makes two bonds [C–C and C–O] at gem-α,α′-di-Me groups in a single operation, offering access to unusual benzo-fused peripheral-substituted caprolactones. The transformation tolerates labile functional groups and allows the construction of a wide range of caprolactones with structural diversity. Mechanistic studies reveal the participation of monomeric Pd species in the catalytic cycle. The synthetic versatility of the complex molecular entities is also presented.