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.