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

Illustrated herein is a Pd-(II)-catalyzed direct difunctionalizationof two C-(sp(3))-H bonds of aliphatic carboxylic acidderivatives by bifunctional reagents (BFRs) of the 2-iodobenzoic acidseries. The methyl 2-pyridyl sulfoximine (MPyS) bidentate directinggroup (DG), 2-chloro-5-trifluoromethylpyridine ligand, AgOAc as abase, and NaBrO3 as a co-oxidant help the concerted metalationdeprotonation (CMD) of inert C-(sp(3))-H bonds, aswell as the reductive elimination; density functional theory (DFT)studies shed light on these crucial steps. This process makes twobonds [C-C and C-O] at gem-alpha,alpha '-di-Megroups in a single operation, offering access to unusual benzo-fusedperipheral-substituted caprolactones. The transformation tolerateslabile functional groups and allows the construction of a wide rangeof caprolactones with structural diversity. Mechanistic studies revealthe participation of monomeric Pd species in the catalytic cycle.The synthetic versatility of the complex molecular entities is alsopresented.

Automated summary

This article presents a Pd-(II)-catalyzed direct difunctionalization of two C-(sp(3))-H bonds of aliphatic carboxylic acid derivatives using bifunctional reagents (BFRs) of the 2-iodobenzoic acid series. Various directing groups, ligands, bases, and co-oxidants are employed to facilitate the reaction, leading to the formation of benzo-fused peripheral-substituted caprolactones. Mechanistic studies provide insights into the crucial steps involved in the transformation. The versatility of the complex molecular entities is also showcased.