Palladium-Catalyzed Coupling of Amides and Cyclopropanols for the Synthesis of γ-Diketones

A palladium catalytic method has been developed for the coupling of amides and cyclopropanols to γ-diketones. Heteroatom ligand exchange and heteroatom-to-carbon ligation mode switch provide the mechanistic basis for avoiding the use of any stoichiometric organometallic reagent and base. The molecular cross-coupling reactivity can be programmed through the adjustment of structural context surrounding the amide N-atom, enabling the establishment of a set of reactivity order chemistry. With chemistry set, a collection of transformations with defined (especially quantitative) reactivity relations, as the fundamental synthetic planning unit, a synthetic programming strategy, set chemistry, can be envisioned. The γ-diketone synthesis can be further elaborated into an alkyl-alkyl coupling protocol, furnishing an alternative surrogate synthetic scheme for this to-a-certain-extent challenging reaction.