Copper-Catalyzed Ring-Opening Defluorinative Alkylation of Siloxydifluorocyclopropanes: Synthesis of γ‑Fluoro-δ-Ketoesters and γ,δ-Diketonitriles

In
view of the importance of both fluorinated synthons and homoenolate
equivalents, synthetic application of difluorocyclopropanols is desired
but remains challenging due to their thermodynamic instability. Herein,
we use siloxydifluorocyclopropanes as difluorocyclopropanol precursors
to carry out new Cu-catalyzed ring-opening defluorinative alkylation.
With α-bromo carboxylic esters as coupling partners, the reaction
affords γ-fluoro-δ-ketoesters via a CuI/CuII catalytic cycle. Interestingly, by the use
of α-bromoamides, the ring-opening defluorinative alkylation
is followed by an additional intramolecular C–N oxidative coupling
to deliver a lactam intermediate, which further undergoes defluorination,
hydrolysis, ring opening, and dehydration cascade via a CuI/CuII/CuIII catalytic pathway,
leading to γ,δ-diketonitriles as the final products.