Stereospecific Nickel-Catalyzed Cross-Electrophile Coupling Reaction of Alkyl Mesylates and Allylic Difluorides to Access Enantioenriched Vinyl Fluoride-Substituted Cyclopropanes

Cross-electrophile coupling reactions involving direct
C–O
bond activation of unactivated alkyl sulfonates or C–F bond
activation of allylic gem-difluorides remain challenging.
Herein, we report a nickel-catalyzed cross-electrophile coupling reaction
between alkyl mesylates and allylic gem-difluorides
to synthesize enantioenriched vinyl fluoride-substituted cyclopropane
products. These complex products are interesting building blocks with
applications in medicinal chemistry. Density functional theory (DFT)
calculations demonstrate that there are two competing pathways for
this reaction, both of which initiate by coordination of the electron-deficient
olefin to the low-valent nickel catalyst. Subsequently, the reaction
can proceed by oxidative addition of the C–F bond of the allylic gem-difluoride moiety or by directed polar oxidative addition
of the alkyl mesylate C–O bond.