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

Abstract

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.