Palladium and copper co-catalyzed chloro-arylation of -difluorostyrenes - use of a nitrite additive to suppress β-F elimination.

The installation of fluorine and fluorinated functional groups in organic molecules perturbs the physicochemical properties of those molecules and enables the development of new therapeutics, agrichemicals, biological probes and materials. However, current synthetic methodologies cannot access some fluorinated functional groups and fluorinated scaffolds. One such group, the -difluorobenzyl motif, might be convergently synthesized by reacting a nucleophilic aryl precursor and an electrophilic -difluoroalkene. Previous attempts have relied on forming unstable anionic or organometallic intermediates that rapidly decompose through a β-F elimination process to deliver monofluorovinyl products. In contrast, we report a fluorine-retentive palladium and copper co-catalyzed chloro-arylation of -difluorostyrenes that takes advantage of a nitrite (NO ) additive to avoid the favorable β-F elimination pathway that forms monofluorinated products, instead delivering difluorinated products.