Palladium-Catalyzed Enantioselective α-Arylation of α-Fluoroketones

The transition-metal-catalyzed alpha-arylation of carbonyl compounds is a widely practiced method for C-C bond formation. Several enantioselective versions of this process have been reported, but intermolecular, enantioselective coupling reactions of aryl electrophiles with alpha-fluoro carbonyl compounds have yet to be disclosed. We report enantioselective coupling of aryl and heteroaryl bromides and triflates with alpha-fluoroindanones catalyzed by palladium complexes of a BINOL-derived monophosphine and Segphos, respectively. The enolates were generated directly from alpha-fluoroindanones in the presence of potassium phosphate base during the reactions. We also report that reactions of alpha-fluorotetralones occur in high yields and enantioselectivities when conducted with enolates generated by elimination of trifluoroacetate from trifluoromethyl beta-diketone hydrates. These reactions were catalyzed by palladium complexes of the commercially available bisphosphine Difluorphos. Thus, the formation of enantioenriched alpha-aryl-alpha-fluoroketones can be readily achieved by C-C bond formation when the appropriate palladium catalyst and alpha-fluoro enolate precursor were used.