Palladium-Catalyzed Enantioselective α‑Arylation of α‑Fluoroketones

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