Catalytic Asymmetric Synthesis of Tertiary Alkyl Fluorides: Negishi Cross-Couplings of Racemic α,α-Dihaloketones

The
development of new approaches to the construction of fluorine-containing
target molecules is important for a variety of scientific disciplines,
including medicinal chemistry. In this Article, we describe a method
for the catalytic enantioselective synthesis of tertiary alkyl fluorides
through Negishi reactions of racemic α-halo-α-fluoroketones,
which represents the first catalytic asymmetric cross-coupling that
employs geminal dihalides as electrophiles. Thus, selective reaction
of a C–Br (or C–Cl) bond in the presence of a C–F
bond can be achieved with the aid of a nickel/bis­(oxazoline) catalyst.
The products of the stereoconvergent cross-couplings, enantioenriched
tertiary α-fluoroketones, can be converted into an array of
interesting organofluorine compounds.