Asymmetric Fluorination of α‑Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids

We
report a study involving the successful merger of two separate
chiral catalytic cycles: a chiral anion phase-transfer catalysis cycle
to activate Selectfluor and an enamine activation cycle, using a protected
amino acid as organocatalyst. We have demonstrated the viability of
this approach with the direct asymmetric fluorination of α-substituted
cyclohexanones to generate quaternary fluorine-containing stereocenters.
With these two chiral catalytic cycles operating together in a matched
sense, high enantioselectivites can be achieved, and we envisage that
this dual catalysis method has the potential to be more broadly applicable,
given the breadth of enamine catalysis. It also represents a rare
example of chiral enamine catalysis operating successfully on α-branched
ketones, substrates commonly inert to this activation mode.