Hydrogen Bonding Phase-Transfer Catalysis with Potassium Fluoride: Enantioselective Synthesis of β‑Fluoroamines

Potassium fluoride
(KF) is an ideal reagent for fluorination because
it is safe, easy to handle and low-cost. However, poor solubility
in organic solvents coupled with limited strategies to control its
reactivity has discouraged its use for asymmetric C–F bond
formation. Here, we demonstrate that hydrogen bonding phase-transfer
catalysis with KF provides access to valuable β-fluoroamines in high yields and enantioselectivities. This methodology employs
a chiral N-ethyl bis-urea catalyst that brings solid
KF into solution as a tricoordinated urea-fluoride complex. This operationally
simple reaction affords enantioenriched fluoro-diphenidine (up to
50 g scale) using 0.5 mol % of recoverable bis-urea catalyst.