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 beta-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.