Hydrogen Bonding Phase-Transfer Catalysis with Potassium Fluoride: Enantioselective Synthesis of β-Fluoroamines.
Pupo G., Vicini AC., Ascough DMH., Ibba F., Christensen KE., Thompson AL., Brown JM., Paton RS., Gouverneur V.
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.