Hydrogen Bonding Phase-Transfer Catalysis with Ionic Reactants: Enantioselective Synthesis of γ‑Fluoroamines

Ammonium
salts are used as phase-transfer catalysts for fluorination
with alkali metal fluorides. We now demonstrate that these organic
salts, specifically azetidinium triflates, are suitable substrates
for enantioselective ring opening with CsF and a chiral bis-urea catalyst. This process, which highlights the ability of hydrogen
bonding phase-transfer catalysts to couple two ionic reactants, affords
enantioenriched γ-fluoroamines in high yields. Mechanistic studies
underline the role of the catalyst for phase-transfer, and computed
transition state structures account for the enantioconvergence observed
for mixtures of achiral azetidinium diastereomers. The N-substituents
in the electrophile influence the reactivity, but the configuration
at nitrogen is unimportant for the enantioselectivity.