Synergistic Phase-Transfer Catalysis for Nucleophilic Fluorination

Keywords

phase-transfer catalysis - S_N2 mechanism - fluorination

Significance

Paton, Lloyd-Jones, Gouverneur and co-workers report an enantioconvergent nucleophilic substitution of benzylic bromides and α-bromoketones with potassium fluoride (KF) to afford alkyl fluorides in high yields (52–94 %) and enantioselectivities (up to 98:2). Key to the success of this reaction was the use of the chiral bis-urea hydrogen bond donor (S)-1/2 and an onium salt: PPh₄PI or Et₄NI.

Comment

In-depth NMR and computational studies confirm the presence of a chiral ternary complex between (S)-1/2, the onium cation and fluoride anion. It was found that this ternary complex was crucial for solubilization of potassium fluoride. Kinetic isotope effects suggest an S_N2-like pathway in combination with rapid starting material racemization leading to enantioconvergence.

Publication History

Article published online:
22 April 2025