Dooley C,
Ibba F,
Botlik BB,
Palladino C,
Goult CA,
Goa Y,
Lister A,
Paton RS *,
Lloyd-Jones GC *,
Gouverneur V *.
Colorado State University, Fort Collins, USA, University of Edinburgh, and University
of Oxford, UK
Enantioconvergent Nucleophilic Substitution via Synergistic Phase-Transfer Catalysis.
Nat. Catal. 2025;
8: 107-115
DOI:
10.1038/s41929-024-01288-0
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 SN2-like pathway in combination with rapid starting material racemization leading to
enantioconvergence.
