Peptide-based Hydrogen Bonding Phase-Transfer Catalysis for Asymmetric Nucleophilic Fluorination

Asymmetric nucleophilic fluorination remains one of the most challenging transformations in organic chemistry. In light of the importance of chiral fluorochemicals for the pharmaceutical sector, the development of innovative enantioselective fluorination methods with alkali metal fluoride is highly desirable. In this work, we propose to merge two conceptual manifolds, namely peptide-based organocatalysis and hydrogen bonding phase-transfer catalysis. We propose to investigate experimentally the binding ability of an extensive β-turn-based peptide library to fluoride, a fundamental unprecedented study. The insight into the binding profiles and conformational properties of these peptides will be essential for developing an asymmetric catalytic nucleophilic fluorination procedure. In this context, we shall first focus on synthesising pharmaceutically relevant cyclic β-fluoroamines. Subsequently, the peptide-catalyst design will be further refined by introducing a substrate binding region for targeting aryl amides, esters, thioesters, and sulfones. Upon completion, this work will provide medicinal chemists with a novel peptide-catalysed asymmetric nucleophilic fluorination reaction, an advance expanding the scope of organocatalytic nucleophilic fluorination reactions.