Hydrogen Bonding: Regulator for Nucleophilic Fluorination

The recent advances in nucleophilic fluorination, regulated through hydrogen bonding interactions are summarized. Two main categories of fluorine nucleophiles are discussed. Alkali-metal fluorides are widely used in various fluorination transformations because they are inexpensive and safe nucleophilic fluorine sources. But the non-controllable nucleophilicity and strong basicity of some of them cause undesired side reactions, which led to the introduction of hydrogen bonding to fine tune their nucleophilicity and basicity. In contrast, an HF-based fluorine nucleophile, HF/DMPU, is in some aspects superior to the conventional HF/pyridine (Olah's reagent) or HF/Et3N because of the higher hydrogen bond basicity of DMPU. It has been used in several nucleophilic fluorinations such as fluorination of alkynes, fluoro-Prins reaction and fluorination of aziridines.