Synthesis of Heterobenzylic Fluorides

Fluorination at heterobenzylic positions can have a significant impact on basicity, lipophilicity, and metabolism of drug leads. As a consequence, the development of new methods to access heterobenzylic fluorides has particular relevance to medicinal chemistry. This Short Review provides a survey of common methods used to synthesize heterobenzylic fluorides and includes fluoride displacement reactions of previously functionalized molecules (e.g., deoxyfluorination and halide exchange) and electrophilic fluorination of resonance stabilized heterobenzylic anions. In addition, recent advances in the direct fluorination of heterobenzylic C(sp3)-H bonds and monofluoromethylation of heterocyclic C(sp2)-H bonds are presented.