Fluorinated Five‐Membered Heterocycles Containing Oxygen, Sulfur, Selenium, and Phosphorus

In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides

“…Considering the independent importance of five-membered heterocycles and aryl fluorides in the pharmaceutical industry, there is a surprising lack of five-membered heteroaryl fluorides that have been prepared and studied for potential biological activity. 7 This is likely due to the limited methods available for the fluorination of five-membered heteroarenes, 8 which include thermal 9a or photochemical 9b Balz–Schiemann reactions, Halex reactions, 10 electrophilic fluorinations of metalated heteroarenes, 11 and direct fluorinations with F 2 . 12 All of these methods suffer from severe drawbacks in terms of safety, functional group tolerance, generality, and/or formation of complex mixtures of products, which limit their utility.…”

Tetramethylammonium Fluoride Tetrahydrate for SNAr Fluorination of 4-Chlorothiazoles at a Production Scale

“…The high π-electron density at these positions further exacerbates the requirement for forcing reaction conditions, which can limit functional group tolerance and lead to the formation of undesired impurities . In fact, there are relatively few procedures of any kind that have been reported for the preparation of 4-fluoroazoles. , Moreover, many of these conditions involve the use of expensive electrophilic fluorinating reagents . Thus, there is a need for the development of scalable, process-friendly methods for the production of five-membered fluoroarenes.…”