2.8 Selective Radical Fluorinations

AbstractFluorine atoms are found in numerous industrially relevant materials, including pharmaceuticals, agrochemicals, and plastics. In the pharmaceutical industry alone, more than 20% of all therapeutics and a majority of the top-grossing drugs contain fluorine. The ubiquity of fluorinated compounds in industry has necessitated the development of new methods for selective fluorination. Historically, selective fluorination has relied upon electrophilic or nucleophilic processes. Recent breakthroughs in the discovery of mild radical fluorine-transfer reagents have led to a renaissance in selective radical fluorinations. This review provides a brief overview of the known fluorine-transfer reagents, including molecular fluorine, hypofluorites, xenon difluoride, electrophilic N–F reagents, and metal–F reagents. A survey of a range of radical fluorination reactions is covered, including fluorodecarboxylation, fluorination of alkenes, fluorination of boronic acid derivatives, C—H activation and fluorination, C—C activation and fluorination, deoxyfluorination, and halogen-exchange reactions. This review primarily focuses on advances in the last ten years, with an emphasis on the most practical methods.