In 2018, about 50% of the FDA approved small-molecule drugs contained at least one fluorine atom, as the incorporation of a fluorine atom impacts many properties, including biological potency and metabolic stability. These drugs are mainly constructed from simpler fluorinated building blocks because their late-stage functionalization has proven to be difficult with common fluorination methods. Here we evaluated a variety of different C(sp<sup>3</sup>)–H fluorination reactions to directly compare their selectivity and reactivity towards biologically relevant scaffolds. Common motifs in pharmaceuticals such as benzylic substrates, heterocycles such as pyridines and furans, and aliphatic amines were assessed. Our results have shown significant differences in reactivity and selectivity, even though these methods have been proposed to proceed via a similar mechanism.

Direct comparison of fluorination methods for the functionalization of biologically relevant molecules

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.