Towards Viable Pharmaceutics: Manganese-Mediated Radical Fluorination and Coupled Olefin Addition

Abstract

Fluorine is a highly desirable substituent in pharmaceutics, as its unique properties can greatly increase the bioavailability and potency of drug molecules. However, a far-ranging and selective fluorination method that does not involve the use of harsh gases, costly reagents, or precious metals has yet to be discovered. Pioneering works by the Sammis and Groves groups in 2012 introduced radical fluorination as a viable fluorination pathway, veering away from traditional nucleophilic and electrophilic methods. Inspired by these methods, this work presents a novel fluorination protocol using inexpensive, bench-stable manganese (III) fluoride complexes to transfer fluorine to carbon radicals. Using a light-mediated, decarboxylative method, yields of up to 60% were obtained for benzylic, tertiary, and secondary aliphatic substrates. These reagents were also successful in coupling fluorination with olefin addition, displaying potential for coupling with other types of radical-chain chemistry. By diversifying the scope of fluorination while streamlining the synthetic process, these results show great promise in expanding the fluorination toolkit available to pharmaceutical chemists.