Late-stage fluorination of biologically relevant molecules is of critical importance in drug development strategies as well as in radioimaging applications. Utilizing fluorine as a bioisostere in small molecule therapeutics has emerged as successful strategy to impart metabolic stability, enhanced bioactivity, and improved pharmacokinetic properties. In light of the growing need to introduce C-F bonds into small molecules, new methods for fluorination are in high demand. Herein we report a mild, redox-neutral nucleophilic fluorination strategy. Photocatalytically generated carbocation intermediates have been intercepted in a S<sub>N</sub>1 nucleophilic fluorination mechanism. We have further exploited the carbocation intermediate to trap a wide array of nucleophiles thereby generating C-C, C-O, and C-X bonds. We anticipate that this method will be significant for synthetic chemists and radiochemists and will advance the synthesis of therapeutic positron emission tomography (PET) imaging molecules.

Nucleophilic fluorination enabled by photoredox catalysis

ACS Fall 2020 Virtual Meeting

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