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Nucleophilic (Radio)Fluorination of Redox-Active Esters via Radical-Polar Crossover Enabled by Photoredox Catalysis

preprint
submitted on 19.03.2020 and posted on 20.03.2020 by Eric Webb, John Park, Erin L. Cole, David J. Donnelly, Samuel Bonacorsi, Jr., William R. Ewing, Abigail Doyle

We report a redox-neutral method for nucleophilic fluorination of N-hydroxyphthalimide esters using an Ir photocatalyst under visible light irradiation. The method provides access to a broad range of aliphatic fluorides, including primary, secondary, and tertiary benzylic fluorides as well as unactivated tertiary fluorides, that are typically inaccessible by nucleophilic fluorination due to competing elimination. In addition, we show that the decarboxylative fluorination conditions are readily adapted to radiofluorination with [18F]KF. We propose that the reactions proceed by two electron transfers between the Ir catalyst and redox-active ester substrate to afford a carbocation intermediate that undergoes subsequent trapping by fluoride. Examples of trapping with O- and C-centered nucleophiles and deoxyfluorination via N-hydroxyphthalimidoyl oxalates are also presented, suggesting that this approach may offer a general blueprint for affecting redox-neutral SN1 substitutions under mild conditions.

Funding

NSF CHE-1565983

History

Email Address of Submitting Author

agdoyle@princeton.edu

Institution

Princeton University

Country

United States

ORCID For Submitting Author

0000-0002-6641-0833

Declaration of Conflict of Interest

The authors declare no competing financial interest

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