Catalysis

Nucleophilic addition

Photochemistry

Crossover

Computer science

Medicinal chemistry

Redox

Combinatorial chemistry

Physics

Organic chemistry

Photoredox catalysis

Astronomy

Nucleophile

Polar

Radical ion

Artificial intelligence

Carbocation

Chemistry

Photocatalysis

Halogenation

Journal of the American Chemical Society

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.

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