Photocatalytic C-F bond activation in small molecules and polyfluoroalkyl substances.

Liu, Xin; Sau, Arindam; Green, Alexander R; Popescu, Mihai V; Pompetti, Nicholas F; Li, Yingzi; Zhao, Yucheng; Paton, Robert S et al. · Nature · 2025

basic_science · Level V

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Abstract

Organic halides are highly useful compounds in chemical synthesis, in which the halide serves as a versatile functional group for elimination, substitution and cross-coupling reactions with transition metals or photocatalysis<sup>1-3</sup>. However, the activation of carbon-fluorine (C-F) bonds-the most commercially abundant organohalide and found in polyfluoroalkyl substances (PFAS), or 'forever chemicals'-is much rarer. Current approaches based on photoredox chemistry for the activation of small-molecule C-F bonds are limited by the substrates and transition metal catalysts needed<sup>4</sup>. A general method for the direct activation of organofluorines would have considerable value in organic and environmental chemistry. Here we report an organic photoredox catalyst system that can efficiently reduce C-F bonds to generate carbon-centred radicals, which can then be intercepted for hydrodefluorination (swapping F for H) and cross-coupling reactions. This system enables the general use of organofluorines as synthons under mild reaction conditions. We extend this method to the defluorination of PFAS and fluorinated polymers, a critical challenge in the breakdown of persistent and environmentally damaging forever chemicals.