Outcompeting Thermodynamics: Ion-Pairing and Coulombic Interactions to Trigger Perfluoroacetate Intra-Ionic Photooxidation for Perfluoroalkylation Reactions

作者：Pengju Li, Céline Bourgois, Felix Glaser, Simon De Kreijger, Alejandro Cadranel, Ludovic Troian‐Gautier, Ke Hu · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.5c00129 · 被引用次数：21 · 研究领域：Fluorine in Organic Chemistry、Inorganic Fluorides and Related Compounds、Per- and polyfluoroalkyl substances research

Trifluoromethylation is a key transformation in drug and agrochemical synthesis, yet current reagents often suffer from high cost, low atom economy, and low scalability. Trifluoroacetate derivatives represent ideal reagents as they are highly abundant and cheap, but their very positive one electron oxidation potential (∼2.3 V vs NHE) often hampers their widespread use in photoredox catalysis. Indeed, at these potentials, selectively oxidizing trifluoroacetate over reaction solvent or partner substrates becomes challenging. Herein, we present a novel approach that circumvents these limitations through the use of a pentacationic Ir(III) photosensitizer that forms a strong 1:1 ion-pair with trifluoroacetate in acetonitrile ( K eq = 6 × 10 4 M –1 ). This ion-pair formation enables rapid and efficient photooxidation of trifluoroacetate in ∼90 ps without significant solvent or partner substrate oxidation, as indicated by femtosecond and nanosecond UV–visible transient absorption spectroscopy. The CF 3 • radicals so generated are shown to trifluoromethylate a range of partner substrates, including aromatic compounds, heterocycles, natural products and pharmaceutically relevant products, in moderate yields (20–60%). Control experiments reveal that ion-pairing is crucial for the successful generation of CF 3 • as photosensitizers that oxidize trifluoroacetate without forming ion pairs were ineffective for trifluoromethylation. This probably originates from the more thermodynamically a...