Late-stage Installation of Emerging Fluorinated Motifs Onto Aromatic Compounds

- Late-stage installation of emerging fluorinated motifs onto aromatic compounds 11 June 2026 In a paper just out in the Journal of the American Chemical Society (JACS), researchers of the Flow Chemistry group at the Van 't Hoff Institute for Molecular Sciences describe a method for the late-stage installation of emerging fluorinated motifs onto aromatic compounds. The paper presents a practical platform to install these groups across a broad range of substrates, including several drug-like molecules. Image: HIMS / JACS. The NCF 3 and SCF 3 fluorinated motifs have attracted increasing interest in medicinal and agrochemical chemistry, but methods for introducing them at a late stage remain scarce. In their JACS paper, the researchers present how this can be achieved by combining the on-demand generation of NCF 3 and SCF 3 anions in flow, with the copper-mediated photocatalytic coupling of aryl thianthrenium salts. By generating the highly reactive fluorinated intermediates only when needed, they can be handled safely while also minimising fluorinated waste. The study brings together the areas that have been central to the research of the Flow Chemistry group over the past years: flow chemistry, fluorine chemistry, photocatalysis, and late-stage functionalisation. Abstract, as published with the paper The incorporation of heteroatom-linked trifluoromethyl groups, such as N-trifluoromethyl (NCF 3 ) and trifluoromethylthio (SCF 3 ) motifs, remains challenging, particularly in the context of late-stage aryl functionalisation. Herein, we report a flow-enabled platform that allows for the late-stage installation of NCF 3 and SCF 3 groups onto aryl frameworks through the coupling of flow-generated nucleophilic heteroatom-CF 3 anions with aryl thianthrenium salts. In this strategy, readily available organic precursors are converted on demand into NCF 3 and SCF 3 anions using a CsF-packed bed reactor, allowing safe handling of highly r...