Late-Stage Aryl NCF ₃ and SCF ₃ Installation Enabled by Coupling Flow-Generated Anions with Aryl Thianthrenium Salts

The incorporation of heteroatom-linked trifluoromethyl groups, such as N-trifluoromethyl (NCF3) and trifluoromethylthio (SCF3) motifs, remains challenging, particularly in the context of late-stage aryl functionalization. Herein, we report a flow-enabled platform that allows for the late-stage installation of NCF3 and SCF3 groups onto aryl frameworks through the coupling of flow-generated nucleophilic heteroatom–CF3 anions with aryl thianthrenium salts. In this strategy, readily available organic precursors are converted on demand into NCF3 and SCF3 anions using a CsF-packed bed reactor, allowing safe handling of highly reactive fluorinated intermediates while minimizing fluorinated waste. The resulting anions are subsequently engaged in a copper-mediated, photocatalytic cross-coupling, enabling efficient formation of aryl–NCF3 and aryl–SCF3 bonds under mild conditions. The method exhibits broad substrate scope and functional group tolerance, and is applicable to the late-stage diversification of medicinally and agrochemically relevant molecules. Overall, this work expands the scope of nucleophilic CF3X anions as viable partners in late-stage aryl functionalization and provides a modular platform for the discovery-oriented synthesis of fluorinated molecules.