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Abstract We report copper(II) and copper(III) trifluoromethyl complexes supported by a pyridinedicarboxamide ligand (L) as a platform for investigating the role of electron transfer in C(sp²)−H trifluoromethylation. While the copper(II) trifluoromethyl complex is unreactive towards (hetero)arenes, the formal copper(III) trifluoromethyl complex performs C(sp²)−H trifluoromethylation of a wide range of (hetero)arenes. Mechanistic studies using the copper(III) trifluoromethyl complex suggest that the mechanism of arene trifluoromethylation is substrate‐dependent. When the thermodynamic driving force for electron transfer is high, the reaction proceeds through a previously unidentified single electron transfer (SET) mechanism, where an initial electron transfer occurs between the substrate and oxidant prior to CF₃group transfer. Otherwise, a CF₃radical release/electrophilic aromatic substitution (S_EAr) mechanism is followed. These studies provide valuable insights into the role of strong oxidants and potential mechanistic dichotomy in Cu‐mediated C(sp²)−H trifluoromethylation. 

Abstract We outline a new synthetic method to prepare mono‐ and polyfluoroepoxides from a diverse pool of electrophiles (ketones, acyl chlorides, esters) and fluoroalkyl anion equivalents. The initially formed α‐fluoro alkoxides undergo subsequent intramolecular ring closure when heated. We demonstrated the versatility of the method through the isolation of 16 mono‐ and polyfluoroepoxide products. These compounds provide unique entry points for further diversification via either fluoride migration coupled with ring opening, or defluorinative functionalization reactions, the latter of which can be used as a late‐stage method to install select bioactive moieties. The reaction sequences described herein provide a pathway to functionalize the commonly observed products formed from 1,2‐addition into carbonyl electrophiles 

Fluorine-containing allyl compounds are prevalent in drugs and bioactive molecules. Here, we report a straightforward and efficient radical pentafluorosulfanylation of allyl sulfones using sulfur chloride pentafluoride (SF₅Cl) to synthesize structurally diverse pentafluorosulfanyl allylic compounds. This transformation exhibits excellent functional group tolerance and achieves an impressive isolated yield of up to 98% in just 1 minute under ultraviolet light. Mechanistic studies suggest that the sulfonyl group acts as a free radical leaving group, with the capability of abstracting the chlorine atom from SF₅Cl. This radical chain propagation pathway facilitates the rapid regeneration of the sulfur pentafluoride radical, resulting in a notably high quantum yield. Moreover, this light-driven radical pentafluorosulfanylation simplifies the synthetic pathway to modify complex and bioactive molecules. In addition, the drug-modified pentafluorosulfanyl compounds exhibited promising effects in inhibiting cancer cell proliferation, both in vitro and in vivo. Therefore, this protocol provides a practical synthetic route to radical pentafluorosulfanylation, highlighting its potential in drug discovery. 

A metal-free strategy to access tertiary difluoromethylene-containing molecules from RCF₂H (R = aryl, H, F) precursors, vinyl-pinacol boronic ester (BPin) reagents, and proradical reagents is reported. 

The selection of electronically-different thiolate-based photosensitizers is employed to achieve a precise and specific C–F bond defluorination of a broad range of trifluoromethylarenes, enabling the synthesis of 88 α,α-difluoromethyl compounds. 

We report a metal-free strategy to access fluoroalkyl–olefin linkages from RCF₂H (R = aryl, H, F and fluoroalkyl) precursors and vinyl-pinacol boronic ester (BPin) reagents. 

Using a Lewis acid-quenched CF2Ph- reagent, we show C–C bond formation through nucleophilic addition reactions to prepare molecules containing internal –CF2– linkages. We demonstrate C(sp2)–C(sp3) coupling using both SNAr reactions and Pd-catalysis. Finally, C(sp3)–C(sp3) bonds are forged using operationally simple SN2 reactions that tolerate medicinally-relevant motifs.