Electrochemical metal-free functionalization of ArCF₃: efficient construction of C–S, C–Se, C–D, C–H, and C–C bonds

Abstract

Herein, we report an innovative metal-free catalytic electrochemical defluorination method for constructing C–S, C–Se, C–D, C–H, and C–C bonds. This approach offers excellent versatility, starting from simple trifluoroarylbenzene as a starting material and enabling coupling with disulfides, diselenides, thiols, silyl thioethers, and sulfonyl thioethers, which greatly extends the substrate range compared to conventional methods. Furthermore, variation of the solvent allows for controlled defluorofunctionalization, enabling hydrodefluorination (ArCF₂H), deuterodefluorination (ArCF₂D), complete hydrogenation (ArCH₃), and complete deuteration (ArCD₃). The deuterodefluorination proceeds with a high deuterium incorporation ratio. By employing a continuous flow reactor system, we have succeeded in expanding the reaction process while halving the reaction time, increasing productivity and practical applicability. This green synthetic protocol features multiple advantages including catalyst-free conditions, ambient temperature operation, and high atom economy, effectively avoiding the environmental concerns associated with transition metal catalysts. Particularly noteworthy is its excellent functional group tolerance and chemoselectivity, which enables precise molecular editing of fluorinated compounds.

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Green foundation

1. This study developed a mild, metal-free electrochemical method for selective C–F bond cleavage in ArCF₃, enabling efficient construction of C–S, C–Se, C–H, C–D, and C–C bonds and providing an innovative green synthesis route for high-value sulfur- and selenium-containing compounds.

2. The strategy adheres to green chemistry principles by using electricity as a clean reductant and low-cost electrodes under ambient conditions, reducing energy consumption while offering scalability. It significantly enhances process sustainability and expands the transformation scope compared to conventional noble-metal catalysis.

3. Systematic optimization confers excellent substrate generality. The approach efficiently constructs high-value bonds (e.g., C–S, C–Se) via continuous-flow technology. Simple solvent variation enables precise control over defluorination pathways, achieving efficient hydro/deuterodefluorination to complete hydrogenation/deuteration, with the reusable deuterated solvent underscoring its atom economy and environmental compatibility.

Introduction

Perfluoroalkyl substances (PFAS) incorporating trifluoromethyl (CF₃) or difluoromethylene (–CF₂–) moieties have been identified as environmentally persistent contaminants of emerging concern.¹ These synthetic fluorinated chemicals are extensively utilized across multiple industrial sectors, including pharmaceutical development, agricultural chemistry, surfactant production, refrigeration systems, and polymer engineering, owing to their distinctive physicochemical characteristics and biological activity.² The exceptional stability of carbon–fluorine bonds confers valuable thermal resistance and chemical inertness, while their amphiphilic nature enables surface tension modification capabilities.³

However, the same structural features contribute to environmental persistence and bioaccumulation potential through resistance to natural degradation processes. The combination of carbon–fluorine bond stability and bioaccumulation potential has led to their global environmental distribution and classification as emerging contaminants of concern.^2,3,4

It has been shown that a variety of transition metal salts can significantly contribute to the C–F bond activation reaction of benzene trifluoride through the synergistic action of metal hydrides.^1,3b,5 Specifically, compounds such as niobium pentachloride (NbCl₅),⁶ titanium tetrachloride (TiCl₄),⁷ nickel dichloride (NiCl₂),⁸ and palladium acetate (Pd(OAc)₂)⁹ exhibit excellent catalytic performance in a hydrogen transfer defluorination system, which mediates the stepwise defluorination of aryl trifluoromethyls through the formation of reactive metal hydrogen species.

The photochemical transformations of polyfluoroalkanes primarily encompass two distinct categories: (1) non-selective defluorinative processes including hydrogenation and deuteration¹⁰ and (2) controlled defluorinative functionalization enabling regioselective modification.¹¹ Notably, recent advances in radical-mediated mechanisms have allowed precise manipulation of C–F bond cleavage patterns, facilitating not only controlled hydrogenation/deuteration but also the installation of diverse functional groups through defluorinative cross-coupling. These methodologies demonstrate particular utility in constructing partially fluorinated architectures and synthesizing pharmaceutically relevant precursors via late-stage functionalization strategies.

The electrochemical defluorination of polyfluorinated alkanes was first reported in the 19th century,¹² and recent studies have primarily focused on defluorinative carboxylation, deuteration, and hydrogenation.¹³ However, the scope of electrochemical defluorination reactions remains limited, and systematic exploration in this field is still lacking. Herein, we develop a versatile electrochemical strategy to achieve defluorinative sulfenylation, selenylation, and arylation of polyfluorinated alkanes. This approach enables diverse transformations of inert C–F bonds into C–S, C–Se, C–D, C–H and C–C bonds under mild conditions, significantly expanding the scope of electrochemical defluorination reactions and providing new pathways for functionalizing fluorinated building blocks (Scheme 1).

Scheme 1 (a) Defluorinative functionalisation of perfluoroalkyl compounds, (b) electrochemical defluorination, and (c) this work.

Building upon previous advancements in electrochemical defluorination, we aim to degrade fluorinated alkanes into valuable, high-value-added products. Sulfur-containing compounds, particularly thioethers (sulfides), represent a pivotal class of structural motifs ubiquitously present in natural products and biologically active molecules.¹⁴ Their unique physicochemical properties and versatile reactivities have rendered them indispensable in advanced materials sciences, pharmaceutical development, and agrochemical innovations. The strategic construction of carbon–sulfur bonds, as a fundamental synthetic challenge, has consequently emerged as a focal point in contemporary organic synthesis. Over the past decade, significant advancements have been achieved through the integration of emerging synthetic technologies,¹⁵ including photoinduced radical coupling mechanisms,¹⁶ electrochemical mediation strategies,^15b,c,17 and transition-metal-catalyzed cross-coupling protocols.¹⁸ These methodologies not only address traditional limitations in regioselectivity and functional group compatibility but also provide atom-economical pathways for efficient C–S bond formation.

Results and discussion

To achieve the desired transformation, we employed 4-methoxybenzotrifluoride (1a) and diphenyl disulfide (2a) as model substrates for reaction optimization. Systematic evaluation of electrochemical parameters revealed that optimal conditions involved using magnesium as the sacrificial anode and stainless steel (SST) as the cathode in N-methyl-2-pyrrolidone (NMP) containing tetrabutylammonium bromide (TBAB) as the electrolyte, operated at a constant current of 5.0 mA in an undivided cell for 10 h at room temperature. Under these conditions, the target product 3a was obtained in 93% isolated yield (entry 1). The critical role of electrode materials was unequivocally demonstrated through systematic experimentation: substitution of the magnesium anode with iron or zinc completely suppressed product formation (entry 2), while replacing the stainless steel (SST) cathode with alternative materials (nickel foam, copper, nickel, graphite, or platinum) resulted in a substantial decrease in product yield (entry 3). Comprehensive solvent screening demonstrated the superior efficacy of N-methyl-2-pyrrolidone (NMP), with reaction efficiencies in dichloromethane (DCM), acetone, dimethyl sulfoxide (DMSO), or N,N-dimethylformamide (DMF) showing significant reductions (63–90% decrease, entries 4 and 5). Electrolyte optimization studies unveiled composition-dependent effects: TBAB demonstrated maximal efficacy (93% yield, entry 1), whereas TBAPF₆ (40%), TBABF₄ (51%), TBAI (67%), TBAClO₄ (73%), and LiClO₄ (21%) showed markedly inferior performance (entry 7). Current density optimization showed that increasing the current to 20 mA led to complete reaction failure, likely due to over-reduction of both the starting material and the product under higher current conditions. This systematic investigation highlights the delicate balance required between electrode materials, solvent environment, electrolyte selection, and current density for successful electrochemical transformation (entry 8) (Table 1).

Table 1 Optimization of the reaction conditions^a

Entry	Deviation from the above	Yield^b %
a Reaction conditions: 1a (0.4 mmol), 2a (0.2 mmol), TBAB (0.05 M), in NMP (8 mL) under argon for 10 hours, magnesium anode, stainless steel cathode, NFE = nickel foam electrode. b Detected by GC, with Ph–Ph as an internal standard.
1	None	93
2	Fe, Zn instead of Mg	n.d., n.d.
3	NFE, Cu, Ni, C, Pt instead of SST	28, 32, 32, 16, 21
4	DCM, acetone, CH3CN as solvent	Trace, n.d., 43
5	DMA, DMF, DMSO as solvent	27, 8, 8
6	TBAPF6, TBABF4, TBAI instead of TBAB	40, 51, 67
7	TBAClO4, LiClO4 instead of TBAB	73, 21
8	7.5 mA, 10 mA, 20 mA	75, 80, trace
9	No electricity	n.d.
10	Under air	n.d.

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Critical evaluation of control experiments revealed that the application of electrical current and maintenance of a nitrogen atmosphere were indispensable for achieving efficient electrochemical defluorination of sulfides, as evidenced by comparative analyses under non-electrified and aerobic conditions (entries 9 and 10).

To establish the optimal reaction conditions, we systematically explored the substrate compatibility of aryl benzenes and disulfides (Scheme 2).

Scheme 2 Substrate scope of disulfides, aryl-CF₃ and dideuterothioethers. Reaction conditions: 1a (0.4 mmol, 2.0 equiv.), 2a (0.20 mmol, 1 equiv.), TBAB (0.05 M or 0.1 M), NMP (8 mL) or CD₃CN (4 mL), magnesium anode, stainless steel cathode, 5 mA, 10 h, under an argon atmosphere. The isolated yield is reported.

Initial investigations focused on diaryl disulfides bearing diverse electronic substituents. Notably, both electron-donating (e.g., Me, ^tBu) and electron-withdrawing (e.g., F, Cl) group-substituted diaryl disulfides underwent smooth conversion to afford the corresponding products in satisfactory yields (68–93%). Notably, both electron-rich and electron-poor thiophenol (thiophene), oxygen-containing (furan), and nitrogen-containing (pyridine) heterocyclic disulfides displayed competitive reactivity, delivering the target products in 45–71% isolated yields. This successful adaptation to heteroaromatic systems significantly expands the synthetic utility of our methodology.

A particularly noteworthy achievement lies in its successful application to aliphatic disulfides – a class traditionally challenging in such transformations. Primary dialkyl disulphides were highly reactive, with conversions ranging from 60–75%, while cyclohexyl disulfides afforded products in 75% yields. Most remarkably, the method proved capable of overcoming severe steric hindrance, as evidenced by the successful transformation of highly hindered tertiary disulfides (78% yield), a feat rarely achieved in conventional systems.

For the aryl-CF₃ substrates investigated, systematic studies revealed a pronounced electronic effect on reaction efficiency. Substrates bearing electron-donating groups (EDGs) demonstrated superior reactivity compared to their electron-withdrawing group (EWG)-substituted counterparts, with isolated yields ranging from 65% to 82% for EDG-modified substrates. However, the system exhibited partial tolerance toward moderately electron-withdrawing substituents including fluorine (–F), chlorine (–Cl), methoxycarbonyl (–CO₂Me), and cyano (–CN) groups, delivering the corresponding products in 35–55% yields.

Complete reaction failure was observed in the presence of strongly electron-deficient substituents such as nitro (–NO₂) and methylsulfonyl (–SO₂Me) groups.

This reactivity pattern aligns with the proposed reaction mechanism, where electron-donating groups likely stabilize key intermediates through resonance or inductive effects. The complete inhibition by –NO₂ and –SO₂Me substituents may stem from their combined electronic deactivation and potential coordination effects with the catalytic system. These findings underscore the critical balance between electronic modulation and steric accessibility required for successful transformation in this electrochemical platform. By switching to CD₃CN as the solvent, we achieved the construction of dideuterated sulfides, and various substrates demonstrated good compatibility under these conditions. After the reaction is completed, deuterated acetonitrile can be recycled by distillation under reduced pressure while still maintaining a high deuterium content.

A systematic investigation was conducted on various sulfur reagents, with particular emphasis on thiophenol derivatives (Scheme 3). The reaction demonstrated good functional group tolerance toward diverse aryl thiophenols, including substrates bearing electron-donating (e.g., 4-tert-butyl), electron-withdrawing (e.g., 4-chloro and 4-fluoro), and extended aromatic systems. Notably, naphthalenethiol proved to be a viable substrate, achieving a moderate isolated yield of 56%. Interestingly, heteroatom-containing thiophenols (e.g., thiophene-based derivatives) also exhibited acceptable compatibility under the optimized conditions. Beyond aryl thiophenols, the protocol was successfully extended to a range of alkyl thiophenols with different substitution patterns. Primary, secondary, and tertiary alkyl thiophenols all delivered satisfactory results, with representative examples including cyclohexanethiol (secondary, 72% yield) and tert-butylthiol (tertiary, 68% yield), demonstrating the broad applicability of this methodology.

Scheme 3 Substrate scope of thiophenols and mercaptan. Reaction conditions: 1a (0.4 mmol, 2.0 equiv.), TBAB (0.05 M), NMP (8 mL), magnesium anode, stainless steel cathode, 10 mA, 10 h, under an argon atmosphere. The isolated yield is reported.

In addition to disulfides and thiophenols, we also tried other sulfide reagents, for example, silyl sulfide and sulfone sulfide, under standard conditions (Scheme 4). Silyl sulfide, sulfone sulfide and 4-methoxybenzotrifluoride were able to provide the corresponding products in moderate yields, and, to our astonishment, for diphenyl diselenide also the reaction system was tolerant and achieved fifty per cent isolated yield. In the attempt of defluorination to construct the carbon–carbon bond, we found that the separation yield of trifluorotoluene and p-benzenedicarbonitrile was 18% when magnesium was used as the anode, nickel foam was used as the cathode, DMA was used as the solvent, and TBAI was used as the electrolyte, and further attempts were made to defluorinate to construct the carbon–carbon bond.

Scheme 4 Different sulfuring reagents and p-phthalonitrile. Reaction conditions: 1a (0.4 mmol, 2.0 equiv.), TBAB (0.05 M), NMP (8 mL) or DMA (8 mL), magnesium anode, stainless steel cathode, 5 mA, 10 h, under an argon atmosphere. The isolated yield is reported.

Controlled defluorohydrogenation and defluorodeuteration of aryl-CF₃

The Ar-CF₂H and Ar-CF₂D moieties are featured in an increasing number of bioactive compounds due to their unique combination of properties (Scheme 5).

Scheme 5 Controlled defluorohydrogenation and defluorodeuteration of aryl-CF₃. Reaction conditions: 1a (0.2 mmol), TBAB (0.1 M), CH₃CN (4 mL) or CD₃CN (4 mL), magnesium anode, stainless steel cathode, 5 mA, 5 h, under an argon atmosphere. The isolated yield is reported.

Under standard conditions, we successfully achieved the synthesis of ArCF₂H and ArCF₂D by switching the solvent to acetonitrile and deuterated acetonitrile. To our delight, the deuteration ratio of ArCF₂D reached as high as 99%. After the reaction is completed, deuterated acetonitrile can be recycled by distillation under reduced pressure while still maintaining a high deuterium content.

Full deuteration via defluorination of aryl-CF₃

Under standard conditions, using DMF and CD₃CN as a mixed solvent system, we achieved complete defluorodeuteration of aryl-CF₃ with broad substrate compatibility (Scheme 6). It is noteworthy that the defluorination achieved excellent results for some drug-derived ArCF₃, such as sugar, menthol, citronellol and so on.

Scheme 6 Full deuteration via defluorination of aryl-CF₃, and sequential defluorination of aryl-CF_3. Reaction conditions: 1a (0.2 mmol), TBAB (0.1 M), CH₃CN (4 mL) or CD₃CN (4 mL), magnesium anode, stainless steel cathode, 5 mA, 10 h, under an argon atmosphere. The isolated yield is reported.

Sequential defluorination of aryl-CF₃

Under standard conditions, the use of acetonitrile or deuterated acetonitrile as the solvent enables the formation of ArCF₂H or ArCF₂D. Without the need for isolation, these intermediates can undergo further defluorination to yield methyl and fully deuterated methyl groups, achieving a combined yield of 72% in two steps.

Full hydrogenation via defluorination of aryl-CF₃

Under the standard conditions, we also tried substrate expansion for full hydrogenation via defluorination of aryl-CF₃, and the reaction was excellent for ArCF₃ with electron-donating groups and a little less effective for ArCF₃ with electron-withdrawing groups, and it is noteworthy that the defluorination achieved excellent results for some drug-derived ArCF₃, such as sugar, menthol, citronellol and so on (Scheme 7).

Scheme 7 Full hydrogenation via defluorination of aryl-CF₃. Reaction conditions: all reactions were carried out with 1a (0.2 mmol, 1.0 equiv.), TBAI (0.1 M), DMA (8 mL), magnesium anode, stainless steel cathode, 10 mA, 2 h, under an argon atmosphere. The isolated yield is reported.

Gram-scale experiment

We used 4-methoxybenzotrifluoride as a template substrate to scale up the reaction to a gram scale, and we were pleased that the reaction achieved 82% yield, and we obtained 1.5 g of the target product of hydrogenation.

Investigation of the reaction in continuous flow

In a continuous flow reaction, at a constant current of 10 mA and a flow rate of 0.1 mL min⁻¹, only a trace amount of the product was observed. At a constant current, we reduced the flow rate to 0.01 mL min⁻¹ and achieved a yield of 64%, and when the flow rate was lowered to 0.005 mL min⁻¹, the reaction system underwent over-reduction, and the product generated was reduced, and only a trace amount of the product could be detected. Changing the current at a flow rate of 0.01 mL min⁻¹ revealed that 10 mA was the optimal current condition, and the successful realisation of the continuous flow reaction laid the foundation for transferring the reaction from the laboratory to industry. Under the optimal continuous flow reaction conditions, we also made attempts with different substrates, all of which resulted in good yields and greatly reduced the reaction time (Scheme 8).

Scheme 8 Investigation of the reaction in continuous flow. Reaction conditions: 1a (0.4 mmol, 2.0 equiv.), 2a (0.20 mmol, 1 equiv.), TBAB (0.1 M), NMP (4 mL), magnesium anode, stainless steel cathode, under an argon atmosphere. The isolated yield is reported.

Cyclic voltammetry

In order to gain insight into the reaction mechanism, a series of cyclic voltammetry (CV) experiments were performed. These cyclic voltammetry experiments were conducted with 1a and 2a as the substrates, ⁿBu₄NBF₄ as the electrolyte, and NMP as the solvent. As shown in Scheme 9B, 2a showed a reduction peak at 2.00 V. In comparison, a reduction peak at 2.60 V was observed for 1a, indicating that it was more difficult to reduce than 2a. The reduction potential of the product (3a) is lower compared to that of the starting material, making it more difficult to reduce, which has also been confirmed in previous literature reports.

Scheme 9 (A) Mechanistic study, 1. radical trapping experiment, 2. control experiments, 3. stepwise experiments, 4. reaction monitoring, (B) CV, (C) possible mechanism.

Mechanistic study

In radical trapping experiments, when 2 equiv. of TEMPO or BHT were added to the reaction system under standard conditions, no reaction products were found and the reaction was completely inhibited. In addition, 2 equiv. of 1,1-diphenylethylene were added to the reaction system under standard conditions, and GCMS was performed during the reaction, and the system showed a product of the benzyl radical coupled with the 1,1-diphenylethylene.

In the absence of diphenyl disulfide, ArCF₃ undergoes reductive defluorination to form the compound ArCF₂H. Under standard conditions, the reaction did not proceed in the absence of electrical power, demonstrating that the process involves electrochemical reduction and that electrons are an essential requirement for the reaction to occur.

For sulphide, whether aryl sulphide or alkyl sulphide, self-coupling products are generated under standard conditions, and we carried out not only GCMS detection, but also separation and NMR verification of the self-coupling products.

Under standard conditions, ArCF₃ and diphenyl disulfide can form the final product. In comparison, ArCF₂H and diphenyl disulfide can also generate the corresponding product, albeit with a lower yield. When the solvent is switched to CH₃CN or CD₃CN, deuterated thioether products can be obtained.

Under the mixed solvent system of DMF and deuterated acetonitrile, monitoring of the reaction system revealed the initial formation of CF₂D products. With prolonging of the reaction time, the yield of CF₂D increased progressively. After two hours, CD₃-containing products began to accumulate gradually, reaching maximum formation after 6 hours.

Possible mechanisms

Under electrochemical conditions, disulfide undergoes reductive cleavage to generate radicals and anions. This reaction process may proceed through two possible pathways. Aryl-CF₃ in the cathode surface is quickly reduced and defluorinated to generate aryl-CF₂ radicals, under standard conditions, sulfur radicals initially generate free radicals followed by radical coupling to form difluoromethyl aryl sulfide (Ar-CF₂SPh). Ar-CF₂SPh undergoes further defluorination to afford the corresponding product.

General procedure for the continuous-flow reaction

First, a flow electrochemistry device was assembled and installed, with a Mg electrode as the anode, SST as the cathode and a cell volume of 3 mL. Second, 1a (0.1 M), 2a (0.05 M), and ⁿBu₄Br (0.05 M) were dissolved in NMP (30 mL), with dodecane as the internal standard. The reaction mixture was pumped into the flow cell via a syringe and electrolyzed at a constant current of 10 mA at room temperature. The flow rate was 0.05 mL min⁻¹ and the residence time was 5 h. The out flow of the reaction mixture was collected and monitored.

General procedure for product 3a formation

In a glovebox, an oven-dried undivided reactor (10 mL) equipped with 1a (0.4 mmol, 2.0 equiv.), 2a (0.2 mmol, 1 equiv.), TBAB (0.15 M) and a stir bar before adding NMP (8 mL) was placed. The reactor was equipped with a Mg electrode (53 × 8 × 2 mm) as the anode and a foamed SST electrode (53 × 8 × 2 mm) as the cathode. The reaction mixture was stirred and electrolyzed at a constant current of 5 mA. (The dual display potentiostat was operated in constant current mode) at room temperature for 10 h. When the reaction was completed, the solution was extracted with ethyl acetate (3 × 15 mL), and the combined organic layers were concentrated with a rotary evaporator. The crude product was purified by PTLC to afford the corresponding product (hexane : ethyl acetate = 20 : 1).

Conclusions

In conclusion, we have developed a highly efficient method of defluorination from trifluoroarylbenzene to complete the construction of C–S, C–Se, C–D, C–H, C–C bonds, which is simple, atomically economical, and has mild conditions. It is not only applicable to reactions in reaction vials, but also capable of being developed into a electrochemical continuous flow method, which greatly shortens the time of the reaction by enlarging the specific surface area of the reaction, which provides the basis for the industrialisation of the reaction.

Author contributions

Y. W. designed and guided this project. Z. M. X. is responsible for the planning and implementation of the experimental work. All authors co-wrote the manuscript, analysed the data, discussed the results and commented on the manuscript.

Conflicts of interest

The authors declare no competing interests.

Data availability

The data that support the findings of this study are available in the supplementary information (SI) or on request from the corresponding author.

The Supplementary Information for this article contains detailed experimental procedures, characterization data (NMR spectra, mass spectrometry data), and synthetic methods for relevant compounds. See DOI: https://doi.org/10.1039/d5gc05060j.

Acknowledgements

We gratefully acknowledge the financial support from the National Natural Science Foundation of China (No. 22071101, 22271147 and 22471123).

References

1. (a) T. Stahl, H. F. T. Klare and M. Oestreich, ACS Catal., 2013, 3, 1578–1587; (b) G. Yan, Chem. – Eur. J., 2022, 28, e202200231.
2. (a) H. Zhang, J.-X. Chen, J.-P. Qu and Y.-B. Kang, Nature, 2024, 635, 610–617; (b) X. Liu, A. Sau, A. R. Green, M. V. Popescu, N. F. Pompetti, Y. Li, Y. Zhao, R. S. Paton, N. H. Damrauer and G. M. Miyake, Nature, 2025, 637, 601–607.
3. (a) B. Trang, Y. Li, X.-S. Xue, M. Ateia, K. N. Houk and W. R. Dichtel, Science, 2022, 377, 839–845; (b) Q. Wan, R. Liu, Z. Zhang, X. Wu, Z. Hou and L. Wang, Chin. J. Chem., 2024, 42, 1913–1928.
4. L. Yang, Z. Chen, C. A. Goult, T. Schlatzer, R. S. Paton and V. Gouverneur, Nature, 2025, 640, 100–106.
5. J.-L. Röckl, E.-L. Robertson and H. Lundberg, Org. Biomol. Chem., 2022, 20, 6707–6720.
6. (a) K. Fuchibe, Y. Ohshima, K. Mitomi and T. Akiyama, J. Fluorine Chem., 2007, 128, 1158–1167; (b) K. Fuchibe, Y. Ohshima, K. Mitomi and T. Akiyama, Org. Lett., 2007, 9, 1497–1499.
7. (a) T. Akiyama, K. Atobe, M. Shibata and K. Mori, J. Fluorine Chem., 2013, 152, 81–83; (b) T. Yamada, K. Saito and T. Akiyama, Adv. Synth. Catal., 2016, 358, 62–66.
8. J. Wu and S. Cao, ChemCatChem, 2011, 3, 1582–1586.
9. H. Dang, A. M. Whittaker and G. Lalic, Chem. Sci., 2016, 7, 505–509.
10. R. Sun, G. Li, F. Xie, Q. Zhang, Y. J. Sun and W. Dai, Org. Lett., 2024, 26, 928–932.
11. (a) C. M. Hendy, C. J. Pratt, N. T. Jui and S. B. Blakey, Org. Lett., 2023, 25, 1397–1402; (b) J. Huang, Q. Gao, T. Zhong, S. Chen, W. Lin, J. Han and J. Xie, Nat. Commun., 2023, 14, 8292; (c) J. Li, Z. Guo, X. Zhang, X. Meng, Z. Dai, M. Gao, S. Guo and P. Tang, Green Chem., 2023, 25, 9292–9300; (d) C. Liu, K. Li and R. Shang, ACS Catal., 2022, 12, 4103–4109; (e) J. B. I. Sap, N. J. W. Straathof, T. Knauber, C. F. Meyer, M. Médebielle, L. Buglioni, C. Genicot, A. A. Trabanco, T. Noël, C. W. am Ende and V. Gouverneur, J. Am. Chem. Soc., 2020, 142, 9181–9187; (f) D. B. Vogt, C. P. Seath, H. Wang and N. T. Jui, J. Am. Chem. Soc., 2019, 141, 13203–13211; (g) J. Xu, J.-W. Liu, R. Wang, J. Yang, K.-K. Zhao and H.-J. Xu, ACS Catalysis., 2023, 13, 7339–7346.
12. (a) C. Saboureau, M. Troupel, S. Sibille and J. Périchon, J. Chem. Soc., Chem. Commun., 1989, 1138–1139; (b) O. Sock, M. Troupel and J. Perichon, Tetrahedron Lett., 1985, 26, 1509–1512; (c) H. Hebri, E. Duñach and J. Périchon, Synth. Commun., 1991, 21, 2377–2382; (d) C. P. Andrieux, A. Le Gorande and J. M. Savéant, J. Am. Chem. Soc., 1992, 114, 6892–6904; (e) C. P. Andrieux, C. Combellas, F. Kanoufi, J. M. Savéant and A. Thiébault, J. Am. Chem. Soc., 1997, 119, 9527–9540; (f) P. Clavel, M. P. Léger-Lambert, C. Biran, F. Serein-Spirau, M. Bordeau, N. Roques and H. Marzouk, Synthesis, 1999, 829–834; (g) P. Clavel, G. Lessene, C. Biran, M. Bordeau, N. Roques, S. Trévin and D. de Montauzon, J. Fluorine Chem., 2001, 107, 301–310; (h) J.-L. Röckl, E.-L. Robertson and H. Lundberg, Org. Biomol. Chem., 2022, 20, 6707–6720; (i) L. Radom, W. J. Hehre and J. A. Pople, J. Am. Chem. Soc., 1971, 93, 289–300; (j) H.-A. Bent, Chem. Rev., 1961, 61, 275–311; (k) P.-J. Elving and J.-T. Leone, J. Am. Chem. Soc., 1957, 79, 1546–1550; (l) H. Lund, I. Fischmeister, E. Stenhagen, G. Andersson, E. Stenhagen and H. Palmstierna, Acta Chem. Scand., 1959, 13, 192–194; (m) H. Senboku, Y. Yamauchi, T. Fukuhara and S. Hara, Synlett, 2008, 438–442.
13. (a) J.-R. Box, M.-E. Avanthay, D.-L. Poole and A. J. J. Lennox, Angew. Chem., Int. Ed., 2023, 62, e202218195; (b) S. Mondal, B. Stevanovic, E. Butler, J.-W. Wang and M.-W. Meanwell, Chem. Commun., 2023, 59, 6694–6697; (c) J. Kuzmin, J. Röckl, N. Schwarz, J. Djossou, G. Ahumada, M. Ahlquist and H. Lundberg, Angew. Chem., Int. Ed., 2023, 62, e202304272; (d) M. Söderström, E. O. Håkansson and L. R. Odell, Chem. Commun., 2025, 61, 145–148; (e) L. Zhou, Molecules, 2021, 26, 7051; (f) W. Xu, Q. Zhang, Q. Shao, C. Xia and M. Wu, Asian J. Org. Chem., 2021, 10, 2454–2472; (g) G. Yan, Chem. – Eur. J., 2022, 28, e202200231; (h) Q. Wan, R. Liu, Z. Zhang, X. Wu, Z. Hou and L. Wang, Chin. J. Chem., 2024, 42, 1913–1928; (i) S. Roy and T. Besset, JACS Au, 2025, 5, 466–485; (j) C. Cheng, Y. Huang, L. Wang, M. Luo and Q. Xiao, Adv. Synth. Catal., 2025, e2025888; (k) P. S. Shinde, V. S. Shinde, C. Zhu and M. Rueping, ACS Catal., 2025, 15, 17198–17205; (l) J. L. R. Collazo, C. Westlund, H. Keita and S. J. Meek, Angew. Chem., Int. Ed., 2025, e202515710; (m) X. Kong, Y. Chen, S. Zhang, K. Feng, X. Chen, L. H. Dong, M. H. Li, Y. Q. Xu and Z. Y. Cao, Chem. Sci., 2025, 16, 14161–14169; (n) M. Guo, Z.-P. Ye, Y.-Q. Ye, X.-Q. Chen, K. Chen and H. Yang, Org. Chem. Front., 2025, 12, 6569–6574; (o) N. Feng, M. Jiang, H. Wang, Y. Zhong, Y. Sun, D. Yang and F. Zhou, Org. Chem. Front., 2025, 12, 4750–4756; (p) Z. Zhang, J. Liu, Z. Zhang, G. Liu, Y.-Y. Jiang and Y. Zhao, Org. Lett., 2025, 27, 6422–6428.
14. (a) K. Choudhuri, M. Pramanik and P. Mal, J. Org. Chem., 2020, 85, 11997–12011; (b) N. Sundaravelu, S. Sangeetha and G. Sekar, Org. Biomol. Chem., 2021, 19, 1459–1482; (c) D. Xiao, Y. Wang, X. Hu, W. Kan, Q. Zhang, X. Jiang, Y. Zhou, J. Li and W. Lu, Eur. J. Med. Chem., 2019, 176, 419–430.
15. (a) Q. Zhang, X. Li, W. Zhang, Y. Wang and Y. Pan, Org. Lett., 2021, 23, 5410–5414; (b) Y. Liu, X. Tao, Y. Mao, X. Yuan, J. Qiu, L. Kong, S. Ni, K. Guo, Y. Wang and Y. Pan, Nat. Commun., 2021, 12, 6745; (c) H. Shu, X. Tao, S. Ni, J. Liu, J. Xu, Y. Pan and Y. Wang, Chem. Sci., 2025, 16, 2682–2689; (d) Y. Wang, L. Deng, X. Wang, Z. Wu, Y. Wang and Y. Pan, ACS Catal., 2019, 9, 1630–1634; (e) F. Zhang, Y. Wang, Y. Wang and Y. Pan, Org. Lett., 2021, 23, 7524–7528; (f) W. Zhang, M. Huang, Z. Zou, Z. Wu, S. Ni, L. Kong, Y. Zheng, Y. Wang and Y. Pan, Chem. Sci., 2021, 12, 2509–2514; (g) Z. Zou, H. Li, M. Huang, Y. Shen, J. Liu, Z. Wang, W. Zhang, Y. Wang and Y. Pan, Chinese J. Org. Chem., 2024, 44, 1831–1852.
16. (a) J. Grover, G. Prakash, C. Teja, G. K. Lahiri and D. Maiti, Green Chem., 2023, 25, 3431–3436; (b) D. Cao, P. Pan, C.-J. Li and H. Zeng, Green Synth. Catal., 2021, 2, 303–306; (c) Y. Dong, P. Ji, Y. Zhang, C. Wang, X. Meng and W. Wang, Org. Lett., 2020, 22, 9562–9567.
17. Y. Li, H. Wang, Z. Wang, H. Alhumade, Z. Huang and A. Lei, Chem. Sci., 2023, 14, 372–378.
18. (a) J. Semenya, Y. Yang and E. Picazo, J. Am. Chem. Soc., 2024, 146, 4903–4912; (b) Y. Chen, F. Wang, B.-X. Liu, W.-D. Rao and S.-Y. Wang, Org. Chem. Front., 2022, 9, 731–736; (c) Y.-Z. Yang, Y. Li, G.-F. Lv, D.-L. He and J.-H. Li, Org. Lett., 2022, 24, 5115–5119.

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Footnote

† These authors contributed equally to this work.

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