Photoredox-catalyzed three-component radical coupling of potassium alkyltrifluoroborates, DABSO and polyfluoroarenes

Abstract

Polyfluoroarylsulfones not only exhibit distinctive biological and pharmacological activities but also serve as versatile building blocks in organic synthesis, functional materials, polymer photosensitizers, etc. The direct incorporation of the polyfluoroaryl sulfonyl moiety into organic compounds remains an unexplored yet intriguing challenge. In this study, we present a visible light-driven three-component coupling of RBF₄K, DABSO reagent, and polyfluoroarenes through radical–polar crossover mechanisms. Interestingly, this methodology achieves direct C(sp²)–F bond cleavage of polyfluoroarenes under mild conditions, establishing DABSO/polyfluoroarenes as unprecedented polyfluoroarylsulfonation reagents. The synergistic integration of the high reactivity of radical species with the precise regioselectivity of S_NAr processes constitutes the foundation of this innovative strategy. This approach provides a modular platform for synthesis of polyfluoroarylsulfones.

---

Introduction

The polyfluoroaryl sulfonyl skeleton, as a distinctive class of aryl sulfonyl compounds, exhibits unique biological and pharmacological activities,^1–3 thereby holding significant potential for applications in pharmaceutical and medicinal chemistry (Scheme 1A). For example: (i) ciprofloxacin modified with the pentafluoropyridine sulfone derivative A exhibits strong bacteriostatic properties;¹ (ii) polyfluorobenzenesulfonamides B demonstrate inhibitory activity against carbonic anhydrases (CA);² (iii) pentafluorobenzenesulfonamide derivatives C show broad-spectrum cytotoxicity against tumor cells.³ Furthermore, polyfluoroarylsulfones serve as versatile synthons in organic synthesis,⁴ functional materials,⁵ and polymer-based photosensitizers.⁶ However, the scarcity of robust synthetic methodologies has severely hindered their practical utilization. Conventional approaches involve two distinct pathways: (i) oxidation-mediated routes comprising polyfluoroaryl thiophenol oxidation to sulfonyl bromides followed by subsequent transformations⁷ (Scheme 1Ba, upper); (ii) multistep S_NAr sequences requiring thiol coupling with polyfluoroarenes and subsequent oxidation⁴ (Scheme 1Ba, lower). These methods are frequently compromised by harsh reaction conditions and limited functional group tolerance. While sulfinate salt-based S_NAr reactions⁸ provide direct access to polyfluoroarylsulfones (Scheme 1Bb, upper), their dependence on pre-synthesized sodium sulfinate salts diminishes synthetic efficiency. The direct polyfluoroarylsulfonation of alkyl radicals (Scheme 1Bb, lower) employing readily accessible precursors constitutes a promising and conceptually distinct strategy for the precise assembly of polyfluoroarylsulfone scaffolds; however, this approach remains underexplored.

Scheme 1 Motivation for developing PC-catalysed three-component radical coupling for polyfluoroarylsulfones.

On the other hand, direct integration of the sulfonyl group into organic molecules represents a promising avenue for sulfonyl-containing motifs.^9–11 Sulfur dioxide (SO₂) emerges as an ideal candidate; however, its toxicity and cumbersome operation restrict its further applications. For this purpose, DABSO¹⁰ was employed as a convenient and stable SO₂ surrogate to participate in multicomponent coupling reactions. Visible light catalysis¹² has become a powerful tool in radical SO₂ chemistry, as it promotes cascade sulfonation under extremely mild conditions.^11,13 Inspired by these results, we designed a three-component coupling of reductive alkyl radical sources, DABSO, and polyfluoroarenes¹⁴ under photoredox conditions (Scheme 1C). According to our proposed reaction scenario, photooxidatively generated alkyl radicals can be efficiently trapped by SO₂, followed by photoreductive conversion into sulfonyl anions that undergo polar S_N2 substitution to yield the target products. However, alkyl radicals may also engage in direct addition to polyfluoroarenes,¹⁵ necessitating precise kinetic control throughout the reaction process. Building upon our ongoing research in visible-light photoredox catalysis¹⁶ and C–F bond activation,¹⁷ we herein report a photoredox-catalyzed radical–polar crossover¹⁸ involving RBF₄K, DABSO, and polyfluoroarenes under redox-neutral conditions, enabling direct assembly of otherwise challenging-to-access polyfluoroarylsulfones.

Results and discussion

We attempted the coupling of potassium tert-butyl fluoroborate (3a, 0.3 mmol), DABSO (2a, 0.3 mmol) and methyl pentafluorobenzoate (1a, 0.2 mmol) employing 4-CzIPN (1.5 mol%) as a photocatalyst and K₃PO₄ (1.0 eq.) as a base under blue LED irradiation for 24 h in DMSO (2.0 mL), and the desired polyfluoroarylsulfone 4aa was isolated in 12% yield. To our delight, the reaction could proceed without the base, resulting in an improved yield of 4aa. Based on the solvent screening, it appears that the reaction can only be carried out in polar aprotic solvents such as DMSO, DMF, or DMAc. DCM, CH₃CN, or THF failed to produce the expected products. Next, different photocatalysts were tested, and the reactivity seemed sensitive to the oxidation ability of the photocatalyst. PC-5 and PC-6 provided excellent results, while for PC-2 to PC-4, nearly no 4aa was formed. Thus, PC-6 was chosen as the optimized PC for further reaction parameter screening. The coupling could not be carried out without a PC or light irradiation, or under an air atmosphere. Evaluation of alternative sulfur dioxide sources revealed that most could successfully generate the desired polyfluoroarylsulfones. Sodium hydrogen sulfite (NaHSO₃) proved to be the most effective among them, affording the product in 67% yield, albeit lower than the yield obtained with DABSO. We further investigated the effect of the reactant ratio on the yield. Reducing the amount of 2a to 1.0 equivalent had no impact on yield, while reducing it to 0.5 equivalents resulted in a significant decline in yield. Reducing the amount of 3a to 1.0 equivalent resulted in 68% yield for 4aa. Thus, the conditions shown in the equation in Table 1 were identified as the standard conditions for further exploration of the substrate scope.

Table 1 Optimization of the reaction conditions^a

a Unless otherwise noted, all the reactions were carried out with 1a (0.2 mmol), 2 (0.3 mmol, 1.5 eq.), 3a (0.3 mmol, 1.5 eq.), and PC (1.5 mol%), anhydrous solvent (2 mL) at room temperature, 40 W blue LEDs, 24 h in nitrogen. Yield of the isolated product based on 1a. b K₃PO₄ (1.0 equiv.) was added. c w/o a PC.

---

With the optimized conditions in hand, we next evaluated the range of substrates applicable in the three-component coupling system, and the results are summarised in Scheme 2. As demonstrated in Scheme 2A, a wide range of polyfluoroarenes could undergo a defluorination cross-coupling reaction with DABSO (2a) and potassium tert-butyl fluoroborate (3a), resulting in the formation of polyfluoroarylsulfones 4aa–4qa in moderate to excellent yields. Polyfluorobenzoates derived from primary (4aa and 4ea), secondary (4ba, 4fa, and 4ga), and tertiary (4ca) alcohols or phenol (4da) were employed in this radical–polar cascade, producing the corresponding defluorination/sulfonylation products in high yields (up to 99% in most cases). Other electron-withdrawing groups, such as cyano (4ia), trifluoromethyl (4ja), carbonyl (4ka), and polyfluoroaryl-substituted perfluoroarenes (4la), have been proven to be effective starting materials, providing the corresponding sulfones in 63–82% yields. Perfluoropyridine was also found to be well tolerated, resulting in the generation of 4ma with a yield of 68%. Moreover, 3-chloro-tetrafluoropyridine could deliver 4na in 52% yield. Excellent chemoselectivity was demonstrated by using radical-sensitive benzyloxy (4ea and 4fa) or internal alkyne (4ha) groups in the coupling. This strategy can be used to functionalize polyfluorobenzoates derived from natural products like menthol (4oa, 99%), diacetonefructose (4pa, 98%), or vanillylacetone (4qa, 99%). Excellent site selectivity was demonstrated, as the defluorination coupling occurred specifically at the para-position of the electron-withdrawing groups in all cases.

Scheme 2 Substrate scope of the three-component coupling system. Reaction conditions: unless otherwise noted, all the reactions were carried out with 1 (0.2 mmol), 2 (0.2 mmol, 1.0 eq.), 3 (0.3 mmol, 1.5 eq.), and PC-6 (1.5 mol%) in DMSO (2 mL) at room temperature, with irradiation with a blue LED (40 W) for 24 h under a nitrogen atmosphere. Isolated yield. ^a 3a (3.0 equiv.), 96 h.

Next, the scope of potassium alkyltrifluoroborates was tested by coupling with DABSO and 1a. The reaction was compatible with a range of potassium alkyltrifluoroborates, including both secondary (4ab and 4ae–4ag) and primary (4ac, 4ad, 4ah, and 4ai–4am) alkyl chains, delivering the corresponding products in moderate to high yields. Simple primary alkyltrifluoroborates demonstrated lower reactivity, affording products 4ac, 4ad, 4ah, and 4am in only moderate yields even with prolonged reaction times. This is likely due to the inherent challenge in generating primary alkyl radicals and their subsequent instability. In contrast, potassium benzyltrifluoroborate exhibited high reactivity, delivering products 4ai–4ak in 79–83% yields. However, the yield of 4al was significantly diminished (40%) despite modified conditions, an outcome we attribute to steric hindrance from the adjacent substituents. Cyclic alkyl potassium trifluoroborates were suitable for this transformation, delivering targets 4ae–4ag in 81–94% yields. However, attempts to employ aryl or vinyl analogues were unsuccessful.

Interestingly, pentafluorobenzoate (1r) derived from 3-methylbut-2-en-1-ol could undergo chemodivergent transformations with DABSO (2a) and potassium tert-butyl fluoroborate (3a), delivering the defluorination/sulfonylation product 4 or the further de-esterification product 4′. When the reaction was quenched in 24 hours, conventional cascade products 4ra, 4rb and 4re were isolated in 72–82% yields, while when extending the reaction time to 96 hours, tetrafluoroarylsulfones 4ra′ (90%), 4rb′ (76%), and 4re′ (70%) were generated as sole products. This methodology provides direct synthesis of otherwise difficult-to-access tetrafluoroarylsulfone derivatives.

Large-scale synthesis and late-stage functionalization were carried out to prove the synthetic value of the cascade defluorination/sulfonylation system. The 1 mmol scale synthesis of 4ka and 4ma provides targets in 75% and 53% yields, respectively (Scheme 3A). By employing sodium borohydride, 4ka can be reduced to 5a in 90% yield (Scheme 3B, left). 4ma could undergo cascade defluorinative cyclization with N¹,N²-dimethylethane-1,2-diamine, generating the tetrahydropyrido[2,3-b]pyrazine scaffold 5b in 86% yield (Scheme 3B, right).

Scheme 3 Large-scale synthesis and late-stage functionalization reactions.

We conducted preliminary mechanistic investigations to gain an understanding of the probable reaction pathways. Control experiments indicated that visible light irradiation and a photoredox catalyst were indispensable for the formation of 4aa (Scheme 4A). The addition of TEMPO (3.0 eq.) as a radical inhibitor prevented the formation of product 4ai. Additionally, the coupling product 6a can be detected in 19% yield, which suggests the possibility of formation of an alkyl radical species in the coupling system. The addition of 1,3,5-trimethoxybenzene has nearly no effect on the yield, which contradicts the involvement of multifluoroaryl radicals.¹⁹ Fluorescence quenching experiments were carried out, and the excited state of PC* was preferably quenched by 3a rather than 1a; thus, the oxidative quenching mechanism seems unlikely. A reductive quenching mechanism seems preferred in combination with the reductive potential of PC* and the oxidative potential of potassium tert-butyl fluoroborate. The aforementioned conclusion is in line with the results obtained during the screening of photocatalysts provided in Table 1. Furthermore, we conducted a two-step experiment to evaluate the possibility of the formation of an intermediate. As shown in Scheme 4D, 3a and 2a were reacted under blue LED irradiation employing PC-6 as the photocatalyst for 24 h; then, 1a was added to the mixture and reacted for an additional 24 h in the absence of light. Interestingly, 4aa was isolated in 83% yield, indicating the possibility of formation of a sulfonate intermediate. Consequently, we obtained the ¹H NMR spectra of the reaction mixture at different stages as shown in Scheme 4D: the initial state (0 h), after 24 h of LED irradiation, and after a subsequent 24 h following the addition of polyfluoroarene 1a. ¹H NMR monitoring of the reaction mixture clearly showed the generation of the potential sulfinate intermediate 7, followed by its transformation into product 4aa by the addition of 1a.

Scheme 4 Preliminary mechanistic investigation.

Based on previous reports and mechanistic experiments, a plausible catalytic cycle for the three-component defluorination/sulfonylation system is proposed in Scheme 5. Under LED irradiation, the generated PC* undergoes reductive quenching with 3a, generating alkyl radical species I, which is rapidly trapped by DABSO, delivering sulfonyl radical II, PCⁿ⁻¹ and DABCO. The reduced state PCⁿ⁻¹ undergoes single-electron-transfer with II, delivering the sulfonate intermediate III and regenerating ground-state PC, completing the photocatalysis cycle. Sulfonate III undergoes S_NAr with polyfluoroarenes via cleavage of C–F bonds, delivering the polyfluoroarylsulfones.

Scheme 5 Proposed catalytic cycle.

Conclusions

In summary, we have achieved the three-component synthesis of polyfluoroarylsulfones through the utilization of DABSO as a sulfonyl source under visible-light photoredox catalysis. This protocol employs RBF₄K as an alkyl radical precursor and polyfluoroarenes as arylation reagents via C–F bond activation, enabling the efficient construction of value-added polyfluoroarylsulfones with broad functional group compatibility. Mechanistic studies indicate that the transformation proceeds through a cascade sequence involving photooxidative generation of alkyl radicals, SO₂ trapping, SET reduction, and nucleophilic aromatic substitution (S_NAr). The synergy between the high reactivity of radical intermediates and the excellent chemoselectivity of the S_NAr reaction constitutes the key to the success of this radical–polar crossover strategy. This methodology enables direct C(sp²)–F bond cleavage of polyfluoroarenes under mild conditions, establishing the combination of DABSO and polyfluoroarenes as a novel, formal radical-type polyfluoroarylsulfonation surrogate that participates in the reaction, and potentially provides a modular platform for the synthesis of polyfluoroarylsulfones and their derivatives. Further application of this defluorination/sulfonylation system is ongoing in our laboratory.

Author contributions

J. S. and G. Z. conceived and designed the experiments. Y. G., J. X., K. C., K. J., Y. D., T. X., and G. Z. performed the experiments and analyzed the data. J. S., J. Q., and Q. Z. co-wrote the manuscript. All authors contributed to the discussions.

Conflicts of interest

There are no conflicts to declare.

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information is available. See DOI: https://doi.org/10.1039/d5qo01163a.

Acknowledgements

We acknowledge the Natural Science Foundation of Jilin Province (20230101047JC), the National Key R&D Program of China (2024YFA1509704), the NSFC (22471034, 22201033, 22193012, and 21831002) and the Fundamental Research Funds for the Central Universities for generous financial support.

References

1. A. Darehkordi, M. Ramezani, F. Rahmani and M. Ramezani, Design, Synthesis and Evaluation of Antibacterial Effects of a New Class of Piperazinylquinolone Derivatives, J. Heterocycl. Chem., 2015, 53, 89–94.
2. V. Dudutiene, A. Zubriene, A. Smirnov, J. Gylyte, D. Timm, E. Manakova, S. Grazulis and D. Matulis, 4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII, Bioorg. Med. Chem., 2013, 21, 2093–2106.
3. (a) A. Scozzafava, A. Mastrolorenzo and C. T. Supuran, Arylsulfonyl-N,N-diethyl-dithiocarbamates: a novel class of antitumor agents, Bioorg. Med. Chem. Lett., 2000, 10, 1887–1891; (b) J. C. Medina, B. Shan, H. Beckmann, R. P. Farrell, D. L. Clark, R. M. Learned, D. Roche, A. Li, V. Baichwal, C. Case, P. A. Baeuerle, T. Rosen and J. C. Jaen, Novel antineoplastic agents with efficacy against multidrug resistant tumor cells, Bioorg. Med. Chem. Lett., 1998, 8, 2653–2656; (c) B. Shan, J. C. Medina, E. Santha, W. P. Frankmoelle, T.-C. Chou, R. M. Learned, M. R. Narbut, D. Stott, P. Wu, J. C. Jaen, T. Rosen, P. B. M. W. M. Timmermans and H. Beckmann, Selective, covalent modification of β-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors, Proc. Natl. Acad. Sci. U. S. A., 1999, 96, 5686–5691.
4. (a) C. A. Hargreaves, G. Sandford, R. Slater, D. S. Yufit, J. A. K. Howard and A. Vong, Synthesis of tetrahydropyrido[2,3-b]pyrazine scaffolds from 2,3,5,6-tetrafluoropyridine derivatives, Tetrahedron, 2007, 63, 5204–5211; (b) L. Politanskaya and E. Tretyakov, Directed synthesis of fluorine containing 2,3-dihydrobenzo[b,][1,4]oxathiine derivatives from polyfluoroarenes, J. Fluorine Chem., 2020, 236, 109592; (c) V. V. Litvak, A. S. Kondrat'ev and V. D. Shteimgarts, Synthesis of β-functionalized ethyl polyfluoroaryl sulfides, sulfoxides, and sulfones underlain by pentafluorobenzoic acid, Russ. J. Org. Chem., 2009, 45, 1637–1643.
5. N. Du, G. P. Robertson, J. Song, I. Pinnau, S. Thomas and M. D. Guiver, Polymers of Intrinsic Microporosity Containing Trifluoromethyl and Phenylsulfone Groups as Materials for Membrane Gas Separation, Macromolecules, 2008, 41, 9656–9662.
6. J. D. Smith, A. M. Jamhawi, J. B. Jasinski, F. Gallou, J. Ge, R. Advincula, J. Liu and S. Handa, Organopolymer with dual chromophores and fast charge-transfer properties for sustainable photocatalysis, Nat. Commun., 2019, 10, 1837.
7. (a) R. A. Bredikhin, A. M. Maksimov and V. E. Platonov, Reaction of polyfluoroarenesulfonyl bromides with allyl bromide. Synthesis of allyl polyfluoroaryl sulfones, Russ. J. Org. Chem., 2011, 47, 374–378; (b) R. A. Bredikhin, D. O. Usatenko, A. M. Maksimov and V. E. Platonov, Pentafluorobenzenesulfonyl Bromide: Synthesis and Reactions with Alkenes, Procedia Chem., 2015, 15, 265–271; (c) V. E. Platonov, R. A. Bredikhin, A. M. Maksimov and V. V. Kireenkov, A novel and efficient method for the synthesis of polyfluoroarenesulfonyl bromides from polyfluoroarenethiols, J. Fluorine Chem., 2010, 131, 13–16.
8. (a) H. Amii and K. Uneyama, C-F bond activation in organic synthesis, Chem. Rev., 2009, 109, 2119–2183; (b) A. Baron, G. Sandford, R. Slater, D. S. Yufit, J. A. Howard and A. Vong, Polyfunctional tetrahydropyrido[2,3-b]pyrazine scaffolds from 4-phenylsulfonyl tetrafluoropyridine, J. Org. Chem., 2005, 70, 9377–9381; (c) J. D. Smith, T. N. Ansari, M. P. Andersson, D. Yadagiri, F. Ibrahim, S. Liang, G. B. Hammond, F. Gallou and S. Handa, Micelle-enabled clean and selective sulfonylation of polyfluoroarenes in water under mild conditions, Green Chem., 2018, 20, 1784–1790.
9. (a) P. Bisseret and N. Blanchard, Taming sulfur dioxide: a breakthrough for its wide utilization in chemistry and biology, Org. Biomol. Chem., 2013, 11, 5393–5398; (b) E. J. Emmett and M. C. Willis, The Development and Application of Sulfur Dioxide Surrogates in Synthetic Organic Chemistry, Asian J. Org. Chem., 2015, 4, 602–611; (c) G. Qiu, K. Zhou, L. Gao and J. Wu, Insertion of sulfur dioxide via a radical process: an efficient route to sulfonyl compounds, Org. Chem. Front., 2018, 5, 691–705; (d) G. Qiu, K. Zhou and J. Wu, Recent advances in the sulfonylation of C-H bonds with the insertion of sulfur dioxide, Chem. Commun., 2018, 54, 12561–12569; (e) S. Ye, G. Qiu and J. Wu, Inorganic sulfites as the sulfur dioxide surrogates in sulfonylation reactions, Chem. Commun., 2019, 55, 1013–1019; (f) S. Liang, K. Hofman, M. Friedrich and G. Manolikakes, Recent Advances in the Synthesis and Direct Application of Sulfinate Salts, Eur. J. Org. Chem., 2020, 4664–4676; (g) S. Ye, M. Yang and J. Wu, Recent advances in sulfonylation reactions using potassium/sodium metabisulfite, Chem. Commun., 2020, 56, 4145–4155; (h) D. Joseph, M. A. Idris, J. Chen and S. Lee, Recent Advances in the Catalytic Synthesis of Arylsulfonyl Compounds, ACS Catal., 2021, 11, 4169–4204; (i) Q. Tang, X. Yin, R. R. Kuchukulla and Q. Zeng, Recent Advances in Multicomponent Reactions with Organic and Inorganic Sulfur Compounds, Chem. Rec., 2021, 21, 893–905; (j) G. Chen and Z. Lian, Multicomponent Reactions Based on SO₂ Surrogates: Recent Advances, Eur. J. Org. Chem., 2023, e202300217.
10. (a) M. S. Hashtroudi, V. F. Vavsari and S. Balalaie, DABSO as a SO₂ gas surrogate in the synthesis of organic structures, Org. Biomol. Chem., 2022, 20, 2149–2163; (b) M. C. Willis and J. A. Andrews, DABSO – A Reagent to Revolutionize Organosulfur Chemistry, Synthesis, 2022, 1695–1707.
11. (a) J. Zhu, W. C. Yang, X. D. Wang and L. Wu, Photoredox Catalysis in C-S Bond Construction: Recent Progress in Photo–Catalyzed Formation of Sulfones and Sulfoxides, Adv. Synth. Catal., 2017, 360, 386–400; (b) S. Ye, X. Li, W. Xie and J. Wu, Photoinduced Sulfonylation Reactions through the Insertion of Sulfur Dioxide, Eur. J. Org. Chem., 2019, 1274–1287.
12. (a) K. P. S. Cheung, S. Sarkar and V. Gevorgyan, Visible Light-Induced Transition Metal Catalysis, Chem. Rev., 2022, 122, 1543–1625; (b) L. Capaldo, D. Ravelli and M. Fagnoni, Direct Photocatalyzed Hydrogen Atom Transfer (HAT) for Aliphatic C-H Bonds Elaboration, Chem. Rev., 2022, 122, 1875–1924; (c) T. P. Yoon, M. A. Ischay and J. Du, Visible light photocatalysis as a greener approach to photochemical synthesis, Nat. Chem., 2010, 2, 527–532; (d) C. K. Prier, D. A. Rankic and D. W. MacMillan, Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis, Chem. Rev., 2013, 113, 5322–5363; (e) R. Francke and R. D. Little, Redox catalysis in organic electrosynthesis: basic principles and recent developments, Chem. Soc. Rev., 2014, 43, 2492–2521; (f) N. A. Romero and D. A. Nicewicz, Organic Photoredox Catalysis, Chem. Rev., 2016, 116, 10075–10166; (g) K. L. Skubi, T. R. Blum and T. P. Yoon, Dual Catalysis Strategies in Photochemical Synthesis, Chem. Rev., 2016, 116, 10035–10074; (h) K. Kwon, R. T. Simons, M. Nandakumar and J. L. Roizen, Strategies to Generate Nitrogen-centered Radicals That May Rely on Photoredox Catalysis: Development in Reaction Methodology and Applications in Organic Synthesis, Chem. Rev., 2022, 122, 2353–2428; (i) P. Melchiorre, Introduction: Photochemical Catalytic Processes, Chem. Rev., 2022, 122, 1483–1484; (j) J. Beaudelot, S. Oger, S. Perusko, T. A. Phan, T. Teunens, C. Moucheron and G. Evano, Photoactive Copper Complexes: Properties and Applications, Chem. Rev., 2022, 122, 16365–16609; (k) A. Y. Chan, I. B. Perry, N. B. Bissonnette, B. F. Buksh, G. A. Edwards, L. I. Frye, O. L. Garry, M. N. Lavagnino, B. X. Li, Y. Liang, E. Mao, A. Millet, J. V. Oakley, N. L. Reed, H. A. Sakai, C. P. Seath and D. W. C. MacMillan, Metallaphotoredox: The Merger of Photoredox and Transition Metal Catalysis, Chem. Rev., 2022, 122, 1485–1542; (l) N. H. Douglas and D. A. Nicewicz, Photoredox-Catalyzed C-H Functionalization Reactions, Chem. Rev., 2022, 122, 1925–2016; (m) N. L. Reed and T. P. Yoon, Oxidase reactions in photoredox catalysis, Chem. Soc. Rev., 2021, 50, 2954–2967; (n) J. Xuan, X. K. He and W. J. Xiao, Visible light-promoted ring-opening functionalization of three-membered carbo- and heterocycles, Chem. Soc. Rev., 2020, 49, 2546–2556; (o) S. Dutta, J. E. Erchinger, F. S. Kalthoff, R. Kleinmans and F. Glorius, Energy transfer photocatalysis: exciting modes of reactivity, Chem. Soc. Rev., 2024, 53, 1068–1089; (p) F. S. Kalthoff, M. J. James, M. Teders, L. Pitzer and F. Glorius, Energy transfer catalysis mediated by visible light: principles, applications, directions, Chem. Soc. Rev., 2018, 47, 7190–7202.
13. (a) T. Liu, Y. Ding, X. Fan and J. Wu, Photoinduced synthesis of (E)-vinyl sulfones through the insertion of sulfur dioxide, Org. Chem. Front., 2018, 5, 3153–3157; (b) X. Wang, M. Yang, W. Xie, X. Fan and J. Wu, Photoredox-catalyzed hydrosulfonylation reaction of electron-deficient alkenes with substituted Hantzsch esters and sulfur dioxide, Chem. Commun., 2019, 55, 6010–6013; (c) S. Tanaka, Y. Nakayama, Y. Konishi, T. Koike and M. Akita, Fluoroalkanesulfinate Salts as Dual Fluoroalkyl and SO₂ Sources: Atom-Economical Fluoroalkyl-Sulfonylation of Alkenes and Alkynes by Photoredox Catalysis, Org. Lett., 2020, 22, 2801–2805; (d) H. Wang, P. Bellotti, X. Zhang, T. O. Paulisch and F. Glorius, A base-controlled switch of SO₂ reincorporation in photocatalyzed radical difunctionalization of alkenes, Chem, 2021, 7, 3412–3424; (e) V. T. Nguyen, G. C. Haug, V. D. Nguyen, N. T. H. Vuong, G. B. Karki, H. D. Arman and O. V. Larionov, Functional group divergence and the structural basis of acridine photocatalysis revealed by direct decarboxysulfonylation, Chem. Sci., 2022, 13, 4170–4179; (f) H. Li, Y. Zhang, X. Yang, Z. Deng, Z. Zhu, P. Zhou, X. Ouyang, Y. Yuan, X. Chen, L. Yang, M. Liu and C. Shu, Synthesis of Multifluoromethylated gamma-Sultines by a Photoinduced Radical Addition-Polar Cyclization, Angew. Chem., Int. Ed., 2023, 62, e202300159; (g) S. Senapati, S. K. Parida, S. S. Karandikar and S. Murarka, Organophotoredox-Catalyzed Arylation and Aryl Sulfonylation of Morita-Baylis-Hillman Acetates with Diaryliodonium Reagents, Org. Lett., 2023, 25, 7900–7905; (h) C. P. Yuan, Y. Zheng, Z. Z. Xie, K. Y. Deng, H. B. Chen, H. Y. Xiang, K. Chen and H. Yang, Photosensitized Vicinal Sulfonylamination of Alkenes with Oxime Ester and DABCO·(SO₂)₂, Org. Lett., 2023, 25, 1782–1786; (i) X. Yuan, J. Liu, H. Lv, L. Z. Qin, X. Duan, J. Wang, M. Y. Wu, B. Chen, J. K. Qiu and K. Guo, Visible-light-induced selective alkylsulfonylation of unactivated alkenes via remote heteroaryl migrations, Green Synth. Catal., 2023, 5, 126–130; (j) J. Huang, F. Liu, L. H. Zeng, S. Li, Z. Chen and J. Wu, Accessing chiral sulfones bearing quaternary carbon stereocenters via photoinduced radical sulfur dioxide insertion and Truce-Smiles rearrangement, Nat. Commun., 2022, 13, 7081; (k) H. Li, Y. Zhang, X. Zou, X. Yang, P. Zhou, X. Ma, S. Lu, Q. Sun and C. Shu, Photoinduced Regioselective Sulfonylsulfination of Alkenes, ACS Catal., 2024, 14, 3664–3674; (l) M. Chen, W. Sun, J. Yang, L. Yuan, J. Q. Chen and J. Wu, Metal-free photosensitized aminosulfonylation of alkenes: a practical approach to β-amido sulfones, Green Chem., 2023, 25, 3857–3863; (m) J. E. Erchinger, R. Hoogesteger, R. Laskar, S. Dutta, C. Humpel, D. Rana, C. G. Daniliuc and F. Glorius, EnT-Mediated N-S Bond Homolysis of a Bifunctional Reagent Leading to Aliphatic Sulfonyl Fluorides, J. Am. Chem. Soc., 2023, 145, 2364–2374; (n) V. D. Nguyen, R. Trevino, S. G. Greco, H. D. Arman and O. V. Larionov, Tricomponent Decarboxysulfonylative Cross-Coupling Facilitates Direct Construction of Aryl Sulfones and Reveals a Mechanistic Dualism in the Acridine/Copper Photocatalytic System, ACS Catal., 2022, 12, 8729–8739; (o) C. A. Vincent, M. I. Chiriac, L. T. Gautier and U. K. Tambar, Photocatalytic Sulfonyl Fluorination of Alkyl Organoboron Substrates, ACS Catal., 2023, 13, 3668–3675; (p) Y. Dong, N. Xiong, Z. Rong and R. Zeng, Decarboxylative Sulfonylation of Carboxylic Acids under Mild Photomediated Iron Catalysis, Org. Lett., 2024, 26, 2381–2386; (q) W. Xiao, J. Chen and J. Wu, Radical sulfonylation with sulfur dioxide surrogates, Chem. Soc. Rev., 2025, 54, 6832–6926; (r) F. Zhou, X. He, M. Zhou, N. Li, Q. Wang, X. Zhang and Z. Lian, Generation of perthiyl radicals for the synthesis of unsymmetric disulfides, Nat. Commun., 2025, 16, 23; (s) Z. Chang, X. Zhang, H. Lv, H. Sun and Z. Lian, Three-Component Radical Cross-Coupling: Asymmetric Vicinal Sulfonyl-Esterification of Alkenes Involving Sulfur Dioxide, Adv. Sci., 2024, 2309069.
14. M. O. Zubkov and A. D. Dilman, Radical reactions enabled by polyfluoroaryl fragments: photocatalysis and beyond, Chem. Soc. Rev., 2024, 53, 4741–4785.
15. (a) J. Xie, M. Rudolph, F. Rominger and A. S. K. Hashmi, Photoredox-Controlled Mono- and Di-Multifluoroarylation of C(sp³)-H Bonds with Aryl Fluorides, Angew. Chem., Int. Ed., 2017, 56, 7266–7270; (b) A. Singh, C. J. Fennell and J. D. Weaver, Photocatalyst size controls electron and energy transfer: selectable E/Z isomer synthesis via C-F alkenylation, Chem. Sci., 2016, 7, 6796–6802; (c) Y. Yuan, M. Zhang, X. Tang, J. L. Piper, Z. H. Peng, J. A. Ma, J. Wu and F. G. Zhang, Photoinduced Defluorinative Branch-Selective Olefination of Multifluoro (Hetero)arenes, Org. Lett., 2023, 25, 883–888; (d) X. Sun and T. Ritter, Decarboxylative Polyfluoroarylation of Alkylcarboxylic Acids, Angew. Chem., Int. Ed., 2021, 60, 10557–10562.
16. (a) T. Liang, Y. Wu, J. Sun, M. Li, H. Zhao, J. Zhang, G. Zheng and Q. Zhang, Visible Light–Mediated Cobalt and Photoredox Dual–Catalyzed Asymmetric Reductive Coupling for Axially Chiral Secondary Alcohols, Chin. J. Chem., 2023, 41, 3253–3260; (b) J. Xia, R. Ma, L. Wang, J. Sun, G. Zheng and Q. Zhang, NHC and photoredox catalysis dual-catalyzed 1,4-mono-/di-fluoromethylative acylation of 1,3-enynes, Org. Chem. Front., 2024, 11, 3089–3099; (c) J. Xia, Y. Guo, Z. Lv, J. Sun, G. Zheng and Q. Zhang, Visible Light-Mediated Monofluoromethylation /Acylation of Olefins by Dual Organo-Catalysis, Molecules, 2024, 29, 790; (d) J. Sun, L. Wang, G. Zheng and Q. Zhang, Recent advances in three-component radical acylative difunctionalization of unsaturated carbon–carbon bonds, Org. Chem. Front., 2023, 10, 4488–4515; (e) L. Wang, J. Sun, J. Xia, R. Ma, G. Zheng and Q. Zhang, Visible light-mediated NHC and photoredox co-catalyzed 1,2-sulfonylacylation of allenesviaacyl and allyl radical cross-coupling, Org. Chem. Front., 2023, 10, 1047–1055; (f) L. Wang, J. Sun, J. Xia, M. Li, L. Zhang, R. Ma, G. Zheng and Q. Zhang, Visible light-mediated NHCs and photoredox co-catalyzed radical 1,2-dicarbonylation of alkenes for 1,4-diketones, Sci. China: Chem., 2022, 65, 1938–1944; (g) L. Wang, R. Ma, J. Sun, G. Zheng and Q. Zhang, NHC and visible light-mediated photoredox co-catalyzed 1,4-sulfonylacylation of 1,3-enynes for tetrasubstituted allenyl ketones, Chem. Sci., 2022, 13, 3169–3175; (h) M. Li, Y. Wu, X. Song, J. Sun, Z. Zhang, G. Zheng and Q. Zhang, Visible light-mediated organocatalyzed 1,3-aminoacylation of cyclopropane employing N-benzoyl saccharin as bifunctional reagent, Nat. Commun., 2024, 15, 8930; (i) M. Li, X. Song, X. Lu, J. Xia, G. Zheng and Q. Zhang, Visible light-mediated 1,3-acylative chlorination of cyclopropanes employing benzoyl chloride as bifunctional reagents in NHC catalysis, Sci. China: Chem., 2025, 68, 3628–3635.
17. (a) X. Li, B. Fu, Q. Zhang, X. Yuan, Q. Zhang, T. Xiong and Q. Zhang, Copper-Catalyzed Defluorinative Hydroarylation of Alkenes with Polyfluoroarenes, Angew. Chem., Int. Ed., 2020, 59, 23056–23060; (b) Y. Zhao, B. Fu, S. Wang, Y. Li, X. Yuan, J. Yin, T. Xiong and Q. Zhang, Copper-Catalyzed Defluorinative Boroarylation of Alkenes with Polyfluoroarenes, Org. Lett., 2023, 25, 2492–2497.
18. (a) M. Liu, X. Ouyang, C. Xuan and C. Shu, Advances in photoinduced radical–polar crossover cyclization (RPCC) of bifunctional alkenes, Org. Chem. Front., 2024, 11, 895–915; (b) R. J. Wiles and G. A. Molander, Photoredox-Mediated Net-Neutral Radical/Polar Crossover Reactions, Isr. J. Chem., 2020, 60, 281–293; (c) S. Sharma, J. Singh and A. Sharma, Visible Light Assisted Radical–Polar/Polar–Radical Crossover Reactions in Organic Synthesis, Adv. Synth. Catal., 2021, 363, 3146–3169; (d) X. Hou, H. Liu and H. Huang, Iron-catalyzed fluoroalkylative alkylsulfonylation of alkenes via radical-anion relay, Nat. Commun., 2024, 15, 1480.
19. (a) S. Senaweera and J. D. Weaver, Dual C-F, C-H Functionalization via Photocatalysis: Access to Multifluorinated Biaryls, J. Am. Chem. Soc., 2016, 138, 2520–2523; (b) A. Singh, J. J. Kubik and J. D. Weaver, Photocatalytic C-F alkylation; facile access to multifluorinated arenes, Chem. Sci., 2015, 6, 7206–7212; (c) F. Xue, H. Deng, C. Xue, D. K. B. Mohamed, K. Y. Tang and J. Wu, Reaction discovery using acetylene gas as the chemical feedstock accelerated by the “stop-flow” micro-tubing reactor system, Chem. Sci., 2017, 8, 3623–3627; (d) A. U. Meyer, T. Slanina, C. J. Yao and B. König, Metal-Free Perfluoroarylation by Visible Light Photoredox Catalysis, ACS Catal., 2015, 6, 369–375; (e) Y. J. Chen, W. H. Deng, J. D. Guo, R. N. Ci, C. Zhou, B. Chen, X. B. Li, X. N. Guo, R. Z. Liao, C. H. Tung and L. Z. Wu, Transition-Metal-Free, Site-Selective C-F Arylation of Polyfluoroarenes via Electrophotocatalysis, J. Am. Chem. Soc., 2022, 144, 17261–17268.

---