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DOI: https://doi.org/10.6023/A26060191

Article

Visible-Light-Induced Electron Donor-Acceptor Complex Driven 1,3-Sulfonylation/Heteroarylation of [1.1.1]Propellane with Cyclic N-Sulfonyl Aldimines and Sulfonyl Chlorides

  • Xinchang Wang ,
  • Yating Du ,
  • An Chen ,
  • Yue Zhang ,
  • Pengfei Zhang ,
  • Jun Xu
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  • College of Material, Chemistry and Chemical Engineering, Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Zhejiang Key Laboratory of Organosilicon Material Technology, Hangzhou Normal University, Hangzhou, 311121, China

Received date: 2026-06-09

  Online published: 2026-07-21

Supported by

National Natural Science Foundation of China (No. 22508079, 22478090) and Zhejiang Provincial Natural Science Foundation of China (LQN26B060020).

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Abstract

Herein, we report a visible-light-induced difunctionalization of [1.1.1]propellane via an electron donor-acceptor (EDA) complex, enabling selective 1,3-sulfonylation/heteroarylation with cyclic N-sulfonyl aldimines and sulfonyl chlorides. This protocol provides an efficient route to 1-sulfonyl-3-heteroaryl bicyclo[1.1.1]pentanes (BCPs), rigid three-dimensional scaffolds valuable as bioisosteric substitutes for para-substituted arenes in drug discovery. Under standard conditions, the desired products were obtained in moderate to excellent yields. This transformation operates under visible light at room temperature without transition-metal catalysts or external photosensitizers. The EDA complex serves as the pivotal intermediate; upon photoexcitation, it triggers single-electron transfer to generate sulfonyl radicals and radical anions, initiating a cascade that constructs both C-S and C-C bonds at the bridgehead positions. This unique mechanism avoids precious metal usage and suppresses side reactions typical of UV or thermal conditions. Optimization studies identified triethylamine as the preferred base, 1,2-dichloroethane as the optimal solvent, 405 nm as the best light source, and 6 hours as the ideal reaction time. In a typical procedure, a nitrogen-purged Schlenk tube charged with cyclic N-sulfonyl aldimine (0.2 mmol), p-toluenesulfonyl chloride (0.3 mmol), [1.1.1]propellane (0.3 mmol), and triethylamine (0.4 mmol) in DCE (2 mL) is irradiated at 405 nm for 6 hours. Purification by column chromatography affords the corresponding products. The substrate scope was systematically examined, covering various cyclic N-sulfonyl aldimines and sulfonyl chlorides bearing pharmaceutically relevant groups. Scale-up reactions delivered comparable results, and subsequent derivatizations converted BCP products into diverse architectures, illustrating synthetic utility. Mechanistic studies, including radical trapping and UV-vis spectroscopy, confirmed radical intermediates and EDA complex formation. Based on these findings, a plausible pathway is proposed: photoinduced electron transfer, sulfonyl radical generation, regioselective addition to [1.1.1]propellane, and radical trapping to forge the C-heteroaryl bond. Collectively, this work offers a mild, sustainable, and scalable approach to functionalized BCPs, enriching the medicinal chemistry toolbox with sp3-rich building blocks.

Key words： cyclic N-sulfonyl aldimines; [1.1.1]propellane; sulfonylation; visible-light-induced; EDA complex

Cite this article

Xinchang Wang , Yating Du , An Chen , Yue Zhang , Pengfei Zhang , Jun Xu . Visible-Light-Induced Electron Donor-Acceptor Complex Driven 1,3-Sulfonylation/Heteroarylation of [1.1.1]Propellane with Cyclic N-Sulfonyl Aldimines and Sulfonyl Chlorides[J]. Acta Chimica Sinica, 0 : 0 . DOI: 10.6023/A26060191

References

[1] (a) Hendricks R. T.; Spencer S. R.; Blake J. F.; Fell J. B.; Fischer J. P.; Stengel P. J.; Leveque V. J. P.; LePogam S.; Rajyaguru S.; Najera I.; Josey J. A.; Swallow, S. Bioorg. Med. Chem. Lett.2009, 19, 410; (b) Elsayed, M. S. A.; El-Araby, M. E.; Serya, R. A. T.; El-Khatib, A. H.; Linscheid, M. W.; Abouzid, K. A. M. Eur. J. Med. Chem. 2013, 61, 122; (c) Chang, S.-Y.; Bae, S.; Lee, M. Y.; Baek, S.-H.; Chang, S.; Kim, S. H. Bioorg. Med. Chem. Lett. 2011, 21, 727; (d) Kiefer, L.; Gorojankina, T.; Dauban, P.; Faure, H.; Ruat, M.; Dodd, R. H. Bioorg. Med. Chem. Lett. 2010, 20, 7483; (e) Zheng, K.; Shen, H.; Ma, X.; Chen, C.; Shen, C. Adv. Synth. Catal. 2026, 368, e70646.
[2] Wang J.; Liu X.; Wu Z.; Li F.; Qin T.; Zhang S.; Kong W.; Liu, L. Chin. Chem. Lett.2021, 32, 2777.
[3] Guin S.; Majee D.; Samanta S. Chem. Commun.2021, 57, 9010.
[4] (a) Luo Y.; Hepburn H. B.; Chotsaeng N.; Lam, H. W. Angew. Chem. Int. Ed.2021, 51, 8309; (b) Zhang, H.-X.; Nie, J.; Cai, H.; Ma, J.-A. Org. Lett. 2014, 16, 2542; (c) Jia, C.-M.; Zhang, H.-X.; Nie, J.; Ma, J.-A. J. Org. Chem. 2016, 81, 8561; (d) Cui, X.-Y.; Duan, H.-X.; Zhang, Y.; Wang, Y.-Q. Chem. Asian J. 2016, 11, 3118; (e) Quan, M.; Tang, L.; Shen, J.; Yang, G.; Zhang, W. Chem. Commun. 2017, 53, 609; (f) De Munck, L.; Monleon, A.; Vila, C.; Pedro, J. R. Adv. Synth. Catal. 2017, 359, 1582; (g) Jethava, K. P.; Fine, J.; Chen, Y.; Hossain, A.; Chopra, G. Org. Lett. 2020, 22, 8480; (h) Li, Y.-L.; Liu, J.-X.; Chen, X.-P.; Zhou, Y.; Xiao, Y.-C.; Chen, F.-E. Adv. Synth. Catal. 2020, 362, 3202; (i) Mondal, S.; Aher, R. D.; Bethi, V.; Lin, Y.-J.; Taniguchi, T.; Monde, K.; Tanaka, F. Org. Lett. 2022, 24, 1853.
[5] (a) Xia A.-J.; Kang T.-R.; He L.; Chen L.-M.; Li W.-T.; Yang J.-L.; Liu, Q.-Z. Angew. Chem. Int. Ed.2016, 55, 1441; (b) Yang, Z.; Yu, H.; Zhang, L.; Wei, H.; Xiao, Y.; Chen, L.; Guo, H. Chem. Asian J. 2014, 9, 313.
[6] (a) Lai B.-N.; Qiu J.-F.; Zhang H.-X.; Nie J.; Ma J.-A. Org. Lett.2016, 18, 520; (b) Spielmann, K.; Lee, A.; Figueiredo, R. M.; Campagne, J.-M. Org. Lett. 2018, 20, 1444; (c) Shi, W.; Zhou, L.; Mao, B.; Wang, Q.; Wang, C.; Zhang, C.; Li, X.; Xiao, Y.; Guo, H. J. Org. Chem. 2019, 84, 679; (d) Zhou, J.; Zhang, H.; Chen, X.-L.; Qu, Y.-L.; Zhu, Q.; Feng, C.-G.; Chen, Y.-J. J. Org. Chem. 2019, 84, 9179; (e) Xiao, J.-A.; Cheng, X.-L.; Peng, H.; Li, J.-L.; Xie, Z.-Z.; Chen, W.-Q.; Liu, Z.-P.; Xiao, Q.; Su, W.; Yang, H. Sci. China Chem. 2020, 63, 785; (f) Wang, H.-X.; Li, Z.-H.; Li, W.-W.; Qu, G.-R.; Yang, Q.-L.; Guo, H.-M. Green Chem. 2022, 24, 8377.
[7] (a) Wang J.; Li F.; Liu K.; Li C.; Cao S.; Wu Y.; Yuan Y.; Teng F.; Wang T.; Zhou, Y. Green Synth. Catal.2024, 5, 315; (b) Liu, J.; Li, X.; Chen, G.; Luo, H. Adv. Synth. Catal. 2025, 367, e202500002.
[8] Ji H.-T.; Lu Y.-H.; Liu Y.-T.; Huang Y.-L.; Tian J.-F.; Liu F.; Zeng Y.-Y.; Yang H.-Y.; Zhang Y.-H.; He, W.-M. Chin. Chem. Lett.2025, 36, 110568.
[9] Wu C.-L.; Wu S.-J.; Huang Q.-F.; Sun K.; Huang X.-Q.; Wang J.-J.; Yu, B. Chin. Chem. Lett.2025, 36, 110250.
[10] (a) Zhou B.; Dong M.; Wang W.; Yu S.; Yue H.; Wei W.; Yi, D. J. Org. Chem.2024, 89, 18337; (b) Wang, J.; Qin, Y.; Cui, K.; Li, X.; Cui, M.; Cao, S.; Zhang, L.; Shen, Q.; Wang, T.; Li, F. Chem. Commun. 2025, 61, 3359; (c) Xia, Z.-H.; Liu, W.-H.; Sun, X.-Y.; Liu, X.-Y.; Liu, M.-Q.; Zhao, H.-Q. Chem. Synth. 2025, 5, 56.
[11] Honorio K. M.; Moda T. L.; Andricopulo, A. D. Med. Chem.2013, 9, 163.
[12] Kadam G. A.; Midya S.; Levchenko V.; Sham V.; Mykhailiuk P. K.; Hari, D. P. J. Am. Chem. Soc.2026, 148, 388.
[13] (a) Han H.; Zhu B.; Du X.; Zhu Y.; Yu C.; Jiang X. Green Chem.2021, 23, 10132; (b) Donnelly, K.; Baumann, M. Chem. Commun. 2021, 57, 2871; (c) Zhang, X.; Smith, R. T.; Le, C.; McCarver, S. J.; Shireman, B. T.; Carruthers, N. I.; MacMillan, D. W. C. Nature. 2020, 580, 220; (d) Sharland, J. C.; Davies, H. M. L. Org. Lett. 2023, 25, 5214; (e) Gao, X.-Y.; Xiao, Y.; Peng, Q.; Yang, F.; Li, D.; Wang, G.; Qian, Y.; Feng, J.-J. Angew. Chem. Int. Ed. 2025, 64, e202513768.
[14] Liu S.; Ning Y.; Song W.; Sivaguru P.; Wang Y.; Gan Y.; Anderson E. A.; Bi, X. Angew. Chem. Int. Ed.2025, 64, e202514232.
[15] Auberson Y. P.; Brocklehurst C.; Furegati M.; Fessard T. C.; Koch G.; Decker A.; Vecchia L. L.; Briard E. ChemMedChem.2017, 12, 590.
[16] Westphal M. V.; Wolfstädter B. T.; Plancher J.-M.; Gatfield J.; Carreira E. M. ChemMedChem.2015, 10, 461.
[17] Dong, W.; Yen-Pon E.; Li, L.; Bhattacharjee, A.; Jolit A.; Molander, G. A. Nat. Chem.2022, 14, 1068.
[18] (a) Chen A.; Wang Z.; Li W.; Xu, J. Chin. J. Org. Chem.2026, 46, 2177; (b) Zhang, F.; Wen, H.; Jiang, Y. ACS Catal. 2026, 16, 3013; (c) Liu, C.; Li, W.; Li, R.; Merchant, R. R.; Kanda, Y.; Qin, T. Nat Commun. 2026, 17, 477; (d) Shire, B. R.; Anderson, E. A. JACS Au. 2023, 3, 1539; (e) Dong, J.; Xue, D. Chin. J. Org. Chem. 2026, 46, 1464; (f) Livesley, S.; Sterling, A. J.; Robertson, C. M.; Goundry, W. R. F.; Morris, J. A.; Duarte, F.; Aïssa, C. Angew. Chem. Int. Ed. 2022, 61, e202111291; (g) Kanazawa, J.; Maeda, K.; Uchiyama, M. J. Am. Chem. Soc. 2017, 139, 17791; (h) Ma, X.; Han, Y.; Bennett, D. J. Org. Lett. 2020, 22, 9133; (i) Ma, X.; Chen, J. L.; Gaskins, B. E. Org. Lett. 2024, 26, 1947; (j) Shelp, R. A.; Walsh, P. J. Angew. Chem. Int. Ed. 2018, 57, 15857; (k) Liu, Y.-Z.; Jiang, Y.; Zhang, J.-L.; Mei, Y.; Li, D.-J.; Pan, F. Org. Chem. Front. 2023, 10, 4616; (l) Shen, J.; Yang, L.-F.; Ge, K.; Xu, H.; Shen, C. Org. Lett. 2025, 27, 6179.
[19] (a) Zhu H.; Wu S.; Zhu B.; Li J.; Lan D.; Xu W.; Xu G.; Zhu Y.; Yu C.; Jiang X. Chem. Commun.2023, 59, 5213; (b) Xu, J.; Li, L.; Pang, Q.; Chen, M.; Wang, H.; Zhang, P. Sci. Adv. 2026, 12, eaeg5293.
[20] (a) Yang S.-H.; Song J.-C.; Yang H.; Zhou M.-Y.; Wei Z.-H.; Gao J.-H.; Dong D.-Q.; Wang, Z.-L. Chin. Chem. Lett.2023, 34, 108131; (b) Chen, X.; Ouyang, W.-T.; Li, X.; He, W.-M. Chin. J. Org. Chem. 2023, 43, 4213; (c) Tu, J.-L.; Zhu, Y.; Li, P.; Huang, B. Org. Chem. Front. 2024, 11, 5278; (d) Hu, D.; Dang, H.; Liang, Z.; Wang, D.; Du, Y.; Shen, C.; Shen, J.; Wang, M. Org. Lett. 2024, 26, 10797; (e) Xin, C.; Jiang, J.; Deng, Z.-W.; Ou, L.-J.; He, W.-M. Acta Chim. Sinica, 2024, 82, 1109; (f) Peng, Q.; Peng, J.; Cai, Y.; Wang, Z.; Yi, R.; Shen, C.; He, W. Acta Chim. Sinica, 2025, 83, 1013; (g) Meng, F.; Li, G.; Zhao, J.; Xiao, W.; Shi, D.; Chen, J. Acta Chim. Sinica, 2025, 83, 1472; (h) Shen, J.; Ma, X.; Jian, G.; Xu, H.; Shen, C. J. Org. Chem. 2026, 91, 9895; (i) Cheng, H.; Zhou, Z.; Shen, C.; Zhang, P. Adv. Synth. Catal. 2026, 368, e70628; (j) Wang, D.; Zheng, C.; Shen, C.; Wang, M.; Shen, J. Org. Chem. Front. 2026, 13, 3468; (k) Shen, J.; Hu, D.; Chen, Y.; Xu, H.; Wang, D.; Ge, K.; Shen, C.; Wang, M. J. Org. Chem. 2026, 91, 5201; (l) Ge, K.; Zhao, Y.; Dang, H.; Wang, M.; Shen, J. Org. Biomol. Chem. 2026, 24, 824.
[21] (a) Sun J.; Wang C.; Wu C.; Wang W.; Zeng Y.; Song S.; Chen Z.; Li J. Green Chem.2024, 26, 3301; (b) Huang, P.; Lv, C.; Song, H.; Wang, C.; Du, J.; Li, J.; Sun, B.; Jin, C. Green Chem. 2024, 26, 7198; (c) Castillo-Pazos, D. J.; Lasso, J. D.; Hamzehpoor, E.; Ramos-Sánchez, J.; Salgado, J. M.; Cosa, G.; Perepichka, D. F.; Li, C.-J. Chem. Sci. 2023, 14, 3470; (d) Lasky, M. R.; Salvador, T. K.; Mukhopadhyay, S.; Remy, M. S.; Vaid, T. P.; Sanford, M. S. Angew. Chem. Int. Ed. 2022, 61, e202208741; (e) Lei, P.; Su, Q.; Wang, D.; Shahid, A. K.; Ablajan, K. Acta Chim. Sinica, 2025, 83, 1379; (f) Han, C.; Wang, L.; Zhao, X.; Qiao, B.; Jiang, Z. Sci. China Chem. 2025, 68, 5025; (g) Zheng, K.; Chen, C.; Xu, H.; Mao, J.; Shen, C. J. Org. Chem. 2025, 90, 15567.
[22] (a) Lv S.; Zheng F.; Wang Z.; Hayat K.; Veiga M. C.; Kennes C.; Chen, J. Sci. Total Environ.2024, 908, 168339; (b) Mu, S.; Li, H.; Wu, Z.; Peng, J.; Chen, J.; He, W. Chin. J. Org. Chem. 2022, 42, 4292; (c) Yao, J.; Mei, Y.; Yuan, B.; Zheng, F.; Wang, Z.; Chen, J. Environ. Res. 2024, 241, 117613.
[23] (a) Zhu J.; Guo Y.; Zhang Y.; Li W.; Zhang P.; Xu J. Green Chem.2023, 25, 986; (b) Zhu, J.; Hong, Y.; Wang, Y.; Guo, Y.; Zhang, Y.; Ni, Z.; Li, W.; Xu, J. ACS Catal. 2024, 14, 6247; (c) Guo, Y.; Zhu, J.; Wang, Y.; Li, Y.; Hu, H.; Zhang, P.; Xu, J.; Li, W. ACS Catal. 2024, 14, 619.
[24] (a) Lasso J. D.; Castillo-Pazos D. J.; Salgado J. M.; Ruchlin C.; Lefebvre L.; Farajat D.; Perepichka D. F.; Li, C.-J. J. Am. Chem. Soc.2024, 146, 2583; (b) Saxena, B.; Patel, R. I.; Sharma, A. Adv. Synth. Catal. 2023, 365, 1538; (c) Yang, Z.; Liu, Y.; Cao, K.; Zhang, X.; Jiang, H.; Li, J. Beilstein J. Org. Chem. 2021, 17, 771; (d) Crisenza, G. E. M.; Mazzarella, D.; Melchiorre, P. J. Am. Chem. Soc. 2020, 142, 5461; (e) Gui, Q.-W.; Wang, B.-B.; Zhu, S.; Li, F.-L.; Zhu, M.-X.; Yi, M.; Yu, J.-L.; Wu, Z.-L.; He, W.-M. Green Chem. 2021, 23, 4430; (f) Wortman, A. K.; Stephenson, C. R. J. Chem. 2023, 9, 2390.
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