Access to N-Fused Heteroarenes via Radical-Mediated Functional Group Migration-Cyclization Cascade

doi:10.6023/cjoc202512005

Abstract

Nitrogen-containing heteroarenes constitute privileged scaffolds in pharmaceuticals and functional molecules, and their efficient synthesis remains a longstanding objective in organic chemistry. Over the past decade, radical-mediated functional group migration (FGM) has emerged as a powerful strategy for alkene functionalization. Herein, we report a step-economical and practical method for synthesizing N-heteroarenes directly from alkenes through a functional group migration-cyclization cascade. A new class of heterocyclizing agents featuring a sulfoxide linkage has been designed for this transformation. Under visible-light irradiation, these reagents engage with various alkenes in a radical “dock-migration” process, followed by intramolecular cyclization, enabling the modular construction of diverse N‑fused heteroarenes in a single operation. The reaction proceeds under mild conditions, exhibits broad substrate scope and excellent functional group tolerance, and offers a green, efficient synthetic tool for the late-stage modification of complex bioactive molecules.

Key words: radical reactions, N-fused heteroarenes, functional group migration, photocatalysis, cyclization reactions

Cite this article

Yang Shan,chen Yasu, Zhu Chen. Access to N-Fused Heteroarenes via Radical-Mediated Functional Group Migration-Cyclization Cascade[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202512005.

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References

[1] For selected reviews:
(a) Huang H.-M.; Bellotti P.; Glorius, F. Chem. Soc. Rev.2020, 49, 6186.
(b) Jiang H.; Studer, A. Chem. Soc. Rev.2020, 49, 1790.
(c) Li Z.-L.; Fang G.-C.; Gu Q.-S.; Liu, X.-Y. Chem. Soc. Rev.2020, 49, 32.
(d) Sun J.; Wang L.; Zheng G.; Zhang, Q. Org. Chem. Front.2023, 10, 4488.
(e) Wang Y.; Bao Z.-P.; Mao, X.-D. Hou M.; Wu. X.-F. Chem. Soc. Rev.2025, 54, 9530.
(f) Cao G.-M.; Yan S.-S.; Song L.; Jiang Y.-X.; Gao T.-Y.; Chen Z.; Zhang W.; Ye J.-H.; Yu, D.-G. Chem. Soc. Rev.2025, 54, 6726.
[2] For selected reviews:
(a) Chen Z.-M.; Zhang X.-M.; Tu, Y.-Q. Chem. Soc. Rev.2015, 44, 5220.
(b) Li W.; Xu W.; Xie J.; Yu S.; Zhu, C. Chem. Soc. Rev.2018, 47, 654.
(c) Wu, X.; Zhu, C.Acc. Chem. Res. 2020, 53, 1620.
(d) Wu X.; Ma Z.; Feng T.; Zhu, C. Chem. Soc. Rev.2021, 50, 11577.
(e) Wei, Y.; Wu, X.; Zhu, C.Synlett 2022, 33, 1017.
(f) Ma, Z.; Wu, X.; Zhu, C.Chem. Rec. 2023, 23, e202200221.
(g) Chen Y.-S.; Cao Z.; Wu X.-X.; Zhu, C. Sci. Sin. Chim.2023, 53, 289 (in chinese).
(陈亚苏, 曹柱, 吴鑫鑫, 朱晨, 中国科学化学, 2023, 53, 289.)
(h) Lee W.; Park I.; Hong, S. Sci. China Chem.2023, 66, 1688.
(i) Chen, F.; Cao, Z.; Zhu, C.Chem. Commun. 2024, 60, 14912.
(j) Chen, F.; Cao, Z.; Zhu, C. Angew. Chem. Int. Ed. 2025, 64, e202424667.
(k) He, C.; Zhou, Y.; Duan, X.; Liu, L.Chin. J. Org. Chem. 2025, 45, 1478.
[3] For selected examples:
(a) Wu, Z.; Ren, R.; Zhu, C.Angew. Chem. Int. Ed. 2016, 55, 10821.
(b) Wu, Z.; Wang, D.; Liu, Y.; Huan, L.; Zhu, C.J. Am. Chem. Soc. 2017, 139, 1388.
(c) Xu, Y.; Wu, Z.; Jiang, J.; Ke, Z.; Zhu, C.Angew. Chem. Int. Ed. 2017, 56, 4545.
(d) Wu X.; Wang M.; Huan L.; Wang D.; Wang J.; Zhu, C. Angew. Chem. Int. Ed.2018, 57, 1640.
(e) Wu, S.; Wu, X.; Wang, D.; Zhu, C.Angew. Chem. Int. Ed. 2019, 58, 1499.
(f) Wang Z.-S.; Chen Y.-B.; Zhang H.-W.; Sun Z.; Zhu C.; Ye, L.-W. J. Am. Chem. Soc.2020, 142, 3636.
(g) Kweon, B.; Kim, C.; Kim, S.; Hong, S.Angew. Chem., Int. Ed. 2021, 60, 26813.
(h) Zhao G.; Lim S.; Musaev D. G.; Ngai, M.-Y. J. Am. Chem. Soc.2023, 145, 8275.
(i) Sun, Y.; Wu, X.; Cao, Z.; Zhu, C.Sci. China Chem. 2023, 66, 1435.
(j) Wang S.; Luo X.; Wang Y.; Liu Z.; Yu Y.; Wang, X; Ren D.; Wang P.; Chen Y.-H.; Qi X.; Yi H.; Lei A. Nat. Chem.2024, 16, 1621.
(k) Zheng Y.; Dong Q.-X.; Wen S.-Y.; Ran H.; Huang, H.-M. J. Am. Chem. Soc.2024, 146, 18210.
(l) Sephton T.; Large J. M.; Natrajan L. S.; Butterworth S.; Greaney, M. F. Angew. Chem. Int. Ed.2024, 63, e202407979.
(m) Wang Y.; Yang H.; Zheng Y.; Hu M.; Zhu J.; Bao Z.-P.; Zhao Y.; Wu X.-F. Nat. Catal.2024, 7, 1065.
(n) Wang X.; Wang S.; Song S.; Chen Y.; Sun H.; Zhu C. Sci. Adv.2024, 10, eadp7385.
(o) Xu J.; Li R. H.; Ma Y.; Zhu J.; Shen C.; Jiang H. Nat. Commun.2024, 15, 6791.
(p) Song S.; Wang S.; Wang Z.; Sun H.; Wang X.; Zhu, C. Angew. Chem. Int. Ed.2024, 64, e202418350.
(q) Wen S.-Y.; Chen J.-J.; Zheng Y.; Han J.-X.; Huang, H.-M. Angew. Chem. Int. Ed.2025, 64, e202415495.
(r) Chen Y.; Wang S.; Wang T.; Wang X.; Sun H.; Zhu, C. Angew. Chem. Int. Ed.2025, 64, e202507557.
(s) Gao K.; Wang X.; Wang T.; Song S.; Zhu, C. Angew. Chem. Int. Ed.2025, 64, e202500153.
(t) Wang, Z.; Chen, Y.; Li, J.; Zhu, C.Sci. China Chem. 2025, 68, 241.
(u) Li J.-Y.; Liu Y.; Sun D.; Wu G.; Yue S.-S.; Yang H.-Y.; Zhang H.; Zhang W.; Zheng M.-M.; Xue X.-S.; Guo, S. J. Am. Chem. Soc.2025, 147, 26124.
(v) Zhou H.; Lunic D.; Sanosa N.; Sampedro D.; Funes-Ardoiz I.; Teskey, C. J. Angew. Chem. Int. Ed.2025, 64, e202418869.
(w) Wang Z.; Chen Y.; Zhu, C. Chin. J. Chem.2025, 43, 437.
(x) Wang, Z.; Shao, X.; Chen, Y.; Zhu, C.Chem. Res. Chin. Univ. 2025, 41, DOI:10.1007/s40242-025-5146-1.
(y) Wen S.-Y.; Chen J.-J.; Zheng Y.; Huang H.-M. CCS Chem.2025, 7, 2721.
[4] For selected examples from our group:
(a) Yu J.; Wu Z.; Zhu, C. Angew. Chem. Int. Ed.2018, 57, 17156.
(b) Wang M.; Zhang H.; Liu J.; Wu X.; Zhu, C. Angew. Chem. Int. Ed.2019, 58, 17646.
(c) Liu J.; Wu S.; Yu J.; Lu C.; Wu Z.; Wu X.; Xue X.-S.; Zhu, C. Angew. Chem. Int. Ed.2020, 59, 8195.
(d) Zhang H.; Wang M.; Wu X.; Zhu, C. Angew. Chem. Int. Ed.2021, 60, 3714.
(e) Yu, J.; Zhang, H.; Wu, X.; Zhu, C.CCS Chem. 2021, 3, 1426.
(f) Wei Y.; Zhang H.; Wu X.; Zhu, C. Angew. Chem. Int. Ed.2021, 60, 20215.
(g) Yu J.; Zhang X.; Wu X.; Liu T.; Zhang Z.-Q.; Wu J.; Zhu C. Chem2023, 9, 472.
(h) Wang J.; Wu X.; Cao Z.; Zhang X.; Wang X.; Li J.; Zhu C. Adv. Sci.2024, 11, 2309022.
(i) Liu, J.; Ma, J.; Wang, T.; Xue, X.-S.; Zhu, C.JACS Au 2024, 4, 2108.
(j) Cao Z.; Sun Y.; Chen Y.; Zhu, C. Angew. Chem. Int. Ed.2024, 63, e202408177.
(k) Wang X.; Li H.; Chen Y.; Wang Z.; Wu X.; Zhu C. Nat. Commun.2025, 16, 4702.
(l) Wang, J.; Kang, H.; Yang, S.; Cao, Z.; Chen, X.; Zhu, C.Chem. Sci. 2025, DOI:10.1039/D5SC07904G.
[5] For selected examples from other groups:
(a) Monos T. M.; McAtee R. C.; Stephenson, C. R. J. Science2018, 361, 1369.
(b) Moon Y.; Lee W.; S. Hong, J. Am. Chem. Soc.2020, 142, 12420.
(c) Lee W.; Koo Y.; Jung H.; Chang S.; Hong S. Nat. Chem.2023, 15, 1091.
(d) Kim M.; Lee K.; Kim S.; Hong S. Synlett2023, 34, 1437.
(e) Babcock D. J.; Wolfram A. J.; Barney J. L.; Servagno S. M.; Sharma A.; Nacsa, E. D. Chem. Sci.2024, 15, 4031.
(f) Noten E. A.; Ng C. H.; Wolesensky R. M.; Stephenson, C. R. J. Nat. Chem.2024, 16, 599.
(g) Hervieu C.; Kirillova M. S.; Hu Y.; Cuesta-Galisteo S.; Merino E.; Nevado C. Nat. Chem.2024, 16, 607.
(h) He, C.; Wang, M.; Wang, Y.; Zhao, L.; Zhou, Y.; Zhang, K.; Shen, S.; Su, Y.; Duan, X.-H.; Liu, L.Sci. China Chem. 2024, 67, 2022.
(i) Zhang, K.; Wang, M.; Jiang, Q.; Dong, B.; Duan, X.-H.; Liu, L.Sci. China Chem. 2025, DOI:10.1007/s11426-025-2806-5.
(j) Barney, J. L.; Wolfram, A. J.; Litvak, R.; Nacsa, E. D.ACS Catal. 2025, 15, 2139.
(k) Yang Y.; Xie D.; Ma, X. Angew. Chem. Int. Ed.2025, 64, DOI:10.1002/anie.202519794.
[6] (a) Heravi M. M.; Zadsirjan V. RSC Adv.2020, 10, 44247.
(b) Kerru, N.; Gummidi, L.; Maddila, S.; Gangu, K. K.; Jonnalagadda, S. B.Molecules 2020, 25, 1909.
(c) Aatif M.; Raza M. A.; Javed K.; Nashre-ul-Islam S. M.; Farhan M.; Alam M. W. Antibiotics2022, 11, 1750.
(d) Wang Y.-X.; Deng Z.; Bibi A.; Fang B.; Zhou, C.-H. Chin. J. Chem.2024, 42, 1741.
(e) Ramanathan M.; Moussa, Z. Org. Chem. Front.2025, 12, 256.
(f) Garg A.; Dureja, D. Pasricha R.; Saini P. D. K.; Bhalla, A. Med. Chem. Res.2025, 34, 1145.
[7] Marshall C. M.; Federice J. G.; Bell C. N.; Cox P. B.; Njardarson, J. T. J. Med. Chem.2024, 67, 11622.
[8] Kabir E.; Uzzaman M. Results Chem.2022, 4, 100606.
[9] Ghara S.; Paritosh B.; Shouvik G.; Sandip G.; Arabinda M.; Chandana P.; Mohammed I.; Shubhendu D.; Shubhankar, S. Org. Chem. Front.2025, 12, 2790.
[10] CCDC number:2480115

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