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DOI: 10.1055/a-2726-4405
Cp*Rh-Catalyzed NH-Indole-Directed C–H Activation/Annulation Toward Indole-Fused Polycyclic Compounds
Authors
Financial support from NSFC (Grant Nos. 21872028), Natural Science Foundation of Fujian Province (Grant No. Grant No.2025H0007, 2024H6034), the Fujian Province University Fund for New Century Excellent Talents are great acknowledged.
Supported by: NSFC 21872028
Supported by: Natural Science Foundation of Fujian Province 2024H6034,2025H0007
Abstract
Indole-fused polycyclic compounds, prevalent in bioactive natural products and pharmaceuticals with antiviral, anti-tumor, and antibacterial activities, represent privileged scaffolds in medicinal chemistry. Consequently, the development of efficient strategies remains ongoing. As a powerful complement to traditional multistep approaches, NH-indole-directed C–H activation/annulation, leveraging the inherent directing ability of the indole N–H group, has emerged as a particularly efficient and step-economical approach. This review comprehensively summarizes recent key progress in the synthesis of diverse indole-fused polycycles encompassing [1,2]-, [2,3]-, and [1,7]-fused derivatives through Cp*Rh(III)-catalyzed NH-indole-directed C–H functionalization. The transformations discussed utilize readily available arylindoles and versatile coupling partners such as alkenes, alkynes, diazo compounds, and carbon monoxide, enabling rapid access to structurally complex indole polycycles under generally mild conditions. While significant strides have been made, future challenges including mechanistic elucidation, cost-effective catalyst alternatives, and the synthesis of elusive medium-sized indole-fused rings are also highlighted.
Keywords
Rhodium-catalyzed - NH-indole-directed - C–H activation - Annulation - Indole-fused polycyclic compoundsPublication History
Received: 10 September 2025
Accepted after revision: 17 October 2025
Accepted Manuscript online:
17 October 2025
Article published online:
20 November 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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References
- 1 Ueura K, Satoh T, Miura M. Org Lett 2007; 9: 1407
- 2a Song G, Li X. Acc Chem Res 2015; 48: 1007
- 2b Ye B, Cramer N. Acc Chem Res 2015; 48: 1308
- 2c Piou T, Rovis T. Acc Chem Res 2017; 51: 170
- 2d Singh Chauhan AN, Mali G, Dua G, Samant P, Kumar A, Erande RD. ACS Omega 2023; 8: 27894
- 2e Liu J, Liang R, Yan Q, Zheng L, Liu Z-Q, Pu S. Org Chem Front 2025; 12: 3065
- 3a Kochanowska-Karamyan AJ, Hamann MT. Chem Rev 2010; 110: 4489
- 3b Chadha N, Silakari O. Eur J Med Chem 2017; 134: 159
- 3c Umer SM, Solangi M, Khan KM, Saleem RSZ. Molecules 2022; 27: 7586
- 4a Humphrey GR, Kuethe JT. Chem Rev 2006; 106: 2875
- 4b Youn SW, Ko TY. Asian J Org Chem 2018; 7: 1467
- 4c Neto JSS, Zeni G. Org Chem Front 2020; 7: 155
- 4d Das S. New J Chem 2023; 47: 13729
- 5a Gandeepan P, Müller T, Zell D, Cera G, Warratz S, Ackermann L. Chem Rev 2018; 119: 2192
- 5b Dhawa U, Kaplaneris N, Ackermann L. Org Chem Front 2021; 8: 4886
- 5c Sinha SK, Guin S, Maiti S, Biswas JP, Porey S, Maiti D. Chem Rev 2021; 122: 5682
- 5d Liu J, Xiao X, Lai Y, Zhang Z. Org Chem Front 2022; 9: 2256
- 5e Docherty JH, Lister TM, McArthur G. et al. Chem Rev 2023; 123: 7692
- 5f Goethe OF, Zhou D, Zhu X, Sevelda P, Szyperek A, Tomanik M. ACS Catal 2025; 15: 9013
- 5g Tang X, Van der Eycken EV, Song L. Chin Chem Lett. 2025 in press
- 6a Sandtorv AH. Adv Synth Catal 2015; 357: 2403
- 6b Kumar P, Nagtilak PJ, Kapur M. New J Chem 2021; 45: 13692
- 6c Prabagar B, Yang Y, Shi Z. Chem Soc Rev 2021; 50: 11249
- 6d Urbina K, Tresp D, Sipps K, Szostak M. Adv Synth Catal 2021; 363: 2723
- 6e Wen J, Shi Z. Acc Chem Res 2021; 54: 1723
- 6f Awasthi SK, Mishra A, Gope B. Synthesis 2023; 56: 1815
- 7a Li Y-H, Yu J-Q. J Am Chem Soc 2025; 147: 20233
- 7b Chen Y-Q, Wang Z, Wu Y. et al. J Am Chem Soc 2018; 140: 17884
- 7c Zhang Z-Z, Liu B, Xu J-W, Yan S-Y, Shi B-F. Org Lett 2016; 18: 1776
- 7d Gupta S, Sravani Galla M, Prasad Suhas K, Shankaraiah N. Adv Synth Catal 2025; 367: e202500093
- 7e Bag S, Patra T, Modak A. et al. J Am Chem Soc 2015; 137: 11888
- 7f Zhang Z, Tanaka K, Yu J-Q. Nature 2017; 543: 538
- 8a Mandal R, Garai B, Sundararaju B. ACS Catal 2022; 12: 3452
- 8b Zhang M, Zhong Z, Liao L, Zhang AQ. Org Chem Front 2022; 9: 3882
- 8c Castellino NJ, Montgomery AP, Danon JJ, Kassiou M. Chem Rev 2023; 123: 8127
- 8d Li W-B, Huang X-C, Liu P, Kong J, Yang G-P. Chin Chem Lett 2025; 36: 110543
- 8e Sharma P, Luxami V, Paul K. Org Chem Front 2025; 12: 4066
- 9a Stempel E, Gaich T. Acc Chem Res 2016; 49: 2390
- 9b Xu Z, Wang Q, Zhu J. Chem Soc Rev 2018; 47: 7882
- 9c Ciulla MG, Zimmermann S, Kumar K. Org Biomol Chem 2019; 17: 413
- 9d Shelke YG, Hande PE, Gharpure SJ. Org Biomol Chem 2021; 19: 7544
- 9e Mei H, Aradi K, Kiss L, Han J. Chin Chem Lett 2023; 34: 108657
- 10a Qi X, Li Y, Bai R, Lan Y. Acc Chem Res 2017; 50: 2799
- 10b Rani N, Mazumder S. Organometallics 2022; 41: 1659
- 10c Cao Y, Kacker A, Kou KGM. Asian J Org Chem 2025; 14: e00559
- 11a Omae I. Coord Chem Rev 2011; 255: 139
- 11b Wu X-F, Neumann H, Beller M. Chem Rev 2012; 113: 1
- 11c Yu Z-X, Li C-L. Chin J Org Chem 2024; 44: 1045
- 12 Huang Q, Han Q, Fu S. et al. J Org Chem 2016; 81: 12135
- 13 Guo X, Han Q, Tang Z. et al. Tetrahedron Lett 2018; 59: 1568
- 14 Lu P, Zhuang W, Lu L. et al. J Org Chem 2022; 87: 10967
- 15 Moritanl I, Fujiwara Y. Tetrahedron Lett 1967; 8: 1119
- 16 Han Q, Guo X, Tang Z. et al. Adv Synth Catal 2018; 360: 972
- 17 Zhuang W, Zhang J, Zheng Y, Huang Q. Molecules 2021; 26: 5329
- 18 Liu A, Han Q, Zhang X, Li B, Huang Q. Org Lett 2019; 21: 6839
- 19 Guo S, Liu Y, Zhao L, Zhang X, Fan X. Org Lett 2019; 21: 6437
- 20 Shinde VN, Rangan K, Kumar D, Kumar A. J Org Chem 2021; 86: 2328
- 21a Duarah G, Kaishap PP, Begum T, Gogoi S. Adv Synth Catal 2018; 361: 654
- 21b Saha A, Shankar M, Sau S, Sahoo AK. Chem Commun 2022; 58: 4561
- 21c Doraghi F, Karimtabar MS, Ghasemi M, Larijani B, Mahdavi M. Chem Rec 2024; 24: e202400069
- 22 Morimoto K, Hirano K, Satoh T, Miura M. Org Lett 2010; 12: 2068
- 23 Ackermann L, Wang L, Lygin AV. Chem Sci 2012; 3: 177
- 24 Obata A, Sasagawa A, Yamazaki K, Ano Y, Chatani N. Chem Sci 2019; 10: 3242
- 25 Liu Y, Yang Z, Chauvin R. et al. Org Lett 2020; 22: 5140
- 26 Xiang G, Wang Y, Lu L, Zhang X, Huang Q. J Org Chem 2024; 89: 5589
- 27 Wang M, Yan S, Li B. et al. J Org Chem 2024; 89: 7828
- 28 Wang M, Xu Y, Hou H, Zhang X, Fan X. Chem Commun 2024; 60: 6536
- 29 Wang X, Zhang J, Chen D. et al. Org Lett 2019; 21: 7038
- 30 Nunewar S, Kumar S, Priyanka P, Girase P, Kanchupalli V. Chem Commun 2022; 58: 6140
- 31 Guo S, Liu Y, Wang Y, Zhang X, Fan X. J Org Chem 2020; 85: 8910
- 32 Wang Y-J, Wang T-T, Liang C-C, Li Z-H, Zhao L-M. Org Lett 2021; 23: 6272
- 33 Pan G, Lu L, Zhuang W, Huang Q. J Org Chem 2021; 86: 16753
- 34a Xiang Y, Wang C, Ding Q, Peng Y. Adv Synth Catal 2018; 361: 919
- 34b Doraghi F, Baghershahi P, Ghasemi M, Mahdavi M, Al-Harrasi A. RSC Adv 2024; 14: 39337
- 35 Li B, Zhang B, Zhang X, Fan X. Chem Commun 2017; 53: 1297
- 36 Zhang Z, Liu K, Chen X, Su S-J, Deng Y, Zeng W. RSC Adv 2017; 7: 30554
- 37 Yuan Y, Guo X, Zhang X, Li B, Huang Q. Org Chem Front 2020; 7: 3146
- 38 Li B, Shen N, Wang K, Fan X, Zhang X. Asian J Org Chem 2022; 11: e202100710
- 39 Zhang Q, Li Q, Wang C. RSC Adv 2021; 11: 13030
- 40 Zheng G, Duan X, Chen L. et al. J Org Chem 2020; 85: 4543
- 41 Yang X, Li Y, Kong L, Li X. Org Lett 2018; 20: 1957
- 42 Li B, Guo C, Shen N, Zhang X, Fan X. Org Chem Front 2020; 7: 3698
- 43 Chen G, Zhang X, Jia R, Li B, Fan X. Adv Synth Catal 2018; 360: 3781
- 44 Yuan Y, Pan G, Zhang X, Huang Q. Org Chem Front 2020; 7: 53
- 45 Yuan Y, Pan G, Zhang X, Li B, Xiang S, Huang Q. J Org Chem 2019; 84: 14701
- 46 Yuan Y, Zhu J, Yang Z, Ni S-F, Huang Q, Ackermann L. CCS Chem 2022; 4: 1858