Catalytic Intermolecular [4+2]-Cycloaddition toward the Stereo­selective C2–C3 Annulation of Indoles

Abstract

Catalytic dearomative cycloaddition involving the C2–C3 bond of indoles is a powerful strategy for the synthesis of fused indoline scaffolds. Through dearomative cycloaddition/annulation, planar indole substrates can be readily transformed into rigid, three-dimensional polycyclic complex structures in one step. Molecules with architectural complexity are generally considered to have drug-like properties. Hence, annulation products have tremendous potential for discovering therapeutic properties, and this strategy has become an important part of the medicinal chemistry toolbox. Using appropriate catalyst control, desirable stereoselectivity can be achieved. Previous literature reports reveal that [3+2]-cycloadditions of indoles have been extensively studied. In contrast, the catalytic [4+2]-cycloaddition/dearomatization of indoles has been much less investigated. In this short review, we focus specifically on six-membered ring annulations via [4+2]-cycloaddition with the C2–C3 bond of indoles and discuss the various catalytic methods that have been developed toward this objective.

1 Introduction

2 [4+2]-Cycloaddition/Annulation of Indoles

2.1 Electron-Rich Indoles

2.1.1 Transition-Metal Catalysis

2.1.2 Organocatalysis

2.2 Electron-Deficient Indoles

2.2.1 Transition-Metal Catalysis

2.2.2 Organocatalysis

3 Summary and Outlook

Key words

cycloaddition - indoles - six-membered-ring annulation - transition-metal catalysis - organocatalysis

Publication History

Received: 31 May 2024

Accepted after revision: 09 August 2024

Accepted Manuscript online:
09 August 2024

Article published online:
25 September 2024

• References

• 1a Sundberg RJ. The Chemistry of Indoles . Academic Press; New York: 1970
• 1b Takano S, Ogasawara K. Alkaloids 1989; 36: 225
• 1c Takano S, Ogasawara K. Alkaloids of the Calabar Bean . In The Alkaloids: Chemistry and Pharmacology, Vol. 36, Chap. 5. Brossi A. Academic Press; San Diego: 1990. 225
• 1d Sundberg RJ. Indoles 1996
• 1e Saxton JE. In The Alkaloids, Vol. 51. Cordell GA. Academic Press; New York: 1998: 1-197
• 1f Barton DH, Nakanishi K, Cohn OM. Comprehensive Natural Products Chemistry . Elsevier; Oxford: 1999
• 1g Dewick PM. Medicinal Natural Products: A Biosynthetic Approach, 2nd ed. John Wiley & Sons; Chichester: 2002
• 1h Knölker H.-J, Reddy KR. Chem. Rev. 2002; 102: 4303
• 1i Marti C, Carreira EM. Eur. J. Org. Chem. 2003; 2209
• 1j Fattorusso E, Scafati OT. Modern Alkaloids . Wiley-VCH; Weinheim: 2008
• 1k Ruiz-Sanchis P, Savina SA, Albericio F, Álvarez M. Chem. Eur. J. 2011; 17: 1388
• 1l Schmidt AW, Reddy KR, Knölker H.-J. Chem. Rev. 2012; 112: 3193
• 1m Głuszyńska A. Eur. J. Med. Chem. 2015; 94: 405
• 1n Zi W, Zuo Z, Ma D. Acc. Chem. Res. 2015; 48: 702
• 1o Tsutsumi LS, Gundisch D, Sun D. Curr. Top. Med. Chem. 2016; 16: 1290
• 1p Wertjes WC, Southgate EH, Sarlah D. Chem. Soc. Rev. 2018; 47: 7996
• 1q Wang Y, Xie F, Lin B, Cheng M, Liu Y. Chem. Eur. J. 2018; 24: 14302
• 1r Hua T.-B, Xiao C, Yang Q.-Q, Chen J.-R. Chin. Chem. Lett. 2020; 31: 311

For selected reviews, see:
• 2a Pape AR, Kaliappan KP, Kündig EP. Chem. Rev. 2000; 100: 2917
• 2b Roche SP, Porco JA. Jr. Angew. Chem. Int. Ed. 2011; 50: 4068
• 2c Zhuo C.-X, Zhang W, You S.-L. Angew. Chem. Int. Ed. 2012; 51: 12662
• 2d Xia Z.-L, Xu-Xu Q.-F, Zheng C, You S.-L. Chem. Soc. Rev. 2020; 49: 286
• 3 Feher M, Schmidt JM. J. Chem. Inf. Comput. Sci. 2003; 43: 218
• 4a Lovering F, Bikker J, Humblet C. J. Med. Chem. 2009; 52: 6752
• 4b Meyers J, Carter M, Mok NY, Brown N. Future Med. Chem. 2016; 8: 1753
• 5a Repka LM, Ni J, Reisman SE. J. Am. Chem. Soc. 2010; 132: 14418
• 5b Liao L, Shu C, Zhang M, Liao Y, Hu X, Zhang Y, Wu Z, Yuan W, Zhang X. Angew. Chem. Int. Ed. 2014; 53: 10471
• 5c Rivinoja DJ, Gee YS, Gardiner MG, Ryan JH, Hyland CJ. T. ACS Catal. 2017; 7: 1053
• 5d Gee YS, Rivinoja DJ, Wales SM, Gardiner MG, Ryan JH, Hyland CJ. T. J. Org. Chem. 2017; 82: 13517
• 5e Laugeois M, Ling J, Ferárd C, Michelet V, Vidal VR, Vitale MR. Org. Lett. 2017; 19: 2266
• 5f Wan Q, Xie J.-H, Zheng C, Yuan Y.-F, You S.-L. Angew. Chem. Int. Ed. 2021; 60: 19730
• 5g Liu Y.-Z, Song H, Zheng C, You S.-L. Nat. Synth. 2022; 1: 203
• 6a Roy S, Kishbaugh TL. S, Jasinski JP, Gribble GW. Tetrahedron Lett. 2007; 48: 1313
• 6b Lee S, Diab S, Queval P, Sebban M, Chataigner I, Piettre SR. Chem. Eur. J. 2013; 19: 7181
• 6c Awata A, Arai T. Angew. Chem. Int. Ed. 2014; 53: 10462
• 6d Vivekanand T, Satpathi B, Bankar SK, Ramasastry SS. V. RSC Adv. 2018; 8: 18576
• 6e Suo J.-J, Liu W, Du J, Ding C.-H, Hou X.-L. Chem. Asian J. 2018; 13: 959
• 6f Zhang J.-Q, Tong F, Sun B.-B, Fan W.-T, Chen J.-B, Hu D, Wang X.-W. J. Org. Chem. 2018; 83: 2882
• 6g Sun M, Zhu Z.-Q, Gu L, Wan X, Mei G.-J, Shi F. J. Org. Chem. 2018; 83: 2341
• 6h Cheng Q, Zhang F, Cai Y, Guo Y.-L, You S.-L. Angew. Chem. Int. Ed. 2018; 57: 2134
• 7 Zhang G, Huang X, Li G, Zhang L. J. Am. Chem. Soc. 2008; 130: 1814
• 8 Zhang Y, Stephens D, Hernandez G, Mendoza R, Larionov OV. Chem. Eur. J. 2012; 18: 16612
• 9 Gilchrist TL. Chem. Soc. Rev. 1983; 12: 53
• 10 Tong M.-C, Chen X, Li J, Huang R, Tao H, Wang C.-J. Angew. Chem. Int. Ed. 2014; 53: 4680
• 11a Jiang X.-X, Wang R. Chem. Rev. 2013; 113: 5515
• 11b Huang G, Kouklovsky C, de laTorre A. Chem. Eur. J. 2021; 27: 4760
• 11c Lu Y, Xu M.-M, Zhang Z.-M, Zhang J, Cai Q. Angew. Chem. Int. Ed. 2021; 60: 26610
• 11d Huang G, Guillot R, Kouklovsky C, Maryasin B, de la Torre A. Angew. Chem. Int. Ed. 2022; 61: e202208185
• 11e Zhang F, Ren BT, Zhou Y, Liu Y, Feng X. Chem. Sci. 2022; 13: 5562
• 12 Gao R.-D, Xu Q.-L, Zhang B, Gu Y, Dai L.-X, You S.-L. Chem. Eur. J. 2016; 22: 11601
• 13 Feng L.-W, Ren H, Xiong H, Wang P, Wang L, Tang Y. Angew. Chem. Int. Ed. 2017; 56: 3055
• 14 Shao W, You S.-L. Chem. Eur. J. 2017; 23: 12489
• 15 Wang Q, Li T.-R, Lu L.-Q, Li M.-M, Zhang K, Xiao W.-J. J. Am. Chem. Soc. 2016; 138: 8360
• 16 Li T.-R, Cheng B.-Y, Wang Y.-N, Zhang M.-M, Lu L.-Q, Xiao W.-J. Angew. Chem. Int. Ed. 2016; 55: 12422
• 17 Shao W, Xu-Xu Q.-F, You S.-L. Chem. Asian J. 2020; 15: 2462
• 18 Liang X, Zhang T.-Y, Zeng X.-Y, Zheng Y, Wei K, Yang Y.-R. J. Am. Chem. Soc. 2017; 139: 3364
• 19 Cai Q, You S.-L. Org. Lett. 2012; 14: 3040
• 20a Ishihara K, Nakano K. J. Am. Chem. Soc. 2005; 127: 10504
• 20b Ishihara K, Nakano K. J. Am. Chem. Soc. 2007; 129: 8930

For selected papers on iminium catalysis, see:
• 21a Lelais G, MacMillan DW. C. Aldrichimica Acta 2006; 39: 79
• 21b Erkkila A, Majander I, Pihko PM. Chem. Rev. 2007; 107: 5416
• 21c Mukherjee S, Biswas B. ChemistrySelect 2020; 5: 10704
• 21d Pandey G, Khamrai J, Mishra A, Maity P, Chikkade PK. Tetrahedron 2018; 74: 6317
• 21e Midya A, Khalse LD, Ghorai P. Eur. J. Org. Chem. 2023; 26: e202201409

For recent reviews on using iminium-enamine chemistry in cascade reactions, see:
• 22a Wang W, Li H, Wang J, Zu L. J. Am. Chem. Soc. 2006; 128: 10354
• 22b Enders D, Grondal C, Hüttl MR. M. Angew. Chem. Int. Ed. 2007; 46: 1545
• 22c Simmons B, Walji AM, MacMillan DW. C. Angew. Chem. Int. Ed. 2009; 48: 4349
• 22d Zhang X, Zhang S, Wang W. Angew. Chem. Int. Ed. 2010; 49: 1481
• 23 Chen Z, Wang B, Wang Z, Zhu G, Sun J. Angew. Chem. Int. Ed. 2013; 52: 2027
• 24 Zuend SJ, Jacobsen EN. J. Am. Chem. Soc. 2009; 131: 15358
• 25 Robert EG. L, Pirenne V, Wodrich MD, Waser J. Angew. Chem. Int. Ed. 2023; 62: e202302420
• 26 Pirenne V, Robert EG. L, Waser J. Chem. Sci. 2021; 12: 8706
• 27 Zhang J.-Y, Chen J.-Y, Gao C.-H, Yu L, Ni S.-F, Tan W, Shi F. Angew. Chem. Int. Ed. 2023; 62: e202305450
• 28 Shikari A, Parida C, Pan SC. Org. Lett. 2024; 26: 5057

For selected recent reviews, see:
• 29a Parmar D, Sugiono E, Raja S, Rueping M. Chem. Rev. 2014; 114: 9047
• 29b Woldegiorgis AG, Suleman M, Lin X. Eur. J. Org. Chem. 2022; e202200624
• 29c Jiménez EI. Org. Biomol. Chem. 2023; 21: 3477
• 30 Suo J.-J, Du J, Jiang Y.-J, Chen D, Ding C.-H, Hou X.-L. Chin. Chem. Lett. 2019; 30: 1512
• 31 Bird MJ, Wales SM, Richardson C, Hyland CJ. T. Synlett 2020; 31: 916
• 32 Dou P.-H, Yuan S.-P, Chen Y, Zhao J.-Q, Wang Z.-H, You Y, Zhang Y.-P, Zhou M.-Q, Yuan W.-C. J. Org. Chem. 2022; 87: 6025
• 33 Pandit S, Pandey VK, Adhikari AS, Kumar S, Maurya AK, Kant R, Majumdar N. J. Org. Chem. 2023; 88: 97
• 34 Li Y, Tur F, Nielsen RP, Jiang H, Jensen F, Jørgensen KA. Angew. Chem. Int. Ed. 2016; 55: 1020
• 35 Andreini M, De Paolis M, Chataigner I. Catal. Commun. 2015; 63: 15
• 36 Yue D.-F, Zhao J.-Q, Chen X.-Z, Zhou Y, Zhang X.-M, Xu X.-Y, Yuan W.-C. Org. Lett. 2017; 19: 4508
• 37 Zhou S, Qian H.-L, Zhao J.-Q, You Y, Wang Z.-H, Yin J.-Q, Zhang Y.-P, Chen M.-F, Yuan W.-C. Org. Biomol. Chem. 2023; 21: 1373
• 38 Wang H, Hu Q, Wang M, Guo C. iScience 2020; 23: 100840
• 39 Wang K.-K, Li Y.-L, Li L.-X, Yao W.-W, Li Y.-F, Wang W.-F, Chen R, Hu Y.-F, Sun A. J. Heterocycl. Chem. 2024; 61: 528
• 40 Wang K.-K, Du W, Zhu J, Chen Y.-C. Chin. Chem. Lett. 2017; 28: 512