Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Download PDF
Synlett
DOI: 10.1055/a-2744-1923
DOI: 10.1055/a-2744-1923
Letter
Published as part of the Special Topic Alkynes in Organic Synthesis
Palladium-Catalyzed C−H/N−H Annulations of (E,Z)-3-Arylidene Indolin-2-ones with Alkynes: A Synthesis of Benzazepine Derivatives
Authors
We greatly acknowledge DST-SERB (CRG/2021/001634) New Delhi, India, for the financial support for this research. The author thanks RUSA 2.0 (RI &QI) for the financial support. We thank DST-FIST for NMR and HRMS facilities. M. P thanks RUSA 2.0 (RI &QI) for fellowship support.
Supported by: New Delhi, India RUSA 2.0
Abstract
We developed an efficient palladium-catalyzed synthesis of benzazepine derivatives from (E,Z)-3-(arylidene)indolin-2-ones with alkynes, affording the desired products in good yields. The reaction proceeds via a palladium-catalyzed C−H/N−H activation, followed by alkyne insertion and reductive elimination sequences. Furthermore, we have also demonstrated the gram scale reaction as well as some synthetic transformations of the annulated products.
Publication History
Received: 18 August 2025
Accepted after revision: 11 November 2025
Accepted Manuscript online:
11 November 2025
Article published online:
11 December 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1a Rouden J, Lasne M-C, Blanchet J. Baudoux J Chem Rev 2014; 114: 712
- 1b Novoa A, Van Dorpe S, Wynendaele E. et al. J Med Chem 2012; 55: 9549
- 1c Tewes B, Frehland B, Schepmann D. et al. J Med Chem 2015; 58: 6293
- 2a Chen Q, Zhu XL, Jiang LL, Liu ZM, Yang GF. Eur J Med Chem 2008; 43: 595
- 2b Asif M. Int J Biol Chem 2017; 2: 146
- 3a Wu D, Kong L, Li Y, Ganguly R, Kinjo R. Nat Commun 2015; 6: 7340
- 3b Papadopoulosb A, Munoz-Castroa A, Charistosb N. New J Chem 2016; 40: 5090
- 4 Yadav Y, Kishore D, Vandana A. Orient J Chem 2013; 29: 1643
- 5a Decaux G, Soupart A, Vassart G. Lancet 2008; 371: 1624
- 5b Ghose AK, Herbertz T, Torsten H, Robert L, Dorsey BD, Mallamo JP. ACS Chem Neurosci 2012; 3: 50
- 5c Robertson GL. Nat Rev Endocrinol 2011; 7: 151
- 5d Hou F, Zhang X, Zhang G. et al. N Engl J Med 2006; 354: 131
- 5e Nicolas RN, Hernandez-Gallego R. CardiovascTher 2012; 30: 193
- 5f Gillman PK. Br J Pharmacol 2007; 151: 737
- 5g Stahl S. Stahl’s Essential Psychopharmacology: The Prescriber_S Guide. New York: Cambridge University Press; 2009
- 5h Albert U, Aguglia E, Maina G, Bogetto F. J Clin Psychiatry 2002; 63: 1004
- 5i Ganellin CR, Triggle DJ. Dictionary of Pharmacological Agents. London: Chapman & Hall/CRC; 1996
- 6 Dalton T, Faber T, Glorius F. ACS Cent Sci 2021; 7: 245
- 7 Lei A, Crabtree RH. Chem Rev 2017; 117: 8481
- 8a Phukon J, Gogoi S. Chem Commun 2020; 56: 1133
- 8b Lin H, Li SS, Dong L. Org Biomol Chem 2015; 13: 11228
- 8c Wang L, Yu Y, Yang M. et al. Adv Synth Catal 2017; 359: 3818
- 8d Biswas A, Giri D, Das D, De A, Patra SK, Samanta R. J Org Chem 2017; 82: 10989
- 8e Chen D, Zhou L, Liu Y, Wan J-P. Chem Commun 2023; 59: 4036
- 8f Li H, Yan X, Zhang J, Guo W, Jiang J, Wang J. Angew Chem Int Ed 2019; 58: 6732
- 8g Yan X, Jiang J, Wang J. Angew Chem Int Ed 2022; 134: e202201522
- 8h Oh H, Byun HW, Moon K. et al. J Org Chem 2021; 86: 16349
- 8i Thavaselvan S, Parthasarathy K. Org Biomol Chem 2022; 20: 4309
- 8j Bera S, Sarkar S, Pal J, Samanta R. Org Lett 2022; 24: 8470
- 8k Prusty N, Banjare SK, Mohanty SR, Nanda T, Yadav K, Ravikumar PC. Org Lett 2021; 23: 9041
- 9 Ge GC, Dinga CH, Hou XL. Org Chem Front 2014; 1: 382
- 10 Zuo Z, Liu J, Nan J. et al. Angew Chem Int Ed 2015; 54: 15385
- 11 Li D, Park Y, Yoon W, Yun H, Yun J. Org Lett 2019; 21: 9699
- 12 Shi Q, Liao Z, Liu Z. et al. Nat Commun 2022; 13: 4402
- 13 Zhang X, Gao Y, Miao Z. Adv Synth Catal 2023; 365: 381
- 14 Monteferrante OE, Houghtling KE, Kropiwnicki AR, Paradine SM. Chem Eur J 2024; e202402587
- 15 Luo F, Wang W, Xiang C. et al. Org Lett 2024; 26: 10224
- 16 Zhou Q, Xu H, Gao C, Gong Y, Zhang X, Fan X. J Org Chem 2025; 90: 5244
- 17 Wang L, Huang J, Peng S, Liu H, Jiang X, Wang J. Angew Chem Int Ed 2013; 52: 1768
- 18a Prabhakaran M, Sanjana R, Parthasarathy K. Org Biomol Chem 2024; 22: 9348
- 18b Kumaran S, Parthasarathy K. J Org Chem 2022; 87: 11989
- 19 (E) and (Z) -7-(arylidene)-1,2,3,4-tetraphenylazepino[3,2,1-hi]indol-6(7H)-one (3/3′); typical procedure A Schlenk tube (20 mL) was loaded with (E,Z)-3-(arylidene)indolin-2-one 1 (0.30 mmol), alkyne 2 (0.63 mmol), Pd(OAc)2 (10 mol%), and AgOAc (2 equiv). To this, 1,4-dioxane/MeCN (1:1) (2 mL) was added through a syringe and the reaction mixture was allowed to stir at 110 °C for 24 h. The reaction was monitored by TLC and the reaction mixture was diluted with CH2Cl2 (10 mL). The mixture was filtered through a Celite pad and the Celite pad was washed with dichloromethane (3 × 20 mL). The combined filtrate was concentrated and the residue was purified by silica gel column chromatography using hexane/ethyl acetate (92:8) as eluent to give the pure product 3a/3a′.