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Synlett 2025; 36(04): 341-346
DOI: 10.1055/a-2341-9185
DOI: 10.1055/a-2341-9185
letter
Metal-Free Synthesis of 2-Benzylideneindolin-3-ones via a Nucleophilic/Rearrangement/Azide–Alkene Cascade Reaction
This work was supported by the National Science Foundation of China (Nos. 22301160, 21702121, 21602123), the Natural Science Foundation of Hubei Province (2023AFB026), China Postdoctoral Science Foundation (2023M742043), Hubei Three Gorges Laboratory Foundation (SC232008, SC213008), and the Foundation of Hubei Key Laboratory of Natural Products Research and Development (2022NPRD04).
Abstract
A metal-free synthesis of 2-benzylideneindolin-3-ones through a formal [4+1] annulation from o-azidobenzaldehydes and terminal alkynes has been developed. The method features operational simplicity, mild reaction conditions, and ready availability of starting materials. A broad range of 2-benzylideneindolin-3-ones were prepared in moderate to excellent yields. Mechanistic studies indicated that the reaction might proceed through a nucleophilic addition/rearrangement/azide–alkene cycloaddition pathway to produce 2-benzylideneindolin-3-ones.
Key words
metal-free synthesis - benzylideneindolinones - azidobenzaldehydes - terminal alkynes - azide–alkene cycloaddition - cascade reactionSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2341-9185.
- Supporting Information
Publication History
Received: 28 April 2024
Accepted after revision: 10 June 2024
Accepted Manuscript online:
10 June 2024
Article published online:
02 July 2024
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References and Notes
- 1a Liu J.-F, Jiang Z.-Y, Wang R.-R, Zheng Y.-T, Chen J.-J, Zhang X.-M, Ma Y.-B. Org. Lett. 2007; 9: 4127
- 1b Wu P.-L, Hsu Y.-L, Jao C.-W. J. Nat. Prod. 2006; 69: 1467
- 1c Pedras MS. C, Sarma-Mamillapalle VK. Bioorg. Med. Chem. 2012; 20: 3991
- 1d Lee J.-H, So JH, Jeon JH, Choi EB, Lee Y.-R, Chang Y.-T, Kim CH, Bae MA, Ahn JH. Chem. Commun. 2011; 47: 7500
- 1e Baran PS, Corey EJ. J. Am. Chem. Soc. 2002; 124: 7904
- 1f Parra A, Alfaro R, Marzo L, Moreno-Carrasco A, García Ruano JL, Alemán J. Chem. Commun. 2012; 48: 9759
- 1g Pal K, Shukla RK, Volla CM. R. Org. Lett. 2017; 19: 5764
- 1h Yadav J, Dolas AJ, Iype E, Rangan K, Ohshita J, Kumar D, Kumar I. J. Org. Chem. 2021; 86: 17213
- 2a Liu D.-Q, Mao S.-C, Zhang H.-Y, Yu X.-Q, Feng M.-T, Wang B, Feng L.-H, Guo Y.-W. Fitoterapia 2013; 91: 15
- 2b Souard F, Okombi S, Beney C, Chevalley S, Valentin A, Boumendjel A. Bioorg. Med. Chem. 2010; 18: 5724
- 2c Leclerc S, Garnier M, Hoessel R, Marko D, Bibb JA, Snyder GL, Greengard P, Biernat J, Wu Y.-Z, Mandelkow EM, Eisenbrand G, Meijer L. J. Biol. Chem. 2001; 276: 251
- 2d Meijer L, Skaltsounis A.-L, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R, Crovace C, Tarricone C, Musacchio A, Roe SM, Pearl L. Chem. Biol. 2003; 10: 1255
- 2e Polychronopoulos P, Magiatis P, Skaltsounis A.-L, Myrianthopoulos V, Mikros E, Tarricone A, Musacchio A, Roe SM, Pearl L, Leost M, Greengard P, Meijer L. J. Med. Chem. 2004; 47: 935
- 2f Gein VL, Tatarinov VV, Rassudikhina NA, Vakhrin MI, Voronina ÉV. Pharm. Chem. J. 2011; 45: 231
- 2g Campaniço A, Carrasco MP, Njoroge M, Seldon R, Chibale K, Perdigão J, Portugal I, Warner DF, Moreira R, Lopes F. ChemMedChem 2019; 14: 1537
- 2h Campaniço A, Harjivan SG, Freitas E, Serafini M, Gaspar MM, Capela R, Gomes P, Jordaan A, Madureira AM, André V, Silva AB, Duarte MT, Portugal I, Perdigão J, Moreira R, Warner DF, Lopes F. ChemMedChem 2023; 18: e202300410
- 2i Duindam N, van Dongen M, Siegler MA, Wezenberg SJ. J. Am. Chem. Soc. 2023; 145: 21020
- 3 Gai L, Zhang R, Shi X, Ni Z, Wang S, Zhang J.-L, Lu H, Guo Z. Chem. Sci. 2023; 14: 1434
- 4a Shu C, Li L, Xiao X.-Y, Yu Y.-F, Ping Y.-F, Zhou J.-M, Ye L.-W. Chem. Commun. 2014; 50: 8689
- 4b Buzas A, Merour J.-Y. Synthesis 1989; 458
- 4c Merour J.-Y, Chichereau L, Desarbre E, Gadonneix P. Synthesis 1996; 519
- 4d Guo C, Schedler M, Daniliuc CG, Glorius F. Angew. Chem. Int. Ed. 2014; 53: 10232
- 4e Zhou J, Wang B, He X.-H, Liu L, Wu J, Lu J, Peng C, Rao C.-L, Han B. J. Org. Chem. 2019; 84: 5450
- 4f Aksenov NA, Aksenov DA, Arutiunov NA, Aksenova DS, Aksenov AV, Rubin M. RSC Adv. 2020; 10: 18440
- 5a Chowdhury MG, Das R, Vyas H, Sasane T, Mori O, Kamble S, Patel S, Shard A. ChemistrySelect 2022; 7: e202201468
- 5b Li R, Qi X, Wu X.-F. Org. Biomol. Chem. 2017; 15: 6905
- 5c Zhuang S.-Y, Tang Y.-X, Chen X.-L, Wu Y.-D, Wu A.-X. J. Org. Chem. 2021; 86: 17101
- 5d Song X, Zhao X, Zeng Z, Rominger F, Rudolph M, Hashmi AS. K. Isr. J. Chem. 2023; 63: e202300094
- 5e Soam P, Mandal D, Tyagi V. J. Org. Chem. 2023; 88: 11023
- 6 Bott TM, Atienza BJ, West FG. RSC Adv. 2014; 4: 31955
- 7 Xiong W, Wu B, Zhu B, Tan X, Wang L, Wu W, Qi C, Jiang H. ChemCatChem 2021; 13: 2843
- 8 Zhu Y.-L, Dong Y.-F, Wang S.-R, Li Y.-G, Wu X, Ye L.-W. Org. Lett. 2024; 26: 631
- 9a Ren Z.-L, Lu W.-T, Cai S, Xiao M.-M, Yuan Y.-F, Ping H, Ding M.-W. J. Org. Chem. 2019; 84: 14911
- 9b Ren Z.-L, Su L, Cai S, Lu W.-T, Qiao Y, He P, Ding M.-W. Asian J. Org. Chem. 2019; 8: 1394
- 9c Ren Z.-L, Liu J.-C, Ding M.-W. Synthesis 2017; 49: 745
- 9d Fan H.-J, Li T.-A, Li J, Du Z.-Q, Wang L, Zhou X.-M, He P, Ren Z.-L. ChemistrySelect 2023; 8: e202204294
- 9e Wang Y, Yu P, Ren Q, Jia F.-C, Chen Y, Wu A. J. Org. Chem. 2020; 85: 2688
- 9f Jia F.-C, Zhou Z.-W, Xu C, Cai Q, Li D.-K, Wu A.-X. Org. Lett. 2015; 17: 4236
- 9g Jia F.-C, Xu C, Zhou Z.-W, Cai Q, Li D.-K, Wu A.-X. Org. Lett. 2015; 17: 2820
- 9h Yang M.-L, Zhao L, Chen H.-R, Ding M.-W. J. Org. Chem. 2023; 88: 16424
- 9i Yang M.-L, Zhao L, Chen H.-R, Ding M.-W. J. Org. Chem. 2023; 88: 1898
- 9j Yang M.-L, Chen H.-R, Zhao L, Ding M.-W. Synthesis 2023; 55: 465
- 9k Xiong J, Min Q, Yao G, Zhang J.-A, Yu H.-F, Ding M.-W. Synlett 2019; 30: 1053
- 9l Xie S, Proietti G, Ramström O, Yan M. J. Org. Chem. 2019; 84: 14520
- 9m Nguyen TK, Titov GD, Khoroshilova OV, Kinzhalov MA, Rostovskii NV. Org. Biomol. Chem. 2020; 18: 4971
- 9n Chiba S, Zhang L, Lee J.-Y. J. Am. Chem. Soc. 2010; 132: 7266
- 9o Baykal A, Plietker B. Eur. J. Org. Chem. 2020; 1145
- 9p Baykal A, Zhang D, Knelles J, Alt IT, Plietker B. Chem. Asian J. 2019; 14: 3003
- 10a Hommelsheim R, van Nahl R, Hanek LM, Ward JS, Rissanen K, Bolm C. Adv. Synth. Catal. 2024; 366: 717
- 10b Hommelsheim R, Bausch S, Selvakumar A, Amer MM, Truong K.-N, Rissanen K, Bolm C. Chem. Eur. J. 2023; 29: e202203729
- 10c Stopka T, Niggemann M. Chem. Commun. 2016; 52: 5761
- 10d Bao M, Lu W, Su H, Qiu L, Xu X. Org. Biomol. Chem. 2018; 16: 3258
- 10e Su H, Bao M, Pei C, Hu W, Qiu L, Xu X. Org. Chem. Front. 2019; 6: 2404
- 10f Xia X.-D, Xuan J, Wang Q, Lu L.-Q, Chen J.-R, Xiao W.-J. Adv. Synth. Catal. 2014; 356: 2807
- 10g Wu W, Wen S, Zhang X, Lin Q, Weng Z. Org. Lett. 2021; 23: 6352
- 10h Wu W, Chen Q, Tian Y, Xu Y, Huang Y, You Y, Weng Z. Org. Chem. Front. 2020; 7: 1878
- 10i Weng C.-Y, Zhu G.-Y, Zhu B.-H, Qian P.-C, Zhu X.-Q, Zhou J.-M, Ye L.-W. Org. Chem. Front. 2022; 9: 2773
- 10j Liu X, Wang Z.-S, Zhai T.-Y, Luo C, Zhang Y.-P, Chen Y.-B, Deng C, Liu R.-S, Ye L.-W. Angew. Chem. Int. Ed. 2020; 59: 17984
- 10k Shu C, Wang Y.-H, Shen C.-H, Ruan P.-P, Lu X, Ye L.-W. Org. Lett. 2016; 18: 3254
- 10l Wang Y, Wang Y.-J, Liang X.-C, Shen M.-H, Xu H.-D, Xu D. Org. Biomol. Chem. 2021; 19: 5169
- 10m Chen P, Sun C.-H, Wang Y, Xue Y, Chen C, Shen M.-H, Xu H.-D. Org. Lett. 2018; 20: 1643
- 10n Shu W.-M, Zhang X.-F, Zhang X.-X, Li M, Wang A.-J, Wu A.-X. J. Org. Chem. 2019; 84: 14919
- 11a Liu J.-N, Liu N, Yang Q, Wang L. Org. Chem. Front. 2021; 8: 5296
- 11b Liu N, Chao F, Liu M.-G, Huang N.-Y, Zou K, Wang L. J. Org. Chem. 2019; 84: 2366
- 11c Chen N, Long T.-Y, Kong H.-H, Wu Z.-W, Yang Q.-Q, Huang N.-Y, Wang L. Org. Chem. Front. 2024; 11: 2780
- 11d Wu Z.-W, Kong H.-H, Wei Y, Zhou W.-C, Wang L, Lu L.-Q, Yang Q.-Q. Green Synth. Catal. 2024; in press
- 11e Pei M.-Y, Tian A.-Q, Yang Q.-Q, Huang N.-Y, Wang L, Li D.-S. Green Synth. Catal. 2023; 4: 135
- 11f Luo X.-H, Tian A.-Q, Pei M.-Y, Yan J.-Y, Liu X, Wang L. Chem. Eur. J. 2022; 28: e202103361
- 11g Li M.-J, Mei S.-X, Zheng Y, Wang L, Ye L.-Q. Chem. Commun. 2023; 59: 13478
- 11h Liu J, Li Y, Liu N, Huang N, Wang L, Li D. Org. Chem. Front. 2022; 9: 6179
- 11i Yan C.-Y, Wu Z.-W, He X.-Y, Ma Y.-H, Peng X.-R, Wang L, Yang Q.-Q. J. Org. Chem. 2023; 88: 647
- 11j Kong H.-H, Zhu C, Deng S, Xu G, Zhao R, Yao C, Xiang H.-M, Zhao C, Qi X, Xu H. J. Am. Chem. Soc. 2022; 144: 21347
- 11k Hua T.-B, Ma Y.-H, He X.-Y, Wang L, Yan J.-Y, Yang Q.-Q. Org. Chem. Front. 2022; 9: 3558
- 11l Ma Y.-H, He X.-Y, Wang L, Yang Q.-Q. J. Org. Chem. 2022; 87: 11852
- 12 Velezheva V, Marshakov VY. Chem. Heterocycl. Compd. 1992; 28: 478
- 13 Dong L, Wang X, Nie Y, Yu S, Li H, Zhao Q, Fan Z, Wang Y, Tan X, Yu Z. Eur. J. Org. Chem. 2022; e202200842
- 14 Su H, Bao M, Huang J, Qiu L, Xu X. Adv. Synth. Catal. 2019; 361: 826
- 15 Zhou X, Zhang G, Huang R, Huang H. Org. Lett. 2021; 23: 365
- 16a Schmidt EY, Cherimichkina NA, Bidusenko IA, Protzuk NI, Trofimov BA. Eur. J. Org. Chem. 2014; 4663
- 16b Ishikawa T, Mizuta T, Hagiwara K, Aikawa T, Kudo T, Saito S. J. Org. Chem. 2003; 68: 3702
- 17a De R, Savarimuthu A, Ballav T, Singh P, Nanda J, Hasija A, Chopra D, Bera MK. Synlett 2020; 31: 1587
- 17b Barabanov I, Fedenok L, Polyakov N, Shvartsberg M. Russ. Chem. Bull. 2001; 50: 1663
- 17c Ding Z.-C, Yang Y, Cai S.-N, Wen J.-J, Zhan Z.-P. Chem. Lett. 2016; 45: 925
- 17d Shan C, Chen F, Pan J, Gao Y, Xu P, Zhao Y. J. Org. Chem. 2017; 82: 11659
- 18a Xie S, Ramström O, Yan M. Org. Lett. 2015; 17: 636
- 18b Xie Y.-Y, Wang Y.-C, He Y, Hu D.-C, Wang H.-S, Pan Y.-M. Green Chem. 2017; 19: 656
- 18c Xie S, Lopez SA, Ramström O, Yan M, Houk KN. J. Am. Chem. Soc. 2015; 137: 2958
- 18d Xie S, Fukumoto R, Ramström O, Yan M. J. Org. Chem. 2015; 80: 4392
- 18e Xie S, Zhang Y, Ramström O, Yan M. Chem. Sci. 2016; 7: 713
- 19 2-Benzylideneindolin-3-one5b (3a); Typical Procedure A round-bottomed flask equipped with a stirrer bar was sequentially charged with o-azidobenzaldehyde (1a; 0.5 mmol, 1.0 equiv), DMSO (5.0 mL), phenylacetylene (2a; 0.75 mmol, 1.5 equiv), and 50 wt% aq Bu4NOH (0.8 mmol, 1.6 equiv). The mixture was stirred at r.t. under air until the reaction was complete (TLC). The reaction was then quenched with H2O, and the mixture was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel) to give an orange solid; yield: 88 mg (79%); mp 189.8–191.0 °C. 1H NMR (400 MHz, CDCl3): δ = 7.74 (d, J = 7.7 Hz, 1 H), 7.55 (d, J = 7.4 Hz, 2 H), 7.49–7.41 (m, 3 H), 7.32 (t, J = 7.4 Hz, 1 H), 6.98 (dt, J = 14.9, 8.2 Hz, 3 H), 6.86 (s, 1 H). 13C NMR (101 MHz, CDCl3): δ = 186.82, 153.39, 136.33, 135.49, 134.84, 129.66, 129.32, 128.66, 125.16, 121.80, 120.77, 112.14, 111.80.