Synlett 2021; 32(11): 1093-1097
DOI: 10.1055/a-1507-4275
letter

Cesium Carbonate Mediated Cyclization of Oxotryptamines with Allenoates: An Approach to Spiro[azepane-4,3′-indol]-2′(1′H)-ones

Ze-ren Yang
,
Min Shi
State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, University of Chinese Academy of Sciences, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China
› Author Affiliations
We are grateful for the financial support from the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB20000000), sioczz201808, and the National Natural Science Foundation of China (21372250, 21121062, 21302203, 20732008, 21772037, 21772226, 21861132014 and 91956115).


Abstract

A new method was developed for the synthesis of spiro[azepane-4,3′-indol]-2′(1′H)-ones in yields of up to 96% with a broad substrate scope by using oxotryptamines as dual-nucleophilic reagents to react with allenoates in the presence of cesium carbonate under mild conditions. In accord with previous works and a deprotonation-tracing experiment, a plausible reaction mechanism is proposed.

Supporting Information



Publication History

Received: 13 April 2021

Accepted after revision: 11 May 2021

Publication Date:
11 May 2021 (online)

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  • References and Notes


    • For selected examples of natural and biologically active spirocyclic indoles, see:
    • 1a Galliford CV, Scheidt KA. Angew. Chem. Int. Ed. 2007; 46: 8748
    • 1b Liu Y, McWhorter WW. J. Am. Chem. Soc. 2003; 125: 4240
    • 1c Lin H, Danishefsky SJ. Angew. Chem. Int. Ed. 2003; 42: 36

      For selected examples of natural and biologically active N-heterocyclic oxindoles, see:
    • 2a de Lucas AI, Vega JA, Matesanz E, Linares ML, García Molina A, Tresadern G, Lavreysen H, Trabanco AA, Cid JM. ACS Med. Chem. Lett. 2020; 11: 303
    • 2b Pellegrino S, Ruscica M, Magni P, Vistoli G, Gelmi ML. Bioorg. Med. Chem. 2013; 21: 5470
    • 2c Rojas-Duran R, González-Aspajo G, Ruiz-Martel C, Bourdy G, Doroteo-Ortega VH, Alban-Castillo J, Robert G, Auberger P, Deharo E. J. Ethnopharmacol. 2012; 143: 801

      For selected reviews on N-heterocyclic oxindoles, see:
    • 3a Boddy AJ, Bull JA. Org. Chem. Front. 2021; 8: 1026
    • 3b Singh GS, Desta ZY. Chem. Rev. 2012; 112: 6104
    • 3c Williams RM, Cox RJ. Acc. Chem. Res. 2003; 36: 127

      For selected examples of three-membered spiro-N-heterocyclic oxindoles, see:
    • 4a Sakla AP, Kansal P, Shankaraiah N. Org. Biomol. Chem. 2020; 18: 8572
    • 4b Huang N, Zou L, Peng Y. Org. Lett. 2017; 19: 5806
    • 4c Hajra S, Roy S, Maity S. Org. Lett. 2017; 19: 1998
    • 4d Chai G.-L, Han J.-W, Wong HN. C. J. Org. Chem. 2017; 82: 12647
    • 4e Kuang Y, Lu Y, Tang Y, Liu X, Lin L, Feng X. Org. Lett. 2014; 16: 4244
    • 4f Schulz V, Davoust M, Lemarié M, Lohier J.-F, Sopkova de Oliveira Santos J, Metzner P, Brière J.-F. Org. Lett. 2007; 9: 1745

      For selected examples of five-membered spiro-N-heterocyclic oxindoles, see:
    • 5a Qian C, Li P, Sun J. Angew. Chem. Int. Ed. 2021; 60: 5871
    • 5b Huang Z.-C, Zou Y, Xiang M, Li C.-Y, Li X, Tian F, Wang L.-X. Org. Lett. 2021; 23: 2227
    • 5c Akaev AA, Bezzubov SI, Desyatkin VG, Vorobyeva NS, Majouga AG, Melnikov MY, Budynina EM. J. Org. Chem. 2019; 84: 3340
    • 5d Ryu H, Seo J, Ko HM. J. Org. Chem. 2018; 83: 14102
    • 5e He W, Hu J, Wang P, Chen L, Ji K, Yang S, Li Y, Xie Z, Xie W. Angew. Chem. Int. Ed. 2018; 57: 3806
    • 5f Gui H.-Z, Gao Y.-N, Wei Y, Shi M. Chem. Eur. J. 2018; 24: 10038
    • 5g Zhu G, Wei Q, Chen H, Zhang Y, Shen W, Qu J, Wang B. Org. Lett. 2017; 19: 1862

      For selected examples of six-membered spiro-N-heterocyclic oxindoles, see:
    • 6a Xu Y.-W, Li L, Hu X.-P. Org. Lett. 2020; 22: 9534
    • 6b Sun Q.-S, Sun J, Pan L.-N, Yan C.-G. J. Org. Chem. 2020; 85: 12117
    • 6c Luo Y, Zhang H, Wang S, Zhou Y, Dong S, Feng X. Org. Lett. 2020; 22: 2645
    • 6d Lai Y.-H, Wu R.-S, Huang J, Huang J.-Y, Xu D.-Z. Org. Lett. 2020; 22: 3825
    • 6e Sivasankara C, Satham L, Namboothiri IN. N. J. Org. Chem. 2017; 82: 12939
    • 6f Wu H.-R, Cheng L, Kong D.-L, Huang H.-Y, Gu C.-L, Liu L, Wang D, Li C.-J. Org. Lett. 2016; 18: 1382
    • 6g Wang S, Jiang Y, Wu S, Dong G, Miao Z, Zhang W, Sheng C. Org. Lett. 2016; 18: 1028

      For selected examples of four-membered spiro-N-heterocyclic oxindoles, see:
    • 7a Halskov KS, Kniep F, Lauridsen VH, Iversen EH, Donslund BS, Jørgensen KA. J. Am. Chem. Soc. 2015; 137: 1685
    • 7b Hell SM, Meyer CF, Laudadio G, Misale A, Willis MC, Noël T, Trabanco AA, Gouverneur V. J. Am. Chem. Soc. 2020; 142: 720
    • 7c Overman LE, Poon DJ. Angew. Chem. Int. Ed. 1997; 36: 518
  • 8 Nibbs AE, Montgomery TD, Zhu Y, Rawal VH. J. Org. Chem. 2015; 80: 4928
  • 9 Liu J.-Y, Lu H, Li C.-G, Liang Y.-M, Xu P.-F. Synlett 2016; 27: 1287
  • 10 Liu D, Hu Z, Zhang Y, Gong M, Fu Z, Huang W. Chem. Eur. J. 2019; 25: 11223
  • 11 Bordwell FG. Acc. Chem. Res. 1988; 21: 456
  • 12 CCDC 2022579 contains the supplementary crystallographic data for compound 3ba. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
    • 13a Ni C, Chen J, Zhang Y, Hou Y, Wang D, Tong X, Zhu S.-F, Zhou Q.-L. Org. Lett. 2017; 19: 3668
    • 13b Ni C, Yuan Y, Zhang Y, Chen J, Wang D, Tong X. Org. Biomol. Chem. 2017; 15: 4807
    • 13c Wang Y.-F, He C.-Y, Hou L, Tian P, Lin G.-Q, Tong X. Synlett 2018; 29: 1176
    • 13d Wu X.-Y, Gao Y.-N, Shi M. Eur. J. Org. Chem. 2019; 1620
  • 14 Spiro[azepane-4,3′-indol]-2′(1′H)-ones 3aa–3am; General Procedure A dried 25 mL Schlenk tube was charged with the appropriate 3-(2-aminoethyl)indolin-2-one 2 (0.1 mmol, 1.0 equiv) and Cs2CO3 (0.2 mmol, 1.0 equiv), then evacuated and backfilled with argon three times. Allenoate 1 (0.24 mmol, 1.2 equiv) and anhyd MeCN (4.0 mL) were added under argon, and the mixture was stirred at 60 °C for 12 h. The mixture was then concentrated under reduced pressure and purified by flash chromatography [silica gel, PE–EtOAc (4:1)]. Ethyl {1′-Methyl-2′-oxo-1-tosyl-1,1′,2,2′,3,5-hexahydrospiro[azepine-4,3′-indol]-7-yl}acetate (3aa) White solid; yield: 90.0 mg (96%); mp 144–145 °C; Rf = 0.53 (PE–EtOAc, 2:1). IR (EtOH): 2932, 2249, 1707, 1610, 1493, 1344, 1156, 1085, 1026, 961, 910, 814 cm–1. 1H NMR (400 MHz, CDCl3, TMS): δ = 7.83 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 7.4 Hz, 1 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.27 (td, J = 7.7, 1.3 Hz, 1 H), 7.01 (td, J = 7.6, 1.1 Hz, 1 H), 6.84 (dd, J = 7.8, 0.9 Hz, 1 H), 5.60 (dd, J = 8.2, 6.0 Hz, 1 H), 4.21–4.05 (m, 3 H), 3.85 (d, J = 17.3 Hz, 1 H), 3.82–3.71 (m, 1 H), 3.40 (d, J = 17.4 Hz, 1 H), 3.16 (s, 3 H), 2.45 (s, 3 H), 2.29 (t, J = 11.6 Hz, 1 H), 2.20–2.10 (m, 1 H), 1.80 (dd, J = 14.2, 8.3 Hz, 1 H), 1.66 (d, J = 11.0 Hz, 1 H), 1.27 (t, J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3, TMS): δ = 179.3, 170.9, 143.5, 142.6, 137.8, 136.9, 132.2, 129.6, 127.9, 127.0, 126.3, 124.6, 122.2, 108.0, 60.7, 44.8, 43.8, 41.8, 35.7, 31.8, 26.0, 21.4 (d, J = 1.7 Hz), 14.0. HRMS (ESI): m/z [M + H]+ Calcd for C25H29N2O5S: 469.1792; found: 469.1799.