Download PDF
Synlett 2021; 32(09): 930-934
DOI: 10.1055/a-1468-5725
letter

Brønsted Acid Catalyzed Cyclization of Inert N-Substituted Pyrroles to Benzo[f]pyrrolo[1,2-a][1,4]diazepines

Zeng Gao
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. of China
b   University of Chinese Academy of Sciences, Beijing 100049, P. R. of China
,
Jinlong Qian 
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. of China
,
Huameng Yang
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. of China
,
Jinlong Zhang∗
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. of China
,
Gaoxi Jiang∗
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. of China
› Author AffiliationsFinancial support from the National Natural Science Foundation of China (21602231) and the Natural Science Foundation of Jiangsu Province (BK20191197 and BK20181373) is gratefully acknowledged.
› Further Information
    Permissions and Reprints All articles of this category


Abstract

Two approaches involving intramolecular and intermolecular cyclization, respectively, have been developed for the direct and practical construction of a series of important benzo[f]pyrrolo[1,2-a][1,4]azepines by using Brønsted acid catalysts. Upon catalysis by TsOH, the intramolecular dehydroxylation/ring closure of 3-hydroxy-2-[2-(1H-pyrrol-1-yl)benzyl]isoindolin-1-ones provided various racemic benzo[f]pyrrolo[1,2-a][1,4]azepines in high yields. Furthermore, enantioenriched benzo[f]pyrrolo[1,2-a][1,4]azepines were also obtained by chiral phosphoric acid catalyzed intermolecular addition of [2-(1H-pyrrol-1-yl)phenyl]methanamines to 2-formylbenzoates under mild conditions.

Key words

Brønsted acid catalysis - cyclization - pyrroles - intermolecular addition - azepines - asymmetric catalysis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1468-5725.
  • Supporting Information


Publication History

Received: 14 December 2020

Accepted after revision: 27 March 2021

Accepted Manuscript online:
27 March 2021

Article published online:
16 April 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References and Notes

    • 1a Snow GA. Bacteriol. Rev. 1970; 34: 99
      CrossrefPubMed
    • 1b Lin W.-H, Ye Y, Xu R.-S. J. Nat. Prod. 1992; 55: 571
      Crossref
    • 1c Thurston DE, Bose DS. Chem. Rev. 1994; 94: 433
      CrossrefPubMed
    • 1d Murakami S, Takemoto T, Shimizu Z. J. Pharm. Soc. Jpn. 1953; 73: 1026
  • 2 Hall IH, Murthy AR. K, Wyrick SD. J. Pharm. Sci. 1986; 75: 622
    CrossrefPubMed
    • 3a Page PC. B, Bartlett CJ, Chan Y, Day D, Parker P, Buckley BR, Rassias GA, Slawin AM. Z, Allin SM, Lacour J, Pinto A. J. Org. Chem. 2012; 77: 6128
      CrossrefPubMed
    • 3b Kano T, Sugimoto H, Maruoka K. J. Am. Chem. Soc. 2011; 133: 18130
      CrossrefPubMed
    • 3c Page PC. B, Pearce CA, Chan Y, Parker P, Buckley BR, Rassias GA, Elsegood MR. J. J. Org. Chem. 2015; 80: 8036
      CrossrefPubMed
  • 4 Saudan LA, Bernardinelli G, Kündig EP. Synlett 2000; 483
    • 5a Willoughby CA, Buchwald SL. J. Am. Chem. Soc. 1994; 116: 8952
      Crossref
    • 5b Chang M, Li W, Hou G, Zhang X. Adv. Synth. Catal. 2010; 352: 3121
      Crossref
    • 5c Zhang Y, Kong D, Wang R, Hou G. Org. Biomol. Chem. 2017; 15: 3006
      CrossrefPubMed
    • 5d Guo C, Sun D.-W, Yang S, Mao S.-J, Xu X.-H, Zhu S.-F, Zhou Q.-L. J. Am. Chem. Soc. 2015; 137: 90
      CrossrefPubMed
    • 5e Chen F, Ding Z, Qin J, Wang T, He Y, Fan Q.-H. Org. Lett. 2011; 13: 4348
      CrossrefPubMed
    • 5f Gao K, Yu C.-B, Li W, Zhou Y.-G, Zhang X. Chem. Commun. 2011; 47: 7845
      CrossrefPubMed
    • 5g Gao K, Wu B, Yu C.-B, Chen Q.-A, Ye Z.-S, Zhou Y.-G. Org. Lett. 2012; 14: 3890
      CrossrefPubMed
    • 5h Guo R.-N, Gao K, Ye Z.-S, Shi L, Li Y, Zhou Y.-G. Pure Appl. Chem. 2013; 85: 843
      Crossref
    • 5i Shen H.-Q, Gao X, Liu C, Hu S.-B, Zhou Y.-G. Org. Lett. 2016; 18: 5920
      CrossrefPubMed
    • 5j Balakrishna B, Bauzá A, Frontera A, Vidal-Ferran A. Chem. Eur. J. 2016; 22: 10607
      CrossrefPubMed
    • 5k Wang J. Tetrahedron Lett. 2013; 54: 5956
      Crossref
    • 5l Li P, Huang Y, Hu X, Dong X.-Q, Zhang X. Org. Lett. 2017; 19: 3855
      CrossrefPubMed
    • 5m Rueping M, Merino E, Koenigs RM. Adv. Synth. Catal. 2010; 352: 2629
      Crossref
    • 5n Zawodny W, Montgomery SL, Marshall JR, Finnigan JD, Turner NJ, Clayden J. J. Am. Chem. Soc. 2018; 140: 17872
      CrossrefPubMed
    • 5o Ding Z.-Y, Chen F, Qin J, He Y.-M, Fan Q.-H. Angew. Chem. Int. Ed. 2012; 51: 5706
      CrossrefPubMed
    • 5p Yang Z, Ding Z, Chen F, He Y.-M, Yang N, Fan Q.-H. Eur. J. Org. Chem. 2017; 1973
    • 5q Miao T, Ma B, Ding Z, Liu Y, He Y.-M, Fan Q.-H. Asian J. Org. Chem. 2017; 1219
    • 5r Liu Y, Chen F, He Y.-M, Li C, Fan Q.-H. Org. Biomol. Chem. 2019; 17: 5099
      CrossrefPubMed
    • 6a Cheetham CA, Massey RS, Pira SL, Pritchard RG, Wallace TW. Org. Biomol. Chem. 2011; 9: 1831
      CrossrefPubMed
    • 6b France SP, Aleku GA, Sharma M, Mangas-Sanchez J, Howard RM, Steflik J, Kumar R, Adams RW, Slabu I, Crook R, Grogan G, Wallace TW, Turner NJ. Angew. Chem. Int. Ed. 2017; 56: 15589
      CrossrefPubMed
    • 6c Liu J, Yang X, Zuo Z, Nan J, Wang Y, Luan X. Org. Lett. 2018; 20: 244
      CrossrefPubMed
    • 6d Yang T, Guo X, Yin Q, Zhang X. Chem. Sci. 2019; 10: 2473
      CrossrefPubMed
  • 7 Postikova S, Sabbah M, Wightman D, Nguyen IT, Sanselme M, Besson T, Brière JF, Oudeyer S, Levacher V. J. Org. Chem. 2013; 78: 8191
    CrossrefPubMed
    • 8a Reinecke MG, Johnson HW, Sebastian JF. J. Am. Chem. Soc. 1963; 85: 2859
      Crossref
    • 8b Belen’kii LI. Heterocycles 1994; 37: 2029
      Crossref
    • 9a Joule JA, Mills K, Smith GF. Heterocyclic Chemistry, 3rd ed. Chapman and Hall; London: 1995: 231
      Google Scholar
    • 9b Schofield K. Hetero-Aromatic Nitrogen Compounds: Pyrroles and Pyridines. Plenum Press; New York: 1967
      Google Scholar
    • 9c Jorapur YR, Lee C.-H, Chi DY. Org. Lett. 2005; 7: 1231
      CrossrefPubMed

      For asymmetric addition of unprotected pyrroles, see:
    • 10a Trost BM, Müller C. J. Am. Chem. Soc. 2008; 130: 2438
      CrossrefPubMed
    • 10b Sheng Y.-F, Gu Q, Zhang A.-J, You S.-L. J. Org. Chem. 2009; 74: 6899
      CrossrefPubMed
    • 10c Sheng Y.-F, Li G.-Q, Kang Q, Zhang A.-J, You S.-L. Chem. Eur. J. 2009; 15: 3351
      CrossrefPubMed
    • 10d Hong L, Sun W, Liu C, Wang L, Wong K, Wang R. Chem. Eur. J. 2009; 15: 11105
      CrossrefPubMed
    • 10e Yokoyama N, Arai T. Chem. Commun. 2009; 3285
      PubMed
    • 10f Hong L, Liu C, Sun W, Wang L, Wong K, Wang R. Org. Lett. 2009; 11: 2177
      CrossrefPubMed
    • 10g Blay G, Fernández I, Monleón A, Pedro JR, Vila C. Org. Lett. 2009; 11: 441
      CrossrefPubMed
    • 10h Singh PK, Singh VK. Org. Lett. 2010; 12: 80
      CrossrefPubMed
    • 10i Blay G, Fernández I, Muñoz MC, Pedro JR, Recuenco A, Vila C. J. Org. Chem. 2011; 76: 6286
      CrossrefPubMed
    • 10j Zhang K.-F, Nie J, Guo R, Zheng Y, Ma J.-A. Adv. Synth. Catal. 2013; 355: 3497 ; corrigendum: Adv. Synth. Catal. 2014, 356, 2133
      Crossref
    • 10k Hua Y.-Z, Han X.-W, Yang X.-C, Song X, Wang M.-C, Chang J.-B. J. Org. Chem. 2014; 79: 11690
      CrossrefPubMed
    • 10l Li C, Guo F, Xu K, Zhang S, Hu Y, Zha Z, Wang Z. Org. Lett. 2014; 16: 3192
      CrossrefPubMed
    • 10m Wu K, Zhuo M.-H, Sha D, Fan Y.-S, An D, Jiang Y.-J, Zhang S. Chem. Commun. 2015; 51: 8054
      CrossrefPubMed
    • 10n Hu Y, Li Y, Zhang S, Li C, Li L, Zha Z, Wang Z. Org. Lett. 2015; 17: 4018
      CrossrefPubMed
    • 10o Nakamura S, Matsuda N, Ohara M. Chem. Eur. J. 2016; 22: 9478
      CrossrefPubMed
    • 10p Lou H, Wang Y, Jin E, Lin X. J. Org. Chem. 2016; 81: 2019
      CrossrefPubMed
    • 10q Sun J, Hu Y, Li Y, Zhang S, Zha Z, Wang Z. J. Org. Chem. 2017; 82: 5102
      CrossrefPubMed
    • 10r Gui Y, Li Y, Sun J, Zha Z, Wang Z. J. Org. Chem. 2018; 83: 7491
      CrossrefPubMed
    • 11a Paras NA, MacMillan DW. C. J. Am. Chem. Soc. 2001; 123: 4370
      CrossrefPubMed
    • 11b Li G, Rowland GB, Rowland EB, Antilla JC. Org. Lett. 2007; 9: 4065
      CrossrefPubMed
    • 11c Cao C.-L, Zhou Y.-Y, Sun X.-L, Tang Y. Tetrahedron 2008; 64: 10676
      Crossref
    • 11d Sibi MP, Coulomb J, Stanley LM. Angew. Chem. Int. Ed. 2008; 47: 9913
      CrossrefPubMed
    • 11e Huang Y, Tokunaga E, Suzuki S, Shiro M, Shibata N. Org. Lett. 2010; 12: 1136 ; corrigendum: Org. Lett. 2010, 12, 3570
      CrossrefPubMed
    • 11f He Y, Lin M, Li Z, Liang X, Li G, Antilla JC. Org. Lett. 2011; 13: 4490
      CrossrefPubMed
    • 11g You Y, Cui B.-D, Zhou M.-Q, Zuo J, Zhao J.-Q, Xu X.-Y, Zhang X.-M, Yuan W.-C. J. Org. Chem. 2015; 80: 5951
      CrossrefPubMed
    • 11h Majer J, Kwiatkowski P, Jurczak J. Org. Lett. 2011; 13: 5944
      CrossrefPubMed
    • 11i Gutierrez EG, Wong CJ, Sahin AH, Franz AK. Org. Lett. 2011; 13: 5754
      CrossrefPubMed
    • 11j Cai Y, Tang Y, Atodiresei I, Rueping M. Angew. Chem. Int. Ed. 2016; 55: 14126
      CrossrefPubMed
    • 11k Li H, Tong R, Sun J. Angew. Chem. Int. Ed. 2016; 55: 15125
      CrossrefPubMed
    • 11l Gade AB, Patil NT. Synlett 2017; 28: 1096
      Article in Thieme Connect
    • 11m Gao Z, Zhang J, Yang H, Jiang G. J. Org. Chem. 2018; 83: 11407
      CrossrefPubMed
    • 11n Wei Z, Zhang J, Yang H, Jiang G. Adv. Synth. Catal. 2019; 361: 3694
      Crossref
    • 11o Wei Z, Zhang J, Yang H, Jiang G. Org. Lett. 2019; 21: 2790
      CrossrefPubMed
    • 11p Gao Z, Wang F, Qian J, Yang H, Xia C, Zhang J, Jiang G. Org. Lett. 2021; 23: 1181
      CrossrefPubMed
  • 12 9H-Isoindolo[1,2-c]pyrrolo[1,2-a][1,4]benzodiazepin-11(15bH)-ones 2a–q; General Procedure (Intramolecular Reaction) The appropriate isoindolone 1 (0.2 mmol, 1.0 equiv) and TsOH (1 mol%) were stirred in CH2Cl2 (1 mL) at r.t. When the reaction was complete, the solvent was removed and the crude mixture was purified by flash column chromatography (silica gel, hexane–EtOAc). 9H-Isoindolo[1,2-c]pyrrolo[1,2-a][1,4]benzodiazepin-11(15bH)-ones 2a, 2q–t; General Procedure (Intermolecular Reaction) The appropriate amine 3 (0.1 mmol, 1.0 equiv), methyl 2-formylbenzoate (4a, 0.15 mmol, 1.5 equiv), chiral phosphoric acid A5 (5.0 mol%), and 4 Å MS (100 mg) were stirred in toluene (1.0 mL) at r.t. under N2. Upon completion of the reaction, the solvent was removed and the crude mixture was purified by flash column chromatography. 9H-Isoindolo[1,2-c]pyrrolo[1,2-a][1,4]benzodiazepin-11(15bH)-one (2a) White solid; yield: 53.2 mg (93%); mp 192-195 °C. 1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 7.5 Hz, 1 H), 7.64–7.44 (m, 6 H), 7.35 (t, J = 7.4 Hz, 1 H), 7.10 (d, J = 2.9 Hz, 1 H), 6.26 (t, J = 3.3 Hz, 1 H), 5.94 (d, J = 3.5 Hz, 1 H), 5.40 (s, 1 H), 5.06 (d, J = 13.9 Hz, 1 H), 4.17 (d, J = 13.9 Hz, 1 H). 13C NMR (101 MHz, CDCl3): δ = 167.0, 141.7, 140.2, 133.6, 131.5, 131.2, 130.0, 128.9, 128.5, 127.3, 124.0, 123.6, 121.8, 109.5, 107.2, 56.4, 44.6. CCDC 1964245 contains the supplementary crystallographic data for compound 2a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.