Skip to main content
SpringerLink
Log in

Synthesis of isoindolin-1-one derivatives via multicomponent reactions of methyl 2-formylbenzoate and intramolecular amidation

  • Original Article
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

Four series of heterocyclic compounds were obtained using Ugi-type multicomponent reactions (MCRs) with methyl 2-formylbenzoate as one of the starting materials. A facile and efficient one-pot procedure was suitable for all the MCRs under acidic conditions. This process provided access to four series of complex and potentially biologically active scaffolds.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Scheme 2
Scheme 3
Scheme 4

Similar content being viewed by others

References

  1. Dömling A (2006) Recent developments in isocyanide based multicomponent reactions in applied chemistry. Chem Rev 106:17–89. doi:10.1021/cr0505728

    Article  PubMed  Google Scholar 

  2. Dömling A, Ugi I (2000) Multicomponent reactions with isocyanides. Angew Chem Int Ed 39:3168–3210. doi:10.1002/1521-3773(20000915)39:18<3168:AID-ANIE3168>3.0.CO;2-U

  3. Banfi L, Basso A, Guanti G, Riva R (2003) Passerini reaction—Amine Deprotection-Acyl Migration (PADAM): a convenient strategy for the solid-phase preparation of peptidomimetic compounds. Mol Divers 14:227–235. doi:10.1023/B:MODI.0000006778.42751.7f

    Google Scholar 

  4. Moliner FD, Bigatti M, Rosa CD, Banfi L, Riva R, Basso A (2014) Synthesis of triazolo-fused benzoxazepines and benzoxazepinones via Passerini reactions followed by 1,3-dipolar cycloadditions. Mol Divers 18:473–482. doi:10.1007/s11030-014-9530-x

    Article  PubMed  Google Scholar 

  5. Biggs-Houck JE, Younai A, Shaw JT (2010) Recent advances in multicomponent reactions for diversity-oriented synthesis. Curr Opin Chem Biol 14:371–382. doi:10.1016/j.cbpa.2010.03.003

    Article  CAS  PubMed  Google Scholar 

  6. Kalinski C, Lemoine H, Schmidt J, Burdack C, Kolb J, Umkehrer M, Ross G (2008) Multicomponent reactions as a powerful tool for generic drug synthesis. Synthesis 24:4007–4011. doi:10.1055/s-0028-1083239

    Article  Google Scholar 

  7. Kalinski C, Umkehrer M, Weber L, Kolb J, Burdack C, Ross G (2010) On the industrial applications of MCRs: molecular diversity in drug discovery and generic drug synthesis. Mol Divers 14:513–522. doi:10.1007/s11030-010-9225-x

    Article  CAS  PubMed  Google Scholar 

  8. Hulme C, Gore V (2003) Multi-component reactions: emerging chemistry in drug discovery. From Xylocain to Crixivan. Curr Med Chem 10:51–80. doi:10.2174/0929867033368600

    Article  CAS  PubMed  Google Scholar 

  9. Dömling A, Wang W, Wang K (2012) Chemistry and biology of multicomponent reactions. Chem Rev 112:3083–3135. doi:10.1021/cr100233r

    Article  PubMed  PubMed Central  Google Scholar 

  10. Harriman GCB (1997) Synthesis of small and medium sized 2,2-disubstituted lactams via the “intramolecular” three component Ugi reaction. Tetrahedron Lett 38:5591–5594. doi:10.1016/S0040-4039(97)01265-3

    Article  CAS  Google Scholar 

  11. Zhang J, Jacobson A, Rusche JR, Herlihy W (1999) Unique structures generated by Ugi 3CC reactions using bifunctional starting materials containing aldehyde and carboxylic acid. J Org Chem 64:1074–1076. doi:10.1021/jo982192a

    Article  CAS  PubMed  Google Scholar 

  12. Hanusch-Kompa C, Ugi I (1998) Multi-component reactions 13: synthesis of \(\upgamma \)-lactams as part of a multiring system via Ugi-4-centre-3-component reaction. Tetrahedron Lett 39:2725–2728. doi:10.1016/S0040-4039(98)00428-6

    Article  CAS  Google Scholar 

  13. Waller RW, Diorazio LJ, Taylor BA, Motherwell WB, Sheppard TD (2010) Isocyanide based multicomponent reactions of oxazolidines and related systems. Tetrahedron 66:6496–6507. doi:10.1016/j.tet.2010.05.083

    Article  CAS  Google Scholar 

  14. Bachman M, Mann SE, Sheppard TD (2012) Rapid synthesis of highly functionalised a-amino amides and medium ring lactones using multicomponent reactions of amino alcohols and isocyanides. Org Biomol Chem 10:162–170. doi:10.1039/c1ob06534c

    Article  CAS  PubMed  Google Scholar 

  15. Borthwick AD, Liddle J, Davies DE, Exall AM, Hamlett C, Hickey DM, Mason AM, Smith IE, Nerozzi DF, Peace S, Pollard D, Sollis SL, Allen MJ, Woollard PM, Pullen MA, Westfall TD, Stanislaus DJ (2012) Pyridyl-2,5-diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists: synthesis, pharmacokinetics, and in vivo potency. J Med Chem 55:783–796. doi:10.1021/jm201287w

    Article  CAS  PubMed  Google Scholar 

  16. Gunawan S, Hulme C (2013) Bifunctional building blocks in the Ugi-azide condensation reaction: a general strategy toward exploration of new molecular diversity. Org Biomol Chem 11:6036–6039. doi:10.1039/C3OB40900G

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Narhe BD, Tsai M, Sun C (2014) Rapid two-step synthesis of benzimidazo[\(1^\prime \),\(2^\prime \):1,5]pyrrolo[2,3-\(c\)]isoquinolines by a three-component coupling reaction. ACS Comb Sci 16:421–427. doi:10.1021/co500049r

    Article  CAS  PubMed  Google Scholar 

  18. Khoury K, Sinha MK, Nagashima T, Herdtweck E, Dömling A (2012) Efficient assembly of iminodicarboxamides by a “truly” four-component reaction. Angew Chem Int Ed 51:10280–10283. doi:10.1002/anie.201205366

    Article  CAS  Google Scholar 

  19. Sinha MK, Khoury K, Herdtweck E, Dömling A (2013) Various cyclization scaffolds by a truly Ugi 4-CR. Org Biomol Chem 11:4792–4796. doi:10.1039/C3OB40523K

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Xu Z, Ayaz M, Cappelli AA, Hulme C (2012) General one-pot, two-step protocol accessing a range of novel polycyclic heterocycles with high skeletal diversity. Acs Comb Sci 14:460–464. doi:10.1021/co300046r

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tanaka Y, Hasui T, Suginome M (2007) Acid-free, aminoborane-mediated Ugi-type reaction leading to general utilization of secondary amines. Org Lett 9:4407–4410. doi:10.1021/ol701570c

    Article  CAS  PubMed  Google Scholar 

  22. Suginome M, Tanaka Y, Hasui T (2006) Reductive amination of aldehydes using aminoboranes as iminium ion generators. Synlett 7:1047–1050. doi:10.1055/s-2006-939070

    Article  Google Scholar 

  23. Xu Z, Shaw AY, Nichol GA, Cappelli P, Hulme C (2012) Applications of ortho-phenylisonitrile and ortho-\(N\)-Boc aniline for the two-step preparation of novel bis-heterocyclic chemotypes. Mol Divers 16:607–612. doi:10.1007/s11030-012-9374-1

    Article  CAS  PubMed  Google Scholar 

  24. Xu Z, Shaw AY, Dietrich JA, Cappelli P, Nichol G, Hulme C (2012) Facile, novel two-step syntheses of benzimidazoles, bis-benzimidazoles, and bis-benzimidazole-dihydroquinoxalines. Mol Divers 16:73–79. doi:10.1007/s11030-011-9354-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chen Z, Zhang J, Tang D, Xu Z (2014) Synthesis of fused benzimidazole-quinoxalinones via UDC strategy and following the intermolecular nucleophilic substitution reaction. Tetrahedron Lett 55:2742–2744. doi:10.1016/j.tetlet.2014.03.063

    Article  CAS  Google Scholar 

  26. Song G, Li S, Yang Z, Yuan J, Wang M, Zhu J, Chen Z, Xu Z (2015) Microwave-assisted synthesis of fused piperazine-benzimidazoles via a facile, one-pot procedure. Tetrahedron Lett 56:4616–4618. doi:10.1016/j.tetlet.2015.06.035

    Article  CAS  Google Scholar 

  27. Thompson MJ, Adams H, Chen B (2009) Development of a diversity-oriented approach to oxazole-5-amide libraries. J Org Chem 74:3856–3865. doi:10.1021/jo900425w

    Article  CAS  PubMed  Google Scholar 

  28. Azuaje J, El Maatougui A, Perez-Rubio JM, Coelho A, Fernandez F, Sotelo E (2013) Multicomponent assembly of diverse pyrazin-2(1H)-one chemotypes. J Org Chem 78:4402–4409. doi:10.1021/jo4003163

    Article  CAS  PubMed  Google Scholar 

  29. Shaw AY, Xu Z, Hulme C (2012) Ugi/Robinson-Gabriel reactions directed toward the synthesis of 2,4,5-trisubstituted oxazoles. Tetrahedron Lett 53:1998–2000. doi:10.1016/j.tetlet.2012.02.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ugi I, Steinbruckner C (1961) Isonitrile, II. Reaktion von isonitrilen mit carbonylverbindungen, aminen und stickstoffwasserstoffsäure. Chem Ber 94:734–742. doi:10.1002/cber.19610940323

    Article  CAS  Google Scholar 

  31. Bienaymé H, Bouzid K (1998) Synthesis of rigid hydrophobic tetrazoles using an Ugi multi-component heterocyclic condensation. Tetrahedron Lett 39:2735–2738. doi:10.1016/S0040-4039(98)00283-4

    Article  Google Scholar 

  32. Nixey T, Kelly M, Semin D, Hulme C (2002) Short solution phase preparation of fused azepine-tetrazoles via a UDC (Ugi/de-Boc/cyclize) strategy. Tetrahedron Lett 43:3681–3684. doi:10.1016/S0040-4039(02)00636-6

    Article  CAS  Google Scholar 

  33. Marcos CF, Marcaccini S, Menchi G, Pepino R, Torroba T (2008) Studies on isocyanides: synthesis of tetrazolyl-isoindolinones via tandem Ugi four-component condensation/intramolecular amidation. Tetrahedron Lett 49:149–152. doi:10.1016/j.tetlet.2007.10.154

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the Chongqing Research Program of Basic Research and Frontier Technology (cstc2015jcyjA1328), the Scientific Research Foundation of Chongqing University of Arts and Sciences (Grant Nos. R2013XY01, R2013XY02), and SRF for ROCS, SEM. We would also like to thank Ms H.Z. Liu for obtaining the LC/MS and NMR data.

Author information

Authors and Affiliations

  1. Key Laboratory for Asymmetric Synthesis and Chiral Technology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, 610041, China

    Jie Lei

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Jie Lei & Jin Zhu

  3. Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, No. 319 Honghe Ave., Yongchuan, Chongqing, 402160, China

    Jie Lei, Zhi-Gang Xu, Shi-Qiang Li, Jia Xu, Jin Zhu & Zhong-Zhu Chen

Authors
  1. Jie Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi-Gang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shi-Qiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jia Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhong-Zhu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhi-Gang Xu or Zhong-Zhu Chen.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (pdf 6977 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lei, J., Xu, ZG., Li, SQ. et al. Synthesis of isoindolin-1-one derivatives via multicomponent reactions of methyl 2-formylbenzoate and intramolecular amidation. Mol Divers 20, 859–865 (2016). https://doi.org/10.1007/s11030-016-9679-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-016-9679-6

Keywords

Search

Navigation