Skip to main content
SpringerLink
Log in

Synthesis of highly functionalized organic compounds through Ugi post-transformations started from propiolic acids

  • Short Review
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

The Ugi four-component (Ugi-4CR) post-transformation reactions have emerged as a prominent tool to construct complex organic molecules utilizing readily available starting materials. Propiolic acid derivatives are promising choice of substrates due to their versatile reactivity. Over the last decade, Ugi post-transformations starting from propiolic acid derivatives have experienced a rapid growth to afford atom-efficient processes and enantioselective transformations. This review has focused on the recent advances in the Ugi post-transformations starting from propiolic acids and their application for the preparation of highly functionalized organic compounds.

Graphic abstract

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
Scheme 5
Scheme 6
Scheme 7
Scheme 8
Scheme 9
Scheme 10
Scheme 11
Scheme 12
Scheme 13
Scheme 14
Scheme 15
Scheme 16
Scheme 17
Scheme 18
Scheme 19
Scheme 20
Scheme 21
Scheme 22
Scheme 23
Scheme 24
Scheme 25
Scheme 26
Scheme 27
Scheme 28
Scheme 29
Scheme 30
Scheme 31
Scheme 32
Scheme 33
Scheme 34
Scheme 35
Scheme 36
Scheme 37
Scheme 38
Scheme 39
Scheme 40
Scheme 41
Scheme 42
Scheme 43
Scheme 44
Scheme 45
Scheme 46
Scheme 47
Scheme 48
Scheme 49
Scheme 50
Scheme 51
Scheme 52
Scheme 53
Scheme 54
Scheme 55
Scheme 56
Scheme 57
Scheme 58
Scheme 59
Scheme 60
Scheme 61
Scheme 62
Scheme 63

Similar content being viewed by others

References

  1. Ugi I (1962) The α-addition of immonium ions and anions to isonitriles accompanied by secondary reactions. Angew Chem Int Ed Engl 1:8–21. https://doi.org/10.1002/anie.196200081

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Ugi I, Werner B, Dömling A (2003) The chemistry of isocyanides, their multicomponent reactions and their libraries. Molecules 8:53–66. https://doi.org/10.3390/80100053

    Article  CAS  PubMed Central  Google Scholar 

  4. Tempest PA (2005) Recent advances in heterocycle generation using the efficient Ugi multiple-component condensation reaction. Curr Opin Drug Discov Devel 8:776–788

    CAS  PubMed  Google Scholar 

  5. Ugi I, Heck S (2001) The multicomponent reactions and their libraries for natural and preparative chemistry. Comb Chem High Throughput Screen 4:1–34

    Article  CAS  Google Scholar 

  6. Bienaymé H, Hulme C, Oddon G, Schmitt P (2000) Maximizing synthetic efficiency: multi-component transformations lead the way. Chem Eur J 6:3321–3329. https://doi.org/10.1002/1521-3765(20000915)6:18%3c3321:AID-CHEM3321%3e3.0.CO;2-A

    Article  PubMed  Google Scholar 

  7. Dömling A, Ugi I (2000) Multicomponent reactions with isocyanides. Angew Chem Int Ed Engl 39:3168–3210. https://doi.org/10.1002/1521-3773(20000915)

    Article  PubMed  Google Scholar 

  8. Banfi L, Basso A, Riva R (2010) Synthesis of heterocycles through classical Ugi and Passerini reactions followed by secondary transformations involving one or two additional functional groups. Top Heterocycl Chem 23:1–39. https://doi.org/10.1007/7081_2009_23

    Article  CAS  Google Scholar 

  9. Hulme C, Dietrich J (2009) Emerging molecular diversity from the intra-molecular Ugi reaction: iterative efficiency in medicinal chemistry. Mol Divers 13:195

    Article  CAS  Google Scholar 

  10. Koopmanschap G, Ruijter E, Orru RV (2014) Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics. Beilstein J Org Chem 10:544–598. https://doi.org/10.3762/bjoc.10.50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sharma UK, Sharma N, Vachhani DD, Van der Eycken EV (2015) Metal-mediated post-Ugi transformations for the construction of diverse heterocyclic scaffolds. Chem Soc Rev 44:1836–1860

    Article  CAS  Google Scholar 

  12. Bararjanian M, Balalaie S, Movassagh B, Bijanzadeh HR (2010) Efficient synthesis of 1, 4-disubstituted polyfunctional piperazines via a sequential one-pot Ugi/nucleophilic addition five-component reaction. Tetrahedron Lett 51:3277–3279. https://doi.org/10.1016/j.tetlet.2010.04.054

    Article  CAS  Google Scholar 

  13. Bararjanian M, Balalaie S, Rominger F, Movassagh B, Bijanzadeh HR (2011) Novel and efficient one-pot five-and six-component reactions for the stereoselective synthesis of highly functionalized enaminones and dithiocarbamates. Mol Divers 15:583–594. https://doi.org/10.1007/s11030-010-9286-x

    Article  CAS  PubMed  Google Scholar 

  14. Maghari S, Ramezanpour S, Balalaie S, Darvish F, Rominger F, Bijanzadeh HR (2013) Synthesis of functionalized pseudopeptides through five-component sequential Ugi/nucleophilic reaction of N-substituted 2-alkynamides with hydrazides. J Org Chem 78:6450–6456. https://doi.org/10.1021/jo4003294

    Article  CAS  PubMed  Google Scholar 

  15. Peshkov AA, Peshkov VA, Li Z, Pereshivko OP, Van der Eycken EV (2014) Assembly of a 1H-pyrrol-2 (5H)-one core through a cascade Ugi reaction/5-endo-dig carbocyclization/retro-Claisen fragmentation process. Eur J Org Chem 29:6390–6393. https://doi.org/10.1002/ejoc.201402723

    Article  CAS  Google Scholar 

  16. Li Z, Kumar A, Peshkov A, Van der Eycken EV (2016) A domino Ugi/Michael approach for the synthesis of α, β-unsaturated γ-lactams. Tetrahedron Lett 57:754–756. https://doi.org/10.1016/j.tetlet.2016.01.014

    Article  CAS  Google Scholar 

  17. Li SQ, Gao H, Lei J, Wang J, Xu J, Chen ZZ, Xu ZG (2016) Efficient and facile synthesis of fused benzimidazole-diazepinones and dibenzimidazole-diazepines via a UDC strategy and the hydroamination of an alkyne. RSC Adv 6:8461–8464

    Article  CAS  Google Scholar 

  18. Li Y, Meng JP, Lei J, Chen ZZ, Tang DY, Zhu J, Zhang J, Xu ZG (2017) Efficient synthesis of fused oxazepino-isoquinoline scaffolds via an Ugi, followed by an intramolecular cyclization. ACS Comb Sci 19:324–330. https://doi.org/10.1021/acscombsci.7b00002

    Article  CAS  PubMed  Google Scholar 

  19. Ghabraie E, Balalaie S, Mehrparvar S, Rominger F (2014) Synthesis of functionalized β-lactams and pyrrolidine-2, 5-diones through a metal-free sequential Ugi-4CR/cyclization reaction. J Org Chem 79:7926–7934. https://doi.org/10.1021/jo5010422

    Article  CAS  PubMed  Google Scholar 

  20. Ramanivas T, Parameshwar M, Gayatri G, Nanubolu JB, Srivastava AK (2017) Asymmetric synthesis of functionalized 2, 5-pyrrolidinediones and β-lactams through diastereospecific cycloisomerization/rearrangement of chiral ethanolamine-derived Ugi adducts. Eur J Org Chem 2017:2245–2257. https://doi.org/10.1002/ejoc.201700031

    Article  CAS  Google Scholar 

  21. Yugandhar D, Kuriakose S, Nanubolu JB, Srivastava AK (2016) Synthesis of alkaloid-mimicking tricyclic skeletons by diastereo-and regioselective Ugi/ipso-cyclization/aza-Michael cascade reaction in one-pot. Org Lett 18:1040–1043. https://doi.org/10.1021/acs.orglett.6b00164

    Article  CAS  PubMed  Google Scholar 

  22. Nechaev AA, Peshkov AA, Peshkov VA, Van der Eycken EV (2016) The application of multicomponent Ugi and Passerini reactions for the one-pot synthesis of pyrrolones and butenolides. Synthesis 48:2280–2286. https://doi.org/10.1055/s-0035-1561422

    Article  CAS  Google Scholar 

  23. Yugandhar D, Srivastava AK (2015) Efficient construction of azaspiro [4.5] trienone libraries via tandem Ugi 4CC/electrophilic ipso-iodocyclization in one-pot. ACS Comb Sci 17:474–481. https://doi.org/10.1021/acscombsci.5b00065

    Article  CAS  PubMed  Google Scholar 

  24. Wright DL, Robotham CV, Aboud K (2002) Studies on the sequential multi-component coupling/Diels–Alder cycloaddition reaction. Tetrahedron Lett 43:943–946. https://doi.org/10.1016/S0040-4039(01)02299-7

    Article  CAS  Google Scholar 

  25. Ghoshal A, Yugandhar D, Nanubolu JB, Srivastava AK (2017) An efficient one-pot synthesis of densely functionalized fused-quinolines via sequential Ugi4CC and acid-mediated Povarov-type reaction. ACS Comb Sci 19:600–608. https://doi.org/10.1021/acscombsci.7b00095

    Article  CAS  PubMed  Google Scholar 

  26. Ambasana PA, Vachhani DD, Galli M, Jacobs J, Van Meervelt L, Shah AK, Van der Eycken EV (2014) Solvent switchable cycloaddition: a (one-pot) metal-free approach towards N-substituted benzo [e]-or [f] isoindolones via C sp2–H functionalization. Org Biomol Chem 12:8861–8865. https://doi.org/10.1039/C4OB01644K

    Article  CAS  PubMed  Google Scholar 

  27. Akritopoulou-Zanze I, Gracias V, Djuric SW (2004) A versatile synthesis of fused triazolo derivatives by sequential Ugi/alkyne–azide cycloaddition reactions. Tetrahedron Lett 45:8439–8441. https://doi.org/10.1016/j.tetlet.2004.09.117

    Article  CAS  Google Scholar 

  28. Reddy BS, Majumder N, Rao TP (2014) Four-component, one-pot synthesis of N-alkyl-4-oxo-3-phenylhexahydro-4H-spiro {[1, 3] dioxolo [4′, 5′: 4, 5] furo [2, 3-f][1, 2, 3] triazolo [1, 5-a][1, 4] diazepine-9, 1′-cyclohexane}-6-carboxamide derivatives. Synthesis 46:3408–3414. https://doi.org/10.1055/s-0034-1379031

    Article  CAS  Google Scholar 

  29. Balalaie S, Vaezghaemi A, Zarezadeh N, Rominger F, Bijanzadeh HR (2018) Catalyst-free synthesis of fused triazolo-diazepino [5, 6-b] quinoline derivatives via a sequential Ugi-4CR–nucleophilic substitution-intramolecular click reaction. Synlett 29:1095–1101. https://doi.org/10.1055/s-0036-1591531

    Article  CAS  Google Scholar 

  30. Bararjanian M, Balalaie S, Rominger F, Movassagh B, Bijanzadeh HR (2010) Six-component reactions for the stereoselective synthesis of 3-arylidene-2-oxindoles via sequential one-pot Ugi/Heck carbocyclization/Sonogashira/nucleophilic addition. J Org Chem 75:2806–2812. https://doi.org/10.1021/jo902713x

    Article  CAS  PubMed  Google Scholar 

  31. Bararjanian M, Hosseinzadeh S, Balalaie S, Bijanzadeh HR (2011) Palladium catalyzed stereoselective synthesis of 3-(anilinoarylmethylene)-2-oxindoles as Hesperadin analogoues. Tetrahedron 67:2644–2650. https://doi.org/10.1016/j.tet.2011.02.005

    Article  CAS  Google Scholar 

  32. Balalaie S, Motaghedi H, Bararjanian M, Tahmassebi D, Bijanzadeh HR (2011) Pd-catalyzed synthesis of 3-(diarylmethylene)-2-oxindoles and 3-(arylmethylene)-2-oxindoles. Tetrahedron 67:9134–9141. https://doi.org/10.1016/j.tet.2011.09.089

    Article  CAS  Google Scholar 

  33. Welsch SJ, Umkehrer M, Ross G, Kolb J, Burdack C, Wessjohann LA (2011) PdII/IV catalyzed oxidative cyclization of 1, 6-enynes derived by Ugi-4-component reaction. Tetrahedron Lett 52:6295–6297. https://doi.org/10.1016/j.tetlet.2011.09.094

    Article  CAS  Google Scholar 

  34. Zhou F, Liu J, Ding K, Liu J, Cai Q (2011) Copper-catalyzed tandem reaction of isocyanides with N-(2-haloaryl) propiolamides for the synthesis of pyrrolo [3, 2-c] quinolin-4-ones. J Org Chem 76:5346–5353. https://doi.org/10.1021/jo2006939

    Article  CAS  PubMed  Google Scholar 

  35. Vachhani DD, Kumar A, Modha SG, Sharma SK, Parmar VS, Van der Eycken EV (2013) Diversely substituted triazolo [1, 5-a][1, 4] benzodiazepinones: a post-Ugi copper-catalyzed tandem azide–alkyne cycloaddition/Ullmann C–N coupling approach. Eur J Org Chem 2013:1223–1227. https://doi.org/10.1002/ejoc.201201587

    Article  CAS  Google Scholar 

  36. Modha SG, Vachhani DD, Jacobs J, Van Meervelt L, Van der Eycken EV (2012) A concise route to indoloazocines via a sequential Ugi–gold-catalyzed intramolecular hydroarylation. Chem Commun 48:6550–6552. https://doi.org/10.1039/c2cc32586a

    Article  CAS  Google Scholar 

  37. Modha SG, Kumar A, Vachhani DD, Jacobs J, Sharma SK, Parmar VS, Van Meervelt L, Van der Eycken EV (2012) A diversity-oriented approach to spiroindolines: post-Ugi gold-catalyzed diastereoselective domino cyclization. Angew Chem Int Ed 51:9572–9575. https://doi.org/10.1002/anie.201205052

    Article  CAS  Google Scholar 

  38. Schröder F, Ojeda M, Erdmann N, Jacobs J, Luque R, Noël T, Van Meervelt L, Van der Eycken J, Van der Eycken EV (2015) Supported gold nanoparticles as efficient and reusable heterogeneous catalyst for cycloisomerization reactions. Green Chem 17:3314–3318. https://doi.org/10.1039/C5GC00430F

    Article  CAS  Google Scholar 

  39. Kumar A, Li Z, Sharma SK, Parmar VS, Eycken EV (2013) An expedient route to imidazo [1, 4] diazepin-7-ones via a post-Ugi gold-catalyzed heteroannulation. Org Lett 15:1874–1877. https://doi.org/10.1021/ol400526a

    Article  CAS  PubMed  Google Scholar 

  40. Kumar A, Vachhani DD, Modha SG, Sharma SK, Parmar VS, Van der Eycken EV (2013) Post Ugi gold (I)-and platinum (II)-catalyzed alkyne activation: synthesis of diversely substituted fused azepinones and pyridinones. Synthesis 45(18):2571–2582. https://doi.org/10.1055/s-0033-1339474

    Article  CAS  Google Scholar 

  41. Peshkov AA, Peshkov VA, Pereshivko OP, Van der Eycken EV (2015) Diversification of the 3-benzazepine scaffold applying Ugi/reductive Heck sequence. Tetrahedron 71:3863–3871. https://doi.org/10.1016/j.tet.2015.04.022

    Article  CAS  Google Scholar 

  42. Vachhani DD, Galli M, Jacobs J, Van Meervelt L, Van der Eycken EV (2013) Synthesis of (spiro) cyclopentapyridinones via C sp3–H functionalization: a post-Ugi gold-catalyzed regioselective tandem cyclization. Chem Commun 49:7171–7173. https://doi.org/10.1039/C3CC43418D

    Article  CAS  Google Scholar 

  43. Li Z, Zhao Y, Tian G, He Y, Song G, Van Meervelt L, Van der Eycken EV (2016) Synthesis of novel imidazole-based triheterocycles via a domino Ugi/Michael reaction and silver-catalyzed heteroannulation. RSC Adv 6:103601–103605. https://doi.org/10.1039/C6RA23180B

    Article  CAS  Google Scholar 

  44. Ghabraie E, Balalaie S (2014) Sequential Ugi four-component reaction (4-CR)/C—H activation using (diacetoxyiodo) benzene for the synthesis of 3-(diphenylmethylidene)-2, 3-dihydro-1H-indol-2-ones. Helv Chim Acta 97:1555–1563. https://doi.org/10.1002/hlca.201400056

    Article  CAS  Google Scholar 

  45. Li Z, Kumar A, Vachhani DD, Sharma SK, Parmar VS, Van der Eycken EV (2014) Regioselective synthesis of diversely substituted diazoninones through a post-Ugi gold-catalyzed intramolecular hydroarylation process. Eur J Org Chem 2014:2084–2091. https://doi.org/10.1002/ejoc.201301507

    Article  CAS  Google Scholar 

  46. Sharma N, Li Z, Sharma UK, Van der Eycken EV (2014) Facile access to functionalized spiro [indoline-3, 2′-pyrrole]-2, 5′-diones via post-Ugi domino Buchwald–Hartwig/Michael reaction. Org Lett 16:3884–3887. https://doi.org/10.1021/ol5019079

    Article  CAS  PubMed  Google Scholar 

  47. Moni L, Denißen M, Valentini G, Mueller TJ, Riva R (2015) Diversity-oriented synthesis of intensively blue emissive 3-hydroxyisoquinolines by sequential Ugi four-component reaction/reductive Heck cyclization. Chem Eur J 21:753–762. https://doi.org/10.1002/chem.201404209

    Article  CAS  PubMed  Google Scholar 

  48. Li Z, Sharma UK, Liu Z, Sharma N, Harvey JN, Van der Eycken EV (2015) Diversity-oriented synthesis of β-lactams and γ-lactams by post-Ugi nucleophilic cyclization: lewis acids as regioselective switch. Eur J Org Chem 2015:3957–3962. https://doi.org/10.1002/ejoc.201500270

    Article  CAS  Google Scholar 

  49. Moni L, Gers-Panther CF, Anselmo M, Müller TJ, Riva R (2016) Highly convergent synthesis of intensively blue emissive furo [2, 3-c] isoquinolines by a palladium-catalyzed cyclization cascade of unsaturated Ugi products. Chem Eur J 22:2020–2031. https://doi.org/10.1002/chem.201504335

    Article  CAS  PubMed  Google Scholar 

  50. Li Z, Kumar A, Sharma SK, Parmar VS, Van der Eycken EV (2015) Catalyst-controlled exo/endo selectivity in a post-Ugi intramolecular hydroarylation: synthesis of pyrrolopyridinones, pyrroloazepinones, and benzothienopyridines. Tetrahedron 71:3333–3342. https://doi.org/10.1016/j.tet.2015.03.103

    Article  CAS  Google Scholar 

  51. Balalaie S, Ramezani Kejani R, Ghabraie E, Darvish F, Rominger F, Hamdan F, Bijanzadeh HR (2017) Diastereoselective synthesis of functionalized diketopiperazines through post-transformational reactions. J Org Chem 82:12141–12152. https://doi.org/10.1021/acs.joc.7b01855

    Article  CAS  PubMed  Google Scholar 

  52. Ranjan P, Ojeda GM, Sharma UK, Van der Eycken EV (2019) Metal-free dearomatization: direct access to spiroindol(en)ines in batch and continuous-flow. Chem Eur J 25:2442–2446. https://doi.org/10.1002/chem.201805945

    Article  CAS  PubMed  Google Scholar 

  53. Singh K, Malviya BK, Roy TK, Mithu VS, Bhardwaj VK, Verma VP, Chimni SS, Sharma S (2017) Catalyst-controlled structural divergence: selective intramolecular 7-endo-dig and 6-exo-dig post-Ugi cyclization for the synthesis of benzoxazepinones and benzoxazinones. J Org Chem 83:57–68. https://doi.org/10.1021/acs.joc.7b02123

    Article  CAS  PubMed  Google Scholar 

  54. Nechaev AA, Van Hecke K, Zaman M, Kashtanov S, Ungur L, Pereshivko OP, Peshkov VA, Van der Eycken EV (2018) Gold-catalyzed post-Ugi ipso-cyclization with switchable diastereoselectivity. J Org Chem 83:8170–8182. https://doi.org/10.1021/acs.joc.8b00953

    Article  CAS  PubMed  Google Scholar 

  55. Wang D, Cai R, Sharma S, Jirak J, Thummanapelli SK, Akhmedov NG, Zhang H, Liu X, Petersen JL, Shi X (2012) “Silver effect” in gold (I) catalysis: an overlooked important factor. J Am Chem Soc 134:9012–9019. https://doi.org/10.1021/ja303862z

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

    Maryam Mohammadi-Khanaposhtani

  2. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Nafiseh Jalalimanesh, Bagher Larijani & Mohammad Mahdavi

  3. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mina Saeedi

  4. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mina Saeedi

Authors
  1. Maryam Mohammadi-Khanaposhtani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nafiseh Jalalimanesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mina Saeedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bagher Larijani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Mahdavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Nafiseh Jalalimanesh or Mohammad Mahdavi.

Additional information

This paper is dedicated to our respected teacher in chemistry and medicinal chemistry, Professor Abbas Shafiee (1937–2016).

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammadi-Khanaposhtani, M., Jalalimanesh, N., Saeedi, M. et al. Synthesis of highly functionalized organic compounds through Ugi post-transformations started from propiolic acids. Mol Divers 24, 855–887 (2020). https://doi.org/10.1007/s11030-019-09975-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-019-09975-y

Keywords

Search

Navigation