Skip to main content

Passerini and Ugi Multicomponent Reactions in Polymer Science

  • Chapter
  • First Online:

Part of the book series: Advances in Polymer Science ((POLYMER,volume 269))

Abstract

Multicomponent reactions (MCRs) include more than two starting materials and are characterized by highly atom-efficient and straightforward practical procedures. Some of the most important MCRs in organic chemistry are the isocyanide-based MCRs, namely the Passerini three-component and Ugi four-component reaction. These reactions are, for example, often applied in combinatorial and medicinal chemistry due to their easy access to diversity or for the creation of complex structural motifs in the total synthesis of natural products.

Only recently, they also gained great interest in macromolecular chemistry, since the variation of the single components displays an easy tool to adjust the properties of the polymers and facile introduction of functional groups is enabled. Hereby, tailor-made high-performance and smart materials can be obtained, which are currently highly requested for many applications. In order to attain this objective, several strategies are followed: the MCRs are used to synthesize structurally diverse monomers for subsequent polymerization, or by the use of bifunctional components, these reactions are directly utilized as polymerization method. Moreover, the Passerini and Ugi reaction are applied in macromolecular engineering as conjugation method of two kinds of polymers, or as tool for grafting reactions as well as in the creation of defined primary structures. Finally, these valuable reactions are also used in the convergent and divergent synthesis of dendritic architectures.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Passerini M (1921) Gazz Chem Ital 51:126–129

    CAS  Google Scholar 

  2. Ugi I, Steinbrückner C (1960) Über ein neues Kondensations-Prinzip. Angew Chem 72(7–8):267–268

    Article  CAS  Google Scholar 

  3. Wessjohann LA, Neves Filho RAW, Rivera DG (2012) Multiple multicomponent reactions with isocyanides. In: Isocyanide chemistry. Wiley-VCH, Weinheim, pp 233–262

    Chapter  Google Scholar 

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

    Article  Google Scholar 

  5. Mumm O (1910) Ber Dtsch Chem Ges 43:886–893

    Article  CAS  Google Scholar 

  6. Dömling A, Wang W, Wang K (2012) Chemistry and biology of multicomponent reactions. Chem Rev 112(6):3083–3135

    Article  Google Scholar 

  7. Akritopoulou-Zanze I (2008) Isocyanide-based multicomponent reactions in drug discovery. Curr Opin Chem Biol 12(3):324–331

    Article  CAS  Google Scholar 

  8. Weber L (2002) Multi-component reactions and evolutionary chemistry. Drug Discov Today 7(2):143–147

    Article  CAS  Google Scholar 

  9. Dai Q, Xie X, Xu S, Ma D, Tang S, She X (2011) Total syntheses of tardioxopiperazine A, isoechinulin A, and variecolorin C. Org Lett 13(9):2302–2305

    Article  CAS  Google Scholar 

  10. Takiguchi S, Iizuka T, Kumakura Y-s, Murasaki K, Ban N, Higuchi K, Kawasaki T (2010) Total syntheses of (−)-fructigenine A and (−)-5-N-acetylardeemin. J Org Chem 75(4):1126–1131

    Article  CAS  Google Scholar 

  11. Falck JR, Manna S (1981) An intramolecular Passerini reaction: synthesis of hydrastine. Tetrahedron Lett 22(7):619–620

    Article  CAS  Google Scholar 

  12. Kakuchi R (2014) Multicomponent reactions in polymer synthesis. Angew Chem Int Ed 53(1):46–48

    Article  CAS  Google Scholar 

  13. Rudick JG (2013) Innovative macromolecular syntheses via isocyanide multicomponent reactions. J Polym Sci Part A Polym Chem 51(19):3985–3991

    Article  CAS  Google Scholar 

  14. Wang S, Fu C, Wei Y, Tao L (2014) Facile one-pot synthesis of new functional polymers through multicomponent systems. Macromol Chem Phys 215(6):486–492

    Article  CAS  Google Scholar 

  15. Rubinshtein M, James CR, Young JL, Ma YJ, Kobayashi Y, Gianneschi NC, Yang J (2010) Facile procedure for generating side chain functionalized poly(α-hydroxy acid) copolymers from aldehydes via a versatile Passerini-type condensation. Org Lett 12(15):3560–3563

    Article  CAS  Google Scholar 

  16. Kreye O, Tóth T, Meier MAR (2011) Introducing multicomponent reactions to polymer science: Passerini reactions of renewable monomers. J Am Chem Soc 133(6):1790–1792

    Article  CAS  Google Scholar 

  17. Mutlu H, de Espinosa LM, Meier MAR (2011) Acyclic diene metathesis: a versatile tool for the construction of defined polymer architectures. Chem Soc Rev 40(3):1404–1445

    Article  CAS  Google Scholar 

  18. Atallah P, Wagener KB, Schulz MD (2013) ADMET: the future revealed. Macromolecules 46(12):4735–4741

    Article  CAS  Google Scholar 

  19. Simocko C, Atallah P, Wagener KB (2013) A brief examination of the latest ADMET chemistry. Curr Org Chem 17(22):2749–2763

    Article  CAS  Google Scholar 

  20. Mutlu H, Meier MAR (2010) Castor oil as a renewable resource for the chemical industry. Eur J Lipid Sci Technol 112(1):10–30

    Article  CAS  Google Scholar 

  21. Kolb N, Meier MAR (2013) Grafting onto a renewable unsaturated polyester via thiol–ene chemistry and cross-metathesis. Eur Polym J 49(4):843–852

    Article  CAS  Google Scholar 

  22. Kreye O, Trefzger C, Sehlinger A, Meier MAR (2014) Multicomponent reactions with a convertible isocyanide: efficient and versatile grafting of ADMET-derived polymers. Macromol Chem Phys 215(22):2207–2220

    Google Scholar 

  23. Sehlinger A, Kreye O, Meier MAR (2013) Tunable polymers obtained from Passerini multicomponent reaction derived acrylate monomers. Macromolecules 46(15):6031–6037

    Article  CAS  Google Scholar 

  24. Sehlinger A, de Espinosa LM, Meier MAR (2013) Synthesis of diverse asymmetric α,ω-dienes via the Passerini three-component reaction for head-to-tail ADMET polymerization. Macromol Chem Phys 214(24):2821–2828

    Article  CAS  Google Scholar 

  25. Montero de Espinosa M, Meier MAR (2011) Synthesis of star- and block-copolymers using ADMET: head-to-tail selectivity during step-growth polymerization. Chem Commun 47(6):1908–1910

    Article  CAS  Google Scholar 

  26. Chatterjee AK, Choi T-L, Sanders DP, Grubbs RH (2003) A general model for selectivity in olefin cross metathesis. J Am Chem Soc 125(37):11360–11370

    Article  CAS  Google Scholar 

  27. Demel S, Slugovc C, Stelzer F, Fodor-Csorba K, Galli G (2003) Alternating diene metathesis polycondensation (ALTMET) – a versatile tool for the preparation of perfectly alternating AB copolymers. Macromol Rapid Commun 24(10):636–641

    Article  CAS  Google Scholar 

  28. Pirrung MC, Sarma KD (2003) Multicomponent reactions are accelerated in water. J Am Chem Soc 126(2):444–445

    Article  Google Scholar 

  29. Schmidt S, Koldevitz M, Noy J-M, Roth PJ (2015) Multicomponent isocyanide-based synthesis of reactive styrenic and (meth)acrylic monomers and their RAFT (co)polymerization. Polym Chem 6:44–54

    Google Scholar 

  30. Noy J-M, Koldevitz M, Roth PJ (2015) Thiol-reactive functional poly(meth)acrylates: multicomponent monomer synthesis, RAFT (co)polymerization and highly efficient thiol-para-fluoro postpolymerization modification. Polym Chem 6:436–447

    Google Scholar 

  31. Leon F, Rivera DG, Wessjohann LA (2008) Multiple multicomponent macrocyclizations including bifunctional building blocks (MiBs) based on Staudinger and Passerini three-component reactions. J Org Chem 73(5):1762–1767

    Article  CAS  Google Scholar 

  32. Deng X-X, Li L, Li Z-L, Lv A, Du F-S, Li Z-C (2012) Sequence regulated poly(ester-amide)s based on Passerini reaction. ACS Macro Lett 1(11):1300–1303

    Article  CAS  Google Scholar 

  33. Kan X-W, Deng X-X, Du F-S, Li Z-C (2015) Concurrent oxidation of alcohols and the Passerini three-component polymerization for the synthesis of functional poly(ester amide)s. Macromol Chem Phys 215(22): 2221–2228

    Google Scholar 

  34. Ngouansavanh T, Zhu J (2006) Alcohols in isonitrile-based multicomponent reaction: Passerini reaction of alcohols in the presence of O-iodoxybenzoic acid. Angew Chem Int Ed 45(21):3495–3497

    Article  CAS  Google Scholar 

  35. Wang Y-Z, Deng X-X, Li L, Li Z-L, Du F-S, Li Z-C (2013) One-pot synthesis of polyamides with various functional side groups via Passerini reaction. Polym Chem 4(3):444–448

    Article  CAS  Google Scholar 

  36. Obrecht R, Herrmann R, Ugi I (1985) Isocyanide synthesis with phosphoryl chloride and diisopropylamine. Synthesis 1985(04):400–402

    Article  Google Scholar 

  37. Ugi I, Fetzer U, Eholzer U, Knupfer H, Offermann K (1965) Isonitrile syntheses. Angew Chem Int Ed Engl 4(6):472–484

    Article  Google Scholar 

  38. Sehlinger A, Schneider R, Meier MAR (2014) Passerini addition polymerization of an AB-type monomer – a convenient route to versatile polyesters. Eur Polym J 50:150–157

    Article  CAS  Google Scholar 

  39. Zhang L-J, Deng X-X, Du F-S, Li Z-C (2013) Chemical synthesis of functional poly(4-hydroxybutyrate) with controlled degradation via intramolecular cyclization. Macromolecules 46(24):9554–9562

    Article  CAS  Google Scholar 

  40. Deng X-X, Cui Y, Du F-S, Li Z-C (2014) Functional highly branched polymers from multicomponent polymerization (MCP) based on the ABC type Passerini reaction. Polym Chem 5(10):3316–3320

    Article  CAS  Google Scholar 

  41. de Nooy AEJ, Capitani D, Masci G, Crescenzi V (2000) Ionic polysaccharide hydrogels via the Passerini and Ugi multicomponent condensations: synthesis, behavior and solid-state NMR characterization. Biomacromolecules 1(2):259–267

    Article  Google Scholar 

  42. de Nooy AEJ, Masci G, Crescenzi V (1999) Versatile synthesis of polysaccharide hydrogels using the Passerini and Ugi multicomponent condensations. Macromolecules 32(4):1318–1320

    Article  Google Scholar 

  43. Li L, Lv A, Deng X-X, Du F-S, Li Z-C (2013) Facile synthesis of photo-cleavable polymers via Passerini reaction. Chem Commun 49(76):8549–8551

    Article  CAS  Google Scholar 

  44. Li L, Deng X-X, Li Z-L, Du F-S, Li Z-C (2014) Multifunctional photodegradable polymers for reactive micropatterns. Macromolecules 47(14):4660–4667

    Article  CAS  Google Scholar 

  45. Lin W, Sun T, Zheng M, Xie Z, Huang Y, Jing X (2014) Synthesis of cross-linked polymers via multi-component Passerini reaction and their application as efficient photocatalysts. RSC Adv 4(48):25114–25117

    Article  CAS  Google Scholar 

  46. Wang S, Zhang N, Ge X, Wan Y, Li X, Yan L, Xia Y, Song B (2014) Self-assembly of an azobenzene-containing polymer prepared by a multi-component reaction: supramolecular nanospheres with photo-induced deformation properties. Soft Matter 10(27):4833–4839

    Article  CAS  Google Scholar 

  47. Li L, Kan X-W, Deng X-X, Song C-C, Du F-S, Li Z-C (2013) Simultaneous dual end-functionalization of PEG via the Passerini three-component reaction for the synthesis of ABC miktoarm terpolymers. J Polym Sci Part A Polym Chem 51(4):865–873

    Article  CAS  Google Scholar 

  48. Deng X-X, Cui Y, Wang Y-Z, Du F-S, Li Z-C (2014) Graft copolymers with polyamide backbones via combination of Passerini multicomponent polymerization and controlled chain-growth polymerization. Aust J Chem 67(4):555–561

    Article  CAS  Google Scholar 

  49. Merrifield RB (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85(14):2149–2154

    Article  CAS  Google Scholar 

  50. Espeel P, Carrette LLG, Bury K, Capenberghs S, Martins JC, Du Prez FE, Madder A (2013) Multifunctionalized sequence-defined oligomers from a single building block. Angew Chem Int Ed 52(50):13261–13264

    Article  CAS  Google Scholar 

  51. Li X, Liu DR (2004) DNA-templated organic synthesis: nature’s strategy for controlling chemical reactivity applied to synthetic molecules. Angew Chem Int Ed 43(37):4848–4870

    Article  CAS  Google Scholar 

  52. Lutz J-F, Ouchi M, Liu DR, Sawamoto M (2013) Sequence-controlled polymers. Science 341:6146

    Article  Google Scholar 

  53. Lv A, Deng X-X, Li L, Li Z-L, Wang Y-Z, Du F-S, Li Z-C (2013) Facile synthesis of multi-block copolymers containing poly(ester-amide) segments with an ordered side group sequence. Polym Chem 4(13):3659–3662

    Article  CAS  Google Scholar 

  54. Solleder SC, Meier MAR (2014) Sequence control in polymer chemistry through the Passerini three-component reaction. Angew Chem Int Ed 53(3):711–714

    Article  CAS  Google Scholar 

  55. Sowinska M, Urbanczyk-Lipkowska Z (2014) Advances in the chemistry of dendrimers. New J Chem 38(6):2168–2203

    Article  CAS  Google Scholar 

  56. Jee J-A, Spagnuolo LA, Rudick JG (2012) Convergent synthesis of dendrimers via the Passerini three-component reaction. Org Lett 14(13):3292–3295

    Article  CAS  Google Scholar 

  57. Wessjohann LA, Henze M, Kreye O, Rivera DG (2011) MCR dendrimers. Patent WO 2011/134607

    Google Scholar 

  58. Wessjohann LA, Henze M, Kreye O, Rivera DG (2013) MCR dendrimers. European Patent EP 2563847

    Google Scholar 

  59. Kreye O, Kugele D, Faust L, Meier MAR (2014) Divergent dendrimer synthesis via the Passerini three-component reaction and olefin cross-metathesis. Macromol Rapid Commun 35(3):317–322

    Article  CAS  Google Scholar 

  60. Deng X-X, Du F-S, Li Z-C (2014) Combination of orthogonal ABB and ABC multicomponent reactions toward efficient divergent synthesis of dendrimers with structural diversity. ACS Macro Lett 3(7):667–670

    Article  CAS  Google Scholar 

  61. Robotham C, Baker C, Cuevas B, Abboud K, Wright D (2003) A multi-component reaction (MCR) approach to the synthesis of highly diverse polymers with polypeptide-like features. Mol Diversity 6(3–4):237–244

    CAS  Google Scholar 

  62. Kreye O, Türünç O, Sehlinger A, Rackwitz J, Meier MAR (2012) Structurally diverse polyamides obtained from monomers derived via the Ugi multicomponent reaction. Chem-Eur J 18(18):5767–5776

    Article  CAS  Google Scholar 

  63. Keating TA, Armstrong RW (1998) The Ugi five-component condensation using CO2, CS2, and COS as oxidized carbon sources. J Org Chem 63(3):867–871

    Article  CAS  Google Scholar 

  64. Sehlinger A, Schneider R, Meier MAR (2014) Ugi reactions with CO2: access to functionalized polyurethanes, polycarbonates, polyamides, and polyhydantoins. Macromol Rapid Commun 35(21):1866–1871

    CAS  Google Scholar 

  65. Hulme C, Ma L, Romano JJ, Morton G, Tang S-Y, Cherrier M-P, Choi S, Salvino J, Labaudiniere R (2000) Novel applications of carbon dioxide/MeOH for the synthesis of hydantoins and cyclic ureas via the Ugi reaction. Tetrahedron Lett 41(12):1889–1893

    Article  CAS  Google Scholar 

  66. Wessjohann LA, Rivera DG, León F (2007) Freezing Imine exchange in dynamic combinatorial libraries with Ugi reactions: versatile access to templated macrocycles. Org Lett 9(23):4733–4736

    Article  CAS  Google Scholar 

  67. Wessjohann LA, Rivera DG, Vercillo OE (2009) Multiple multicomponent macrocyclizations (MiBs): a strategic development toward macrocycle diversity. Chem Rev 109(2):796–814

    Article  CAS  Google Scholar 

  68. Crescenzi V, Francescangeli A, Capitani D, Mannina L, Renier D, Bellini D (2003) Hyaluronan networking via Ugi’s condensation using lysine as cross-linker diamine. Carbohydr Polym 53(3):311–316

    Article  CAS  Google Scholar 

  69. Bu H, Kjøniksen A-L, Knudsen KD, Nyström B (2004) Rheological and structural properties of aqueous alginate during gelation via the Ugi multicomponent condensation reaction. Biomacromolecules 5(4):1470–1479

    Article  CAS  Google Scholar 

  70. Bu H, Kjøniksen A-L, Nyström B (2005) Effects of pH on dynamics and rheology during association and gelation via the Ugi reaction of aqueous alginate. Eur Polym J 41(8):1708–1717

    Article  CAS  Google Scholar 

  71. Sehlinger A, Dannecker P-K, Kreye O, Meier MAR (2014) Diversely substituted polyamides: macromolecular design using the Ugi four-component reaction. Macromolecules 47(9):2774–2783

    Article  CAS  Google Scholar 

  72. Sehlinger A, Schneider R, Meier MAR (2014) Ugi reactions with CO2: access to functionalized polyurethanes, polycarbonates, polyamides or polyhydantoins. Macromol Rapid Commun 35(21):1866–1871

    Google Scholar 

  73. Yang B, Zhao Y, Fu C, Zhu C, Zhang Y, Wang S, Wei Y, Tao L (2014) Introducing the Ugi reaction into polymer chemistry as a green click reaction to prepare middle-functional block copolymers. Polym Chem 5(8):2704–2708

    Article  CAS  Google Scholar 

  74. Tao L, Xu J, Gell D, Davis TP (2010) Synthesis, characterization, and bioactivity of mid-functional polyHPMA−lysozyme bioconjugates. Macromolecules 43(8):3721–3727

    Article  CAS  Google Scholar 

  75. Barner-Kowollik C, Du Prez FE, Espeel P, Hawker CJ, Junkers T, Schlaad H, Van Camp W (2011) “Clicking” polymers or just efficient linking: what is the difference? Angew Chem Int Ed 50(1):60–62

    Article  CAS  Google Scholar 

  76. Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40(11):2004–2021

    Article  CAS  Google Scholar 

  77. Jevševar S, Kunstelj M, Porekar VG (2010) PEGylation of therapeutic proteins. Biotechnol J 5(1):113–128

    Article  Google Scholar 

  78. Yang B, Zhao Y, Wang S, Zhang Y, Fu C, Wei Y, Tao L (2014) Synthesis of multifunctional polymers through the Ugi reaction for protein conjugation. Macromolecules 47(16):5607–5612

    Article  CAS  Google Scholar 

  79. Yang B, Zhao Y, Ren X, Zhang X, Fu C, Zhang Y, Wei Y, Tao L (2015) The power of one-pot: a hexa-component system containing π–π stacking, Ugi reaction and RAFT polymerization for simple polymer conjugation on carbon nanotubes. Polym Chem 6:509–513

    Google Scholar 

  80. Barreto AdFS, Vercillo OE, Birkett MA, Caulfield JC, Wessjohann LA, Andrade CKZ (2011) Fast and efficient microwave-assisted synthesis of functionalized peptoids via Ugi reactions. Org Biomol Chem 9(14):5024–5027

    Article  CAS  Google Scholar 

  81. Wessjohann LA, Tran TPT, Westermann B (2008) Method for producing condensation products from n-substituted glycine derivatives (peptoids) by sequential Ugi-multicomponent reactions. Patent WO 2008/022800

    Google Scholar 

  82. Barreto AdFS, Vercillo OE, Wessjohann LA, Andrade CKZ (2014) Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids. Beilstein J Org Chem 10:1017–1022

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael A. R. Meier .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Sehlinger, A., Meier, M.A.R. (2014). Passerini and Ugi Multicomponent Reactions in Polymer Science. In: Theato, P. (eds) Multi-Component and Sequential Reactions in Polymer Synthesis. Advances in Polymer Science, vol 269. Springer, Cham. https://doi.org/10.1007/12_2014_298

Download citation

Publish with us

Policies and ethics