Skip to main content
Log in

An Update on Isocyanide-Based Multicomponent Reactions in Polymer Science

  • Review
  • Published:
Topics in Current Chemistry Aims and scope Submit manuscript

Abstract

Developments and progress in polymer science are often inspired by organic chemistry. In recent years, multicomponent reactions—especially the Passerini and Ugi reactions—have become very important tools for macromolecular design, mainly due to their modular character. In this review, the versatility of the Passerini and Ugi reactions in polymer science is highlighted by discussing recent examples of their use for monomer synthesis, as polymerization techniques, and for postpolymerization modification, as well as their suitability for architecture control, sequence control, and sequence definition.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Zhu J, Bienaymé H (2006) Multicomponent reactions. John Wiley, New Jersey

    Google Scholar 

  2. Zhu J, Wang Q, Wang M (2014) Multicomponent reactions in organic synthesis. John Wiley, New Jersey

    Book  Google Scholar 

  3. Strecker A (1850) Liebigs Ann Chem 75:25

    Google Scholar 

  4. Strecker A (1854) Ueber einen neuen aus Aldehyd-Ammoniak und Blausäure entstehenden Körper. Justus Liebigs Annalen der Chemie 91:349

    Article  Google Scholar 

  5. Passerini M (1921) Isonitriles. II. Compounds with aldehydes or with ketones and monobasic organic acids. Gazz Chim Ital 51:181

    CAS  Google Scholar 

  6. Ugi I (1959) Versuche mit Isonitrilen. Angew Chem Int Ed 71:386

    Google Scholar 

  7. Passerini M, Simone L (1921) Sopra gli isonitrili (I). Composto del p-isonitril-azobenzolo con acetone ed acido acetico. Gazz Chim 51:126

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Mumm O (1910) Umsetzung von Säureimidchloriden mit Salzen organischer Säuren und mit Cyankalium. Ber Dtsch Chem Ges 43:886

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Jiang X, Feng C, Lu G, Huang X (2015) Application of named reactions in polymer synthesis. Sci China Chem 58:1695

    Article  CAS  Google Scholar 

  12. Yang B, Zhao Y, Wei Y, Fu C, Tao L (2015) The Ugi reaction in polymer chemistry: syntheses, applications and perspectives. Polym Chem 6:8233

    Article  CAS  Google Scholar 

  13. Sehlinger A, Meier MAR (2015) In: Theato P (ed) Multi-component and sequential reactions in polymer synthesis. Springer International, Cham, p 61

    Google Scholar 

  14. Kakuchi R (2014) Multicomponent reactions in polymer synthesis. Angew Chem Int Ed 53:46

    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 12:3560

    Article  CAS  Google Scholar 

  16. 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 215:2207

    Article  CAS  Google Scholar 

  17. 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 214:2821

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. 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

    Article  CAS  Google Scholar 

  20. 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

    Article  CAS  Google Scholar 

  21. Pei Y, Noy J-M, Roth PJ, Lowe AB (2015) Thiol-reactive Passerini-methacrylates and polymorphic surface functional soft matter nanoparticles via ethanolic RAFT dispersion polymerization and post-synthesis modification. Polym Chem 6:1928

    Article  CAS  Google Scholar 

  22. Pei Y, Dharsana NC, van Hensbergen JA, Burford RP, Roth PJ, Lowe AB (2014) RAFT dispersion polymerization of 3-phenylpropyl methacrylate with poly[2-(dimethylamino)ethyl methacrylate] macro-CTAs in ethanol and associated thermoreversible polymorphism. Soft Matter 10:5787

    Article  CAS  Google Scholar 

  23. von Czapiewski M, Kreye O, Mutlu H, Meier MAR (2013) Cross-metathesis versus palladium-catalyzed C-H activation: Acetoxy ester functionalization of unsaturated fatty acid methyl esters. Eur J Lipid Sci Technol 115:76

    Article  Google Scholar 

  24. von Czapiewski M, Gugau K, Todorovic L, Meier MAR (2016) Synthesis of polyacrylates from limonene by catalytic oxidation and multi-component reaction. Eur Polym J 83:359

    Article  Google Scholar 

  25. Sabitha G, Nayak S, Bhikshapathi M, Yadav JS (2011) Palladium hydroxide catalyzed isomerization of primary allylic alcohols to aldehydes: application to the formal synthesis of (−)-Brevisamide. Org Lett 13:382

    Article  CAS  Google Scholar 

  26. Sehlinger A, Ochsenreither K, Bartnick N, Meier MAR (2015) Potentially biocompatible polyacrylamides derived by the Ugi four-component reaction. Eur Polym J 65:313

    Article  CAS  Google Scholar 

  27. Galperin A, Long TJ, Ratner BD (2010) Degradable, thermo-sensitive poly(N-isopropyl acrylamide)-based scaffolds with controlled porosity for tissue engineering applications. Biomacromolecules 11:2583

    Article  CAS  Google Scholar 

  28. Kawaguchi H (2014) Thermoresponsive microhydrogels: preparation, properties and applications. Polym Int 63:925

    Article  CAS  Google Scholar 

  29. Vignaud T, Ennomani H, Théry M (2014) Polyacrylamide hydrogel micropatterning. Methods Cell Biol 120:93

    Article  Google Scholar 

  30. Algi MP, Okay O (2014) Highly stretchable self-healing poly(N,N-dimethylacrylamide) hydrogels. Eur Polym J 59:113

    Article  CAS  Google Scholar 

  31. Kienberger J, Kreutzwiesner E, Noormofidi N, Klarholz I, Harms C, Slugovc C (2012) Towards the antimicrobial finishing of poly(isoprene). Macromol Symposia 311:98

    Article  CAS  Google Scholar 

  32. Kienberger J, Noormofidi N, Mühlbacher I, Klarholz I, Harms C, Slugovc C (2012) Antimicrobial equipment of poly(isoprene) applying thiol-ene chemistry. J Polym Sci 50:2236

    Article  CAS  Google Scholar 

  33. 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 1:1300

    Article  CAS  Google Scholar 

  34. 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 4:444

    Article  CAS  Google Scholar 

  35. 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 46:9554

    Article  CAS  Google Scholar 

  36. 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

    Article  CAS  Google Scholar 

  37. Zhang J, Zhang M, Du F-S, Li Z-C (2016) Synthesis of functional polycaprolactones via Passerini multicomponent polymerization of 6-oxohexanoic acid and isocyanides. Macromolecules 49:2592

    Article  CAS  Google Scholar 

  38. Lin W, Guan X, Sun T, Huang Y, Jing X, Xie Z (2015) Reduction-sensitive amphiphilic copolymers made via multi-component Passerini reaction for drug delivery. Colloids Surf 126:217

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  41. Gangloff N, Nahm D, Döring L, Kuckling D, Luxenhofer R (2015) Polymerization via the Ugi-reaction using aromatic monomers. J Polym Sci 53:1680

    Article  CAS  Google Scholar 

  42. Hartweg M, Becer CR (2016) Direct polymerization of levulinic acid via Ugi multicomponent reaction. Green Chem 18:3272

    Article  CAS  Google Scholar 

  43. Zhang X, Wang S, Liu J, Xie Z, Luan S, Xiao C, Tao Y, Wang X (2016) Ugi reaction of natural amino acids: a general route toward facile synthesis of polypeptoids for bioapplications. ACS Macro Lett 5:1049

    Article  CAS  Google Scholar 

  44. 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 35:317

    Article  CAS  Google Scholar 

  45. 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 3:667

    Article  CAS  Google Scholar 

  46. Wessjohann L, Henze M, Kreye O, Rivera D (2013) WO Patent 134,607, 2011. European Patent 2563847

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

    Article  CAS  Google Scholar 

  48. Jee J-A, Song S, Rudick JG (2015) Enhanced reactivity of dendrons in the Passerini three-component reaction. Chem Commun 51:5456

    Article  CAS  Google Scholar 

  49. 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 67:555

    Article  CAS  Google Scholar 

  50. 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 51:865

    Article  CAS  Google Scholar 

  51. Oelmann S, Solleder SC, Meier MAR (2016) Controlling molecular weight and polymer architecture during the Passerini three component step-growth polymerization. Polym Chem 7:1857

    Article  CAS  Google Scholar 

  52. Mutlu H, Lutz J-F (2014) Reading polymers: sequencing of natural and synthetic macromolecules. Angew Chem Int Ed 53:13010

    Article  CAS  Google Scholar 

  53. Badi N, Lutz J-F (2009) Sequence control in polymer synthesis. Chem Soc Rev 38:3383

    Article  CAS  Google Scholar 

  54. Qu C, He J (2015) Recent developments in the synthesis of sequence controlled polymers. Sci China Chem 58:1651

    Article  CAS  Google Scholar 

  55. Colquhoun H, Lutz J-F (2014) Information-containing macromolecules. Nat Chem 6:455

    Article  CAS  Google Scholar 

  56. Hartmann L, Häfele S, Peschka-Süss R, Antonietti M, Börner HG (2008) Tailor-made poly(amidoamine)s for controlled complexation and condensation of DNA. Chemistry 14:2025

    Article  CAS  Google Scholar 

  57. Terashima T, Mes T, De Greef TFA, Gillissen MAJ, Besenius P, Palmans ARA, Meijer EW (2011) Single-chain folding of polymers for catalytic systems in water. J Am Chem Soc 133:4742

    Article  CAS  Google Scholar 

  58. Yang L, Zhang Z, Cheng B, You Y, Wu D, Hong C (2015) Two tandem multicomponent reactions for the synthesis of sequence-defined polymers. Sci China Chem 58:1734

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  60. Solleder SC, Wetzel KS, Meier MAR (2015) Dual side chain control in the synthesis of novel sequence-defined oligomers through the Ugi four-component reaction. Polym Chem 6:3201

    Article  CAS  Google Scholar 

  61. Solleder SC, Zengel D, Wetzel KS, Meier MAR (2016) A scalable and high-yield strategy for the synthesis of sequence-defined macromolecules. Angew Chem Int Ed 55:1204

    Article  CAS  Google Scholar 

  62. Sehlinger A, Verbraeken B, Meier MAR, Hoogenboom R (2015) Versatile side chain modification via isocyanide-based multicomponent reactions: tuning the LCST of poly(2-oxazoline)s. Polym Chem 6:3828

    Article  CAS  Google Scholar 

  63. Xue L, Xiong X, Chen K, Luan Y, Chen G, Chen H (2016) Modular synthesis of glycopolymers with well-defined sugar units in the side chain via Ugi reaction and click chemistry: hetero vs. homo. Polym Chem 7:4263

    Article  CAS  Google Scholar 

  64. 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 5:2704

    Article  CAS  Google Scholar 

  65. Wu H, Yang B, Zhao Y, Wei Y, Wang Z, Wang X, Tao L (2016) Fluorescent protein-reactive polymers via one-pot combination of the Ugi reaction and RAFT polymerization. Polym Chem 7:4867

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael A. R. Meier.

Additional information

This article is part of the Topical Collection “Polymer Synthesis Based on Triple-bond Building Blocks”; edited by Ben Zhong Tang, Rongrong Hu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Llevot, A., Boukis, A.C., Oelmann, S. et al. An Update on Isocyanide-Based Multicomponent Reactions in Polymer Science. Top Curr Chem (Z) 375, 66 (2017). https://doi.org/10.1007/s41061-017-0153-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s41061-017-0153-4

Keywords

Navigation