PDF herunterladen
Open Access
CC BY 4.0 · SynOpen 2025; 09(03): 161-173
DOI: 10.1055/s-0040-1720167
graphical review

Vicarious Nucleophilic Substitution of Hydrogen: An Excellent Tool for Porphyrin Functionalization

Authors

  • Stanisław Ostrowski∗

  • Agnieszka Mikus

Weitere Informationen
  Lizenzen und Reprints Alle Artikel dieser Rubrik


Graphical Abstract

Preview

Erratum zu diesem Artikel:

Erratum: Vicarious Nucleophilic Substitution of Hydrogen: An Excellent Tool for Porphyrin FunctionalizationSynOpen 2025; 09(03): e1-e1
DOI: 10.1055/s-0042-1752049

Abstract

This graphical review addresses the functionalization of porphyrin derivatives. Simple porphyrin modifications (by introduction of an electron-withdrawing group, e.g., NO2, CO-R, into parent porphyrin system or complexation of the core ring with a highly electronegative unit, e.g., SnCl2) afford valuable intermediates in this area of chemistry. They are useful materials for further transformations, as such modifications increase the electrophilic character, thus allowing a broad spectrum of subsequent reactions. Such reactions are often utilized in the first steps of designed syntheses, leading to attractive and useful target porphyrin-like compounds featuring a high degree of complexity. In this regard, the vicarious nucleophilic substitution of hydrogen (VNS) has become one of the methods of choice. Specifically, it involves addition of a carbanion, bearing a leaving group X at the reactive center, to an electrophilic arene at positions occupied by hydrogen to form a σH-adduct. Subsequent base-induced β-elimination of HX then gives the product of nucleophilic substitution of hydrogen. This approach enables the synthesis of numerous porphyrins bearing up to ten new substituents on the meso-aryl rings (attached to positions 5, 10, 15, and 20) and up to six substituents at the β-positions. This graphical review is the first comprehensive account concerning VNS reaction in porphyrins.

Key words

porphyrins - vicarious nucleophilic substitution of hydrogen - carbanions - complexes - nitro group - meso-aryl- and β-functionalization


Publikationsverlauf

Eingereicht: 20. November 2024

Angenommen nach Revision: 11. Februar 2025

Artikel online veröffentlicht:
29. Juli 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

    • 1a Bunnett JF, Zahler RE. Chem. Rev. 1951; 49: 273
      Suche in Google Scholar
    • 1b Miller J. Aromatic Nucleophilic Substitution. Elsevier; Amsterdamm: 1968
      Suche in Google Scholar
    • 1c Buncel E, Crampton MR, Strauss MJ, Terrier F. Electron-Deficient Aromatic- and Heteroaromatic-Base Interactions: The Chemistry of Anionic Sigma Complexes. Elsevier; Amsterdam: 1984
      Suche in Google Scholar
    • 1d Terrier F. Nucleophilic Aromatic Displacement: The Influence of the Nitro Group. VCH Publishers; Weinheim: 1991
      Suche in Google Scholar
    • 2a Mąkosza M, Winiarski J. Acc. Chem. Res. 1987; 20: 282
      Suche in Google Scholar
    • 2b Chupakhin ON, Charushin VN, van der Plas HC. Nucleophilic Aromatic Substitution of Hydrogen . Academic Press; San Diego: 1994
      Suche in Google Scholar
    • 2c Mąkosza M. Russ. Chem. Bull. 1996; 45: 491
      Suche in Google Scholar
    • 2d Josephitis CM, Nguyen HM. H, McNally A. Chem Rev. 2023; 123: 7655
      Suche in Google Scholar
    • 3a Mąkosza M, Wojciechowski K. Chem. Rev. 2004; 104: 2631
      Suche in Google Scholar
    • 3b Mąkosza M. Chem. Soc. Rev. 2010; 39: 2855
      Suche in Google Scholar
    • 3c Mąkosza M. Chem. Eur. J. 2020; 26: 15346
      Suche in Google Scholar
    • 3d Carey FA, Sundberg RJ. Advanced Organic Chemistry, Parts A and B, 5th ed. Springer; New York: 2007
      Suche in Google Scholar
    • 3e March J, Smith MB. March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6th ed. John Wiley & Sons; Hoboken: 2007
      Suche in Google Scholar
    • 4a Tyrała A, Mąkosza M. Synthesis 1994; 264
    • 4b Mąkosza M, Danikiewicz W, Wojciechowski K. Liebigs Ann. Chem. 1988; 203
    • 4c Lerman L, Weinstock-Rosin M, Nudelman A. Synthesis 2004; 3043
    • 4d Wojciechowski K, Mąkosza M. Synthesis 1986; 651
    • 4e Mąkosza M, Barbasiewicz M, Moskalev N. Tetrahedron 2004; 60: 347
      Suche in Google Scholar
    • 4f Kraus GA, Selvakumar N. Synlett 1998; 845
    • 4g Kraus GA, Selvakumar N. J. Org. Chem. 1998; 63: 9846
      Suche in Google Scholar
    • 4h Wróbel Z. Tetrahedron 1998; 54: 2607
      Suche in Google Scholar
    • 4i Murphy RA. Jr, Cava MP. Tetrahedron Lett. 1984; 25: 803
      Suche in Google Scholar
    • 4j van der Plas HC. Acc. Chem. Res. 1978; 11: 462
      Suche in Google Scholar
    • 4k van der Plas HC. Tetrahedron 1985; 41: 237
      Suche in Google Scholar
    • 4l van der Plas HC, Woźniak M. Croat. Chem. Acta 1986; 59: 33
      Suche in Google Scholar
    • 4m Mąkosza M, Białecki M. J. Org. Chem. 1992; 57: 4784
      Suche in Google Scholar
    • 4n Mąkosza M, Białecki M. J. Org. Chem. 1998; 63: 4878
      Suche in Google Scholar
    • 4o Szpakiewicz B, Grzegorzek M. Zh. Org. Khim. 2004; 40: 869
      Suche in Google Scholar
    • 4p Mąkosza M, Sienkiewicz K. J. Org. Chem. 1990; 55: 4979
      Suche in Google Scholar
    • 4q Mąkosza M, Sienkiewicz K. J. Org. Chem. 1998; 63: 4199
      Suche in Google Scholar
    • 4r Dainter RS, Suschitzky H, Wakefield BJ, Hughes N, Nelson AJ. Tetrahedron Lett. 1984; 25: 5693
      Suche in Google Scholar
    • 4s Suwiński J, Świerczek K. Tetrahedron 2001; 57: 1639
      Suche in Google Scholar
    • 4t Błażej S, Kwast A, Mąkosza M. Tetrahedron Lett. 2004; 45: 5413
      Suche in Google Scholar
    • 5a Goliński J, Mąkosza M. Tetrahedron Lett. 1978; 19: 3495
      Suche in Google Scholar
    • 5b Angeli A, Angelico F. Gazz. Chim. Ital. 1901; 31: 27
      Suche in Google Scholar
    • 5c Price CC, Voong S.-T. Org. Synth. 1948; 28: 80
      Suche in Google Scholar
    • 5d Price CC, Voong S.-T. Org. Synth. Coll. Vol. 3 1955; 664
    • 6a Malinovskii VL, Vodzinskii SV, Zhilina ZI, Andronati SA, Mazepa AV. Zh. Org. Khim. 1996; 32: 119
      Suche in Google Scholar
    • 6b Krattinger B, Nurco DJ, Smith KM. Chem. Commun. 1998; 757
    • 6c Richeter S, Jeandon C, Ruppert R, Callot HJ. Tetrahedron Lett. 2001; 42: 2103
      Suche in Google Scholar
    • 6d Ostrowski S, Shim YK. Bull. Korean Chem. Soc. 2001; 22: 9
      Suche in Google Scholar
    • 7a Ostrowski S, Mikus A, Shim YK, Lee J.-C, Seo E.-Y, Lee K.-I, Olejnik M. Heterocycles 2002; 57: 1615
      Suche in Google Scholar
    • 7b Mąkosza M, Paszewski M. Polish J. Chem. 2005; 79: 163
      Suche in Google Scholar
    • 7c Ostrowski S. A.Y.: Basic Sci. & Eng. 2003; 12: 523 ; Chem. Abstr. 2005, 142, 347339p
      Suche in Google Scholar
    • 7d Ostrowski S, Mikus A. Mol. Divers. 2003; 6: 315
      Suche in Google Scholar
    • 7e Ostrowski S, Mikus A. Ann. Polish Chem. Soc. 2003; 2: 62
      Suche in Google Scholar
    • 7f Ostrowski S, Mikus A. Molecules-Molbank 2003; M329
    • 7g Ostrowski S, Mikus A. Heterocycles 2005; 65: 2339
      Suche in Google Scholar
    • 7h Wyrębek P, Mikus A, Ostrowski S. Jordan J. Chem. 2006; 1: 39
      Suche in Google Scholar
    • 7i Ostrowski S, Urbańska N, Mikus A. Tetrahedron Lett. 2003; 44: 4373
      Suche in Google Scholar
    • 7j Ostrowski S, Mikus A, Łopuszyńska B. Tetrahedron 2004; 60: 11951
      Suche in Google Scholar
    • 7k Ostrowski S, Mikus A, Borkowska A. Proceedings of ’The Seventh International Electronic Conference on Synthetic Organic Chemistry’. Seijas JA, Ji D.-C, Lin S.-K. Basel,; 2003. [A-002], ISBN 3-906980-13-8 (CD-ROM edition)
      Suche in Google Scholar
    • 7l Ostrowski S, Mikus A. Proceedings of ’The Seventh International Electronic Conference on Synthetic Organic Chemistry’. Seijas JA, Ji D.-C, Lin S.-K. Basel,; 2003. [A-003], ISBN 3-906980-13-8 (CD-ROM edition)
      Suche in Google Scholar
    • 9a Ostrysz S, Mikus A, Ostrowski S. Int. J. Sci. 2014; 3: 99
      Suche in Google Scholar
    • 9b Ostrowski S, Raczko AM. Helv. Chim. Acta 2005; 88: 974
      Suche in Google Scholar
    • 9c Mikus A, Ostrowski S. J. Porphyrins Phthalocyanines 2024; 28: 647
      Suche in Google Scholar
    • 9d Eddahmi M, Moura NM. M, Ramos CI. V, Bouissane L, Faustino MA. F, Cavaleiro JA. S, Rakib EM, Neves MG. P. M. S. Arabian J. Chem. 2020; 13: 5849
      Suche in Google Scholar
    • 10a Mikus A, Rosa M, Ostrowski S. Molecules 2019; 24: 838
      Suche in Google Scholar
    • 10b Mikus A, Ostrowski S. Struct. Chem. 2022; 33: 1251
      Suche in Google Scholar
    • 10c Mikus A, Ostrowski S. Struct. Chem. 2022; 33: 2261
      Suche in Google Scholar
    • 10d Mikus A. Mendeleev Commun. 2024; 34: 70
      Suche in Google Scholar
    • 10e Rosa M, Ostrowski S. ChemistrySelect 2022; 7: e202200290
      Suche in Google Scholar
    • 10f Mikus A, Ostrysz S, Ostrowski S. Eur. J. Org. Chem. 2025; DOI:
    • 11a Ostrowski S, Grzyb S. Tetrahedron Lett. 2012; 53: 6355
      Suche in Google Scholar
    • 11b Richeter S, Hadj-Aïssa A, Taffin C, van der Lee A, Leclercq D. Chem. Commun. 2007; 2148
    • 11c Lefebvre J.-F, Leclercq D, Gisselbrecht J.-P, Richeter S. Eur. J. Org. Chem. 2010; 1912
    • 11d Ostrowski S, Grzyb S, Godlewski B. Curr. Org. Chem. 2024; 28: 1542
      Suche in Google Scholar
    • 11e Ostrysz S, Mikus A, Ostrowski S. Org. Commun. 2025; 18: 100
      Suche in Google Scholar