Download PDF
Synthesis 2021; 53(21): 4068-4074
DOI: 10.1055/a-1534-0624
paper

Cobalt-Catalyzed Preparation of N-Heterocyclic Organozinc Reagents from the Corresponding Heteroaryl Chlorides

Alexander Kremsmair
a   Department Chemie & Biochemie, Ludwig Maximilians-Universität München, Butenandtstrasse 5–13, Haus F, 81377 München, Germany
,
Simon Graßl
a   Department Chemie & Biochemie, Ludwig Maximilians-Universität München, Butenandtstrasse 5–13, Haus F, 81377 München, Germany
,
Christoph J. B. Seifert
a   Department Chemie & Biochemie, Ludwig Maximilians-Universität München, Butenandtstrasse 5–13, Haus F, 81377 München, Germany
,
Edouard Godineau
b   Forschung & Entwicklung Stein, Syngenta Crop Protection AG, Schaffhauserstrasse 101, 4332 Stein, Switzerland
,
Paul Knochel  ∗
a   Department Chemie & Biochemie, Ludwig Maximilians-Universität München, Butenandtstrasse 5–13, Haus F, 81377 München, Germany
› Author AffiliationsWe thank the Ludwig-Maximilians University Munich and Syngenta AG (Stein, Switzerland) for financial support.
› Further Information
    Permissions and Reprints All articles of this category


Abstract

Various substituted and unsubstituted N-heteroaryl chlorides have been converted into their corresponding organozinc species using zinc dust in the presence of zinc pivalate and 10% CoCl2 in benzonitrile at 25 °C. The resulting heteroarylzinc reagents were obtained in 43–98% yield within 9–48 h and reacted with a broad range of electrophiles, leading to the functionalized heteroarenes.

Key words

N-heterocycles - organozinc reagents - cobalt catalysis - pyrimidine - pyridazine

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1534-0624.
  • Supporting Information


Publication History

Received: 08 June 2021

Accepted after revision: 22 June 2021

Accepted Manuscript online:
22 June 2021

Article published online:
29 July 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

    • 1a Dinesh K, Kumar JS. Curr. Med. Chem. 2016; 23: 4338
      CrossrefPubMed
    • 1b Taylor AP, Robinson RP, Fobian YM, Blakemore DC, Jones LH, Fadeyi O. Org. Biomol. Chem. 2016; 14: 6611
      CrossrefPubMed
    • 1c Martins P, Jesus J, Santos S, Raposo LR, Roma-Rodrigues C, Baptista PV, Fernandes AR. Molecules 2015; 20: 16852
      CrossrefPubMed
    • 1d Chen D, Su S.-J, Cao Y. J. Mater. Chem. C 2014; 2: 9565
      Crossref
    • 1e Meanwell NA. J. Med. Chem. 2011; 54: 2529
      CrossrefPubMed
    • 1f Baxter PN. W, Dali-Youcef R. J. Org. Chem. 2005; 70: 4935
      CrossrefPubMed
    • 1g Li X.-Q, Andersson TB, Ahlstrøm M, Weidolf L. Drug Metab. Dispos. 2004; 32: 821
      CrossrefPubMed
    • 1h Anttila SA. K, Leinonen EV. J. CNS Drug Rev. 2001; 7: 249
      CrossrefPubMed
    • 2a Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
      CrossrefPubMed
    • 2b Taylor RD, MacCoss M, Lawson AD. G. J. Med. Chem. 2014; 57: 5845
      CrossrefPubMed
    • 4a Benischke AD, Le Corre G, Knochel P. Chem. Eur. J. 2017; 23: 778
      CrossrefPubMed
    • 4b Boudet N, Sase S, Sinha P, Liu C.-Y, Krasovskiy A, Knochel P. J. Am. Chem. Soc. 2007; 129: 12358
      CrossrefPubMed
    • 4c Piller FM, Metzger A, Schade MA, Haag BA, Gavryushin A, Knochel P. Chem. Eur. J. 2009; 15: 7192
      CrossrefPubMed
    • 4d Metzger A, Argyo C, Knochel P. Synthesis 2010; 882
    • 4e Metzger A, Schade MA, Knochel P. Org. Lett. 2008; 10: 1107
      CrossrefPubMed
    • 4f Krasovskiy A, Malakhov V, Gavryushin A, Knochel P. Angew. Chem. Int. Ed. 2006; 45: 6040
      CrossrefPubMed
    • 4g Zhu L, Wehmeyer RM, Rieke RD. J. Org. Chem. 1991; 56: 1445
      Crossref
    • 4h Rieke RD. Science 1989; 246: 1260
      CrossrefPubMed
    • 4i Burns TP, Rieke RD. J. Org. Chem. 1983; 48: 4141
      Crossref
  • 6 Knochel P. Handbook of Functionalized Organometallics, Vol. 1 and 2. Wiley-VCH; Weinheim: 2005
    CrossrefGoogle Scholar
    • 7a Kazmierski I, Gosmini C, Paris J.-M, Périchon J. Synlett 2006; 881
    • 7b Gosmini C, Amatore M, Claudel S, Périchon J. Synlett 2005; 2171
    • 7c Kazmierski I, Gosmini C, Paris J.-M, Périchon J. Tetrahedron Lett. 2003; 44: 6417
      Crossref
    • 7d Fillon H, Gosmini C, Périchon J. J. Am. Chem. Soc. 2003; 125: 3867
      CrossrefPubMed
  • 8 M.-Y Jin, Yoshikai N. J. Org. Chem. 2011; 76: 1972
    CrossrefPubMed
  • 9 Piller FM, Appukkuttan P, Gavryushin A, Helm M, Knochel P. Angew. Chem. Int. Ed. 2008; 47: 6802
    CrossrefPubMed
    • 10a Polleux L, Labbé E, Buriez O, Périchon J. Chem. Eur. J. 2005; 11: 4678
      CrossrefPubMed
    • 10b Seka S, Buriez O, Périchon J. Chem. Eur. J. 2003; 9: 3597
      CrossrefPubMed
  • 11 For a more detailed screening, see the Supporting Information.
  • 12 Farina V. e-EROS: Encyclopedia for Reagents in Organic Synthesis 2002; DOI: 10.1002/047084289X.rn00126.
    Crossref
    • 13a Balkenhohl M, Jangra H, Lenz T, Ebeling M, Zipse H, Karaghiosoff K, Knochel P. Angew. Chem. Int. Ed. 2019; 58: 9244
      CrossrefPubMed
    • 13b Abou-Hamdan H, Désaubry L. J. Org. Chem. 2018; 83: 2954
      CrossrefPubMed
    • 13c Asif M. Curr. Med. Chem. 2012; 19: 2984
      CrossrefPubMed
    • 13d Perio A, Chambon JP, Calassi R, Heaulme M, Biziere K. J. Pharmacol. Exp. Ther. 1986; 239: 542
      PubMed
  • 14 Vlad G, Horvath IT. J. Org. Chem. 2002; 67: 6550
    CrossrefPubMed
  • 15 Zheng X, Song B, Xu B. Eur. J. Org. Chem. 2010; 4376
  • 16 Metzger A, Melzig L, Despotopoulou C, Knochel P. Org. Lett. 2009; 11: 4228
    CrossrefPubMed
  • 17 Melzig L, Metzger A, Knochel P. Chem. Eur. J. 2011; 17: 2948
    CrossrefPubMed
  • 18 Lin X, Hou C, Li H, Weng Z. Chem. Eur. J. 2016; 22: 2075
    CrossrefPubMed