Synthesis 2019; 51(24): 4582-4589
DOI: 10.1055/s-0039-1690200
paper
© Georg Thieme Verlag Stuttgart · New York

Easy Access to 2-Fluoro- and 2-Iodo-2H-azirines via the Halex Reaction

Anastasiya V. Agafonova
,
Ilia A. Smetanin
,
Nikolai V. Rostovskii
,
,
Mikhail S. Novikov
Saint Petersburg State University, Institute of Chemistry, 7/9 Universitetskaya nab., St. Petersburg, 199034, Russia   Email: m.novikov@spbu.ru
› Author Affiliations
We gratefully acknowledge the financial support of the Russian Science Foundation (Grant No. 17-13-01078).
Further Information

Publication History

Received: 18 July 2019

Accepted after revision: 19 August 2019

Publication Date:
05 September 2019 (online)

Abstract

A simple gram-scale method for the preparation of esters and dialkylamides of 2-(fluoro/iodo)-2H-azirine-2-carboxylic acids via the halogen exchange (Halex) reaction of 2-bromo-substituted analogues is reported. The method operates with inexpensive and safe reagents­, Bu4NF and potassium iodide, providing high product yields. Alternatively, 2-fluoro-2H-azirine-2-carboxylates can be prepared from 2-iodo- and 2-chloro-analogues. The latter compounds can be obtained in practically quantitative yield by treating the 2-iodo- and 2-bromo-2H-azirine-2-carboxylic esters with Bu4NCl.

Supporting Information

 
  • References

  • 1 Groult H, Leroux F, Tressaud A. Modern Synthesis Processes and Reactivity of Fluorinated Compounds, 1st ed. Elsevier; Amsterdam: 2016
  • 2 Dohi T, Kita Y. In Iodine Chemistry and Applications . Kaiho T. Wiley; Hoboken: 2014: 303
  • 3 Berger R, Resnati G, Metrangolo P, Weberd E, Hulliger J. Chem. Soc. Rev. 2011; 40: 3496
    • 4a Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H. Chem. Rev. 2016; 116: 422
    • 4b Barnes-Seeman D, Beck J, Springer C. Curr. Top. Med. Chem. 2014; 14: 855
  • 5 Fluorine and Health: Molecular Imaging, Biomedical Materials and Pharmaceuticals. Tressaud A, Haufe G. Elsevier; Amsterdam: 2008
  • 6 Ametamey SM, Honer M, Schubiger PA. Chem. Rev. 2008; 108: 1501
    • 7a Chacko AM, Divgi CR. Med. Chem. 2011; 7: 395
    • 7b Koehler L, Gagnon K, McQuarrie S, Wuest F. Molecules 2010; 15: 2686

      For recent reviews on 2H-azirine chemistry, see:
    • 8a Khlebnikov AF, Novikov MS, Rostovskii NV. Tetrahedron 2019; 75: 2555
    • 8b Zhou H, Shen M.-H, Xu H.-D. Synlett 2016; 27: 2171
    • 8c Khlebnikov AF, Novikov MS. Top. Heterocycl. Chem. 2015; 41: 143
    • 8d Huang C.-Y, Doyle AG. Chem. Rev. 2014; 114: 8153
    • 8e Khlebnikov AF, Novikov MS. Tetrahedron 2013; 69: 3363
  • 9 Smetanin IA, Novikov MS, Rostovskii NV, Khlebnikov AF, Starova GL, Yufit DS. Tetrahedron 2015; 71: 4616
  • 10 Rostovskii NV, Smetanin IA, Agafonova AV, Sakharov PA, Ruvinskaya JO, Khlebnikov AF, Novikov MS. Org. Biomol. Chem. 2018; 16: 3248
    • 11a Alonso-Cruz CR, Kennedy AR, Rodríguez MS, Suárez E. J. Org. Chem. 2008; 73: 4116
    • 11b Alonso-Cruz CR, Kennedy AR, Rodríguez MS, Suárez E. Tetrahedron Lett. 2007; 48: 7207
  • 12 Pinho e Melo TM. V. D, Lopes CS. J, Cardoso AL, Rocha Gonsalves AM. d'A. Tetrahedron 2001; 57: 6203
  • 13 Zhang Y, Zhao X, Zhuang C, Wang S, Zhang-Negrerie D, Du Y. Adv. Synth. Catal. 2018; 360: 2107
    • 14a Rostovskii NV, Agafonova AV, Smetanin IA, Novikov MS, Ruvinskaya JO, Starova GL. Khlebnikov A. F. Synthesis 2017; 49: 4478
    • 14b Agafonova AV, Smetanin IA, Rostovskii NV, Khlebnikov AF, Novikov MS. Chem. Heterocycl. Compd. 2017; 53: 1068
  • 15 Okamoto K, Nanya A, Eguchi A, Ohe K. Angew. Chem. Int. Ed. 2018; 57: 1039
    • 16a Liang T, Neumann CN, Ritter T. Angew. Chem. Int. Ed. 2013; 52: 8214
    • 16b Langlois B, Gilbert L, Forat G. Ind. Chem. Libr. 1996; 8: 244
  • 17 Worrell BT, Hein JE, Fokin VV. Angew. Chem. Int. Ed. 2012; 51: 11791
  • 18 Allen LJ, Muhuhi JM, Bland DC, Merzel R, Sanford MS. J. Org. Chem. 2014; 79: 5827
  • 19 Agafonova AV, Rostovskii NV, Smetanin IA, Starova GL, Khlebnikov AF, Novikov MS. J. Org. Chem. 2018; 83: 13473
  • 20 Bounioux C, Bar-Hen A, Yerushalmi-Rozen R. Chem. Commun. 2015; 51: 6343
    • 21a Nishiwaki T, Kitamura T, Nakano A. Tetrahedron 1970; 55: 453
    • 21b Clark AD, Janowski WK, Prager RH. Tetrahedron 1999; 55: 3637
  • 22 Golubev AA, Smetanin IA, Agafonova AV, Rostovskii NV, Khlebnikov AF, Starova GL, Novikov MS. Org. Biomol. Chem. 2019; 17: 6821
  • 23 Smetanin IA, Novikov MS, Agafonova AV, Rostovskii NV, Khlebnikov AF, Kudryavtsev IV, Terpilowski MA, Serebriakova MK, Trulioff AS, Goncharov NV. Org. Biomol. Chem. 2016; 14: 4479