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Review
. 2019 Aug 13;9(43):25199-25215.
doi: 10.1039/c9ra04534a. eCollection 2019 Aug 8.

Methods for direct C(sp2)-H bonds azidation

Ying Liu  1 , Abdol Ghaffar Ebadi  2 , Leila Youseftabar-Miri  3 , Akbar Hassanpour  4 , Esmail Vessally  5
Affiliations
Review

Methods for direct C(sp2)-H bonds azidation

Ying Liu et al. RSC Adv. .

Abstract

Direct functionalization of C-H bonds has attracted great attention in recent years from the perspectives of atom and step economy. In this context, a variety of processes have been developed for the construction of synthetically and biologically important organic azides through the oxidative C-H bonds azidation. In this review, we have summarized recent progress in the direct azidation of C(sp2)-H bonds. The review is divided into three major sections: (i) direct azidation of aromatic C-H bonds; (ii) direct azidation of olefinic C-H bonds; and (iii) direct azidation of aldehydic C-H bonds. Mechanistic aspects of the reactions are considered and discussed in detail.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Selected examples of biologically active molecules bearing azido group.
Fig. 1
Fig. 1. Direct C(sp2)–H bonds azidation.
Scheme 2
Scheme 2. (a) Suna's synthesis of indolyl azide 2; (b) mechanistic explanation of the synthesis of indolyl azide 2.
Scheme 3
Scheme 3. . One-pot multistep synthesis of 1,4-disubstituted 1,2,3-triazoles 6.
Scheme 4
Scheme 4. Rh-catalyzed direct ortho-selective C–H azidation of arenes 7 with NaN3.
Scheme 5
Scheme 5. Cu(ii)-catalyzed direct azidation of azacalix[1]arene[3]pyridines 9 with NaN3.
Scheme 6
Scheme 6. Regioselective azidation of N-acylated 8-aminoquinolines 11 with NaN3.
Scheme 7
Scheme 7. The proposed mechanism for the formation of C5-azidated 8-aminoquinolines 12.
Scheme 8
Scheme 8. ortho-Selective azidation of anilines 11 with NaN3.
Scheme 9
Scheme 9. I2-mediated C3–H azidation of indoles 15.
Scheme 10
Scheme 10. Mechanistic pathway for the formation of 3-azido indoles 16.
Scheme 11
Scheme 11. Cu-catalyzed ortho-directed azidation of anilines 17 with TMSN3.
Scheme 12
Scheme 12. Plausible mechanism for Cu(i)-catalyzed azidation of anilines 17 with TMSN3.
Scheme 13
Scheme 13. Substituent-directed regioselective azidation of indoles 19 with TMSN3.
Scheme 14
Scheme 14. PhI(TFA)2-mediated azidation of anisoles 22 with TMSN3.
Scheme 15
Scheme 15. Metal-free regioselective C–H azidation of quinoline N-oxides 24 with TMSN3.
Scheme 16
Scheme 16. Proposed mechanism for azidation of quinoline N-oxides 24 with TMSN3.
Scheme 17
Scheme 17. Cu-catalyzed ortho-azidation of aromatic amines 26 with azido-benziodoxolone 27.
Scheme 18
Scheme 18. Proposed mechanism of the direct azidation of aromatic amines 26 with azido-benziodoxolone 27.
Scheme 19
Scheme 19. Wang's synthesis of azido-(hetero)arenes 30.
Scheme 20
Scheme 20. Selected examples of the Rh-catalyzed direct C–H bond azidation of aromatic rings 31 with Zhdankin's reagent reported by Chen and Wang.
Scheme 21
Scheme 21. Direct ortho-azidation of arenes 33 using benzotriazole sulphonyl azide as azidating agent.
Scheme 22
Scheme 22. Plausible reaction mechanism for the formation of ortho-azide arenes 34.
Scheme 23
Scheme 23. Synthesis of quinoxalines 36 through a tandem oxidative azidation/cyclization of N-arylenamines 35 with TMSN3.
Scheme 24
Scheme 24. Yu's synthesis of enamines 38.
Scheme 25
Scheme 25. Metal-catalyzed electrochemical diazidation of alkenes 39 with NaN3.
Scheme 26
Scheme 26. Plausible mechanism for the formation of 1,2-diazides 40.
Scheme 27
Scheme 27. CrO3-mediated azidation of aldehydes 41 with TMSN3.
Scheme 28
Scheme 28. Proposed mechanisms for the C–H bond azidation of aldehydes 41 with TMSN3.
Scheme 29
Scheme 29. NHC-catalyzed azidation of aldehydes 43 with TMSN3.
Scheme 30
Scheme 30. Direct conversion of aldehydes 45 to acyl azides 46 using NaN3 and PhI(OAc)2.
Scheme 31
Scheme 31. Ackerman's synthesis of acyl azides 48.
Scheme 32
Scheme 32. Visible light-mediated azidation of aldehydes 49 with NaN3.
Scheme 33
Scheme 33. Mechanism proposed to explain the synthesis of acyl azides 50.
Scheme 34
Scheme 34. Direct azidation of aliphatic aldehydes 51 with IN3.
None
Leila Youseftabar-Miri
None
Akbar Hassanpour
None
Esmail Vessally
See this image and copyright information in PMC

References

    1. Amblard F. Cho J. H. Schinazi R. F. Chem. Rev. 2009;109:4207–4220. doi: 10.1021/cr9001462. - DOI - PMC - PubMed
    2. Bräse S. Gil C. Knepper K. Zimmermann V. Angew. Chem., Int. Ed. 2005;44:5188–5240. doi: 10.1002/anie.200400657. - DOI - PubMed
    3. Cramer S. A. Jenkins D. M. J. Am. Chem. Soc. 2011;133:19342–19345. doi: 10.1021/ja2090965. - DOI - PubMed
    4. Huang D. Yan G. Adv. Synth. Catal. 2017;359:1600–1619. doi: 10.1002/adsc.201700103. - DOI
    5. Saeidian H. Sadighian H. Abdoli M. Sahandi M. J. Mol. Struct. 2017;1131:73–78. doi: 10.1016/j.molstruc.2016.11.027. - DOI
    1. Kamal A. Rao N. V. Laxman E. Tetrahedron Lett. 1997;38:6945–6948. doi: 10.1016/S0040-4039(97)01628-6. - DOI
    2. Warrier M. Lo M. K. Monbouquette H. Garcia-Garibay M. A. Photochem. Photobiol. Sci. 2004;3:859–863. doi: 10.1039/B404268A. - DOI - PubMed
    1. Fazio F. Wong C.-H. Tetrahedron Lett. 2003;44:9083–9085. doi: 10.1016/j.tetlet.2003.10.054. - DOI
    2. Xie S. Zhang Y. Ramström O. Yan M. Chem. Sci. 2016;7:713–718. doi: 10.1039/C5SC03510D. - DOI - PMC - PubMed
    3. Zhang F.-L. Zhu X. Chiba S. Org. Lett. 2015;17:3138–3141. doi: 10.1021/acs.orglett.5b01458. - DOI - PubMed
    1. Ramesha A. Bhat S. Chandrasekaran S. J. Org. Chem. 1995;60:7682–7683. doi: 10.1021/jo00128a048. - DOI
    2. Benati L. Bencivenni G. Leardini R. Nanni D. Minozzi M. Spagnolo P. Scialpi R. Zanardi G. Org. Lett. 2006;8:2499–2502. doi: 10.1021/ol0606637. - DOI - PubMed
    3. Lee J. H. Gupta S. Jeong W. Rhee Y. H. Park J. Angew. Chem., Int. Ed. 2012;51:10851–10855. doi: 10.1002/anie.201204483. - DOI - PubMed
    1. Lin T.-S. Prusoff W. H. J. Med. Chem. 1978;21:109–112. doi: 10.1021/jm00199a020. - DOI - PubMed
    2. Smith D. B. Kalayanov G. Sund C. Winqvist A. Maltseva T. Leveque V. J.-P. Rajyaguru S. Pogam S. L. Najera I. Benkestock K. J. Med. Chem. 2009;52:2971–2978. doi: 10.1021/jm801595c. - DOI - PubMed