Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb 9;13(12):3409-3415.
doi: 10.1039/d2sc00294a. eCollection 2022 Mar 24.

Chemo- and regio-divergent access to fluorinated 1-alkyl and 1-acyl triazenes from alkynyl triazenes

Jin-Fay Tan  1 , Carl Thomas Bormann  2 , Kay Severin  2 , Nicolai Cramer  1
Affiliations

Chemo- and regio-divergent access to fluorinated 1-alkyl and 1-acyl triazenes from alkynyl triazenes

Jin-Fay Tan et al. Chem Sci. .

Abstract

The 1,1,2,2-tetrafluoroethylene unit is prevalent in bioactive molecules and functional materials. Despite being in principle a straightforward strategy to access this motif, the direct tetrafluorination of alkynes involves very hazardous or inconvenient reagents. Therefore, safer and convenient alternatives are sought after. We developed a mild and operationally simple perfluorination method converting 1-alkynyl triazenes into 1,1,2,2-tetrafluoro alkyl triazenes, employing cheap and readily accessible reagents. Moreover, a judicious tuning of the reaction conditions enables access to α-difluoro triazenyl ketones. Complementary, electrophilic fluorination of alkynyl triazenes gives rise to the regioisomeric α-difluoro acyl triazenes. These three chemo- and regio-divergent protocols enable access to elusive fluorinated 1-alkyl and 1-acyl triazenes, thus expanding the chemical space for these unusual entities. Furthermore, several reaction intermediates and side products revealed insights on the reaction pathways that may be useful for further fluorination chemistry of alkynes.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1. Selected examples of functional molecules containing 1,1,2,2-tetrafluoroethylene and difluoromethylene linkages.
Scheme 1
Scheme 1. Fluorinative transformations of alkynes and 1-alkynyl triazenes.
Scheme 2
Scheme 2. Functionalization of acyl triazene 6a.
Scheme 3
Scheme 3. Reactivity and mechanistic studies.
Scheme 4
Scheme 4. Suggested pathway map of the formation of fluorinated products and intermediates.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Ni C. Hu J. Chem. Soc. Rev. 2016;45:5441–5454. doi: 10.1039/C6CS00351F. - DOI - PubMed
    2. Hagmann W. K. J. Med. Chem. 2008;51:4359–4369. doi: 10.1021/jm800219f. - DOI - PubMed
    3. O'Hagan D. Chem. Soc. Rev. 2008;37:308–319. doi: 10.1039/B711844A. - DOI - PubMed
    4. Purser S. Moore P. R. Swallow S. Gouverneur V. Chem. Soc. Rev. 2008;37:320–330. doi: 10.1039/B610213C. - DOI - PubMed
    1. Fluorine in Pharmaceutical and Medicinal Chemistry: From Biophysical Aspects to Clinical Applications, ed. V. Gouverneur and K. Müller, Imperial College Press, London, UK, 2012, vol. 6, pp. 1–558
    2. Fluorine in Medicinal Chemistry and Chemical Biology, ed. I. Ojima, Wiley-Blackwell, Chichester, UK, 2009, pp. 1–640
    3. Müller K. Faeh C. Diederich F. Science. 2007;317:1881–1886. doi: 10.1126/science.1131943. - DOI - PubMed
    4. Jeschke P. ChemBioChem. 2004;5:570–589. doi: 10.1002/cbic.200300833. - DOI - PubMed
    5. Harper D. B. O'Hagan D. Nat. Prod. Rep. 1994;11:123–133. doi: 10.1039/NP9941100123. - DOI - PubMed
    1. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, ed. P. Kirsch, Wiley-VCH, Weinheim, 2006, pp. 1–320
    2. Fluorine in Organic Chemistry, ed. R. D. Chambers, Blackwell Publishing Ltd, Oxford, 2004, pp. 1–406
    1. Fujiwara T. O'Hagan D. J. Fluorine Chem. 2014;167:16–29. doi: 10.1016/j.jfluchem.2014.06.014. - DOI
    2. Giornal F. Pazenok S. Rodefeld L. Lui N. Vors J. P. Leroux F. R. J. Fluorine Chem. 2013;152:2–11. doi: 10.1016/j.jfluchem.2012.11.008. - DOI
    3. Boyer J. Arnoult E. Médebielle M. Guillemont J. Unge J. Jochmans D. J. Med. Chem. 2011;54:7974–7985. doi: 10.1021/jm200766b. - DOI - PubMed
    4. Jeschke P. Pest Manage. Sci. 2010;66:10–27. doi: 10.1002/ps.1829. - DOI - PubMed
    5. Christy M. E. Colton C. D. Mackay M. Staas W. H. Wong J. B. Engelhardt E. L. Torchiana M. L. Stone C. A. J. Med. Chem. 1977;20:421–430. doi: 10.1021/jm00213a021. - DOI - PubMed
    1. Jia R. Wang X. Hu J. Tetrahedron Lett. 2021;75:153182. doi: 10.1016/j.tetlet.2021.153182. - DOI
    2. Miele M. Pace V. Aust. J. Chem. 2021;74:623–625. doi: 10.1071/CH21045. - DOI
    3. Rong J. Ni C. Hu J. Asian J. Org. Chem. 2017;6:139–152. doi: 10.1002/ajoc.201600509. - DOI
    4. Ni C. Hu J. Chem. Soc. Rev. 2016;45:5441–5454. doi: 10.1039/C6CS00351F. - DOI - PubMed
    5. Belhomme M.-C. Besset T. Poisson T. Pannecouke X. Chem.–Eur. J. 2015;21:12836–12865. doi: 10.1002/chem.201501475. - DOI - PubMed
    6. Liang T. Neumann C. N. Ritter T. Angew. Chem., Int. Ed. 2013;52:8214–8264. doi: 10.1002/anie.201206566. - DOI - PubMed