Selectfluor™

Chemfiles Volume 5 Article 1

Selectfluor™ (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), or F-TEDA) is a user-friendly, mild, air- and moisture-stable, non-volatile reagent for electrophilic fluorination. Selectfluor™ is capable of introducing fluorine into organic substrates in one step, with a remarkably broad scope of reactivity.1 Many of these reactions display excellent regioselectivity.

Recently, the synthesis of a potent and noncytotoxic nucleoside inhibitor of Hepatitis C virus RNA replication was accomplished using Selectfluor™ (Scheme 10). This ribonucleoside shows a significantly improved enzymatic stability profile compared to the parent 2’-C-methyladenosine.2


Scheme 10


Allylic fluorides can be prepared via a sequential cross-metathesis/ electrophilic fluorodesilylation route (Scheme 11). This route avoids the formation of by-products that result from allylic transposition, which is observed when nucleophilic displacement or ring-opening reaction with DAST is attempted.3


Scheme 11


Selectfluor™ is also capable of effecting other transformations. One recent example uses Selectfluor™ as an alternative to silver or mercury salts in the rearrangement of iodides to alcohols (Scheme 12). In the case of an iodochloride (X=Cl), substitution only occurs at the iodide and not the chloride.4


Scheme 12


Selectfluor™ has even been employed as an efficient catalyst for the preparation of b-hydroxy thiocyanates using ammonium thiocyanate under mild conditions (Scheme 13). In all cases, the reactions proceed rapidly at room temperature without the formation of the corresponding thiiranes, which are generally the exclusive products when Lewis acids such as Sc(OTf)3 and InCl3 are used.5


Scheme 13


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References

  1. For a review of recent highlights: Singh, R. P. and Shreeve, J. M. Acc. Chem. Res. 2004, 37, 31.
  2. Eldrup, A. B. et al. J. Med. Chem. 2004, 47, 5284.
  3. Thibaudeau, S. and Gouverneur, V. Org. Lett. 2003, 5, 4891.
  4. Krow, G. R. et al. Org. Lett. 2004, 6, 1669.
  5. Yadav, J. S. et al. Tetrahedron Lett. 2004, 45, 1291.

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