Iodotoluene difluoride

Chemfiles Volume 5 Article 1

The importance of selectively fluorinating compounds in medicinal chemistry, biology, and organic synthesis is well appreciated and provides a major impetus to the discovery of new fluorinating agents that can operate according to an efficient, safe, and mild criteria. Elemental fluorine, and many electrophilic fluorinating agents have been used in synthesis; however, most of these fluorinating agents are highly aggressive, unstable, and require special equipment and care for safe handling. By contrast, iodotoluene difluoride (tol-IF2) is easy to handle, and is less toxic than many fluorinating agents. Sigma-Aldrich is pleased to introduce this new reagent for oxidation and fluorination.

A new methodology for the synthesis of fluorinated cyclic ethers was recently reported, which utilized tol-IF2 to achieve a fluorinative ring-expansion of four-, five-, and six-membered rings, an example of which is illustrated in Scheme 1.1


 

Scheme 1.

Selective monofluorination of b-ketoesters, b-ketoamides, and diketones takes place without requirement of HF-amine complexes under mild conditions (Scheme 2). The formation of difluoro products were not detected in these reactions.2


 

Scheme 2.

When one equivalent of tol-IF2 is reacted with phenylsulfanylated esters, the a-fluoro sulfide results through a Fluoro-Pummerer reaction. In contrast to diethylaminosulfur trifluoride, two equivalents produces the a,a-difluoro sulfide, and three equivalents of tol-IF2 produces the a,a-difluoro sulfoxide. This behavior was exploited in the one pot synthesis of a 3-fluoro-2(5H)-furanone (Scheme 3).3


 

Scheme 3.

Treatment of phenylsulfanylated lactams with one equivalent of tol-IF2 results in the unsaturated heterocycle in moderate to good yields. When two equivalents of the reagent were used, the lactams were fluorinated in the a - and b-positions resulting in the diastereomeric difluoride (Scheme 4).4


 

Scheme 4.

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References

  1. Inagaki, T. et al. Tetrahedron Lett. 2003, 44, 4117.
  2. Yoshida, M. et al. ARKIVOC 2003, (vi) 36.
  3. Motherwell, W. B. et al. J. Chem. Soc. Perkin Trans. 1 2002, 2809.
  4. Greaney, M. F. et al. Tetrahedron Lett. 2001, 42, 8523.

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