Aryl fluorides, anyone, anyone ?

I thought this article might be a good choice for an article in comparison to the article I posted a while back, regarding the discovery and use of a fluorinase.  “Efficient Synthesis of Aryl Fluorides” by Beller et al, Angewandte Chemie, Int. Ed, Volume 48, p. 1-5, doi: 10.1002/anie.200905855.

To re-iterate what was mentioned before, fluorine is an important element to incorporate in some molecules.  It has been known to increase solubility, increase bioavailability (in the case of a drug) or increase metabolic stability.  I remember when there was a discussion of a fluorinated drug target that had to be synthesized, we would talk about a few options:  One of them being to buy the fluorinated starting material from someone else, who wanted to do a fluorination in-house ?  The methods to introduce fluorine were nasty.  There are a few examples where a fluorinated molecule has gotten to market and here they are:

The above-mentioned paper has a milder method of producing aryl fluorides.  In some cases, the yield reported has been as high as 80 % but this is always subject to the conditions being used and the substrate.

The procedure starts out by making a mixed Grignard reagent mediated by LiCl, renowned by Knochel.  Slow addition of the aryl bromide to the Grignard reagent in the presence of a fluorinating agent at O ºC yields the resultant fluoride.  I wonder how this would scale.

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