Thoughtful polarity arguments

Last December, Dr. Steve Ritter of the Chemical and Engineering News asked me to comment on a paper from the lab of Prof. Petr Beier of the Czech Academy of Sciences. I gladly did (http://cen.acs.org/articles/94/web/2016/12/Fluorinated-azides-click-make-triazoles.html?type=paidArticleContent) and I just want to share my thoughts with you in the event you have not seen the Beier paper.

Every now and then we need a reminder of a rather straightforward kind: if we have trouble making a bond, just reverse the darn polarity of reagents! It is remarkable how infrequently this way of thinking pops into our heads, and I am judging from years of experience. Indeed, unless you are into radical reactions, there are always at least two ways to make a bond by a polar mechanism. In the example described by the Prague team in the Angewandte article, the curious CF3N3 molecule was the target. Attempts to forge the C-N bond using CF3I as the electrophile led nowhere, whereas using the fluoroalkyl portion as the nucleophile delivered CF3N3 and other uncommon azides without a glitch. I know this stuff ultimately relates to the well-known umpolung arguments, but those of us who are in the business of making bonds would still rather search “closer to the lamp post” than reverse reagent polarity. I am convinced that there are a lot of other previously “unmakable” molecules that might be made using this simple logic. We should keep this in mind.

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http://onlinelibrary.wiley.com/doi/10.1002/ange.201609715/abstract

2 thoughts on “Thoughtful polarity arguments

  1. I was forced into “Umpolung by radical” when making ArCF2CO2H building blocks from BrCF2CO2Et. As expected, that bromide is completely lazy towards nucleophiles (related ICF3 has net positive charge on iodine and even forms complexes with DABCO) but when combined with aryl iodide and activated copper powder in DMSO, it does Wurtz cross-coupling under mild conditions (60C) with pretty good isolated yields.

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