It seems quite a few of my readers were interested with Palau’chlor. I still find readers go to this post and why not. Chlorine is an important substituent to introduce into a molecule, no question there. Although somewhat unrelated, it was in the news a short while ago, that artificial sweeteners wreak havoc with gut bacteria causing glucose intolerance. It was published in Nature 514, 181–186 (09 October 2014) doi:10.1038/nature13793 by Eran Elinav et al. You can check it out if this is news to you.
Well, what can I do with saccharin ? Make a trifluoromethylthiolating agent with it. A shelf-stable reagent like Palau’chlor. Consider the following paper in Angewandte Chemie, “N-Trifluoromethylthiosaccharin: An Easily Accessible, Shelf-Stable, Broadly Applicable Trifluoromethylthiolating Reagent” by Chunfa Xu, Bingqing Ma, and Qilong Shen, Angew. Chem. Int. Ed. 2014, 53, 9316 –9320. doi: 10.1002/anie.201403983. I haven’t ever needed to add a trifluoromethylthiol to a molecule, but I am sure, with popularity amongst discovery chemists, we may need to find out how to add such a group to an API. This is the set of reactions to generate this trifluoromethylthiolating agent. But really how good is it ?
These following reagents had been used in the past to electrophilically add a trifluoromethylthiol group. I could elaborate here, but I think it is important to note that this newly discovered saccharin analogue was found to be quite effective at introducing a trifluoromethylthiol in the model reaction.
The N-Trifluoromethylthiosaccharin could be used to add to this ketoester.
Then to this indole.
And to this alcohol.
I picked some of the higher yielding reactions. This seems to have broad applicability. It is interesting that a common molecule, (a sweetener) was converted into a useful reagent with good stability. Hopefully, my custom synthesis folks and pharmaceutical colleagues will be able to make use of this.
I found this on the web, with some applications for trifluoromethylthiolation.