A couple of useful substitutions

I want to talk about two user-friendly aromatic substitutions today. While the mechanisms are entirely different, there is a common link. Both of these reactions made a difference in our approaches to either making or modifying halogenated aromatics. The first reaction is the aromatic bromination process that requires a curious combination of triphenylphosphine sulfide catalyst, an aromatic compound, and N-bromosuccinimide. My PhD student Sean Liew found this remarkably mild process in Gustafson’s Org Lett paper. I can highly recommend this reaction, whose only downfall is the production of phosphorous-based by-products. I don’t think that the role of triphenylphosphine sulfide has been fully delineated, if that is what you are interested in.



The other process is separated from the one above by 8 years. This is when Lilu Yu was doing her Masters degree in my lab and was in need of a mild method to replace aromatic fluorine by the hydroxyl group. I remember this process to be an excellent way to deliver the hydroxide nucleophile, although in a somewhat convoluted way. We used this chemistry, originally described by Green, when nothing else worked, so I would highly recommend this process.



4 thoughts on “A couple of useful substitutions

  1. both reactions are very nice and practical – than you! (I think another good hydroxide equivalent that instantly deprotects itself is TMS-ONa.)

    The phosphine-sulfide halogenation catalyst: Me3P 1M in THF or toluene is affordable, and maybe Me3P=S would leave less phosphine-related stuff behind (Me3PO is water soluble).

  2. I think you are making a good point. It is indeed a great idea to go to Me3P… Solubility will be enhanced (we are in fact trying to make some reagents based on it, perhaps we should try with “S” too).

    • They sell Me3P 1M in toluene and S8 has a decent enough solubility in toluene, maybe one could just dump in sulfur, stir, filter and apply the filtrates directly on a silica column, toluene is quite good for loading poorly hexane-soluble material on a column, and one could nicely see the translucent toluenic front coming through, the marker to start collecting the fractions…

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