A set of reaction conditions for an asymmetric Michael addition that isn’t hard to PEG

If I can get away with a pun or a witty title for a tweet, I will try to do it.  I have been posting a lot of older material from my former website, PHARMNBIOFUEL.COM due to the fact that I have been keeping myself busy on other projects, plus I ran out of articles to talk about.  I usually take the bus into the city, take a few hours peruse some of the journal publishers’ websites and hope I have something interesting in my latest post.  The article I am about present came from my last batch of articles, but I could easily see I might need some background to present it in a better light.  I, personally, have never ran a reaction in PEG-400.  I have analyzed PEG-400 as it is used in ophthalmic solutions, but other than that, haven’t used in since.  It was this article, “Polyethylene glycol (PEG) as a reusable solvent medium for an asymmetric organocatalytic Michael addition. Application to the synthesis of bioactive compounds” by Karla S. Feu, Alexander F. de la Torre, Sandrina Silva,Marco A. F. de Moraes Junior, Arlene G. Corrêa and Márcio W. Paixão* in Green Chem., 2014, 16, 3169, DOI: 10.1039/c4gc00098f.   It was this article that made me realize the utility of PEG-400 as a green solvent. (there has been a lot of literature precedent for reactions using PEG-400, I just didn’t know.)  The catalyst is quite interesting.  What took me so long to produce this post was to search the background into selection of that particular catalyst.  A long alkyl chain ?  Really ?  Apparently, that catalyst was picked for high catalytic activity in aqueous systems.  You can refer to Eur. J. Org. Chem. 2013, 5917–5922 if you have access to it.  Table 1 shows the optimization of the reaction conditions, selecting PEG-400 for the solvent and Benzoic acid as the additive.

nitrostyrene

I picked this article because there were some examples of relevant molecules that were synthesized with excellent diastereoselectivity, one of those being a precursor to Lyrica (pregabalin).bioactive

The reaction solvent was reused 4 times and achieved the desired yield and ee.  The mechanism to this reaction can be found here Angew. Chem. Int. Ed. 2013, 52, 2160 – 2162.  The acid additive assists with the reaction rate where some steps in the mechanism are accelerated by the addition of acid.

Since I have been reposting some older posts and some posts that aren’t process-related, I don’t necessarily post in the LinkedIn Groups.  Check them out if you have the inclination to do so.

They are:

https://developingtheprocess.wordpress.com/2014/07/16/avoiding-a-reactive-starting-material-the-synthesis-of-pa-824/

https://developingtheprocess.wordpress.com/2014/07/09/is-this-the-newest-trend-for-controlling-polymorphism-a-new-strategy-of-transforming-pharmaceutical-crystal-forms/

https://developingtheprocess.wordpress.com/2014/06/28/cooking-in-one-pot-adding-multiple-component-reactions-mcr-to-your-synthesis/

 

This is a paper about a hydrophobic sponge that is capable of soaking up organic solvents, perhaps could be used for oil spill cleanup ?

https://developingtheprocess.wordpress.com/2014/06/130/here-is-a-sponge-clean-up-your-mess/

Feel free to comment on any of these articles.  I have some new literature for posts, so hang in there.  Have a great week.

 

 

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