Efficient site-selective functionalization with TFT #organic_synthesis #organic_chemistry #memo

There are many new functionalization reactions of molecules in these days such as electrochemistry, photo-redox and cross-coupling etc. New reaction will give more choices for synthetic route.

Chemists often use cross coupling or another functinalyzation reactions, but these reactions are required foothold such asAr- halogen or ArOTf groups. And the reaction precursor is synthesized by using halogenation when the compound is not commercially available.
So, I think direct C-H activation reaction is an attractive but I had very few experiences in my project because it often has selectivity and/or functional group tolerance issue. But!!!! today I found an exciting article from Florian Berger’s group in nature.

URL is below
https://www.nature.com/articles/s41586-019-0982-0

The group developed new C-H functinalization chemistry with thianthrene derivatives(TFT). In their reaction, cation radical is generated with TFT and TFT sulfide at first and the the radical reacts the substrate and produces thianthrenated intermediate. The reaction can be conducted with high site selectivity and good yield. And also the reaction is not affected with small amount of water, and oxygen. It means the reaction handling is very easy I think.

In the Fig2 shows many example of the thianthrenation. Most of the reaction proceeded moderate ~ high yield and good selectivity with very wide functional group tolerance. The reactivity is controlled with electronic condition of the substrate if target aromatic ring has electronwithdrawing group they used non fluorinated thiantherene instead of TFT.

And following section the authors shows the wide range application of the intermediate.

The thianothreated intermediate can be used for many reactions, transition metal catalyzed cross couplings such as carbonylation, suzuki, sonogashira, negishi, heck and sulfonynlation and photo redox catalyzed reaction such as borylation, phosphonylation, cyanation, pseudohalogenation(ex. SF5), chlorination, idonation.

There are many applications!

In fig3 the author showed many example of these reactions. One is Strychinine acylation. The yield was 48% in 2 steps. Strychinine is an alkaloid with complex molecular structure, normally it is difficult to conduct direct C-H functionalyzation but can do it by using the reaction.

I would like to use the reaction if I have chance. ;)

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