New scalable Flow photo Chemistry Platform New Flow Chemistry Platform #photochemistry #flowchemistry

Recently visible light used organic reaction is attractive area for me. Because it can make difficult bond in short steps under mild reaction conditions.
But scale up is difficult because key factor of photo reaction is light. It means photo absorbance is important and so it is difficult to scale up. One approach is Plug Flow Reactor. It can increase illumination of the reaction solution by increasing surface-area-to volume ratio. But kilo gram scale up is still difficult.

Today I read an exciting article to overcome the issue. The article is published from researcher of AbbVie.
https://pubs.acs.org/doi/10.1021/acscentsci.8b00728

They proposed to use high intensity lasers for light source and Continuously stirred-tank reactor(CSTR) with Beam Expander. From freely available supporting information, reactor looks like below.

They optimized reaction condition and succeeded to conduct 1.54kg synthesis of substituted benzene derivative with C-N cross coupling in 100ml CSTR. It took only 32h!

CSTR has advantage for solid handling compared to flow reactor. I think this reactor is interesting and attractive for large scale photo chemical reaction.

It is worth to know that big pharma try to develop not only drug but also science and technology I think.

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(new?) medchem tool box for compound synthesis

This mini perspective shows recent progress of the direct C-H alkylation with Alkyl Sulfinates.
https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01303

There are many heterocyclic moieties such as pyridine, pyrrole etc. in drug like molecules.
The C-H alkylation reaction of heterocycles is useful but difficult to conduct it under mild reaction conditions.
So mild and universal reaction is very attractive for chemists I think.

In the article, Phil S. Baran’s group reported many examples of their developed reaction.
They used alkyl sulfinates as a radical precursors and developed many kind of commercial sulfinates, fluoroalkyl, heterocyclic, alkyl, aromatic and linker-type.

Surprisingly most of the reactions proceed room temperature. Also they shows reactivity guid lines, it is very practical!

And also this reaction can apply not only early stage of synthesis but also late stage of synthesis.
(Fig3-6)
It means that this is very specific reaction.
I had few successful cases C-H alkylation with sulfinate…. I would like to use the reaction condition when I have chance.

New finding of the Chan-Lam coupling

Copper catalyzed boronic acids and OH or NH containing reaction is called Chan-Lam reaction. The reaction often perform in mild conditions under oxygen atmosphere.
Yes I have used the reaction to synthesize my target compound. But always yield was moderate and depends on steric effect.
Today I found useful article that is reported by researchers from Pfizer and Scripps research institute.
https://pubs.acs.org/doi/abs/10.1021/acs.joc.7b03100

They focused on cyclopropylation of phenols and azaheterocycles. Because cylopropyl group is very important and unique substituent for Medicinal Chemistry but sometime has difficulty to introduce. So new methodologies are required still now.

At first they optimized the reaction condition for O-cyclopropylation of phenols.
In table1 they found good condition with bidentate ligand and it gave high yield (84%). Next they investigated scope and limitation of the reaction.
It was interesting for me that the condition give high yield against not only para substituted electron rich phenol but also ortho substituted phenols.
And also the condition gave low – moderate yield against para meta substituted electron poor phenols.
Procedure of the reaction is not so complicate. I would like to try to use the reaction if I have chance. Organic synthesis and medicinal chemistry is fun and creative task I think.

BTW, I think that introduction of cyclopropan MMP sounds like sudden.