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Study provides a new way to build molecules

Chemists from Stockholm University present a new study in the high impact publication Chem, “Diarylation of N- and O-nucleophiles through a metal-free cascade reaction”. The method presents an energy efficient, metal-free, robust and sustainable way to produce diaryl- and triarylamines as well as diaryl ethers.

Erika Linde in front of fume hood
PhD student Erika Linde, main author of the article.

In many products, such as solar cells or LEDs, one can find diaryl- and triarylamines. Diaryl ethers are often present in a variety of drugs and agrochemicals used to meet increasing food demands. 

It is of high importance to create efficient production routes for substances of this kind. In the past this has often required expensive and time-consuming synthetic routes that use toxic and/or rare metal reagents. 


Providing an alternative to metal catalysis 

Researchers at Stockholm university have now been able to present a sustainable method for the preparation of complex diaryl amines, triaryl amines and diaryl ethers. The energy efficient method is metal-free, robust and allows for preparation of the target compounds with low amounts of waste utilizing certain iodine reagents known as “diaryliodonium salts”. 

These hypervalent iodine reagents are made from common starting materials and are considered as low toxic. The reaction setup is also streamlined to use fewer synthetic steps and avoid metal catalysts with complex ligands.

This new methodology is thought to be a competitive alternative to established arylation methods due to its efficacy as well as the simple reaction setup, allowing its utility outside of advanced organic chemistry laboratories.


Building blocks of materials, pharmaceuticals and agrochemicals 

Triarylamines are used in functional materials such as solar cells. Diaryl ethers are one of the most common core structures in pharmaceuticals and agrochemicals, and can carry various structural groups giving them different chemical properties. The secondary and tertiary diaryl amine products of this protocol provide quick access to carbazoles, which is a substance class that is applied in both functional materials such as LEDs or solar cells, and as building blocks in pharmaceuticals due to their broad biological activity. 


First of it’s kind

“This is the first example of a metal-free double functionalization where two structurally different aryl groups can be introduced onto a nucleophile in a one-pot reaction. The discovery is based on a new reaction concept, which allows for further discoveries in hypervalent iodine chemistry” explains Berit Olofsson, professor in organic chemistry and Chair of the board of SUCCeSS, Stockholm University’s Center for Sustainable and Circular Systems.

Berit continues, we hope this can lead to new collaborations with researchers interested in triarylamine applications. Our method provides exceptional structural diversity and allows for wide screening of triarylamine properties.

The project has paved the way for several follow-up projects in the Olofsson group, where the new reaction concept is used to reach other product classes in atom-economic ways.


Method developed in accordance with the principles of green chemistry

The project is in accordance with five of the twelve principles of green chemistry, a research area that was developed by SUCCeSS’ senior advisor, Paul Anastas together with John Warner. Green chemistry is focused on using resources efficiently as well as to minimize waste and avoiding reagents that cause harm to humans and the environment. 

The new method is highly efficient and results in what is known as high atom economy – the reagents react efficiently with each other causing low amounts of waste. The method also avoids the use of toxic and/or rare metal reagents and instead relies on the use of non-toxic diaryliodonium salts. Furthermore, the protocol is energy efficient due to the mild conditions and the reactions can often be performed in harmless solvents.

12 Principles of Green Chemistry- American Chemical Society

Link to full full article, Diarylation of N- and O-nucleophiles through a metal-free cascade reaction 

Link to Paul Anastas role as senior advisor of SUCCeSS