New cheap, complementary method chemical reaction developed

New cheap, complementary method for chemical reaction developed

9:23 AM, 24th June 2016
New cheap, complementary method for chemical reaction developed
Typical set-up for metallophotoredox C-N coupling

PRINCETON, US: A team of researchers at Princeton University, the Massachusetts Institute of Technology (MIT) and Merck & Co has developed a cost-effective and complementary approach to a fundamental chemical reaction known as a C-N bond coupling, which is a staple of modern drug development.

Published in the journal Science, the reaction provides a direct route to compounds called anilines, an extremely common structure in medicinal and industrially relevant agents, without the expense of ligands on transition metal catalysts required by traditional methods.

“What we bring to the table is a completely new mechanism to perform this reaction,” said David MacMillan, university professor of chemistry and a corresponding author on the paper.

Whereas established C-N bond couplings rely on tailored ligands to destabilize the metal catalyst and drive the reaction forward, the MacMillan lab proposed that light and a photoredox catalyst could instead take on that role. Once initial results confirmed their hypothesis, they reached out to Stephen Buchwald, professor of chemistry at MIT, whose group had worked extensively in C-N bond couplings, also known as Buchwald-Hartwig aminations.

“While we felt we knew a lot about photoredox, we felt we really needed to work with someone that understood C-N bond formation,” MacMillan said. “Buchwald will undoubtedly win a Nobel Prize for C-N couplings and as such he was the perfect person and group to ask to collaborate on this study. We were lucky he agreed to do so.”

Through teleconferences and email, researchers in both labs worked to optimize the method. They found that the reaction only needed tiny amounts of photoredox catalyst in conjunction with a very cheap and simple nickel catalyst to give efficient yields for a range of coupling partners.

“What I think is very intriguing and cool about this project is that it’s almost the opposite of the way we usually think,” said Michael Pirnot, a postdoc researcher in the Buchwald group and co-author on the paper, “where instead of trying to find a specialized ligand, you can run the reaction without adding any sort of engineered ligand at all.”

An attractive feature of the reaction is that researchers largely employ a mild base, which is helpful when performing chemistry on delicate substrates. Additionally, the homogeneity of the reaction makes it especially amenable to flow conditions, in which the reaction solution is steadily pumped through a reactor. It has been well established that photoredox catalysis can benefit dramatically with faster reaction times in flow given the increased solution concentration and exposure to light.

Finally, the researchers teamed up with Merck & Co to test the utility of their photoredox C-N coupling method on a so-called ‘informer’ library that has been used to benchmark other methods. Using this high-throughput technique, the researchers found that 78 percent of these drug-like compounds in the library underwent successful coupling, suggesting that their protocol would find broad applicability in a medicinal chemistry setting.

“That was one of the most enjoyable parts for me, seeing how other people could benefit from our work,” said Emily Corcoran, a postdoct researcher in the MacMillan lab and lead author on the article.

Like the merger of photoredox and nickel catalysis in the reaction, through collaboration the researchers were able to achieve more than they could have on their own. “You cannot overstate the value of collaboration when it is done well,” MacMillan said.

This work was supported by the National Institutes of Health.

© Princeton University News

0 Comments

Login

Your Comments (Up to 2000 characters)
Please respect our community and the integrity of its participants. WOC reserves the right to moderate and approve your comment.

Related News


Clariant acquires Carboflex consortium full control in Brazil

MUTTENZ, SWITZERLAND: Clariant International Ltd has acquired full stake from Carboflex in the consortium that built and operates the Guanabara Bay pl ...

Read more
BASF, Kingenta partner for fertilizers in China

LINSHU, CHINA: BASF SE has entered into strategic partnership agreement with Chinese fertilizer supplier Kingenta Ecological Engineering Group Co Ltd ...

Read more
Henkel opens new composite lab in Germany

DUSSELDORF, GERMANY: Henkel AG & Company has opened its new state-of-the-art composite test lab in Heidelberg, Germany. Here automotive customers ...

Read more
Umicore opens new emission control catalysts plant in Poland

BRUSSELS, BELGIUM: Umicore NV has officially opened its new production plant for emission control catalysts in Nowa Ruda, Poland (near Wroclaw). The f ...

Read more
BASF, Aspen extend partnership to develop next generation building materials

LUDWIGSHAFEN, GERMANY/ NORTHBOROUGH, US: BASF SE and Aspen Aerogels Inc (Aspen) has expanded their strategic partnership with the signing of an exclus ...

Read more
Sabic’s new packaging solutions to minimize food wastage, lower carbon footprint

SITTARD, THE NETHERLANDS: Sabic said it will launch new products and technologies with a strong focus on sustainability and an underlying theme of &ld ...

Read more