Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New reaction turns feedstock chemical into versatile, chiral building block

24.03.2016

Direct cross-coupling offers a selective route to highly useful 1,2-dihydropyridines

Researchers in the Doyle lab at Princeton have developed a direct cross-coupling reaction to produce nitrogen-containing compounds called 1,2-dihydropyridines, versatile building blocks that are highly useful in pharmaceutical research.


Researchers in the Doyle lab at Princeton have developed a direct and selective cross-coupling reaction that employs a chiral nickel catalyst and an activating agent at low temperatures to couple nucleophilic arenes, common motifs in bioactive compounds, with a feedstock chemical known as pyridine.

Credit: Doyle lab

Published in Chemical Science, the reaction employs a chiral nickel catalyst and an activating agent at low temperatures to couple nucleophilic arenes, common motifs in bioactive compounds, with a feedstock chemical known as pyridine.

"A highlight of the method is being able to use pyridine as a substrate because it's inexpensive and abundant and has rarely been used in transition metal and asymmetric catalysis," said Abigail Doyle, an associate professor of chemistry at Princeton and corresponding author of the article.

Performing transition metal chemistry with pyridine has proven challenging because it can 'poison' the nickel catalyst, essentially binding to the nickel such that the reaction cannot move forward. The research team found that they could overcome this limitation by adding a slight excess of an activating agent, a compound known as iso-butylchloroformate. This addition favors the formation of an intermediate species that will not bind to the catalyst and allows the reaction to proceed.

The method is also highly enantio- and regioselective, meaning that researchers could control the precise geometry and position at which the new chemical bond is formed between the two coupling partners, attractive features that have not been offered by previous methods.

The researchers went a step further by demonstrating the utility of the product by performing nine different elaborations commonly used by medicinal chemists in drug development. "That was my favorite part to do," said Patrick Lutz, a graduate student in the Doyle lab and lead author of the paper. "Optimization is necessary, and exciting when you find ways to improve the reaction, but it was really fun thinking about all the different types of reactions that I could do."

###

Read the full article here:

Lutz, J. P.; Chau, S. T.; Doyle, A. G. "Nickel-catalyzed enantioselective arylation of pyridine." Chem. Sci. 2016, Advance article.

This work was supported by the National Institutes of Health National Institute of General Medical Sciences (R01 GM100985) and a National Science Foundation Graduate Research Fellowship to J.P.L (DGE-1148900).

Media Contact

Tien Nguyen
tienn@princeton.edu
609-258-6523

 @Princeton

http://www.princeton.edu 

Tien Nguyen | EurekAlert!

More articles from Life Sciences:

nachricht How glial cells develop in the brain from neural precursor cells
11.12.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

nachricht Small but ver­sat­ile; key play­ers in the mar­ine ni­tro­gen cycle can util­ize cy­anate and urea
10.12.2018 | Max-Planck-Institut für Marine Mikrobiologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

Im Focus: The force of the vacuum

Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.

The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Small but ver­sat­ile; key play­ers in the mar­ine ni­tro­gen cycle can util­ize cy­anate and urea

10.12.2018 | Life Sciences

New method gives microscope a boost in resolution

10.12.2018 | Physics and Astronomy

Carnegie Mellon researchers probe hydrogen bonds using new technique

10.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>