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).
Tien Nguyen | EurekAlert!
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology