Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Coupling Around

Fused indolines made by asymmetrical carbon–carbon coupling

Many drugs are based on natural substances. Because it is usually difficult, if not impossible, to isolate these in sufficient quantities from plants or microorganisms, they must be synthesized in the laboratory.

This requires linking carbon atoms – with the right spatial orientation (stereochemistry) relative to each other. In the journal Angewandte Chemie, E. Peter Kündig and a team from the University of Geneva (Switzerland) have now introduced a palladium-catalyzed synthesis that allows them to produce indoline derivatives with the correct spatial arrangement.

When synthesizing large, complex organic molecules, it is generally easier to make smaller individual pieces that can then be linked together to make the final product. The award of the 2010 Nobel Prize in chemistry to R. Heck, E. Negishi, and A. Suzuki for their work on palladium-catalyzed cross-coupling indicates the importance of methods for creating bonds between carbon atoms.

Another complication in the synthesis of natural products is that molecules with identical atomic compositions can have different spatial arrangements.

This results from the chirality of carbon centers: when carbon is bound to four different partners, these can be arranged in two different ways that are mirror images of each other (chirality). When two carbon atoms are coupled together, new chiral centers may be formed. Coupling reactions that selectively deliver products with the desired spatial arrangement are thus high on the chemist’s wish list.

Kündig and his co-workers have now made a breakthrough. They have developed a new synthesis for fused indolines, a class of materials that represent an important structural motif in many natural products and pharmaceuticals, including the tumor drug Vinblastin, the antirheumatic drug Ajmalin, and the neurotoxin strychnine. Indoline is a double-ring structure consisting of one aromatic six-carbon ring and a nitrogen-containing five-membered ring; in a fused indoline, the five-membered ring is fused with an additional five- or six-membered ring.

As a starting material, the researchers used a molecule in which the central five-membered ring is still open. One of the carbon atoms to be bound was activated through binding to a bromine atom. Cleavage of the bromine and a hydrogen atom leads to ring closure. This forms a chiral center; so two different spatial arrangements of the product are possible. Thanks to a new special palladium catalyst, the researchers were able to exclusively involve only one C–H bond (of two chemically identical ones) in the reaction. Their success stems form a bulky chiral ligand, known as an N-heterocyclic carbene, which is bound to the palladium atom. The special thing about this novel catalyst is that the selectivity is maintained even at the required high temperatures around 150 °C.

Author: E. Peter Kündig, Université de Genève (Switzerland),
Title: Fused Indolines by Palladium-Catalyzed Asymmetric C-C Coupling Involving an Unactivated Methylene Group

Angewandte Chemie International Edition, Permalink to the article:

E. Peter Kündig | Angewandte Chemie
Further information:

Further reports about: Coupling Nobel Prize carbon atom organic molecule spatial arrangements

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>