Modification of palladium reactivity results in efficient amine synthesis

Publication in Journal of the American Chemical Society

20 August 2014

Chemists at the van 't Hoff Institute for Molecular Sciences (HIMS) have succeeded in transferring base metal reactivity onto a complex of the noble metal palladium. This has enabled selective amination reactivity, which could pave the way for the efficient and selective synthesis of amines as a functional group in both bulk and fine chemicals. The Journal of the American Chemical Society publishes the results today in its print edition, including a graphic highlight on the cover.

The periodic table of the chemical elements contains a sub-section termed the late transition metals, ranging from iron to gold. Although grouped together as such, there are strong differences between the individual late transition metals. Most notably, there is a distinct change in reactivity between the earth-abundant base metals (such as iron and nickel) and their noble metal ‘colleagues’ (ruthenium and palladium, respectively).

late transition metals,

Base metals (upper row) often undergo one-electron processes while the noble metals (lower two rows) typically prefer two-electron conversions. Breaking through this ‘invisible’ reactivity barrier between first- and second-row metals is considered a challenge with fundamentally novel chemistry waiting to be discovered.

Now, chemists at the van 't Hoff Institute for Molecular Sciences (HIMS) at the University of Amsterdam have succeeded in transferring base metal reactivity onto a complex of the noble metal palladium. This has been utilized for the insertion, in a selective fashion, of a nitrogen atom into an unactivated C-H bond (C-H amination). This is a very efficient way to produce amines, which are prevalent as a functional group in both bulk and fine chemicals.

Cover graphic

The research was performed by PhD student Danny Broere under supervision of Dr.ir. Jarl Ivar van der Vlugt of the Homogeneous, Bioinspired and Homogeneous Catalysis Group at HIMS, which is part of the UvA Research Priority Area Sustainable Chemistry. The internationally well-respected Journal of the American Chemical Society publishes the results today in its print edition, including a graphic highlight of the work on the cover.

Palladium is a very versatile catalyst, with the 2010 Noble Prize in Chemistry being awarded for just one aspect of its rich chemistry. However, one-electron (radical) reactivity is very rare for this metal. Traditional strategies in organometallic chemistry and homogeneous catalysis only focus on the metal, with organic stabilizers (ligands) used primarily as supporting scaffold.

There is much current attention to alternative strategies that employ reactivity present within these supporting scaffolds to tune the reactivity of the metal center - or even to completely bypass the metal during a chemical reaction. This could eventually lead to very selective bioinspired chemical processes but still benefit from the advantages of using a noble metal for substrate coordination and pre-activation as well as follow-up metal-based reactivity.

Smart ligand design

Illustration JACS Van der Vlugt

The UvA-HIMS chemists managed to control the redox-activity of modified, inherently redox-active aminophenol ligands using smart ligand design. By coordinating these ligands to palladium, the researchers were able to generate a complex that exhibited very selective and controlled one-electron transfer chemistry. This behaviour was investigated using high-level computational (DFT) calculations, radical trapping experiments, isotopic labelling and various spectroscopic methods.

Most notably, it was found that the ligand could not only be oxidized and reduced by external ‘triggers’ but could also spontaneously transfer one electron to a coordinated organic azide. This resulted in the generation of a nitrene radical on the activated substrate after loss of dinitrogen. By choosing the right starting material, this highly reactive species underwent a cyclization reaction to form a pyrrolidine,  a structural motif often found in pharmaceuticals.

This reaction is a rare example of radical-type C-H amination on a Pd(II) platform, which might open up new opportunities for base metal reactivity with noble metal complexes. The team is currently expanding its efforts in this direction as well as exploring the opposite concept of employing base metals for noble metal reactivity.

ERC grant

The research was funded by the European Union through the ERC Starting Grant EuReCat awarded to Jarl Ivar van der Vlugt. The team has collaborated with crystallography experts from Utrecht and Göttingen.

Article

Daniël L. J. Broere, Bas de Bruin, Joost N. H. Reek, Martin Lutz, Sebastian Dechert, and Jarl Ivar van der Vlugt: Intramolecular Redox-Active Ligand-to-Substrate Single-Electron Transfer: Radical Reactivity with a Palladium(II) Complex, J. Am. Chem. Soc., 2014, 136 (33), pp 11574–11577. DOI: 10.1021/ja502164f

Published by  HIMS