Rare-earth half-sandwiches prove rewarding

May 18, 2012
Figure 1: Modification of nitrogen-bearing pyridine compounds (far left) with olefins (blue spheres, left) at an ortho-C-H position (yellow sphere) can be performed selectively and efficiently, using novel rare-earth catalyst complexes. Credit: 2012 Zhaomin Hou

The chemical frameworks of ’natural products’—molecules generated by biological organisms—have inspired many of today’s most potent pharmaceuticals. But the complexity of these compounds makes time-consuming tricks necessary to produce them at large scales. Bing-Tao Guan and Zhaomin Hou from the RIKEN Advanced Science Institute in Wako, however, have developed a rare-earth catalyst system that promises to make natural product synthesis significantly easier by enabling direct modification of aromatic pyridine compounds.

Pyridine, a benzene-like ring that contains nitrogen and five carbon–hydrogen (C–H) atoms, is a chemical structure found in many natural products. Ideally, chemists would insert double-bonded olefins into pyridine’s C–H groups to synthesize new medicinal compounds. But this approach is rarely viable owing to a lack of efficient and selective catalysts.

The researchers envisaged that their ‘half-sandwich’ rare-earth catalysts, which they have previously used for olefin polymerization, might offer unprecedented control over this transformation. These molecules are named after their shape, in which elements such as scandium (Sc) center above a flat pentagonal ring. They can both dehydrogenate pyridine’s C–H bonds and promote olefin insertion—two critical features in making pyridine modification a success, Hou notes.

When the researchers mixed ethylene gas with a pyridine derivative and an Sc half-sandwich catalyst, they discovered that direct olefin insertion occurred at almost quantitative yields. Crucially, the researchers found that this catalysis was highly selective: the C–H bond addition occurred exclusively at a so-called ortho site adjacent to pyridine’s nitrogen atom (Fig. 1). “Selectivity is one of the most important factors for organic synthesis,” notes Guan.

Mechanistic experiments revealed that the selectivity arose from preferential binding of the rare earth to pyridine’s nitrogen atom—an action that simultaneously stabilizes the catalytic intermediate and activates the ortho-C–H bond. After the insertion of the olefin into the rare earth–pyridine bond, the reactive catalyst dehydrogenated another pyridine molecule. This action produced the newly modified pyridine derivative and regenerated the catalytic intermediate. 

The researchers also found that they could tune the activity and selectivity of these catalysts by changing the central rare-earth of the half-sandwich complex. For example, switching to a rare-earth with a large ionic radius, such as yttrium (Y), enabled them to perform the first selective insertion of bulky styrene derivatives into an ortho-C–H bond of pyridine molecules. Hou and colleagues are hopeful that these versatile catalysts can yield similarly atom-efficient protocols with other synthetic reactions in the future.

Explore further: Heavy Pyridine Crystallizes Differently

More information: Guan B.-T. & Hou, Z. Rare-earth-catalyzed C–H bond addition of pyridines to olefins. Journal of the American Chemical Society  133, 18086–18089 (2011). article
 
Nishiura, M. & Hou, Z. Novel polymerization catalysts and hydride clusters from rare-earth metal dialkyls. Nature Chemistry 2, 257–268 (2010).

Related Stories

Heavy Pyridine Crystallizes Differently

January 7, 2009

(PhysOrg.com) -- The nuclei of ordinary hydrogen atoms contain only a single proton. If a neutron is added, the hydrogen becomes deuterium. In principle, molecules that contain deuterium in place of hydrogen atoms are chemically ...

The new kid on the block

June 3, 2011

In synthetic chemistry, ‘carbene’ species—compounds bearing a carbon atom with two unpaired electrons—have a ferocious reputation. Left uncontrolled, they will react with almost any molecule ...

Economizing chemistry, atom by atom

February 3, 2012

In chemistry, downsizing can have positive attributes. Reducing the number of steps and reagents in synthetic reactions, for example, enables chemists to boost their productivity while reducing their environmental footprint. ...

Recommended for you

Chemists solve major piece of cellular mystery

August 27, 2015

Not just anything is allowed to enter the nucleus, the heart of eukaryotic cells where, among other things, genetic information is stored. A double membrane, called the nuclear envelope, serves as a wall, protecting the contents ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.