The cyclic alkyl amino carbenes or CAACs, attach themselves to metals, such as palladium, to form catalysts that allow chemical transformations otherwise considered impossible. The carbenes modulate the properties of the metals to which they are bound and can facilitate and speed up reactions involving their use carbenes.
Carbene-based catalysts can simplify complex chemical preparations. In addition, only mild temperatures are needed for the catalyst to be effective. Also the catalyst's longevity means only a small amount is needed to achieve the final product.
"All of this can dramatically reduce the cost of manufacturing drugs, given that pharmaceutical companies are increasingly using carbene-supported catalysts for their chemical reactions," said Vincent Lavallo, first author of the study.
A carbene is a molecule that has a carbon atom with six electrons instead of the usual eight. Because of the electron deficiency, carbenes are highly reactive and usually unstable in nature.
In the study, which appears in the Angewandte Chemie International Edition, (published online Aug. 1), the scientists, from the University of California, found that CAAC-based catalysts could be used not only at room temperature but also in smaller amounts than was necessary for the other catalysts.
Because nitrogen atoms stabilise a carbene when they are adjacent to it, chemists believed until now that two nitrogen atoms were necessary in a carbene to make efficient catalysts. But having two nitrogen atoms also imposes structural limitations at the centre of the carbene.
The carbenes synthesized has only one nitrogen atom, which lends the molecule a far more flexible structure. In effect, the carbenes are bigger at the metallic centre of the catalyst, a feature that improves the efficiency of the catalyst.
"The new carbenes we have prepared in the laboratory are such that they protect the metals to which they bind, making the metal catalysts more stable and longer lasting," said Guy Bertrand, the lead author.
For more than a century, most catalysts were prepared using chemical compounds called phosphines. But in the 1990s, carbenes were found to be useful to make catalysts.
A carbene is a molecule that has a carbon atom with six electrons instead of the usual eight. Because of the electron deficiency, carbenes are highly reactive and usually unstable in nature.
Bertrand's research group plans to continue to modify the new carbenes to find more efficient catalysts. "We're looking also for new catalytic reactions facilitated by these new carbene metal complexes," Lavallo said.
"The CAACs have made the field of carbene chemistry more exciting than ever."
The use of catalysts within the pharmaceutical industry has led to the increased efficacy and effectiveness of drug therapies that ordinarily could not be achieved with out the acceleratory properties of catalysts.
There is a clear unmet need for novel catalysts in the pharma sector: to increase yields, reduce costs and deliver more environmentally friendly reactions. One example of a success story is the indoles. They are found in many natural products and popular pharmaceuticals, including the multibillion-dollar statin class of cholesterol-lowering drugs.