The Salt in the Chemical Soup
The insertion of metallic magnesium into a carbon-halogen compound has been a familiar process since the works of Victor Grignard in 1900 – for which he was awarded the Nobel Prize for chemistry twelve years later. It is still the most abundantly used reaction for making organomagnesium compounds. A major disadvantage of this reaction, however, is the low tolerance towards functional groups, which essentially determine the behavior of a molecule. That seriously limits the bandwidth of organomagnesium compounds. Now, for the first time, the team working with Knochel has succeeded in producing already functionalized organomagnesium reagents by introducing the magnesium directly into the aryl and heteroaryl halides.
It turns out that no elaborate tricks are required to achieve this: the simple addition of the salt lithium chloride to the magnesium turnings accelerated the insertion drastically, and thus allowed the novel reaction under very mild conditions. "The broadness of applications for this reaction is unique," reports Knochel. For example, a large number of aromatic and heteroaromatic chlorides and bromides can be used for the insertion. Sensitive functional groups such as esters, nitriles, pivalates and tosylates are tolerated. The magnesium compounds obtained in this way can then be easily stabilized and used in so-called cross-coupling reactions, in which new carbon compounds are created. "Our method will revolutionize the use of magnesium reagents in synthesis," says Knochel. "The reaction is so simple and environmentally friendly that it will be used widely in the chemicals and pharmaceuticals industry."
The new production method can also be applied to organometallics that contain no magnesium. In another study, for example, the researchers demonstrated that organoindium compounds could also be synthesized in this way. The metal indium is directly inserted into aromatic and heterocyclic iodides. These compounds exhibit unique properties among the organometals, and tolerate even very sensitive functional groups. "They can also be used in the most environmentally friendly solvent of all – water," reports Knochel. "As with magnesium-containing organometals, these compounds are also used in cross-coupling reactions." The chemist's further work into this field will be funded in future by the European Research Council (ERC). His research group was awarded an "advanced investigator grant" in August this year, which comes with a total funding of two million euros. The novel strategy for producing polyfunctional metalorganic compounds, funded by the ERC grant, shall next be expanded to include other environmentally friendly metals such as aluminum, manganese, iron and calcium.
"Preparation of Aryl and Heteroaryl Indium (III) Reagents by the Direct Insertion of Indium in the Presence of LiCl",
Yi-Hung Chen, Paul Knochel, Angewandte Chemie Int. Ed. 2008, 47, 7648. (22 September 2008)
"Convenient Preparation of Polyfunctional Aryl Magnesium Reagents by a Direct Insertion in the Presence of LiCl"
Fabian M. Piller, Prasad Appukkuttan, Andrei Garyushin, Matthew Helm, Paul Knochel, Angewandte Chemie Int. Ed. 2008, 47, 6802. (25. August 2008)
Professor Dr. Paul Knochel
Department for Chemistry and Biochemistry of LMU
Tel.: ++49 (0) 89 / 2180 – 77681
Fax: ++49 (0) 89 / 2180 – 77680