Low-Temperature Cross-Coupling of Functionalized Grignard Reagents

doi:10.1055/s-2007-968538

Synfacts 2007(6): 0633-0633
DOI: 10.1055/s-2007-968538

Metal-Mediated Synthesis

Low-Temperature Cross-Coupling of Functionalized Grignard Reagents

Contributor(s):Paul Knochel, Andrei Gavryushin

R. Martin, S. L. Buchwald*
Massachusetts Institute of Technology, Cabridge, USA
Pd-Catalyzed Kumada-Corriu Cross-Coupling Reactions at Low Temperatures Allow the Use of Knochel-type Grignard Reagents
J. Am. Chem. Soc. 2007, 129: 3844-3845

Abstract

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Key words

Kumada-Corriu cross-coupling - palladium catalysis - Grignard reagents

Significance

The Kumada-Corriu cross-coupling process is very attractive since the required (het)arylmagnesium species, including polyfunctionalized ones, can be readily prepared directly by the halogen-magnesium exchange or a metallation reaction. The group of Buchwald report herein a robust protocol, allowing a very efficient coupling of polyfunctionalized arylmagnesium species at the temperatures, which tolerate a vast majority of functional groups. This method is therefore extremely attractive for the direct synthesis of functionalized biaryls starting from (het)aryl halides.

Comment

While the preparation of polyfunctionalized (het)aryl Grignard reagents has become recently a great progress, the low temperatures (around -40 °C in some cases) required for their stability limited their direct use in cross-coupling processes. The use of the new generation of biaryl phosphine catalysts, developed in the group of Buchwald, overcomes this problem. Several reactions can be performed even at -65 °C, which has never been found for a Pd-catalyzed cross-coupling reaction.

Review

For a recent review on the preparation of polyfunctionalized Grignard reagents, see: H. Ila, O. Baron, A. J. Wagner, P. Knochel Chem. Commun. 2006, 583-593.

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