In 1901, F. Ullmann discovered that by reacting two equivalents of an aryl halide with one equivalent of copper powder at high temperature, a symmetrical biaryl compound was formed. The condensation of two aryl halides in the presence of copper to create biaryl products is now known as the Ullmann reaction. Since then, many differing symmetrical and unsymmetrical biaryl products have been synthesized using this route. Reaction efficiency can be improved by activating the copper prior to use, which is achieved by reducing copper iodide with lithium naphthalenide or reducing copper sulphate with zinc powder. Usually, temperatures greater than 100°C are required to initiate the coupling, but using activated copper allows lower temperatures to be used. The most common solvent used is dimethyl formamide (DMF); for higher temperatures, nitrobenzene or para-nitrotoluene can be used.
T.R. Kelly and co-workers utilized the Ullmann reaction to create the central biaryl link, achieving the first total synthesis of the natural product taspine, an alkaloid which acts as a potent acetylcholinesterase inhibitor.
Mechanism of the Ullmann reaction
Review available Thermo Scientific products for the Ullmann reaction:
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