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DOI: 10.1055/sos-SD-045-00510

Black, D. A.; Fagnou, K.Science of Synthesis, (201045547.

For over a century copper-mediated couplings have been employed to prepare symmetric biaryls utilizing the Ullmann reaction.[‌7‌‌11‌] Under typical conditions the arene is reacted in the presence of 110 equivalents of copper powder or copper bronze, forming the bi­aryl compound 1 and a copper halide byproduct. Optimal substrates typically possess electron-withdrawing groups, particularly in the ortho position and, under the classic conditions, certain functions such as hydroxy, amino, or carboxy groups slow down or even stop the desired reaction from occurring due to competitive CO, CN, and CC bond-forming reactions.[‌7‌] Steric factors also influence the reaction rate when a bulky group is situated in the ortho position. Many of these limitations can be alleviated through the use of modern Ullmann protocols (Scheme 1) and, although stoichiometric quantities of copper salts are still commonly required, the reaction remains a useful means of biaryl synthesis.[‌12‌‌14‌] For example, it has been noted that lower reaction temperatures result when dimethylformamide is the solvent;[‌15‌] moreover, the use of an activated copper powder, generated from reduction of a copper(I) iodide complex by lithium naphthalenide, even allows the reaction to be conducted at or below 85°C.[‌16‌]

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