Science of Synthesis

Black, D. A.; Fagnou, K., Science of Synthesis, (2010) 45, 547.

For over a century copper-mediated couplings have been employed to prepare symmetric biaryls utilizing the Ullmann reaction.[‌7‌–‌11‌] Under typical conditions the arene is reacted in the presence of 1–10 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 C—O, C—N, and C—C 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.[‌12‌–‌14‌] 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]

‌Meeeee 8‌ Meeeeeeeeee Meeeeee Meeeeeeeeeee[‌88‌–‌88‌]

‌Meeeeeeeeee 8‌

Meeeee-eeeeeeee eeeeeeeee eee eeee eeeeeeeee eee eee eeeeeeeee ee eeeeeeeeeeeee eeeeeee eeeee eeeeeeeee eeeeee. Meee, eeeeeee eee eeeeee eeeeee ee eeeeeeeeee eee eeeeee ee eee eeeeeeeeeeeee eeeeeeee eee ee eeeeeeeee; eeeeeeee, eeeeeee eeeeeeeeee eee eeeeeeee eeee eee eeeeeeeee eee eeeeeeeee ee e eeeeeeeeeee eeee eeeeeeeee eee eeeeeeeeeeee ee eee eeee eeeeeeee eeeeeeee eeeeeee (eeeee ee eeeeeee ee eeeeee). Meeeeeeeeeeee Meeeeee eeeeeeeee, eeee ee eee eeeeeeee ee eee eeee eeeee ‌8‌ eeee ee eeeeee ee 8-eeee-8-eeeeeeeeeeeeeeee (‌8‌) (‌Meeeee 8‌), eeee eeee eeeeeeee ee Meeeee ee eee eeeeeeeee ee eeeeeeeeeeee eeeeeeeeeeeeeeeeee eee eeee eeeeeeeeeee eeeeeeeeeeee eeeeee.[‌88‌]

‌Meeeee 8‌ Me Meeeeeeeeeeee Meeeeee Meeeeeee[‌88‌]

M eeeeeeeeee eeeeeee eeeeeee eeeeee(M) eeeeeeeee-8-eeeeeeeeeee (MeMM) ee eeeeeee eeeeeeeee ee eeee eeeeeee ‌8‌ ee eeee eeeeeeeeeee, eeeeeeeeee eeeeeeeeeee eeeeeee ‌8‌ (‌Meeeee 8‌).[‌88‌] Meeeeee eeeee-eeeeeeeee eeeeee eee ee eeeeeeee, eeee ee eeeeee, eeeeee, ee eeeee eeeeee, eeeeeeeee eeeeeee ee eeee eeeeee eeeee eeeeeeeeeeeee eeeeee eeeeeeee eeeeeeeeee eeee eeeee eeeeeeee ee eeeeeee Meeeeee eeeeeeeee.

‌Meeeee 8‌ Meeeee(M) Meeeeeeee-8-eeeeeeeeeee ee eee Meeeee Meeeee eee Meee Meeeeeeeeee Meeeeee Meeeeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeeeee 8,8′-Meeeeeeeeeeeeee-8,8′-eeeeeeeeeeeee (‌8‌, M8 = 8-MM8Me-8-MM8):[‌88‌]

Meeeee 8-eeeee-8-eeeeeeeeeeeee (888 e, 8.88 eee) eee eeeeee ee e 888-eM Meeeeeeeee eeeee eeeeeee ee e eeeee eee eeee eeee eee eeee ee 888–888°M. Me eeeeee (88 e, 8.88 eee) eee eeeee ee eeeee eeeeeeee (ee. 8 e) ee 8-eee eeeeeeeee eeee eeeeeeee eeeeeeee. Mee eeeeeeee ee eee Me eeeeee eeeeeeee eeeee 88 eee, eeeee eeeee eee eeeeeee eee eeeeee ee 888–888°M eee eeeeeee eee eeeeeee 88 eee. Meeee eeeeeee, eee eeeee eeeeeeee eeee eeeeeeee eee eeeeee ee eee eee eeeeeeeee ee eeeeeeeee eeee eeeeeee (MMMMMMM: eeeeeeeeee) ee eeeeeeeee eeee eeeeeee ee e Meeeeee eeeeeeeee. Mee eeeeeee eeeee eee eeeeeee eeee eeeeeeeeeeee eeeeee eee eee eeeee eeeeeeee eee eeeeeeeeeeeeee (eeeeeee) ee eeee e eeee eeeee; eeeee: 888 e (88%); ee 888°M.

M,M′-Meeeeeee-8,8′-eeeeeeeeeeeeeee (‌8‌, M8 = MMMe); Meeeeee Meeeeeeee:[‌88‌]

MeMM (8.88 eeee) eee eeeee ee eee eeeeeee ee M-(8-eeeeeeeeee)eeeeeeeee (888 ee, 8.88 eeee) ee MMM (8 eM) eeeee M8. Meeee eeeeeeee ee ee eee 88 eee, MeMMe (88 eM) eee eeeee eee eee eeeeeeeee eeeeee eee eeeeeeee eeeeeee e eeee ee eeeeee eee eeeee MeMMe ee eee eeeeee. Mee eeee eee eeeeee eeee 8 M MM8MM (888 eM) eee eee eeeeeee eeeee eee eeeeeeeee eeee MeMMe (8 × 88 eM). Mee eeeeeeee MeMMe eeeeee eeee eeeeee eeee M8M (88 eM) eee eee eeeeeee eeeee eee eeee eeeeeeeee eeee MeMMe (88 eM). Mee eeeeeeee MeMMe eeeeee eeee eeeee (MeMM8), eeeeeeee, eee eeeeeeeeeeee, eee eee eeeeeee eee eeeeeeeeeeeeee (Me8M/eeeeee) ee eeee e eeeeeeeee eeeee; eeeee: 888 ee (88%); ee 888–888°M.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 8/8e, 888.
• 8.Meeeee-Meee, (8888) 8/8e, 888.