Copper-mediated coupling reaction

The true, all-aromatic system (see 18, below) described by Kime and Norymberski is unusual in the sense that all of the ether linkages bridge aromatic carbons ". Synthesis of 18, therefore, required extensive use of copper mediated coupling reactions. As expected for such reactions, yields were generally low. The aromatics such as 18 were ineffective at binding either alkali metal or ammonium cations ". ... 

Copper-mediated coupling reactions of / -iodocalixarenes with phthalimide followed by hydrazinolysis should be mentioned as an alternative and independent strategy to obtain p-aminocalixarenes . The carbazole-substituted derivatives 50 (Figure 8) were obtained similarly by Ulhnan coupling . CMPO derivatives (51c), urea compounds (51b), available also via the isocyanates (51a), may be mentioned additionally. Mono- (52) and diimides with acidic functions pointing towards the cavity, and the calix[6]arene-based acetylcholine esterase mimic (53) are more sophisticated examples. 

Toumi, M., Gouty, F. and Evano, G. (2007) Total synthesis of the cyclopeptide alkaloid abyssenine A. Application of inter- and intramolecular copper-mediated coupling reactions in organic synthesis. The Journal of Organic Chemistry, 72, 9003-9009. 

Scheme 23. Copper-mediated coupling reactions of alkylidene carbenoids...

These reports on copper-mediated coupling reactions set the stage for pioneering reports by UUmarm and Irma Goldberg (his later wife) on the use of catalytic amounts of copper for coupling reactions of haloarenes. Thus, the arylation of phenol (16) and its derivatives with low catalyst loadings of copper enabled the selective syntheses of diarylethers (Scheme 1.5) [29]. 

At the beginning of 20 century, Fritz Ullmann reported copper-mediated coupling reactions of aryl halides. The formation of biaryls from the reductive coupling of two aryl halides using stoichiometric amounts of copper was the first type of coupling reported by Ullmann s laboratory (Equation 19.91). Two years later, Ullmann reported that stoichiometric amounts of copper compounds mediate the ipso-substitu-tion of an aryl halide by heteroatom nucleophiles, such as phenoxides and arylamines... 

Abstract Although requiring the use of stoichiometric amounts of metal and harsh conditions, the copper-mediated coupling reactions of aryl halides with amines and phenols (Ullmann craidensatiOTis), amides and carbamates (Ullmann-Goldberg condensations), or activated methylene compounds (Ullmann-Hurtley condensations) have been for a long time useful methods for the formation of C(aryl)-N, C(aryl)-0, and C(aryl)-C bonds. In 2001, a renaissance of the Ullmann reaction has been initiated with the discovery of versatile new copper catalytic systems for C-C, C-N, or C-O coupling under mild temperature ccmditions. 

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