Copper-mediated coupling

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 of the aryl iodide derived from l,3-bis(2-hydroxy-hexafluoroisopropyl)benzene with perfluorooctyl iodide gives the desired compound as a dimethyl sulfoxide (DMSO) complex [166] (equation 143) Even bromoarenes can be coupled [167] (equation 144)... 

B-rings of their constituent dihydrochalcone monomers. A concise synthesis of verbenachal-cone (316) by catalytic copper-mediated coupling of phenol and aryl halides has been reported by Xing et al., who also prepared two further derivatives for preliminary structure-activity studies. One of the latter, the corresponding bichalcane (deoxo) derivative of verbenachalcone showed no activity in the neural outgrowth stimulation bioassay mentioned above. 

Isoquinolines can be generated from benzocyclobutanol and 2-cyanopyridine <1994TL9191> (Equation 185). Zirconocene-copper-mediated coupling of benzocyclobutanes in the presence of nitriles gives the isoquinoline, albeit with only select examples of 3-substitution (Scheme 116) <20030L877>. 

Preparation of dioctylzinc by iodine-zinc exchange and its copper-mediated coupling with an electrophile preparation of ethyl 2-nonylacrylate... 

Coupling of the cyclobutadiene complex 88 [48] with the protected acetylene 89 furnished the tetrayne 90, copper-mediated coupling of which, after removal of its acetylenic trime-thylsilyl groups, yielded the organometallic complex 91 [49]. 1H NMR analysis of this... 

The application of zirconocene-copper-mediated coupling of benzocyclobutadiene with nitriles was shown to be effective in one specific case <03OL877>. The only successful transformation is shown below. In contrast, benzonitrile only yielded traces of 3-phenylisoquinolines. 

In addition to aliphatic and aromatic amines, amides275 and sulfonamides285 have also been used as nitrogen nucleophiles for copper-mediated coupling with arylboronic acids, and these reactions provide protected anilines. 

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. 

A Pd-catalyzed copper-mediated coupling of pyrazinylthioether 26 with an arylstannane... 

Scheme 2.122 Proposed mechanism for the copper-mediated coupling...

A different synthetic approach to benzoannelated [2.2]paracyclophanes was realized by the Diels-Alder reaction of bis (methylene) [2.2] paracyclophane (13) and tetrakismethylene[2.2]paracyclophane (15) with para-benzoquinone [20]. The bis(exomethylene)paracyclophane derivatives were obtained from 6 and 7 via a copper-mediated coupling with methyl magnesium bromide, bromination and debromination. The dienes 13 and 15 react readily to the bis- and tris-phanes 16 and 17 when heated with para-benzoquinone in dichlorobenzene. However, both compounds are extremely poorly soluble in organic solvents and... 

Br/Mg exchange converts 1,2-dibromocyclopentene into the p-bromoalkenyl-magnesium chloride (LiCl complex), which reacts normally with carbonyl compounds. It is possible to peform a copper-mediated coupling at the p-carbon site while retaining the C-MgCl unit. ... 

Figure 7.25 Copper mediated coupling of 1,3-diiodohexafluoropropane and 3-iodopyridine.

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. 

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