Copper Ullmann coupling

Meyers has also reported the use of chiral oxazolines in asymmetric copper-catalyzed Ullmann coupling reactions. For example, treatment of bromooxazoline 50 with activated copper powder in refluxing DMF afforded binaphthyl oxazoline 51 as a 93 7 mixture of atropisomers diastereomerically pure material was obtained in 57% yield after a single recrystallization. Reductive cleavage of the oxazoline groups as described above afforded diol 52 in 88% yield. This methodology has also been applied to the synthesis of biaryl derivatives. 

The first series of soluble oligo(/ ara-phenylene)s OPVs 24 were generated by Kern and Wirth [48] and shortly after by Heitz and Ulrich [49]. They introduced alkyl substituents (methyls) in each repeat unit and synthesized oligomers 24 up to the hexamer. Various synthetic methods, like the copper-catalyzed Ullmann coupling, the copper-catalyzed condensation of lithium aryls, and the twofold addition of organomelallic species to cyclohexane-1,4-dione, have been thereby investigated. 

We investigated the catalytic performance of the CU2O coated copper nanoparticles for Ullmann coupling reactions. When the coupling reactions using aryl bromides such as 2-... 

Picryl chloride has been used successfully in a number of copper-mediated Ullmann coupling reactions. 2,2, 4,4, 6,6 -Hexanitrobiphenyl has been synthesized by heating picryl chloride with copper powder. The same reaction in the presence of a hydride source (hot aqueous alcohol) yields 1,3,5-trinitrobenzene (TNB). The Ullmann reactions between picryl chloride and isomeric iodonitrobenzenes with copper bronze in DMF has been used to synthesize 2,2, 4,6-, 2,3, 4,6-, and 2,4,4, 6-tetranitrobiphenyls. ... 

The Ullmann coupling is the classical example of Cu-catalyzed biaryl coupling, wherein (a) a phenol and arylhalide substrate are converted to a bis-arylether or (b) two arenes are coupled to form a bis-arene species. These coupling reactions are of great importance for general organic synthesis as well as pharmaceutical and fine chemicals. The copper-catalyzed phenol coupling to arrive at chiral biphenol derivatives is used extensively as a test reaction for the catalytic activity of new copper complexes [254,255]. 

The activated copper powder was used immediately for the following Ullmann coupling. 

When the Ullmann coupling was conducted with copper powder purchased from suppliers other than Lancaster, the reaction gave the desired product in very low yield. 

It was reasoned that if ferrocene behaved as an aromatic system, haloferro-cenes should undergo the Ullmann coupling reaction. Biferrocenyl (XXXVIII) was obtained from this reaction and was shown to be identical in every respect with the anomalous material isolated previously (82, 84). Somewhat surprisingly, it was found that the reaction of iodoferrocene and copper produces XXXVIII in practically quantitative yield, even at temperatures as low as 60°. 

It is conceivable that Ullmann coupling reactions of iodothiophenes in presence of copper might involve thienylcopper intermediates. Intramolecular versions of this proceed in excellent yield. For instance, nearly quantitative yields of the tricyclic compound (502) by this process has been reported (70JCS(C)273). 

There are two different transformations referred as the Ullmann Reaction. The classic Ullmann Reaction is the synthesis of symmetric biaryls via copper-catalyzed coupling, the Ullmann-type Reactions include copper-catalyzed Nucleophilic Aromatic... 

As part of the proof of the identity of three newly isolated chalcones, B.M. Abegaz et al. developed a synthetic route which involves a microwave irradiation promoted Ullmann coupling [29]. A mixture of the dimethylated phenolic chalcone and the bromochalcone in the presence of potassium carbonate and copper(I)chloride was microwave irradiated (domestic oven) at 180 °C, giving 19% yield of the resulting bichalcone (Scheme 6). This bichal-cone was converted into a mixture of the desired Rhuschalcones, upon treatment with BBr3, followed by chromatographic separation. 

The Ullmann coupling, being a copper-catalyzed N-arylation, is known to be more sluggish than the corresponding palladium-catalyzed transformation. Even so, Wu and coworkers succeeded to accelerate reaction times down to only one hour with preserved chemoselectivity (Scheme 26) [93]. A set of aromatic azaheterocycles produced yields of 49-91% after 1 -22 hours of microwave heating. 

The biaryl synthesis by Ullmann coupling, as well as a large number of related coupling reactions, constitutes another type of copper-mediated or -catalyzed reaction used extensively for the formation of carbon-carbon and carbon-heteroatom bonds. These transformations have been reviewed recently17,177,177a,177b and will not be discussed in detail here. 

The normal Ullmann reaction is the formation of an Ar-Ar bond by a thermally activated coupling of a thienyl halide in the presence of Cu, Ni, Pd, or their compounds, but this method is not suitable for the preparation of oligothio-phene and polythiophene films of nanoscale thickness. A photoactivated Ullmann coupling has now been described for the in situ synthesis of such polythiophene films <2006CC729>. The concept involves the selective photodissociation of the C-I bond in 2,5-diiodothiophene on a copper surface the resultant thienyl radicals react with the copper to produce thienyl-Cu intermediates in a thin monomer film at room temperature. These intermediates react with the monomer and produce polythiophene. 

Since then, experiments have been reported which indicate that (1) organocopper compounds will couple with aryl halides (2) arylcopper compounds can be oxidatively and thermally dimerized (3) arylcopper compounds are intermediates in the Ullmann reaction (4) organocopper compounds are intermediates in copper-catalyzed decarboxylations and (5) copper-promoted coupling reactions are not restricted to aromatic halides. The copper(I) oxide-promoted coupling reactions, however, have still to yield firm evidence of a copper intermediate. 

An organocopper intermediate was detected by Lewin and Cohen in the reaction of / -iodotoluene with copper in a good complexing solvent (184). Analysis of protonated aliquots from a reaction performed in quinoline indicated an accumulation of />-tolylcopper to a maximum of 43% after 95 hours, at which point the iodide was consumed, and then a slow decrease to by dimerization. Other experiments also indicate the formation of an arylcopper compound in Ullmann reactions (127,141, 210). The isolation of deuterated products, presumably from the decomposition of an intermediate organocopper species in deuterated benzene and cyclohexane, suggested decomposition to free radicals (127). Decompositions of certain o-haloarylcopper intermediates by a benzyne mechanism cannot be totally excluded. The formation of a dichlorobenzene and by-products such as dibenzofuran and triphenylene from only the ortho isomer of the chloroiodobenzenes in Ullmann coupling reactions (210)... 

Ullmann coupling reactions of perfluoroaryl ttnd -heteioaiyl iodides and bromides with copper proceed readily. ... 

This reaction is known as the Ullmann coupling. It is believed to involve the intermediacy of aryl copper complexes rather than radical species. The reaction is best suited to the preparation of symmetrical biaryls ( homo-coupled products). Attempts to couple two different halides (Ar X and Ar X) in this way can lead to mixtures of the desired cross-coupled product (Ar -Ar ) and the two homo-coupled species (Ar -Ar and Ar -Ar ). 

A radical species may also be generated by reduction of an electron-deficient compound and a classical entry to 4,4 -bipyridines is the reduction of a pyridine by sodium and subsequent rearomatization. Figure 8a illustrates the use of such a reduction in order to prepare the precursor of a sodium-ion molecular switch [30], A more general route, derived from the ancient copper-catalyzed Ullmann coupling, is the metal-induced dimerization of an aryl halide. The key step is a reductive elimination within the coordination sphere of the metal. A nickel(O) complex, in stoichiometric quantities, is usually selected for this purpose. Constable and Ward have used such a reaction to prepare a bis-terpyridine from an interesting synthon, which would have otherwise required a more specialized strategy with dedicated intermediates (Figure 8b) [31]. 

Bis(tetrathiafulvalenyl) derivatives 703 were prepared from the iodo-TTF precursor 702 via Ullmann coupling (copper in refluxing DMF) or by the reaction with copper(i) thiophene-2-carhoxylate (CuTC) in 1-methylpyrrolidin-2-one (Equation 91) <19988826, 2000JMC1273>. 

The exact mechanistic pathway of the Ullmann coupling is not known. There are two main pathways possible 1) formation of aryl radicals or 2) the formation of aryl copper [ArCu, ArCu " and ArCu " ] intermediates. Currently the most widely accepted mechanism assumes the formation of aryl copper intermediates, since many of these species can be isolated and they can react with aryl halides to give biaryls. 

The first total synthesis of taspine was accomplished by T.R. Kelly and co-workers. The central biaryl link was established by a classical Ullmann coupling using activated copper bronze. It is noteworthy that no other crosscoupling strategy was successful to make the C-C bond between the aromatic rings due to the severe steric hindrance. 

RIeke, R. D., Rhyne, L. D. Preparation of highly reactive metal powders. Activated copper and uranium. The Ullmann coupling and preparation of organometalllc species. J. Org. Chem. 1979, 44, 3445-3446. 

Cohen, T., Poeth, T. Copper-Induced coupling of vinyl halides. Stereochemistry of the Ullmann reaction. J. Am. Chem. Soc. 1972, 94, 4363 364. 

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