Ullmann coupling copper® iodide

Figure 1.17 The classic Ullmann reaction for coupling aryl iodides by reaction with copper metal at high temperatures.

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. ... 

C-Heteroatom Bond Formation. Copper iodide-mediated C-N, C-0, and C-S bond formation are important transformations and have been extensively explored in recent years. 7. These economical copper-mediated systems circumvent or overcome the limitations of classical Ullmann-Goldberg-type couplings, which are known to require harsh reaction conditions. 

C-0 Bond Formation. A simple and mild method for the coupling of aryl iodides and aliphatic alcohols catalyzed by copper iodide which does not require the use of aUcoxide bases has been described. The reaction can be performed in neat alcohol or in toluene as solvent with catalytic quantities of Cul and 1,10-phenanthrohne, and 2 equiv of CS2CO3. This methodology was successfully applied to the formation of allyl vinyl ethers with tetramethyl-l,10-phenanthroline as the ligand. iVAl-Dimethyl glycine is also a good ligand for this copper iodide-catalyzed Ullmann-type diaryl ether synthesis between phenols... 

The replacement of copper by other metals in the Ullmann reaction usually results in milder and more efficient pathways. The common use of Pd in conjunction with copper in the Ullmann coupling can be seen in many examples. Nicolaou et al. utilized such modifications in their total synthesis of kinamycins C, F, and J. Bromide 9 underwent coupling with iodide 10 to give aldehyde 11 in a satisfactory 83% yield. 

The coupling of aryl halides with copper is called the Ullmann reaction.m The reaction is of broad scope and has been used to prepare many symmetrical and unsymmetrical biaryls.187 When a mixture of two different aryl halides is used, there are three possible products, but often only one is obtained. For example, picryl chloride and iodobenzene gave only 2,4,6-trinitrobiphenyl.188 The best leaving group is iodo, and the reaction is most often done on aryl iodides, but bromides, chlorides, and even thiocyanates have been used. 

The Ullmann reaction (Figure 13.4) represents another synthesis of substituted biphenyls. In this process an aryl iodide or—as in the present case—an aryl iodide/aryl chloride mixture is heated with Cu powder. It is presumed that under standard conditions the aryl iodide reacts in situ with Cu to form the aryl copper compound. Usually, the latter couples with the remaining aryl iodide and a symmetric biphenyl is formed. In a few instances it is also possible to generate asymmetric biaryls via a crossed Ullmann reaction. In these cases one employs a mixture of an aryl iodide and another aryl halide (not an iodide ) the other aryl halide must exhibit a higher propensity than the aryl iodide to couple to the arylcopper intermediate. It is presumed that the mechanism of the Ullmann reaction parallels the mechanism of the Cadiot-Chodkiewicz coupling, which we will discuss in Section 13.4. 

The highiy oxygenated antifungai/anticancer naturai product ( )-diepoxin o was prepared in the laboratory of P. Wipf. The coupling of the two substituted naphthalene rings was achieved via the Ullmann condensation of a phenolic compound with 1-iodo-8-methoxynaphthalene. The aryl iodide coupling partner was used in excess and the condensation was conducted in refluxing pyridine in the presence of a full equivalent of copper(l)-oxide. 

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