Aryl copper compounds

Allylic substitutions with nonstabilized C-nucleophiles are an important domain of organocopper chemistry [51]. However, on close inspection of the literature, it becomes apparent that regioselectivity in favor of the branched allylic alkylation products is only obtained with alkyl copper compounds, while aryl copper compounds mainly give the linear alkylation products. This observation was an incentive for Alexakis et al. [52] to probe the reactions of aryl zinc hahdes in the Ir-catalyzed allylic substitution (Scheme 9.18). 

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 formation of copper(I) fluoride in reaction (45) seems unlikely, but low yields of aryl copper compounds are obtained owing to pyrolysis during preparation. 

The decomposition of alkyl and aryl copper compounds has been the subject of much debate. Initially free radical mechanisms were advanced, such theories being supported by the reduced yields of hydrocarbons in the presence of benzoquinone or other free-radical scavengers (24, 150). However, under all conditions very poor yields of dimeric alkanes are obtained. These would be the likely products of a free-radical decomposition. 

Despite its synthetic importance, the mechanism of the copper-quinoline method has been studied very little, but it has been shown that the actual catalyst is cuprous ion. In fact, the reaction proceeds much faster if the acid is heated in quinohne with cuprous oxide instead of copper, provided that atmospheric oxygen is rigorously excluded. A mechanism has been suggested in which it is the cuprous salt of the acid that actually undergoes the decarboxylation. It has been shown that cuprous salts of aromatic acids are easily decarboxylated by heating in quinohne and that aryl-copper compounds are intermediates that can be isolated in some cases. Metallic silver has been used in place of copper, with higher yields. ... 

Organocopper compounds have been trapped by coordination with organic bases." In addition, aryl copper compounds (ArCu) have been independently prepared and shown to give biaryls (Ar—Ar ) when treated with aryl iodides Ar I." ° A similar reaction has been used for ring closure " ... 

The mechanism of the Ullmann reaction has not been fully clarified, however, it should proceed via aryl-copper intermediates [13]. This proposal was supported by an improvement of the method by Koten and Noltes, who reacted an aryl-copper compound with... 

This approach, which obviates the formation of symmetrical products, was also applied to the synthesis of unsymmetrical biaryls [15]. The aryl-copper compound was prepared from corresponding aryl-lithium obtained by direct lithiation of an aryl halide and was coupled with the other aryl halide. 

The perfluoroacetylenic copper compounds undergo coupling reactions with aryl iodides and provide a useful synthetic route to the perfluoroalkyl aryl alkynes [147, 255] (equation 170) Coupling of these copper reagents with the 1-iodo-perfluoroalkynes gives the perfluorodiynes [747 255] (equation 171)... 

The analogous trifluoromethylseleno and pentafluorophenylseleno copper compounds are prepared via reaction of the corresponding diselenide with copper metal [265, 269] Coupling with aryl iodides gives the arylselenium denvative [265] (equation 185)... 

To date, the organometallic chemistry of copper, in terms of isolation and structural characterization of compounds, is essentially limited to the Cu(I) oxidation state. Only a very few examples of other oxidation states are known. The older literature offers a reported synthetic procedure for the synthesis of bis(aryl)copper(II) compounds [33, 34] (see Scheme 1.2), but this result has never been reproduced by others. 

Reactions with hthium or Grignard reagent yield alkyl or aryl copper(I) derivatives, respectively. Such organocopper compounds containing Cu-Cu bonds are formed only by Cu+ and not Cu2+ ions. 

Carboxylic acids can be prepared in moderate-to-high yields by treatment of diazonium fluoroborates with carbon monoxide and palladium acetate383 or copper(II) chloride.384 The mixed anhydride ArCOOCOMe is an intermediate that can be isolated. Other mixed anhydrides can be prepared by the use of other salts instead of sodium acetate.385 An aryl-palladium compound is probably an intermediate.385 OS V, 139. 

All of the neutral (organo-)copper compounds just listed can be arylated by aryl iodides and/or -bromides Ar-Cu and R-C=C-Cu can also be alkynylated by alkynyl iodides and/or -bromides. Table 16.2 summarizes the whole spectrum of corresponding products. After having grasped the mechanism of these reactions by way of Figure 16.3, we will discuss their synthetic potential by means of the examples given in Figures 16.4-16.9. 

Arylation of N, N-dimethylhydrazone 77 with ( fl-chlorobenzene)tricarbonylchromium complex lb can be achieved in 64 % yield. The copper lithium azaenolate 78 is trapped with the chromium complex at 70 °C to give a-phenyl ketone 80 as a result of an ipso substitution (Scheme 35) [59]. This represents an easy access to a-aryl carbonyl compounds, some of which may exhibit anti-inflammatory properties. 

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