Aryl-copper intermediate

The coupling of aryl halides with copper is called the Ullmann reaction The reaction is clearly related to 13-9, but involves aryl copper intermediates. The reaction is of broad scope and has been used to prepare many symmetrical and unsym-metrical biaryls." When a mixture of two different aryl hahdes 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." 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 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 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... 

There has been a wide-ranging review of transmetalation reactions of arenes concentrating on the use of boron-containing compounds. The reaction of arylboronate esters and related compounds with alkyl halides is catalysed by copper(I) formation of an aryl—copper intermediate followed by an 5N2-type reaction with the alkyl electrophile is likely. Palladium complexed with a diimine is an excellent catalyst in the phenylation reaction of Michael acceptors with phenylboronic acid so as to yield products such as (16). The nickel-catalysed reaction of phenylboronic acid with styryl epoxides has been shown to yield a-substituted alcohols such as (17). 

Asymmetric conjugate addition of dialkyl or diaryl zincs for the formation of all carbon quaternary chiral centres was demonstrated by the combination of the chiral 123 and Cu(OTf)2-C H (2.5 mol% each component). Yields of 94-98% and ee of up to 93% were observed in some cases. Interestingly, the reactions with dialkyl zincs proceed in the opposite enantioselective sense to the ones with diaryl zincs, which has been rationalised by coordination of the opposite enantiofaces of the prochiral enone in the alkyl- and aryl-cuprate intermediates, which precedes the C-C bond formation, and determines the configuration of the product. The copper enolate intermediates can also be trapped by TMS triflate or triflic anhydride giving directly the versatile chiral enolsilanes or enoltriflates that can be used in further transformations (Scheme 2.30) [110],... 

Other processes, limited to heteroaromatic systems, include the Sn(ANRORC) reaction (Scheme 4),17,18 and ring transformation reactions.18,19 Reactions which proceed via a-adduct intermediates, but do not lead to substitution on the aromatic nuclei, such as the Sn(AEAE) reaction,20 or give nonaromatic products, are not included. Also not covered are processes involving aryl-metal intermediates, such as most copper-catalyzed aromatic substitutions. 

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. 

Isocyanide complexes of phenylethynyl-, indenyl-, and cyclopentadi-enyl copper have been isolated 86, 172, 246). Organocopper-isocyanide complexes are assumed to be intermediates in certain organic syntheses (245-252). Isocyanides also insert into the aryl-copper bond 281d) [Eq. (35)]. 

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. 

One cannot distinguish between the analogous copper intermediates involved in oxidative electron-transfer and ligand-transfer reactions. In each the ionization of the ligand to copper(II) has an important role in the formation of carbonium ion intermediates. A reaction analogous to the copper-catalyzed decomposition of peroxides is the copper-promoted decomposition of diazonium salts (178). The diazonium ion and copper(I) afford aryl radicals which can undergo ligand-transfer oxidation with copper(II) halides (Sandmeyer reaction) or add to olefins (Meerwein reaction). 

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. ... 

In the scheme the oxidative addition of aryl halide to a Pd(0) species gives an arylpalladium halide and the halide ligand is then replaced by an alkynyl group in the alkynyl-copper intermediate generated by interaction of the alkyne with cop-... 

Zhang s and Yoshida s groups, independently, demonstrated that the dimerizative insertion of arynes into a C(sp)—H a-bond of terminal alkynes 53 was catalyzed efficaciously by a Au(I)-Cu(I) cocatalytic system [26a] or a Cu(I) catalyst [26b], respectively, giving 2-alkynylbiaryls 54 (Scheme 28.20). Each reaction begins with a nucleophilic attack by an in situ-generated alkynyl copper species toward an aryne. Also, a C(sp)-Br a-bond of alkynyl bromides 55 accepted the insertion of arynes under copper catalysis, and the reaction was also applicable to propargyl bromide 56 and allyl bromide 57 (Scheme 28.21) [27], An aryl copper species derived from the insertion of an aryne into a Cu—Br bond is a key intermediate in the reaction. 

In 1901, Ulhnann reported a method for the aryl-aryl coupling of aromatic hahdes [62], He observed that reaction of one or more nitro-groups, containing aromatic halides are converted to the corresponding biaryl derivatives as shown in Scheme 12.17. The exact mechanistic course of the Ullmann reaction has not yet been fully elucidated to date, and two possible pathways are currently considered, which deliver the biaryl species either via radical intermediates or via the formation of aryl copper species. As aryl copper species have been isolated before on several occasions, the second pathway seems more likely. 

Sanford has also described a fluorination of aryl trifluoroborates using Cu(OTf)2 with potassium fluoride as the source of fluoride (Scheme 15.73). The copper is proposed to play a dual role in not only being the mediator for the aryl-F coupling but also as the oxidant to access a proposed Cu (aryl)(F) intermediate. The yields tend to be somewhat lower than the (tBuCN)2CuOTf mediated protocol, though several heterocycles are reported as successful substrates in this system. 

A study, including computational results, of the role of copper enolate complexes in the a-arylation of enolates has shown that the reaction is likely to occur through oxidative addition of the iodoarene to form an aryl-copper(III) intermediate, (46), followed by reductive elimination to give the product. Copper(III) species are also likely to be involved in the meta-selective C-H arylation of acetanilides by diaryliodonium salts. However, radical species may be involved in the rhenium-catalysed electrophilic triflu-oromethylation of arenes using hypervalent iodine reagents. 

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