Reactions Involving Organocopper Intermediates

Many subsequent studies have led to the characterization of several organocop-per compounds that result from reaction of organolithium reagents with copper salts.  

The species from the 2 1 molar ratio are known as cuprates, and they have been used most frequently as synthetic reagents. In solution, lithium dimethylcuprate exists as a dimer, [LiCu(CH3)2]2, but the precise structure is not known. The compound is often represented as four methyl groups attached to a tetrahedral cluster of lithium and copper atoms. 

Discrete R2Cu anions have been observed in crystals in which the lithium cation is complexed by crown ethers.  

An important group of mixed cuprates are prepared from a 2 1 ratio of alkyllithium and CuCN. These compounds are called higher-order cyanocuprates. The composition of the major species in THF solution is R2CuCNLi2, but it is thought that most of the molecules probably are present as dimers. NMR studies have established that individual alkyl groups can exchange between copper centers.  

These reagents are similar to other cuprates in reactivity, but they are more stable than the dialkylcuprates. Because higher-order cuprates usually transfer only one of the two organic groups, it is useful to have a group that normally does not transfer. The 2-thienyl group has been shown to be useful for this purpose. In a 

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Conjugate addition reactions involving organocopper intermediates can be made enantioselective by using chiral ligands.86 Several mixed cuprate reagents containing... 

The mechanism of the reaction involves initial formation of a tri-organocopper intermediate, followed by coupling and loss of RCu. The coupling is not a typical polar nucleophilic substitution reaction of the sort considered in the next chapter. 

These reactions presumably involve fast metal-metal exchange (see Section 7.1.2.4) generating a more nucleophilic organocopper intermediate. The reductive elimination regenerates an active Cu(I) species. 

The involvement of organocopper intermediates in various cross-coupling reactions carried out in the presence of Cu1 is often suggested, although in the majority of cases no experimental proof is provided, and the actual role of Cu1 may be different (Section 9.6.3.2.1). The potential of copper-mediated cross-coupling can be shown by the stereospecific reaction of 3-trimethylsilylallylic alcohols, which takes place via a prior transmetalation of Si to Cu (37).157... 

Another very important method for adding a carbon chain at the -carbon of a,jS-unsaturated carbonyl system involves organometallic reagents, particularly organocopper intermediates. This reaction will be discussed in Chapter 8. 

The basic mechanism of the Stille reaction involves transmetallation, either directly or via an organocopper intermediate, with a Pd(H) intermediate generated by oxidative addition from the aryl halide or triflate. 

The commonest reactions involve the displacement of halide by hydroxide or cyanide ion to yield co-ordinated phenols or nitriles. Once again, the metal may play a variety of different functions. The polarisation of the C-Cl bond is the most obvious, but stabilisation of the product may be of equal importance, as could the involvement of a metal coordinated nucleophile. The availability of a one-electron redox inter-conversion between copper(n) and copper(i) also opens up the possibilities of radical mechanisms involving homolytic cleavage of the C-Cl bond. All of these different processes are known to be operative in various reaction conditions. In other cases, organocopper intermediates are thought to be involved. 

Exchanged copper ions in Y zeolite are located near supercages (47). As it has been proposed that copper carbenoid intermediates are involved in the copper-catalyzed dimerization of aryldiazomethanes (43), organocopper intermediates may be formed in narrow supercages. The excellent cis/trans selectivity is accounted for by the increased stability differences between the two intermediates (13c, 13t) leading to cis- and rrans-1,2-diarylethylenes, respectively, as shown in Fig. 5. Efficient catalysis of zeolite-encapsulated copper ions was proved in reactions of ethyl diazoacetate as well (48, 49). 

The first reaction is catalyzed by copper acetate, and it is supposed to involve two organocopper intermediates, while the C-H hydrogen atom is eliminated at the first step due to deprotonation (Scheme 8) [55]. 

Organocopper intermediates are involved in another broad class of reactions which accomplish the coupling of two organic substrates. The classical example of this type of reaction is the Ullman coupling of aryl halides, which is usually done with a copper-bronze alloy. Good yields in this reaction are limited to halides with electron-attracting substituents. Mechanistic and synthetic work has revealed the... 

The Rosenmund-von Braun reaction involves the treatment of aryl halides with Cu CN or a 2 1-mixture of K CN/Cul in pyridine, quinoline or an appropriate aprotic polar solvent such as A-methylpyrrolidine (NMP), DMF, DMAC, HMPA at temperatures ranging from 150-250°C". This reaction has been postulated to proceed via organocopper intermediates. The reactivity of aryl-halogen bonds is in the order I > Br > Cl F. The difference in reactivity between Ar-Br and Ar Cl is normally sufficient to permit selective cyanation of the Ar—Br bonds (for example, compounds 2 and 3 ) (Figure 7.2). Discrimination between Ar—Br and Ar—1 bonds, however, is more difficult to accomplish, and therefore mixtures of iodo- and bromo-substituted aryl [ C]nitriles can be expected whenever iodo, bromo aryl dihalides are employed The selechve replacement of iodine... 

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