Organocopper Intermediates

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. 

Organolithium compounds can add to a, (3-unsaturated ketones by either 1,2- or 1,4-addition. The most synthetically important version of the 1,4-addition involves organocopper intermediates, and is discussed in Chap 8. However, 1,4-addition is observed under some conditions even in the absence of copper catalysts. Highly reactive organolithium reagents usually react by 1,2-addition, but the addition of small amounts of HMPA has been found to favor 1,4-addition. This is attributed to solvation of the lithium ion, which attenuates its Lewis acid character toward the carbonyl oxygen.111... 

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. 

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

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... 

Alternatively, copper salts can themselves be engaged in transmetalation with a nucleophilic coupling partner to give organocopper intermediates, which then either enter the Pd-catalyzed... 

Arylation of activated double bonds with diazonium salts in the presence of copper catalysts is known as the Meerwin reaction. The reaction is postulated to either proceed through an organocopper intermediate or through a chlorine atom transfer from chiral CuCl complex to the a-acyl radical intermediate. Brunner and Doyle carried out the addition of mesityldiazonium tetrafluoroborate with methyl acrylate using catalytic amounts of a Cu(I)-bisoxazoline ligand complex and were able to obtain 19.5% ee for the product (data not shown) [79]. Since the mechanism of the Meerwin reaction is unclear, it is difficult to rationalize the low ee s obtained and to plan for further modifications. 

To prepare the parent bisallene 118, 116 is first converted into its Grignard reagent (known from spectroscopic studies to possess the allenic structure), from which, presumably, by the addition of cuprous chloride the organocopper intermediate 117 is generated. Addition of further 116 subsequently provides a mixture of 118 and propargylallene (l,2-hexadien-5-yne) (29) (see below) in a 2 3 isomer ratio [44],... 

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. 

The organocopper intermediate can be generated at a more moderate 70 °C using a novel thiophenecarboxylate reagent. The reaction otherwise follows the same reaction path as above. 

The addition of a full equivalent of CuCN to certain ortho-lithiated aromatics allows the introduction of allylic and propargylic side chains. Due to the nature of the organolithium species originally involved, the exact nature of the organocopper intermediate is unknown (equation 28)40. 

In the presence of a copper salt, aromatic aldehydes, a,/3-unsaturated aldehydes, formates, and formamides react with 38 at or below room temperature to give the corresponding insertion products in good yield.289 This catalytic reaction shows similar stereo- and regiochemistry as does the thermal reaction of formamides. A transmetallation mechanism via an organocopper intermediate has been proposed for the Cu-catalyzed insertion. 

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