Organocuprates, reaction with halides

Scheme 8.1 gives several examples of the use of coupling reactions of organocuprate reagents with halides and acetates. Entries 1 to 3 are examples of the... 

Similarly to the alkyl derivatives, the most common route for arylcopper compounds is the reaction of a copper halide and aryllithium compounds (Equation (4)). Organocuprates with aryl groups are obtained by using an appropriate excess of the lithium reagent. Magnesium aryls have also been employed in transmetallation reactions with Cu(l) salts to yield both arylcopper compounds and arylcuprates (Equations (5) and (6)). 

Reactions with cyclopropene.11 Lithium organocuprates react with the cyclo-propenone ketal 1 (12, 152-154) to form a copper species (a) that behaves as an enolate of a cyclopropanone. Thus it reacts with alkyl halides to form cis-2,3-disubstituted derivatives of 1. 

Fig. Reaction of an organocuprate reagent with an alkyl halide.

In addition to their reactions with acid chlorides, epoxides, and a,P-unsaturated carbonyl compounds (Sections 20.13-20.15), organocuprate reagents (R2CuLi) also react with organic halides R X to form coupling products R-R that contain a new C-C bond. Only one R group of the organocuprate is transferred to form the product, while the other becomes part of RCu, a reaction by-product. 

Severe limitations on the usefulness of the classical Wurtz reaction in the production of cross-coupled products have led to the development of many more generally useful variants. In particular, the use of copper catalysis and of stoichiometric organocuprate species have proved very valuable. The reactions of ir-allylnickel halides with sp halides is also represented by equation (1), and the uses of these reagents are treated separately. In order to provide a balanced view of the value of ir-allylnickel halides, some additional reactions with centers other than sp are described. 

There are two major reactions of organocuprates, and both give products reminiscent of a carbon nucleophile (1) reaction with alkyl halides and (2) conjugate addition with a,p-unsaturated ketones. Conjugate addition to a, 3-unsaturated ketones is promoted when ether is used as a solvent.381 The substitution reaction is promoted by the use of THF or ether-HMPA as a solvent. l As mentioned earlier, the mechanism of these reactions probably involves a one-electron transfer, although other mechanistic proposals are in the literature,but the synthetic result is that expected of a carbon nucleophile. 85 The general reactivity of organocuprates with electrophiles follows the order ... 

Coupling reactions with alkyl halides often use large excess of cuprate, as mentioned above, which can be a severe limitation if the halide precursor to the organocuprate is difficult to prepare or unavailable from commercial sources. A solution to this problem is to prepare a cuprate with a ligand that is less reactive, allowing selective transfer of the substituent of choice. An example is the use of 417 in a reaction with 418 that... 

The problem of 1,2 versus 1,4 addition persists with most nucleophiles in their reactions with a,P-unsaturated carbonyl compounds. However, one class of carbanion reagent gives almost exclusively 1,4 addition the organocuprates. These reagents were introduced in Chapter 15 (Section 15.6), where they reacted with alkyl halides to give coupling products. 

Reaction of cis- or trans-i -bromostyrene and organocuprates proceeds with retention of configuration (Corey and Posner, 1967 Whitesides et al., 1969a). Klein and Levene (1972) have accounted for the stereospecific substitution in terms of a mechanism with the transition state of type LXX a nucleophile approaches perpendicularly to the plane of the molecule and the halide ion leaves perpendicularly to the plane from the opposite side. A... 

Reaction of organocuprate reagents with acyl halides is extremely facile and provides a new technique for ketone synthesis (Vig et al., 1968a Jukes et al., 1970a Posner et al., 1970, 1972, 1973 Jallabert et al., 1970 Normant and Bourgain, 1970 Luong-Thi et al., 1971). The reaction proceeds under conditions sufficiently mild that carbonyl, ester, or cyano functionalities are not affected. 

Organocuprates can react with all alkyl halides except tertiary alkyl halides. Because they can react with vinylic halides and aryl halides (an aryl hahde has a hydrogen attached to a benzene ring), they can be used to prepare compounds that cannot be prepared by Sn2 reactions with Grignard reagents or organolithium compounds. (Remember that vinylic and aryl halides cannot undergo nucleophilic attack Section 9.5). 

The most frequently used organocuprates are those m which the alkyl group is pri mary Steric hindrance makes secondary and tertiary dialkylcuprates less reactive and they tend to decompose before they react with the alkyl halide The reaction of cuprate reagents with alkyl halides follows the usual 8 2 order CH3 > primary > secondary > tertiary and I > Br > Cl > F p Toluenesulfonates are somewhat more reactive than halides Because the alkyl halide and dialkylcuprate reagent should both be primary m order to produce satisfactory yields of coupled products the reaction is limited to the formation of RCH2—CH2R and RCH2—CH3 bonds m alkanes... 

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