Halides cuprate reagents

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... 

Suggest a combination of organic halide and cuprate reagent... 

The procedure described here illustrates the preparation of mixed lithium arylhetero(alkyl)cuprate reagents and their reactions with carboxylic acid chlorides,4 These mixed cuprate reagents also react with a,a -dibromoketones,12 primary alkyl halides,4 and a,/3-unsaturated ketones,4 with selective transfer of only the alkyl group. 

Although lower-order cuprate reagents will often engage in displacement reactions with alkyl halides, such reactions are usually slow. They are generally much less facile than 1,4-addition reactions to a,P-unsaturated enones or enoates. The latter processes are particularly facile when trimethylsilyl chloride is employed as an additive. It was Corey and Boaz10 who first recognised the accelerating effect of trimethylsilyl chloride on cuprate addition reactions to a,p-unsaturated carbonyls. Buszek therefore capitalised on Corey s earlier observations in his reaction of 10 with lithium dimethylcuprate to obtain 15. 

In much the same way it is possible to introduce the aryl group (Ar) either as the Ar or Ar synthon. As we have already mentioned, hydrocarbons ArH, or organometallic reagents like ArMgBr and ArLi, can serve as the equivalents of Ar in reactions with appropriate electrophiles. For the less obvious electrophilic Ar" synthon, the aryl halides can serve as suitable equivalents under appropriate conditions. Since aryl halides are usually not prone to react with regular nucleophiles, it is necessary to use cuprate reagents, R2CuLi, as nucleophiles or transition metal complexes as catalysts. 

To correlate the structural features of a specific copper or cuprate reagent with its reactivity, a better understanding of the interaction of such species with metal halides, ligands, solvents, and, last but not least, substrates is required. Such investigations have already begun and seem to have a promising future. In an elegant NMR study by Krause et al. [23] it was demonstrated that the reaction between t-BuCu(CN)Li and methyl propiolate (see Scheme 1.25) could be monitored by NMR. At -100 C, resonances attributable to the presence of a complex between the oi anocuprate and the substrate were observed. After the temperature had been raised to -40 C, the NMR spectrum of a vinylcopper intermediate... 

The stereochemical outcome of the addition was explained in terms of steric interactions, as illustrated in Scheme 10.64. The carbonyl groups of both the crotonyl and pivaloyl esters are co-ordinated by the magnesium organocuprate or the magnesium halides formed during the reaction. The crotonyl ester 191 probably prefers an -rran -conformation. As the /-face of the double bond is shielded by the bulky pivaloyl group, the cuprate reagent approaches from the less... 

As a rule, stoichiometric cuprate reagents have provided the most consistently successful results in reactions with primary alkyl electrophiles. Diethyl ether is the solvent of choice for reactions of alkyl sulfonates, while reactions of alkyl halides appear to be facilitated by THF. The enhanced basicity of the cuprate reagent in THF may be problematic, however, when racemization of an adjacent chiral center or elimination is a competing side reaction. For example, reactions of serine-derived 3-halo esters must be performed in ether, since elimination by-products are the only products isolated when THF is employed as the solvent elimination is more problematic with sulfonate than with halide leaving groups. 

The stabilized carbanion that is formed as an intermediate in the addition of the cuprate reagent to diethyl 2-vinylcyclopropane-l,l-dicarboxylate (6) can be alkylated by various alkyl halides prior to workup. A number of different disubstituted malonates 12 were obtained by this procedure. 

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