Cuprates dialkylcuprates

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... 

A key step in the reaction mechanism appears to be nucleophilic attack on the alkyl halide by the negatively charged copper atom but the details of the mechanism are not well understood Indeed there is probably more than one mechanism by which cuprates react with organic halogen compounds Vinyl halides and aryl halides are known to be very unreactive toward nucleophilic attack yet react with lithium dialkylcuprates... 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

One diastereomer 5 was formed in large excess (98-76% de) on addition of the 2-(l-dimethyl-aminoethyl)phenyl group from the corresponding lithium dialkylcuprate and or lithium alkyl(2-thienyl)cuprate to prostereogenic enones64. 

Lithium bis(2-butyl)cupiate [Lithium bis-(l-methylpropyl)cuprate, 55, 112 Lithium dialkylcuprates, 55, 112 Lithium dimethylcuprate, 55, 112 Lithium diphenylcuprate, 55,112 LITHIUM DIPROPENYLCUPRATE, 55, 103,111... 

These reagents are qualitatively similar to other cuprates in reactivity, but they are more stable than the dialkylcuprates. Because cyanocuprate reagents usually transfer only one of the two organic groups, it is useful to incorporate a group which normally does not transfer. The 2-thienyl group has been used for this purpose.9 In a mixed alkyl-thienyl cyanocuprate, only the alkyl substituent is normally transferred as a nucleophile. 

Lithium bis(2-butyl)cuprate, 55, 112 Lithium bromide 55,129 Lithium, fei7-butyl-, 55, 123 Lithium dialkylcuprates, 55, 112 Lithium dnsopropylamide, 58, 43,58, 113, 122 166,168... 

SAMPLE SOLUTION (a) First inspect the target molecule to see which bonds are capable of being formed by reaction of an alkyl halide and a cuprate, bearing in mind that neither the alkyl halide nor the alkyl group of the lithium dialkylcuprate should be secondary or tertiary. 

Secondary and tertiary dialkylcuprates, lithium dialkenyl-, and even diphenyl-cuprates, add in very good yields to the reactive propionaldehyde diethyl acetal. The syn addition products may be trapped with a variety of electrophiles such as alkyl, alkenyl, alkynyl and aryl halides. The method has been used for the synthesis of several natural products. Substituted alkynic acetals also react with lithium dialkylcuprates in ether to furnish stable dialkenylcuprates of type (128) which do not eliminate to the corresponding alkoxy allenes (129) if the temperature is maintained below -20 C.164-179... 

As stated above, intermolecular coupling reactions between carbon atoms are of limited use. In the classical Wurtz reaction two identical primary alkyl iodide molecules are reduced by sodium. n-Hectane (C100H202), for example, has been made by this method in 60% yield (G. Stallberg, 1956). The unsymmetrical coupling of two alkyl halides can be achieved via dialkylcuprates. The first halide, which may have a branched carbon chain, is lithiated and allowed to react with copper(I) salts. The resulting dialkylcuprate can then be coupled with alkyl or aryl iodides or bromides. Although the reaction probably involves radicals it is quite stereoselective and leads to inversion of chiral halides. For example, lithium diphenyl-cuprate reacts with (R)-2-bromobutane with 90% stereoselectivity to form (S)-2-phenylbutane (G.M. Whitesides, 1969). 

Hindered cuprates. A novel route to lithium dialkylcuprates containing a secondary or a tertiary alkyl group involves reaction of the tosylhydrazone of an aldehyde with a copper reagent, such as dilithium trimethylcuprate (6, 386 7, 115). An example is shown in equation (I) for preparation of a cuprate containing the t-butyl group.1... 

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