Alkyl halides with lithium dialkylcuprates

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... 

Preparation of alkanes using lithium di-alkylcuprates (Section 14.11) Two alkyl groups may be coupled together to form an alkane by the reaction of an alkyl halide with a lithium dialkylcuprate. Both alkyl groups must be primary (or methyl). Aryl and vinyl halides may be used in place of alkyl halides. 

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... 

Alkyl p-toluenesul fonates react with lithium dialkylcuprates in the same way that alkyl halides do. Treatment of the preceding p-toluenesulfonate with lithium dibutylcuprate gives the desired compound. 

The analogy extends toward their reaction with lithium dialkylcuprates. Just as alkyl halides react with lithium dialkylcuprates to form carbon-carbon bonds, so do a,p-unsaturated carbonyl compounds. 

Lithium dialkylcuprates react with alkyl halides to produce alkanes by carbon-carbon bond formation between the alkyl group of the alkyl halide and the alkyl group of the dialkylcuprate... 

Lithium diarylcuprates are prepared m the same way as lithium dialkylcuprates and undergo comparable reactions with primary alkyl halides... 

Another group of Japanese workers91 found that the sulphoxonium salt, 7, was reducible to sulphoxides with either alkyllithiums or lithium dialkylcuprates, the exact reaction pathway being complicated by halide ions originating from the preparation of the metal alkyls. However, good yields of methyl phenyl sulphoxide were obtained by reduction of 7 with sulphur dioxide or a thiol in pyridine (equation 37). 

One alkyl group of the lithium dialkylcuprate undergoes a coupling reaction with the second alkyl halide (R -X) to afford an alkane. 

The final step in the sequence can be accomplished with less reactive halides such as hexyl iodide with two modifications to the reaction conditions the lithium dialkylcuprate must b e generated in 1,2-dimethoxyethane instead of diethyl ether and HMPA must be added along with the alkylating agent as illustrated in the following example ... 

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). 

Reactions of vinylphosphonates j2 with an equimolar amount of lithium dialkylcuprates J result in the formation of complexes 3 containing two different organic ligands. These complexes react with electrophiles in various ways. In each of them a diverse ligand plays the role of a nucleophile. Hydrolysis of 3 or alkylation with alkyl halides affords the corresponding phosphonates k and 5 comprising extended saturated carbon chains bonded to phosphorus. However, in a number of reactions with aldehydes, the complexes 3 were found to undergo almost completely selective transformation into carbinols 6... 

If we want to couple two groups together efficiently, we can do it by using an organocop-per reagent, a lithium dialkylcuprate, to couple with an alkyl halide. 

Lithium dialkylcuprate reagents (Gilman reagents) are formed by the reaction of two equivalents of an organolithium reagent with cuprous iodide. Reaction of the dialkylcuprate with an alkyl, aryl, or vinyl halide forms a new carbon-carbon bond. 

The Corey—Posner, Whitesides—House reaction involves the coupling of a hthium dialkyl-cuprate (called a Gilman reagent) with an alkyl, alkenyl, or aryl halide. The alkyl group of the lithium dialkylcuprate reagent may be primary, secondary, or tertiary. However, the halide with which the Gilman reagent couples must be a primary or cychc secondary alkyl halide if it is not alkenyl or aryl. 

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