Organocuprates coupling with alkyl halides

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... 

Organocuprates are much less prone to 8-hydride elimination reaction and rapidly couple with alkyl halides. In this respect, they complement the palladium reagents. A disadvantage is their basicity and that their most common sources are the strongly basic and nucleophilic alkyl lithium and Grignard reagents, which require protection of sensitive functionalities. 

In addition to organic halides, alkyl tosylates (R OTs, Section 9.13) also react with organocuprates (RgCuU) to form coupling... 

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... 

Alkanes can also be prepared from alkyl halides by reduction, directly with Zn and acetic acid (AcOH) (see Section 5.7.14) or via the Grignard reagent formation followed by hydrolytic work-up (see Section 5.7.15). The coupling reaction of alkyl halides with Gilman reagent (R 2CuLi, lithium organocuprates) also produces alkanes (see Section 5.5.2). 

Coupling of the organocuprate with an alkyl, vinyl, or aryl halide ... 

Coupling of an organocuprate reagent (R2CuLi) with an alkyl halide, R X (26.1)... 

Specifically, if two equivalents of n-butyllithium (28) react with Cul, the product is lithium dibutylcuprate (47). Note the nomenclature that is used, where the alkyl unit of the organolithium reagent is combined with term cuprate, which describes the oxidation state of the copper. The carbon attached to copper in 47 is 6- (it is carbanionic), and organocuprates such as 47 are very reactive with most alkyl halides, leading to the coupling product. In one experiment, 47 was formed in THF at -78°C and then treated with 1-iodoheptane as the temperature was allowed to rise to 0°C. The product of this reaction is undecane (48), isolated in 53% yield. ... 

This is a very general reaction in that primary, secondary, and tertiary alkyl halides react with primary, secondary, or tertiary organocuprates. The halide can be a chloride, a bromide, or an iodide, but iodides are more reactive than bromides, which are more reactive than chlorides. Another example is the reaction of 49 with lithium diphenylcuprate to give 50. The reaction of alkyl halides and organocuprates is the preferred method for coupling an alkyl halide to an organometallic compound. Many different hydrocarbons can be prepared. 

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. 

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