Organocuprates lithium coupling reactions

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). 

The synthetic potential of coupling reactions between vinyliodonium salts and organocuprates has not been exploited. However, some indication of their promise is provided by reported syntheses of bicyclic enediynes in the norbornadiene and 7-oxanor-bornadiene series from the appropriate bisiodonium triflates and lithium dialkynyl-cuprates (equation 221)148. 

In this concluding section, we will recall that a-selanylvinylmetal derivatives can be produced by a-deprotonation of vinylic aryl selenides 11, cleavage of ketene selenoacetals 12 or bromine/lithium exchange of a-bromovinyl selenides 13 (Scheme 49). These strategies involve vinylic selenides whose syntheses are not simple. More recent works have used organocuprate additions, hydrometala-tions (M = Sn, Zr) or hydroborations of readily available acetylenic selenides 14 (Scheme 49). The process can be regio- and stereocontrolled and produce the a-selanylvinylmetal derivatives under mild conditions. The latter can be considered as vinyl dianion equivalents and are very useful intermediates for cross-coupling reactions. 

The stereoselective 1,4-addition of lithium diorganocuprates (R2CuLi) to unsaturated carbonyl acceptors is a valuable synthetic tool for creating a new C—C bond.181 As early as in 1972, House and Umen noted that the reactivity of diorganocuprates directly correlates with the reduction potentials of a series of a,/ -unsaturated carbonyl compounds.182 Moreover, the ESR detection of 9-fluorenone anion radical in the reaction with Me2CuLi, coupled with the observation of pinacols as byproducts in equation (40) provides the experimental evidence for an electron-transfer mechanism of the reaction between carbonyl acceptors and organocuprates.183... 

Coupling with enol esters (7, 93). A new synthesis of an alkyl-substituted alkene involves coupling of a lithium dialkyl cuprate with an enol triflate,1 available from a ketone by reaction with triflic anhydride and 2,6-di-t-butylpyridine.2 A wide variety of organocuprates can be used and the geometry of the enolate is largely retained. Reported yields are in the range 60 100%. 

Likewise, the reaction of iodonium salt 57 with lithium organocuprate reagents affords products of coupling 65 in good yields (Scheme 30) [54]. 

Reaction of the alkenyl iodide with a lithium organocuprate, or with an organometallic species in a palladium-catalysed coupling, gives the corresponding substituted allylic alcohol (in which the substituents originally present in the propargylic alcohol are trans to each other). This method is applicable to a variety of synthetic problems in which the stereoselective introduction of a trisubstituted carbon-carbon double bond is involved. For example, it formed a key step in a synthesis of juvenile hormone (2.64). 

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. 

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. 

Inhibition by HMPA. Finally, it should be added that there are a few cases where HMPA slows the rate of a reaction. Such examples typically involved the inhibition of lithium catalysis by strong coordination of HMPA to lithium. For instance, two-bond NMR coupling in organocuprates is poorly observable... 

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