Zinc-copper reagents, preparation

The same mechanism is operative for the preparation of squaric acid derivatives of type 112. Treatment of 3,4-dicMorocyclobutene-l,2-dione with two different zinc-copper reagents provides the double addition-elimination product 112 in 67% yield (Scheme 2.41) [87]. 

The reaction between zinc-copper reagents and acid chlorides is very general and provides a useful synthesis of ketones [7, 34, 41, 42], This acylation has also been used to prepare various indoles substituted in position 2 (Scheme 2.42) [88],... 

A selective reaction of 1,4-brmetallic alkanes with CuCN 2LiCl allows the preparation of a range of new polyfunctional zinc-copper reagents. Thus, the reaction of 1,4-dizincated butane (94) with CuCN 2LiCl, followed by cyclohexenone in the presence of TMSCl (2 equiv), provides the new zinc-copper reagent 95 which reacts with 3-iodo-2-cyclohexenone, furnishing the diketone 96 in 64% yield (Scheme 33). ... 

Interestingly, bis(methylthio)-l-nitroethylene (380) reacts with dimetallic zinc-copper species leading to the corresponding exo-methylene cycloalkenes, such as 381 (Scheme 100) . / -Disubstitutcd nitroolefins are especially difficult to prepare by nitroaldol condensation. The addition of zinc-copper reagents to nitroolefins followed by a reaction with phenylselenyl bromide produces, after IFO, oxidation, EtZ mixtures of -disubstituted nitroalkenes, such as 382 (Scheme 100) . 

The same group2 now finds that a zinc/copper couple prepared by sonication of Zn and Cul in ethanol/H20 (9 1) permits conjugate addition of alkyl halides to enones and enals. The order of reactivity is RI > RBr and tert > sec primary. THF/H20 or Py/HzO or even pure water can be used as solvent. This reaction can hardly involve a classical organometallic reagent, but probably involves an alkyl radical. 

Addition reaction of zinc-copper reagents to nitro olefins is a versatile method for preparing polyfunctional nitroalkanes.20 A direct ozonolysis of the intermediate zinc nitronate furnishes the corresponding ketone (Nef-reaction).20... 

An example of an SN2 substitution reaction with a mixed zinc-copper reagent is shown in Scheme 22.22. The product 9 was used to prepare the bicyclic enone 10. In this example the starting alcohol gave rise to the asymmetric induction. The substitution was anti-selective.152... 

Alkynylation of zinc-copper compounds has been used for the synthesis of polyfunctional acetylenic ethers [84] and for the preparation of building blocks for pharmaceutically active compounds [85]. Whereas cross-coupling between non-activated iodoalkenes and zinc-copper reagents only proceeds at elevated temperatures and in polar solvents such as NMP or DMPU (60 12 h) [86], alkenyl... 

Polyfunctional zinc-copper reagents react efficiently with 1-bromo- or I-iodoaUcynes furnishing functionalized alkynes in good yields. The reaction proceeds at low temperature (—65 °C to —55 °C) and has been applied to the preparation of pheromones (Scheme 9-23 [53]) and polyfunctional acetylenic ethers [54]. 

This addition-elimination reaction can be applied to the preparation of squaric acid derivatives. Thus, the treatment of 3,4-dichlorocyclobutene-l,2-dione 27 with two different zinc-copper reagents furnishes polyfunctional squaric acid derivatives like 28, provided the first zinc-copper reagent bears a secondary or tertiary alkyl group (Scheme 9-26) [56]. 

One approach that was influential in our research on the synthesis and applications of allylboronates to access a-methylene y-lactones, which was reported by Sidduri and Knochel, utilize a mixed zinc copper reagent that allowed for the one-pot preparation of a-methylene y-lactones (Equation 10). The desired copper-based allylation reagents are formed with high selectivity through a cfs-carbocupration, and the diastereoselectivity of aldehyde addition is high, which suggests a Type I chair-Uke transition state similar to allylboration reactions (see Section 5.1). 

Polyoxygenated metabolites of unsaturated fatty acids have been prepared via the addition of functionalized zinc-copper reagents such as 477 to unsaturated aldehydes in the presence of BF3-OEt2, providing allylic alcohols of type 478 (Scheme 2-142, (eq. 

In 1958 Simmons and Smith described a new and general synthesis of cyclopropanes by treatment of olefins with a reagent prepared from methylene iodide and a zinc-copper couple in ether solution. 

The importance of solvent effects in the preparation of perfluoroalkyzinc reagents is further illustrated in the reaction of perfluoroalkyl iodides with zinc-copper couple. In DMSO, DMF, and HMPA, the main products are the fluo-roolefins The formation of the fluoroolefin is facilitated when the reaction is carried out in the presence of potassium thiocyanate [30] (equation 21)... 

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