Polyfunctional zinc-copper reagent

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). ... 

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]. 

SCHEME 100. Reaction of functionalized zinc-copper reagents with polyfunctional nitroolefins... 

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... 

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... 

The reaction of zinc-copper reagents with acid chlorides has a remarkable generality [7,19] and has found many applications in synthesis (Scheme 9-30) [16,59-64]. The treatment of silyl-protected o-aminated benzylic zinc-copper derivatives such as 33 with an acid chloride leads to a 2-substituted indole 34. Aromatic and heterocyclic zinc compounds provide polyfunctional aromatic or heterocyclic ketones like 35 (see Section 9.6.8 Scheme 9-31) [60]. 

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]. 

In general, copper-zinc compounds, unlike organolithium-derived organocopper reagents, undergo clean addition reactions to nitroolefins. After Michael addition, the resulting zinc nitronates can be oxidatively converted into polyfunctional ketones, such as 117 (Scheme 2.45) [96]. 

Copper catalysed substitution reactions require high reaction temperatures and polar solvents like NMP.9 With activated alkenyl iodides bearing electron-withdrawing groups, copper-zinc reagents react readily leading to addition-elimination products.10-11 This method can be used to prepare a range of polyfunctional unsaturated molecules (Scheme 10.3).10-12... 

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