Zinc-copper reagents reactions with acid chlorides

Ziegeler-Natta conditions 304 zig zag chromophores 217 zinc-copper exchange 275 zinc-copper organometallics 397 zinc-copper reagents 396, 397 reactions with acid chlorides 398 zinc-copper species RCu(CN)ZnX 394 zinc enolates 20 zinc metal, activated 291 zinc organometallics 278, 389 zinc salts 9... 

Another type of o-aminobenzyl synthon is based on o-(bis-trimethylsilylaminobenzyl)copper-zinc reagents <89TL4795>. These are prepared from the corresponding benzylic bromides by reaction with zinc, followed by addition of cuprous cyanide. These reagents react with acid chlorides to give 2-substituted indoles. Since the reactions proceed by C-acylation rather than iV-acylation, the conditions required for cyclization are mild and typically the C-acylated intermediates are not isolated. 

While the reaction of acid chlorides with organoz-inc halide compounds is relatively inefficient, the reaction with the corresponding copper-zinc reagents or the catalysis with Pd salts represents a smooth route for the preparation of ketones in very good yields (equation 58). 

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]. 

The uncatalyzed reaction of acid chlorides with organozincs is sluggish and inefS-cient. It is often complicated by side reactions and leads usually to low yields of the desired acylation products. In contrast, the CuCN 2LiCl-mediated acylation of various zinc reagents affords ketones in excellent yields. The reaction of the zinc-copper reagent 328 obtained by the direct zinc insertion to the iodide 329 followed by a transmetallation with CuCN 2LiCl reacts with benzoyl chloride at 25 °C leading to the ketone 330 in 85% yield [52b]. The functionalized benzylic bromide 331... 

The zinc organo-lialide is prepared for use by heating together the zinc-copper couple, the alkyl or aiyl halide, ethyl acetate, and toluene for about an hour, the reaction being started if necessary with a ciystal of iodine. All the reagents must be well dried, and the colomdess viscous liquid which results is ntilised by adding to it the acid chloride dissolved in toluene, and when the required amount has been added the intermediate zinc complex is decomposed by the addition of dilute sulphuric acid.1... 

With anhydrides, aluminum chloride reacts to form the acid chloride complex. Zinc chloride is more commonly used with acid anhydrides, although this is restricted practically to acetic and other simple anhydrides that can be used as the reaction solvent. This nevertheless remains a useful reagent for acylations, giving predominantly nonconjugated products. Active zinc compounds prepared from a zinc-copper couple and alkyl halides also promote the acylation of alkenes by acyl chlorides at room temperature. ... 

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