Enones organocuprates

Like other carbon-carbon bond forming reactions organocuprate addition to enones is a powerful tool m organic synthesis... 

Reactions of highly electron-rich organometalate salts (organocuprates, orga-noborates, Grignard reagents, etc.) and metal hydrides (trialkyltin hydride, triethylsilane, borohydrides, etc.) with cyano-substituted olefins, enones, ketones, carbocations, pyridinium cations, etc. are conventionally formulated as nucleophilic addition reactions. We illustrate the utility of donor/acceptor association and electron-transfer below. 

Addition of RJCuLi to bridgehead enones.1 Ordinarily organocuprates do not react with a bridgehead halide. However, they can undergo conjugate addition to bridgehead enones generated in situ from p-bromo ketones with potassium t-butoxide or lithium 2,6-di-r-butyl-4-methylphenoxide (6,95). 

The reaction of 1,2-allenyl ketones with organocuprates afforded /3,y-unsaturated enones. The reaction with mixed cuprates RR CuLi delivered, depending on the properties of R and R, two products 430 and 431 [192]. 

Scheme 6.1. Diastereoselectivity in conjugate addition of organocuprates to chiral cyclic enones.

The addition of organocuprates to chiral decalin enone systems has been explored in the context of steroid synthesis. For the addition of lithium dimethylcuprate to enones 28, 31, and 34, the major diastereomer obtained can easily be predicted by employment of a qualitative conformational analysis (Scheme 6.6) [11-13]. Thus,... 

Systematic studies of organocuprate conjugate additions to three pairs of y-epimeric and geometrically isomeric y-chiral acyclic enones and enoates (159a,b) and (160a,b) have allowed one to generalize diastereofacial selectivity of these reactions (Scheme 20). 

Bicyclic or polycyclic enones may give slow or inefficient reaction with organocuprates. In particular, it is those enones which contain substituents arranged so as to create a steric hindrance on the carbon 3 to the carbonyl that see the greatest effect. The yields are often low to moderate, unless additional activation is provided. For example, when the bicyclic enone (23) was treated with R2C11U (R = 3-pentynyl), the -substituted product was formed in only 46% yield,69 while exposure of the same enone to RQ1BF3 (R = 3-pentynyl) gave the same (3-alkylated product in 76% yield (Scheme 9).70... 

The stereoselectivity in reactions of P-alkylthio-a,(3-enones with organocuprates is dependent upon both the solvent and bulk of the ligand in the cuprate. Ether solutions favor inversion, while THF solutions favor retention (Scheme 19). It was proposed that in coordinating solvents such as THF, a more reactive enolate is formed, which eliminates before rotation occurs, thereby giving retention of configuration.108... 

Reaction of die organocuprate intermediate widi water gives the fully reduced product. If die organocuprate intermediate is reacted widi bromine, the a-brominated product is formed. This product has die equivalent oxidation level as the starting enone but differs in that an additional carbon substituent is present. Functionally this is equivalent to the addition of HBr to an enone. Thus functionally no net redox has taken place. If individual steps are considered, it is clear that the first step (addition of the organocuprate to die enone) is a reduction and the second step (reaction of the cuprate with bromine) is an oxidation. 

Tricarbonyliron complexes of enones.1 Reaction of Fe2(CO), with a,f -enones in toluene at 70-75° results in tricarbonyliron complexes, which on reaction with Grignard reagents, organolithium, or organocuprates are converted into 1,4-diketones. 

The copper-catalyzed 1,4-addition of Grignard reagents to enones has been described by Kharasch in 1941, that is, one decade before the discovery of Gilman cuprates (1952) and more than two decades before the first use of organocuprates in conjugate addition reactions. Consequently, numerous variations and applications of the method have been reported over the years.3 5,7 7a 23 Not surprisingly, several of the advances made in the last decade with... 

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