Organocopper compounds addition reactions

Several papers in the literature of the last fifteen years deal with the problem of combining organometallie intermediates and a,/l-unsaturated systems in a 1,4-fashion. With organocopper compounds this reaction is, in general, successful, but with polar organometallie intermediates RM the results (1,2- or 1,4) are very strongly dependent upon the structures of the group R and the acceptor. Substituents can have a profound influence upon the ratio of 1,4- and 1,2-addition. 

Organocopper compounds have been trapped by coordination with organic bases. In addition, arylcopper compounds (ArCu) have been independently prepared and shown to give biaryls (ArAr ) when treated with aryl iodides (Ar I). A similar reaction has been used for ring closure. 

As in the case of addition reactions of carbon nucleophiles to activated dienes (Section HA), organocopper compounds are the reagents of choice for regio- and stereoselective Michael additions to acceptor-substituted enynes. Substrates bearing an acceptor-substituted triple bond besides one or more conjugated double bonds react with organocuprates under 1,4-addition exclusively (equation 51)138-140 1,6-addition reactions which would provide allenes after electrophilic capture were not observed (cf. Section IV). 

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]. 

As is implicit in the fact that the products of the (stoichiometric) 1,6-cuprate addition - the lithium allenyl enolate and the organocopper compound - are formed as independent species, it is also possible to conduct the reaction catalytically through in situ regeneration of the cuprate. The reaction can thus be run in a continuous mode, with only catalytic amounts of the preformed cuprate being necessary (with simultaneous addition of the substrate and the organolithium compound) enabling the desired allenes to be prepared even on larger scales (Eq. 4.17) [3oj. 

The synthetic application of organocopper compounds received a major impetus from the study of the catalytic effect of copper salts on reactions of Grignard reagents with y.,(i-unsaturated ketones.1 Whereas Grignard reagents normally add to conjugated enones to give the 1,2-addition product, the presence of catalytic amounts of Cu(I) results in... 

Analogous to the use of chiral acetals one can employ chiral N,O-acetals, accessible from a, -unsatu-rated aldehydes and certain chiral amino alcohols, to prepare optically active -substituted aldehydes via subsequent Sn2 addition and hydrolysis. However, the situation is more complicated in this case, since the N,0-acetal center constitutes a new stereogenic center which has to be selectively established. The addition of organocopper compounds to a, -ethylenic oxazolidine derivatives prepared from unsaturated aldehydes and ephedrine was studied.70-78 The (diastereo) selectivities were rather low (<50% ee after hydrolysis) in most cases, the highest value being 80% ee in a single case.73 There is a strong solvent effect in these reactions, e.g. in the addition of lithium dimethylcuprate to the ( )-cinnamaldehyde-derived oxazolidine (70 Scheme 28) 73 the (fl)-aldehyde (71) is formed preferentially in polar solvents, while the (S)-enantiomer [ent-71) is the major product in nonpolar solvents like hexane. This approach was utilized in the preparation of citronellal (80% ee) from crotonaldehyde (40% overall yield).78... 

The chiral organocopper compound (186) adds diastereoselectively to 2-methyl-2-cyclopentenone, allowing the preparation of optically active steroid CD-ring building blocks (Scheme 68).202-204 A related method was applied to a synthesis of the steroid skeleton via an intramolecular (transannular) Diels-Alder reaction of a macrocyclic precursor.203 Chiral acetone anion equivalents based on copper azaeno-lates derived from acetone imines were shown to add to cyclic enones with good selectivity (60-80% ee, after hydrolysis).206-208 Even better ee values are obtained with the mixed zincate prepared from (187) and dimethylzinc (Scheme 69). Other highly diastereoselective but synthetically less important 1,4-additions of chiral cuprates to prochiral enones were reported.209-210... 

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