Organocopper compounds preparation

Reactions of Organocopper Compounds Prepared from Chiral Carbanions 227... 

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. 

Cyanocuprates constitute a class of organocopper compounds that finds applications in organic synthesis.234 They are prepared by the direct reaction of an organolithium reagent and CuCN, with two different types of compounds being prepared depending on the stoichiometry employed the 1 1 ratio leads to RCu(CN)Li compounds whereas the 2 1 mixture affords R2Gu(GN)Li2. The lower- order or 1 1 cyanocuprates usually display the Cu-C-N-Li... 

Generally, organocopper compounds can be prepared by transmetallation between copper salts and organometallic reagents such as RLi, RMgX, and RZnX.53,53a,53b Copper alkynides can be obtained by reaction of terminal alkynes... 

During the last decade, a substantial number of novel (sometimes even stereoselective) strategies for the preparation of allenic prostaglandins have been devised. The approach used by Patterson involves a three-component coupling via a 1,4-addi-tion of the organocopper compound 121 to the enone 120, followed by alkylation of the enolate formed with the bromide 122 (Scheme 18.40) [121]. However, due to the notoriously low reactivity in the alkylation of the mixed copper-lithium enolate formed during the Michael addition [122], the desired product 123 was obtained with only 28% chemical yield (the alkylation was not even stereoselective, giving 123 as a 1 1 mixture of diastereomers). 

Since isolable organocopper) 11) compounds do not apparently exist, it is rather surprising that oxidation of the cuprate CdI+[(CF3)2Cu ] (prepared in situ) with thiuram disulfide affords (CF3)2Cu "S2CNEt2 (see Eqn. 1 in Scheme 1.6), the first and so far only example of an organocopper compound with the copper atom in the trivalent oxidation state. The structure of this compound was unambiguously proven by an X-ray crystal structure determination (see Fig. 1.2) [37]. 

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. 

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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