Organocopper compounds chiral

In solution, organocopper compounds may exist as an equilibrium of several species, and a loss of enantioselectivity may be inevitable if this equilibrium process produces some achiral but more reactive cuprate species. The way to overcome this problem is to develop a highly reactive chiral reagent to suppress the undesired, nonchiral species-mediated reactions. 

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

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... 

In solution, organocopper compounds show a dynamic behavior, with equilibria between several species. If this leads to the formation of achiral, but more reactive cuprates, a loss of enantio-selectivity is unavoidable. Therefore, it is crucial to develop chiral reagents which react so rapidly with the substrate that undesired competing reactions are suppressed. 

Organocopper reagents are the most reliable species for conjugate additions and a number of approaches towards chiral cuprates has been developed. The approaches are classified into two categories one is the chiral heterocuprate obtained by treatment with chiral alcohols, amines, sulfonamides, and thiols. The other involves organocopper compounds coordinated by chiral external ligands such as phosphines, sulfides, and oxazolines. 

Nucleophilic substitutions reactions with organocopper compounds or the more widely applied organocyanocuprates in the presence of Lewis acids have been reported on a./S-ethylenic acetals and allylic mesylates or acetates. Mangeney and co-workers have reported regio- and diastereoselective Sn2 or Sn2 reactions on chiral acetals of cyclic aldehydes promoted by PhCu and Furthermore, organocoppers react efficiently... 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

Table 1. Allenes from Propynyl Compounds by Organocopper(i)-Mediated 1,3-Substitution with Chirality Transfer...

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