Chiral enolates

When either or both of the reaction components has a chiral substituent, the reaction can be enantioselective (only one of the four diastereomers formed predominantly), and this has been accomplished a number of times. Enantioselective addition has also been achieved by the use of a chiral catalyst and by using optically active enamines instead of enolates. Chiral imines have also been used. ... 

Reagent control This involves the addition of a chiral enolate or allyl metal reagent to an achiral aldehyde. Chiral enolates are most commonly formed through the incorporation of chiral auxiliaries in the form of esters, acyl amides (oxazolines), imides (oxazolidinones) or boron enolates. Chiral allyl metal reagents are also typically joined with chiral ligands. 

Nu = chiral sulfoximinyl ester enolates, chiral propionyloxazolidinones... 

Diastereomer analysis on the unpurified aldol adduct 52b revealed that the total syn anti diastereoselection was 400 1 whereas enantioselective induction in the syn products was 660 1. On the other hand, Evans in some complementary studies also found that in the condensation of the chiral aldehyde 53 with an achiral enolate 56a only a slight preference was noted for the anti-Cram aldol diastereomer 58a (58a 57a = 64 36). In the analogous condensation of the chiral enolate 56b. however, the yn-stereoselection was approximately the same (57b 58b > 400 1) as that noted for enolate 49 but with the opposite sense of asymmetric induction (Scheme 9.17). Therefore, it can be concluded that enolate chirality transfer in these systems strongly dominates the condensation process with chiral aldehydes. 

Aldol condensation of aldehydes with chiral zirconium enolates. This reaction can exhibit high levels of em/iw-diastcrcosclection. Thus the zirconium enolate of the propanamidc 1, reacts with aldehydes to afford predominately a single aldol diaslercomer (2) in 96 98% cc. The enolate reacts with both (R)- and (S)-aldchydcs to form comparable levels of ervl/iro-selection. Thus enolate chirality suppresses the influence of chirality of the aldehyde.4... 

Keywords Protonation, Metal enolates, Chiral proton sources, Achiral proton sources... 

Michael Addition. Titanium imide enolates are excellent nucleophiles in Michael reactions. Michael acceptors such as ethyl vinyl ketone, Methyl Acrylate, Acrylonitrile, and f-butyl acrylate react with excellent diastereoselection (eq 21 ). - Enolate chirality transfer is predicted by inspection of the chelated (Z)-enolate. For the less reactive unsaturated esters and nitriles, enolates generated from TiCl3(0-j-Pr) afford superior yields, albeit with slightly lower selectivities. The scope of the reaction fails to encompass p-substituted, a,p-unsaturated ketones which demonstrate essentially no induction at the prochiral center. Furthermore, substimted unsamrated esters do not act as competent Michael acceptors at all under these conditions. 

An improvement in aldol diastereoselection for a given boron ligand is obtained when less polar solvents are employed, presumably due to transition state compression in nonpolar solvents. This solvent effect is also significant in enolate chirality transfer in asymmetric aldol reactions. 

Scheme 3.15. Controlled stereoselective enolate formation and asymmetric alkylation of a second generation camphor ester enolate chiral auxiliary [75].

Chirale 3-Acy]-2-oxo-1,3-oxazolidine58 bzw. chirale Carbonsaure-ester IV59 sind ebenfalls hervorragende Reagenzien, um iiber die Enolate chirale a-Alkyl-carbonsauren herzustel-len z. B.59 ... 

Mandelic acid and its derivatives are utilized as convenient precursors for the introduction of a chiral center, and they possess the extra advantage of bearing a useful functional group. Many mandelic acid derivatives also act as chiral auxiliaries for the induction of a chiral center in stereoselective transformations. Numerous natural products, such as macrolides and ionophore antibiotics, possess a carbon framework that may be viewed synthetically as arising from a sequence of highly stereo- and enantioselective aldol condensations. Boron enolates, chiral auxiliaries derived from mandelic acids 1 or 2, provide remarkably high aldol stereoselectivity. 

Within the last 10 years, various methods have been employed to synthesize (7 )-citramalate derivatives with acceptable enantiomeric purity. One of the first methods that produced reasonably enriched product was based on a tin(II) enolate chiral auxiliary-induced asymmetric aldol-type reaction. 

Several syntheses of chiral camphor derivatives make use of the CH acidity of the methylene group attached in a-position to the carbonyl function (C-3). Thus, isoamyl nitrite converts camphor to 3-isonitrosocamphor which readily undergoes hydrolysis to the yellow camphorquinone. Bromination leads to 3-bromocamphor which is sulfonated to 3-bromocamphor-3-sulfonic acid with concentrated sulfuric acid. 3-Lithiated camphor obtained with phenyllithium is carboxylated to endo- and exo-isomers of camphor carboxylic acid. The Claisen condensation of camphor with esters of carboxylic acids provides enolized chiral 1,3-diketones, converting metal cations to chiral metal chelates. 

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