Addition of Enolates

Conjugate addition of enolates under some circumstances can be carried out with a catalytic amount of base. All the steps are reversible. 

Reactions of Carbon Nucleophiles with Carbonyl Compounds 

Retrosynthetically, there are inherently two possible approaches to the products of conjugate addition as represented below, where Y and Z represent two different anion-stabilizing groups. 

When a catalytic amount of base is used, the most effective nucleophiles are enolates derived from relatively acidic compounds such as (J-ketoesters or malonate esters. The adduct anions are more basic than the nucleophile and are protonated under the 

The fluoride ion is an effective catalyst for conjugate additions involving relatively acidic carbon nucleophiles.292 The reactions can be done in the presence of excess 

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Hydroxybutanal (from addition of enolate of acetaldehyde to acetaldehyde)... 

Formation of C — C Bonds by Addition of Enolates to Carbonyl Groups... 

Within this section, the term aldol reaction includes additions of enols and enolates to carbonyl compounds. This section concentrates on aldol additions which deliver nonracemic, /i-hydroxycarbonyl compounds. The chiral information can be located ... 

I.3.4.2.5.I.2. Aldol Additions of Enolates of Chiral Iron-Acetyl Complexes... 

Table 4. / -Hydroxy-lron Acyl Complexes 2 and 3 by Aldol Addition of Enolates 1 to Aldehydes...

The reaction is believed to proceed via a six-membered cyclic transition state, analogously to the carbonyl addition of enolates, but the energy differences between boat- and chair-like arrangements are lower for x-sulfinyl carbanions69. Tor tert-butyl sulfoxides only anti- and, vn-products are obtained, arising from the approach onto the same diastereotopic face of the anion, but with different relative topicity. The exchange of lithium by zinc causes an increase of the anft-produci, but attempts to titanate the anion failed (see Table 3)69. 

Addition of Enolates and Related Compounds to Imino Groups... 

In spite of the steric and electronic differences, the nucleophilic addition of enolates to imines (aza aldoi reaction) proceeds probably through similar pericyclic transition states as the carbonyl compounds do. 

Since /1-lactams can be prepared via reactions of ester enolates with imines, these reactions are of great interest for synthetic and medicinal chemists. The synthesis of naturally occurring antibiotics and other physiologically active //-lactams is an objective of much current work. Though the stereocenters in those reactions are often established by addition of enolates to imines, they are discussed in Section D.1.6.1.3. In this section, only some basic results concerning //-lactams are presented. 

The addition of boron enolates to imincs is useful for the construction of anti-fi-amino acid derivatives8. On the other hand, it is possible to control the direction of the diastereoselective addition of enolates from (A)-phenyl alkanethioates with imines9. 

Addition of Enolates and Azaenolates to, /i-l nsa titrated Carbonyl Compounds... 

Closely related to the 1,4-additions of enolates are the reactions of 1- and 2-azaallyl anions. 

In y-alkoxyfuranones the acetal functionality is ideally suited for the introduction of a chiral auxiliary simultaneously high 71-face selectivity may be obtained due to the relatively rigid structure that is present. With ( + )- or (—(-menthol as auxiliaries it is possible to obtain both (5S)- or (5/ )-y-menthyloxy-2(5//)-furanones in an enantiomerically pure form293. When the auxiliary acts as a bulky substituent, as in the case with the 1-menthyloxy group, the addition of enolates occurs trans to the y-alkoxy substituent. The chiral auxiliary is readily removed by hydrolysis and various optically active lactones, protected amino acids and hydroxy acids are accessible in this way294-29s-400. 

Q Chiral racemic y-alkyl-substituted enones the titanium(IV) chloride mediated addition of enol silanes and silylketene acetals to 7 shows high induced diastereoselection (diastereomeric ratios from 89 11 to more than 97 3) and the major isomer 8 results from addition of the enolsilane with ul topicity288. Re face attack on the S enantiomer of 7.)... 

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