Alkaline earth metal amide enolates

Alkaline earth metal amides have a unique place in enolate chemistry in light of the preceding discussion. Yet, amides without steric demand—from NaNH2 to UNIT,—also are usually not suitable for the formation of enolates, since their nucleophilicities exceed their basicities. On the other hand, the amides LTMP, LDA, and LiHMDS (structures in Figure 4.18) are so bulky that they can never act as nucleophiles and always deprotonate C,H acids to the respective enolates. 

For the quantitative deprotonation of nitroalkanes and active-methylene compounds, there is no need to employ the heavy artillery of lithium amides. Rather, it suffices to employ alkaline earth metal alkoxides or alkaline earth metal hydroxides. In addition, equilibrium reactions between these C,H acids and amines form enough enolate to initiate enolate reactions. 

The addition of an alkaline earth metal enolate A to a carbonyl compound is always an exer-gonic process irrespective of whether the enolate is derived from a ketone, an ester, or an amide and whether the carbonyl compound is an aldehyde or a ketone (Figure 13.44, top). One of the reasons for this exergonicity hes in the fact that the alkaline earth metal ion is part of a chelate in the alkoxide B of the aldol addition product. The driving forces for the additions of alkaline earth metal enolates of esters and amides to carbonyl compounds are further increased because the aldol adducts B are resonance-stabilized, whereas the enolates are not. 

Combination of achiral enolates vith achiral aldehydes mediated by chiral ligands at the enolate counter-ion opens another route to non-racemic aldol adducts. Again, this concept has been extremely fruitful for boron, tin, titanium, zirconium and other metal enolates. It has, ho vever not been applied very frequently to alkaline and earth alkaline metals. The main, inherent, dra vback in the use of these metals is that the reaction of the corresponding enolate, vhich is not complexed by the chiral ligand, competes vith that of the complexed enolate. Because the former reaction path vay inevitably leads to formation of the racemic product, the chiral ligand must be applied in at least stoichiometric amounts. Thus, any catalytic variant is excluded per se. Among the few approaches based on lithium enolates, early vork revealed that the aldol addition of a variety of lithium enolates in the presence of (S,S)-l,4-(bisdimethylamino)-2,3-dimethoxy butane or (S,S)-1,2,3,4-tetramethoxybutane provides only moderate induced stereoselectivity, typical ee values being 20% [177]. Chelation of the ketone enolate 104 by the chiral lithium amide 103 is more efficient - the j5-hydroxyl ketone syn-105 is obtained in 68% ee and no anti adduct is formed (Eq. (47)) [178]. 

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