Aldimines lithium enolate aldol reaction

In general the reaction of an aldehyde with a ketone is synthetically useful. Even if both reactants can form an enol, the a-carbon of the ketone usually adds to the carbonyl group of the aldehyde. The opposite case—the addition of the a-carbon of an aldehyde to the carbonyl group of a ketone—can be achieved by the directed aldol reaction The general procedure is to convert one reactant into a preformed enol derivative or a related species, prior to the intended aldol reaction. For instance, an aldehyde may be converted into an aldimine 7, which can be deprotonated by lithium diisopropylamide (EDA) and then add to the carbonyl group of a ketone ... 

One of these important bases, diisopropylaminomagnesium bromide, was first introduced by Frostick and Hauser in 1949 as a catalyst for the Claisen condensation. However, the most generally useful base has turned out to be lithium diisopropylamide (LDA), which was first used by Hamell and Levine for the same purpose in 1950 (equation 3). After the introduction of LDA, it was more than 10 years before it was used by Wittig for the stoichiometric deprotonation of aldimines in what has come to be known as the Wittig directed aldol condensation.In a seminal paper in 1970, Rathke reported that the lithium enolate of ethyl acetate is formed by reaction of the ester with lithium hexamethyldisilazane in THF. - Rathke found that THF solutions of the lithium enolate are stable indefinitely at -78 °C, and that the enolate reacts smoothly with aldehydes and ketones to give p-hydroxy esters (equation 4). 

The lithium enolate of t-amyl acetate exists as a doubly chelated dimer in the presence of TMEDA (A,A,A, At -tetramethylethylenediamine). Reaction with a simple aldimine such as pflra-F-C6H4-CH=N-Ph gives an iV-lithiated -amino ester as a monomer, observed by Li- and i N-NMR. Kinetic studies by i F-NMR give a reaction order consistent with a TS of stoichiometry [(ROLi)2(TMEDA)2(imine)], supported by DPT calculations. That such aza-aldol condensations involve dimeric mechanistic routes runs counter to many claims that monomers are more reactive. 

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