Directed aldol reaction preformed lithium enolates

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 ... 

A number of methods have been developed to bring about the directed aldol reaction between two different carbonyl compounds to give a mixed-aldol product. Most of them proceed from the preformed enolate or silyl enol ether of one of the components. With enolates, a number of metal counterions have been used and the best results have been obtained with lithium or boron enolates, although zinc or transition-metal enolates have found widespread use. For example, the aldol reaction of acetone with acetaldehyde under basic aqueous conditions is inefficient... 

Condensation Reactions. Traditionally, intermolecular aldol condensation reactions have been performed under equilibrating conditions using weaker bases than r-BuOK in protic solvents. Since the mid-1970s, new methodology has focused on directed aldol condensations which involve the use of preformed Lithium and (jroup 2 enolates, (Troup 13 enolates, and transition metal enolates. Although examples of the use of f-BuOK in intramolecular aldol condensations are limited, complex diketones... 

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