Enolate Problems:

       a.   Enolates may be deprotonated on both sides of the carbonyl

Part of the problem with enolate formation is that many ketones may be deprotonated on either side of the carbonyl functional group.  As such, it is possible to form more than one enolate from any given starting material.  We have learned how to control enolate formation in systems where each side of the carbonyl is quite different, but in systems such as the on shown below, control is not nearly as easy to exert.

             b.   Product from an enolate reaction will also have acidic protons

The product formed in an enolate reaction will also have acidic protons.  As such the product may be deprotonated and a new enolate may be formed from the original product.  This is more of a problem under reversible conditions when base is always present to initiate formation of additional enol or enolate intermediates.  An example of this problem is shown below:

With the use of base, this problem may be circumvented using irreversible conditions and pre-forming the enolate.  We will discuss performing of the enolate in later pages.  Under acidic conditions (enol formation), the problem described above is always going to be a problem.  We will see that enol formation is used often for self-condensation reactions where the enol reacts with protonated starting carbonyl.  In this respect, the carbonyl is both electrophile and nucleophile, cutting down on the possible number of side products.  We will see some examples of self-condensation reactions under both base and acid conditions in the next few pages.

Aldol Reactions/Condensations:

When an enol or enolate of a ketone or aldehyde reacts with the carbonyl form of a ketone or aldehdye, to form a new C-C bond, the reaction is called an Aldol Reaction.  If the OH group is eliminated in the final step, this reaction is then called an Aldol Condensation (loss of water).  A general equation is shown below:

Base Catalyzed Condensation of Aldehydes/Ketones :

Shown below is a base catalyzed condensation of a carbonyl.  When the reaction occurs with either an aldehyde or ketone, it is known as an Aldol Condensation. 

In step 1, the carbonyl is deprotonated under protic conditions.  As such, this step is reversible, and the enolate could pick up a proton from the solvent to reform original starting material.  In step 2, the enolate reacts as a nucleophile with a starting carbonyl (due to the reversible conditions there will always be both enolate and starting carbonyl present in the solution).  The resulting anion will pick up a proton from the solvent to form a beta-hydroxy carbonyl.  Under basic conditions, the reaction may be stopped at this point.  If elimination of the alcohol is desired, the reaction may be heated under basic conditions.  Normally a hydroxy anion is a poor leaving group, however, with heat under highly anionic conditions it can be eliminated as water.  Base catalyzed Aldol condensations are powerful synthetic tools that allow carbon chain extension by the number of carbons present in the carbonyl starting material. Introduction of an alcohol functional group into the product lends nicely to further functional transformation such as an elimination reaction to give an alkene.