Attack by Enolates on the Carbonyl Function Aldol Condensation

ATTACK BY ENOLATES ON THE CARBONYL FUNCTION ALDOL CONDENSATION 

We have seen the dual functional capability of carbonyl compounds electrophilic at the carbonyl carbon, potentially nucleophilic at the adjacent a-carbon. In this section we introduce one of the most frequently employed carbon-carbon bond-forming strategies attack of an enolate ion at a carbonyl carbon. The product of this process is a jS-hydroxy carbonyl compound. Subsequent elimination of water may occur, leading to ,jS-unsaturated aldehydes and ketones. The next three sections describe these reactions in detail, and Real Life 18-1 illustrates them in a biological context. 

Addition of a small amount of dilute aqueous sodium hydroxide to acetaldehyde at low temperature initiates the conversion of the aldehyde into a dimer, 3-hydroxybutanal, with the conunon name aldol (from aWehyde alcohoZ)- Upon heating, this hydroxyaldehyde dehydrates to give the final product, the a,j8-unsaturated aldehyde fra 5-2-butenal. This reaction is an example of the aldol condensation. The aldol condensation is general for aldehydes and, as we shall see, sometimes succeeds with ketones as well. We first describe its mechanism before turning to its uses in synthesis. 

The aldol condensation highlights the two most important facets of carbonyl group reactivity enolate formation and attack of nucleophiles at a carbonyl carbon. The base (hydroxide) is not strong enough to convert all of the starting aldehyde into the corresponding enolate ion, but it does bring about an equilibrium between the aldehyde and a small 

Note that hydroxide ion functions as a catalyst in this reaction. The last two steps of the sequence drive the initially unfavorable equilibrium toward product, but the overall reaction is not very exothermic. The aldol is formed in 50-60% yield and does not react further when its preparation is carried out at low temperature (5°C). 

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Attack by Enolates on the Carbonyl Function Aldol Condensation CHAPTER 18... 

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