Using specific enol equivalents to alkylate aldehydes and ketones

Enolates have two nucleophilic sites the carbon and the oxygen atoms on p. 526 we showed that  

Aldehydes are so electrophilic that, even with LDA at -78°C, the rate at which the deprotonation takes place is not fast enough to outpace reactions between the forming lithium enolate and still-to-be-deproton ated aldehyde remaining in the mixture. Direct addition of the base to the carbonyl group of electrophilic aldehydes can also pose a problem, reactions which compete with aldehyde enolate formation 

Using specific enol equivalents to alkylate aldehydes and ketones 

These side-reactions mean that aldehyde enolates are not generally useful reactive intermediates. Instead, there are a number of aldehyde enol and enolate equivalents in which the aldehyde is present only in masked form during the enolization and alkylation step. The three most important of these specific enol equivalents are  

You met all of these briefly in Chapter 21, and we shall discuss how to use them to alkylate aldehydes shortly. All three types of specific enol equivalent are useful not just with aldehydes, but with ketones as well, and we shall introduce each class with examples for both types of carbonyl compound. 

Enamines are formed when aldehydes or ketones react with secondary amines. The mechanism is given in Chapter 14. The mechanism below shows how they react with alkylating agents to form new 

The overall process, from carbonyl compound to carbonyl compound, amounts to an enolate alkylation, but no strong base or enolates are involved so there is no danger of self-condensation. The example below shows two specific examples of cyclohexanone alkylation using enamines. Note the relatively high temperatures and long reaction times enamines are among the most reactive of neutral nucleophiles, but they are still a lot less nucleophilic than enolates. 

Enamines are formed when aldehydes or ketones react with secondary amines. The mechanism is given in Chapter 11. The mechanism below shows how they react with alkylating agents to form new carbon-carbon bonds the enamine here is the one derived from cyclohexanone and pyrrolidine. The product is at first not a carbonyl compound it s an iminium ion or an enamine (depending on whether an appropriate proton can be lost). But a mild acidic hydrolysis converts the iminium ion or enamine into the corresponding alkylated carbonyl compound. 

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USING SPECIFIC ENOL EQUIVALENTS TO ALKYLATE ALDEHYDES AND KETONES... 

Other useful specific enol equivalents of aldehydes and ketones are enamines and aza-eno-lates, which you saw in use in alkylation reactions in Chapter 25. Aza-enolates—the lithium enoiates of imines—derived from aldehydes are also useful in aldol reactions. Cyclohexylamine gives a reasonably stable imine even with acetaldehyde and this can be isolated and lithiated with LDA to give the aza-enolate. The mechanism is similar to the formation of lithium enoiates and the iithium atom binds the nitrogen atom of the aza-enolate, just as it binds the oxygen atom of an enoiate. 

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