Specific enol equivalents for ketones

Enamines are not generally used in aldol condensations, partly because they are not reactive enough, but mainly because they are too much in equilibrium with the carbonyl compound itself and exchange would lead to self-condensation and the wrong cross-couplings. You will see in the next chapter that enamines come into their own when we want to acylate enols with the much more reactive acid chlorides. 

For crossed aldol reactions with an aldehyde as the enol partner, use 

The enolization of ketones, unless they are symmetrical, poses a special problem. Not only do we need to prevent them self-condensing (though this is less of a problem than with aldehydes), but we also need to control which side of the carbonyl group the ketone enolizes. In this section we shall introduce aldol reactions with unsymmetrical ketones where one of two possible enols or enolates must be made. 

Making the less substituted enolate equivalent kinetic enolates 

Treatment of methyl ketones with LDA usually gives only the lithium enolate on the methyl side.  

Treatment of methyl ketones with LDA usually gives only the lithium enolate on the methyl side. This is the enolate that forms the festest, and is therefore known as the kinetic enolate. It is formed fester because. 

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Among the enolates of carboxylic acid derivatives, esters are the most widely used. Ester enolates cannot be used in crossed aldols with aldehydes because the aldehyde is both more enolizable and more electrophilic than the ester. It will just condense with itself and ignore the ester. The same is true for ketones. A specific enol equivalent for the ester will therefore be needed for a successful ester aldol reaction. 

The second amine can be made by reductive amination of a ketone so we need to think how - -ketone might he made by enolate alkylation. It is ideal for alkylation of an enol or enolate wit . benzyl electrophile. You could have chosen a number of specific enol equivalents for this, we use r -c.iaiLiuic. 

The best specific enol equivalents for aldehydes are enamines (75) and these are also very useful for ketones. They are easily made from the carbonyl compound and a secondary amine, are stable isolable compounds, and react... 

Summary specific enol equivalents for aldehydes and ketones ... 

This is a l,4 diketone and disconnection of the central bond separates the two rings. We require a specific enol equivalent lor (4) - they used activated ketone (6) - and a reagent for unnatural synthon (5) -they used a-chloroketone (7). 

As noted in Chapter 1, this is one of the best methods for generating a specific enolate of a ketone. The enolate generated by conjugate reduction can undergo the characteristic alkylation and addition reactions that are discussed in Chapters 1 and 2. When this is the objective of the reduction, it is important to use only one equivalent of the proton donor. Ammonia, being a weaker acid than an aliphatic ketone, does... 

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. 

In a study of ring closure by metathesis (chapter 15) to produce specific enol equivalents from cyclic ketones, Shibasaki19 decided to use enolates from malonates to make the many starting materials quickly. For example, alkylation followed by conjugate addition gave starting material 143 in two steps. 

In Chapter 20 we established that enolates can be formed from acid chlorides, but that they decompose to ketenes. Enolates can be formed from amides with difficulty, but with primary or secondary amides one of the NH protons is likely to be removed instead. For the remainder of this section we shall look at how to make specific enol equivalents of acids, esters, aldehydes, and ketones. 

The fact that ketones, aldehydes, and geminal diacetates are readily available from these reactions illustrate their complementarity to reactions with allylsilanes. Specifically, the equivalency of allylic ethers to homoenolates allows for the formation of compounds extended by one carbon unit as compared to the products of couplings with enolate equivalents already discussed. 

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