Stable enolate equivalents

The aldol reactions introduced thus far have been performed under basic conditions where enolate species are involved as the reactive intermediate. In contrast to the commonly accepted carbon-anion chemistry, Mukaiyama developed another practical method in which enol species can be used as the key intermediates. He is the first chemist to successfully demonstrate that acid-catalyzed aldol reactions using Lewis acid (such as TiCU) and silyl enol ether as a stable enol equivalent can work as well.17 Furthermore, he developed the boron tri-fluoromethane sulfonate (triflate)-mediated aldol reactions via the formation of formyl enol ethers. 

Enamines are the stable products of a similar reaction between secondary amines (such as pyrrolidine or morpholine) and aldehydes and ketones.218 These vinylamines are reactive reagents of value in synthesis they function as specific enol equivalents of carbonyl compounds, readily undergoing alkylation and acylation processes (e.g. Section 5.9.2, p. 632). 

Among the best enol equivalents for aldehydes are enamines.19 They are stable compounds, easily made from aldehydes 95 and secondary amines, reacting with electrophiles in the same way as enols 96 to give iminium salts 97, hydrolysed to substituted aldehydes 98. 

According to Section 12.3 enamines are just one synthetic equivalent for enols that are not sufficiently represented in equilibrium with a carhonyl compound to allow for a-functional-izations. Enol ethers and silyl enol ethers, which are addressed in this section, are other synthetic equivalents for such enols. An enol ether, for example, is used as an enol equivalent for aldehyde enols, since several aldehydes do not form stable enamines. In addition, enol ethers or silyl enol ethers are usually employed as synthetic equivalents for the enols of ,/i-unsatu-rated carbonyl compounds. The attempt to react ce,/ -unsaturated carhonyl compounds with secondary amines to give a dienamine is often frustrated by a competing 1,4-addition of the amine. The combination of these factors turns the dienol ether B of Figure 12.23 into a species for which there is no analog in enamine chemistry. 

LDA is bulky, so it does not take part in nucleophilic attack at the carbonyl group, and it is basic— the p.KTa of diisopropylamine is about 35—plenty basic enough to deprotonate next to any carbonyl group. The lithium enolate is stable at low temperature (-78 °C) but reactive enough to be useful. Lithium enolates are the most commonly used stable enolate equivalents in chemistry. 

Specific enol equivalents are intermediates that still have the reactivity of enols or enolates but are stable enough to be prepared in good yield from the carbonyl compound. That was all we needed to know in Chapter 26. Now we know that... 

The conjugated ylides derived from aldehydes, ketones, and esters are all sufficiently stable to be commercially available as the ylids—one of the few examples of specific enol equivalents that you can actually buy. The ylid corresponding to the enolate of acetaldehyde is a solid, m.p. 185-188 °C that reacts well with other aldehydes, even if they are enolizable. 

Unsymmetrical ketones often give a single product, even without the use of a specific enol equivalent, as reaction usually occurs on the less substituted side. This is another consequence of the final enolization being the irreversible step. In this example, both possible products may form, but only one of them can enolize. Under the equilibrating conditions of the reaction, only the enolate is stable, and all the material ends up as the isomer shown. 

However, most successful conjugate additions use stable enol or enolate equivalents and we shall continue to discuss them in the next section. 

Bnamines are convenient stable enol equivalents for conjugate addition... 

How silyl enol ethers and lithium enolates can be used as stable enolate equivalents... 

If you want to do a conjugate addition of a carbonyl compound without having a second anion-stabilizing group, you need some stable and relatively unreactive enol equivalent. In Chapters 27 and 28 you saw how enamines are useful in alkylation reactions. These neutral species are also perfect for conjugate addition as they are soft nucleophiles but are more reactive than ends and can be prepared quantitatively in advance. The reactivity of enamines is such that heating the reactants together, sometimes neat, is all that is required. Protic or Lewis acid catalysis can also be used to catalyse the reaction at lower temperature. 

---