Carbonyl compounds alkali metal enolates

Alkali Metal Enolates by Deprotonation of Carbonyl Compounds... 

Alkali Metal Enolates by Addition to a.fi-Unsaturated Carbonyl Compounds 106... 

Contrary to earlier notions that the Pd-catalyzed a-allylation of carbonyl compounds would be limited to those carbonyl compounds that are extrastabilized (the Tsuji-Trost reaction), the use of Zn, B in the forms of BRjK or Li + 2 BR3, where R = Et, and so on, Si, and Sn has been shown to permit the use of those enolates of ordinary ketones, aldehyde esters, and so on, where the pATj of the carbonyl compounds may be 20. In some cases, however, even lithium enolates can provide satisfactory results. Since most of the enolates mentioned above are derived via alkali metal enolates containing Li, Na, or K, these parent enolates should be tested before converting or modilying them with reagents containing other metals. 

LiAlH4 as this avoids protonation of the enolate and the production of any over-reduction products. Cholest-4-en-3-one may be reduced to cholestanone (5a 5/8,1 19) with alkali-metal carbonyl chromates. The studies on intramolecular hydride shifts on hydroxy-ketones and -aldehydes have been extended. " The hydride shifts were examined in a number of y- and 5-hydroxy-carbonyI compounds by heating the substrates with alkaline alumina containing D2O. Exchange of protons on the carbon a to both oxygen functions signals the intramolecular hydride shift typically, the hemiacetals (95) and (96) each incorporate up to six deuterium atoms. The general conclusion, in common with literature precedent, is that, whereas 1,5-shifts are common, 1,4-shifts are rare. 

A number of bases may be used for deprotonation, but the most important ones are lithium amide bases such as those illustrated in Figure 3.3. Although other alkali metals may be used with these amides, lithium is the most common. Amide bases efficiently deprotonate virtually all ctirbonyl compounds, and do so regioselectively with cyclic ketones such as 2-methylcyclohexanone i.e., C2 vs. C6 deprotonation) and stereoselectively with acyclic carbonyls (i.e., E(O)- vs. Z(O)- enolates. If the carbonyl is added to a solution of the lithium amide, deprotonations are irreversible and kinetically controlled [36-38]. Under such conditions, the con-... 

Table 1.1 illustrates the relatively high acidity of compounds in which a C—H bond is activated by two or more carbonyl (or cyano) groups. It is therefore possible to use a comparatively weak base, such as a solution of sodium ethoxide in ethanol, in order to form the required enolate anion. An equilibrium is set up, as illustrated in Scheme 1.4, in which the conjugate acid of the base (BH) must be a weaker acid than the active methylene compound. Another procedure for preparing the enolate of an active methylene compound is to use sodium hydride (or finely divided sodium or potassium metal) in tetrahydrofuran (THF), diethyl ether (Et20) or benzene. The metal salt of the enolate is formed irreversibly with evolution of hydrogen gas. p-Diketones can often be converted into their enolates with alkali-metal hydroxides or carbonates in aqueous alcohol or acetone. 

The synthesis of enantiomerically pure a-alkylated carbonyl compounds was based mainly on the chiral-auxiliary approach, outlined in Section 4.1, that was particularly fruitful for the enolates of alkali metals, mainly lithium. The enantioselective alkylation and allylation of prochiral enolates mediated by chiral catalysts have been developed only in recent years, after seminal contributions were made since the turn of the century. The main problem this concept encounters is the high reactivity of these enolates that react with alkylating agents in a noncatalyzed and necessarily nonstereoselective manner [1]. 

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