Alkali metal enolates deprotonation

Conversion of tight ion pairs into crown ether-separated ion pairs leads in many cases to increased basicity. For example, Dietrich and Lehn (1973) have shown that a homogeneous solution of sodium t-amyloxide in benzene is unable to deprotonate triphenylmethane, whereas the reaction occurs rapidly in the presence of [2.2.2]-cryptand [37]. In THF or diethyl ether, alkali metal enolates do not react with triphenyl- or diphenylmethane (Pierre et al.,... 

Alkali Metal Enolates by Deprotonation of Carbonyl Compounds... 

Alkali Metal Enolates by Deprotonation of Carbonyl Compounds 1.422 Alkali Metal Enolates by Addition to a,fi-Unsaturated Carbonyl Compounds... 

Among alkali metal enolates, those derived from ketones are the most robust one they are stable in etheric solutions at 0 C. The formation of aldehyde enolates by deprotonation is difficult because of the very fast occurring aldol addition. Whereas LDA has been reported to be definitely unsuitable for the generation preformed aldehyde enolates [15], potassium amide in Hquid ammonia, potassium hydride in THE, and super active lithium hydride seem to be appropriate bases forthe metallation of aldehydes [16]. In general, preformed alkali metal enolates of aldehydes did not find wide application in stereoselective synthesis. Ester enolates are very frequently used, although they are more capricious than ketone enolates. They have to be formed fast and quantitatively, because otherwise a Claisen condensation readily occurs between enolate and ester. A complication with ester enolates originates from their inherent tendency to form ketene under elimination... 

A series of alkyl-aryl ketones 31 was converted into cA-enolates 32 in a highly selective manner by deprotonation with LDA in THF, the cisttmns ratio uniformly surpassing 99 1. Only in the substrates 34 with a-t-butyl or a-phenyl substituents the selectivity was moderate, so that, for these ketones, an alternative protocol was elaborated that used the additive DMPU for obtaining sodium enolates cis-35 exclusively. These conditions were also applied for preparing cA-configured sodium enolates 38 from N-acyl pyrroles 37. In all cases, the alkali metal enolates were quenched by silylation to give silyl enol ethers 33, 36, and 39, respectively (Scheme 2.9) [43]. 

The two main problems in the preparation of silyl enol ethers are control of regios-electivity, kinetic and thermodynamic, and stereoselectivity, (E) and (Z). Although many useful procedures are now available for the kinetic deprotonation of ketones by use of alkali metal dialkylamides, there are few practical procedures for thermodynamic deprotonation. Recently, the author and Yamamoto et al. found that the regio- and stereoselective isomerization of a kinetic silyl enol ether to a thermodynamic ether was catalyzed by LBA [138]. 

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-... 

The base-catalysed degradation of the ring of isoxazolium salts is particularly easy, requiring only alkali metal carboxylates to achieve it. The mechanism, illustrated for the acetate-initiated degradation of 2-methyl-5-phenylisoxazolium iodide, involves initial 3-deprotonation with cleavage of the N-O bond subsequent rearrangements lead to an enol acetate which rearranges to a final keto-imide. 

A strong base such as an alkali metal amide (p T 35-40) is typically required to quantitatively convert a simple aldehyde or ketone to an enolate. On the other hand, an alkoxidebase (p/fg 16) is sufficient for deprotonating a )5-diketone or a -ketoester, since the resulting enolate is much more stabilized by resonance ... 

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