Synthesis alkali metal enolates

Silyl enolates undergo Pd-catalyzed arylation with aryl halides in the presence of an additive such as Bu3SnF,327 CuF2,328 or ZnF2.329 The arylation of silyl enolates has higher functional group tolerance than that of alkali metal enolates. The ZnF2-promoted arylation is valuable for efficient, stereoselective synthesis of a-arylated esters and imides (Equation (89)). 

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... 

The Mechanism of the Ethyl Acetoacetate Synthesis—Before the tautomerism of ethyl acetoacetate is discussed we must consider the mechanism of its formation, which for decades has been the subject of lively discussion and was conclusively explained only in recent years (Scheibler). It has been found that even the C=0-group of the simple carboxylic esters, although in other respects inferior in activity to the true carbonyl group, can be enolised by alkali metals. Thus ethyl acetate is converted by potassium into the potassium salt of the tautomeric enol with evolution of hydrogen ... 

The Robinson annulation is the reaction of alkali metal derivatives of cyclohexanones with a-,p>unsaturated methyl ketones to produce cycloketones and polycycloketones. The standard method for Robinson annulation is exemplified in the mechanism shown above. For the synthesis of the 1,5-diketone side chain, the enolate nucleophile reacts with a Michael acceptor this Michael acceptor is usually a substituted vinyl ketone or the parent methyl vinyl ketone (MVK), although the latter gives low yield due to its propensity to polymerize under the standard reaction conditions. To overcome the drawbacks for using MVK, Robinson, McQuillin and Du Feu introduced the Robinson-Mannich variation of the annulation reaction. This modification uses a quatemized Mannich base formed from the vinyl entity the Maimich base is made in situ and acts as a methyl vinyl ketone precursor after it is converted to its methiodides. The formed methiodides of the Mannich adduct 4-(trimethylamino-2-butanone) is condensed with sodioderivatives of ketones or with the parent ketone in the presence of sodium ethoxide. 

Synthesis.— The preparation of a-amino-acids from a-halogeno-acids and ammonia is often unsatisfactory owing to the occurrence of multiple alkylations etc. A way around this problem is to treat a-halogeno-esters with alkali-metal cyanates and an alcohol this gives N-alkoxycarbonyl-a-amino-esters in >90% yield. " The O-arylhydroxylamine (148) is a useful reagent for aminating enolates, especially those derived from malonic esters, which can thus be... 

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]. 

Alkaline Earth Metals. In the early literature, similar to alkali earth metals, alkaline earth metals were usually used to form the enolates, especially magnesium enolates, in the aldol reaction (128,129). Inspired by heterogeneous MgO solid base catalysis (130), alkaline earth metals have been applied successfully as homogeneous catalysts in the aldol reaction (Scheme 23). In 1998, Corey and co-workers described a new magnesium-catalyzed diastereoselective anti-aldol reaction as a key step for the total synthesis of lactacystin (131). The metal requirement is strict, since several salts were tested, for example, TiCl4, SnCL, ZnCl2, and Cu(OTf)2, only Mgl2 functioned as an effective catalyst (Scheme 24). 

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