Alkylation of Stable Carbanion-Enolates

The acidity of an H is greatly enhanced when the C to which it is bonded is a to two C=0 groups  

Problem 17.10 Compare the relative acid strengths of 2,4-pentanedione, CH3COCH2COCH3 (I) ethyl acetoacetate, CH3COCH2COOC2H5 (II) and diethyl malonate, C2H5OOCCH2COOC2H5 (III). Explain your ranking. 

I II III. All three compounds afford resonance-stabilized carbanions. However, COOEt has an electron-releasing O bonded to carbonyl C, which decreases resonance stabilization. There are two COOEt groups in III and one in II, while I has only ketonic carbonyl groups. 

The compounds III and II are useful substrates for the synthesis of carboxylic acids and ketones, respectively, 

MALONIC ESTER SYNTHESIS OF R-SUBSTITUTED ACETIC ACIDS, RCHjCOOH OR R(R ) CHCOOH (R could R) 

MALONIC ESTER SYNTHESIS OF R-SUBSTITUTED ACETIC ACIDS, 

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Stork deduced that the octalone (1) should be convertible into the less stable of iwo possible enolates by reaction with lithium in liquid ammonia, and experimentation showed this prediction to be correct. Reduction of the unsaturated ketone (1) afforded only the fru/ij-jS-decalone (3) as the initial product. The reaction is considered to involve addition of an electron from lithium to ketone (1) to produce a hybrid intermediate (2) with carbanion character at the j3-carbon, and this intermediate abstracts a proton from ammonia to form the product (3). These observations suggested a new method of alkylation." Alkylation of the t .v-2-decalone (4) in the presence of base proceeds through the mure stable enolaie and gives (.5). However, the leas stable enulate (2) can be generated by l.i-NH,i reduction of the unseturated ketone (I) and alkylated to give the liomarlu methylated product (A). 

An aldol reaction can be completed enantioselectively with an a-carbanion of the chiral carbonyl compound reacting as chiral enolate. Since the a-C atom in chiral enolate is planar, alkylation is diastereoselective because of the recognition of diastereotopic faces by the carbonyl counterpart. Alkylation of the configurationally stable tetrahedral carbanion on the a-C atom is a relatively rare case and is known as the memory of chirality. 

Ordinarily nucleophilic addition to the carbon-carbon double bond of an alkene is very rare It occurs with a p unsaturated carbonyl compounds because the carbanion that results IS an enolate which is more stable than a simple alkyl anion... 

As a-alkylated products are thermodynamically more stable, it is significant to note that these ester carbanions undergo both C-silylation and enol silyl-ation (155) the 0,a-dianions of carboxylic acids furnish bistrimethylsilyl enol ethers (156). 

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