Alkylation, enolate ions elimination reactions

The enolate ions of esters or ketones can also be alkylated with alkyl halides to create larger carbon skeletons [Following fig.(b)]. The most successful nucleophilic substitutions are with primary alkyl halides. With secondary and tertiary alkyl halides, the elimination reaction may compete, particularly when the nucleophile is a strong base. The substitution of tertiary alkyl halides is best done in a protic solvent with weakly basic nucleophiles. However, yields may be poor. 

Many of the reactions assembled in Scheme 5.4are of undiminished interest in modern allene chemistry when relatively simple alkyl derivatives are the preparative goal. For example, /3-eliminations of enolphosphates prepared from saturated ketones constitute a simple route to 1,3-dialkylated allenes. Thus 3-octanone (49), on LDA treatment followed by quenching the generated enolate ions with diethyl chlor-ophosphate, affords a mixture of the enolphosphates 50. When these are treated with further LDA in THF at low temperatures, 2,3-octadiene (51) is produced in 50% yield (Scheme 5.5) [15]. 

The enolate ion is nucleophilic at the alpha carbon. Enolates prepared from aldehydes are difficult to control, since aldehydes are also very good electrophiles and a dimerization reaction often occurs (self-aldol condensation). However, the enolate of a ketone is a versatile synthetic tool since it can react with a wide variety of electrophiles. For example, when treated with an unhindered alkyl halide (RX), an enolate will act as a nucleophile in an Sn2 mechanism that adds an alkyl group to the alpha carbon. This two-step a-alkylation process begins by deprotonation of a ketone with a strong base, such as lithium diisopropylamide (LDA) at -78°C, followed by the addition of an alkyl halide. Since the enolate nucleophile is also strongly basic, the alkyl halide must be unhindered to avoid the competing E2 elimination (ideal RX for Sn2 = 1°, ally lie, benzylic). 

In some respects, the alkylation of enolate anions resembles nucleophilic substitution. We recall that many nucleophiles displace leaving groups from primary alkyl halides by an Sj 2 mechanism (Section 9.3). A similar reaction occurs with secondary alkyl halides, but competing elimination reactions also occur. Primary alkyl halides react with carbanions, such as the alkynide ion, by an Sj 2 mechanism. (Secondary alkyl halides react not only in displacement reactions but also in elimination reactions because the alkynide ion is a strong base.)... 

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