Alkylation, enolate ions dialkylation

Ketones, esters, and nitriles can all be alkylated using LDA or related dialkyl-amide bases in THE. Aldehydes, however, rarely give high yields of pure products because their enolate ions undergo carbonyl condensation reactions instead of alkylation. (We ll study this condensation reaction in the next chapter.) Some specific examples of alkylation reactions are shown. 

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]. 

Furans can be prepared by acid catalyzed cyclization of masked 1,4-diketones. /3-Chloroallyl ketones which are obtained by alkylation of enamines or enolate ions behave as masked 1,4-diketones and afford furans on treatment with acid (67JA4557). 2,4-Dialkyl-furans (40) have been prepared by cyclization of the 3-chloroallyl ketone (39), which may be obtained by acylation of allyl chlorides (73KGS1434). 

Enamines are ambident nucleophiles giving C- and N-alkylated products. Acceptable yields of C-alkylated products are obtained by using reactive alkyl halides such as CH3I, ally lie and benzylic halides, and a-halocarbonyl compounds. The resultant iminium ion intermediates no longer behave as a enolates, thus dialkylation is avoided. The stereochemical course of alkylation of the enamine derived from 2-methylcy-clohexanone is depicted below. The reason for the preferred parallel alkylation via a boat-like transition state over antiparallel alkylation via a chair-like transition state is the synaxial RX // CH3 interaction in the latter case. ... 

The copper-mediated 1,4-addition reactions are thought to proceed through complex electron-transfer mechanisms. The first isolable intermediate is an enolate ion, which can be trapped by alkylating species, as shown in Section 18-4. Conjugate addition followed by alkylation constitutes a useful sequence for a,jS-dialkylation of unsaturated aldehydes and ketones. 

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