Alkylation of Simple Ketones

TABLE 17.2 Formation of Enolates from 2-Methylcyclohexanone Reaction Conditions 17.35 17.36 

FIGURE 17.43 Formation of polyalkylated products from enolate alkylation. 

Recently, Li NMR spectroscopy has been used to establish that, in many cases, these oligomers do remain intact in solution. Thus, the enolate of cyclohexanone is dimeric in solution when TMEDA, Me2NCH2CH2NMe2, is added, but is a cubic tetramer in THE solutions. The predominance of dimers in TMEDA seems to be fairly general, including the enolates of cyclopentanone, cycloheptanone, 3,3,-dimethyl-2-butanone, acetophenone, and 2,5- dimethylp entanone. 

FIGURE 17.46 Formation and reaction of silyl enol ethers. 

FIGURE 17.47 Regioselective alkylation of methylcyclohexanone, w a silyl enol ethers. OSiMe, 

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Some examples of regioselective alkylations of simple ketones are presented in Scheme 1.6. These examples illustrate the most useful modes of enolate generation, including deprotonation (entries 3 and 4), enone reduction (entries 1, 2, and 5), and cleavage of silyl enol ethers (entries 6 and 7). 

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