Ketones tandem vicinal difunctionalization

Usually, after an enolate ion is generated from an ocP-unsaturated ketone, it is converted to the P-alkylated product as shown above. But it is often possible to have the enolate react with some other electrophile (tandem vicinal difunctionalization), in some cases at the O and in other cases at the C. For example, if an alkyl halide R X is present (R = primary alkyl or allylic), and the solvent is 1,2-dime-thoxyethane, the enolate (66) can be alkylated directly. Thus, by this method, both the a and p positions of a ketone are alkylated in one synthetic operation (see also 15-23). 

Ketones, specifically 2-alkenones and 2-cycloalkenones, have been used extensively as substrates for tandem vicinal difunctionalization, allowing delineation of various reactivity patterns based upon the structural elements present in the enone. Aldehyde substrates have been used less widely comparison... 

Simple substitution at the a-carbon of the enoate substrate also does not appear to have much effect on the course of the reaction methyl acrylate and methyl methacrylate both function well as substrates in the reaction sequence and isolated yields of the products are similar.100 In certain sterically demanding reaction sequences, a-substitution does reduce the chemical yields of the products but the presence of an a-substituent appears to be of greater importance than the particular identity of the substituent.101 As with ketones, enoate substrates are activated towards tandem vicinal difunctionalization when electron-withdrawing a-substituents are present.102-104... 

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