Asymmetric Alkylation of Stabilized Carbanion

The classical example of alkylation of stabilized carbanion is the alkylation of diethyl malonate. Double alkylation followed by hydrolysis and decarboxylation affords a-substituted carboxylic acids. The same target molecules are available by a-alkylation of carboxylic esters, which requires much stronger bases since the p Ta of the a-CU.2 group is about 25. 

In the following example we consider stereoselective a-alkylation of selected chiral carboxylic acid derivatives. 

Optically pure aminoalcohol 25 is waste in the production of the antibiotic Chloramphenicol by the process that uses its (IR, 2/ )-enantiomer hence, it is a cheap raw material. Protection of the primary OH group in 26 by methylation to 27 was regarded by the authors as a necessary harm when using cheap starting material 25 [16]. 

In conclusion, the asymmetric alkylation of chiral enolates and enamines can be completed with high stereoselectivity affording final products with high optical purity [17], The chiral economy of this and other noncatalytic methods that use chiral auxiliary agents in a stoichiometric quantity depends on their availability and effective recycling in the process. 

Nogradi M (1981) Stereochemistry, basic concepts and applications. Akademia Kiado, Budapest 

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