Chapter 19Enolates and Enamines.ppt

Enamines – Alkylation at a position. The value of enamines is that the ?-carbon is nucleophilic. Enamines undergo SN2 reactions with methyl and 1°?haloalkanes, ?-haloketones, and ?-haloesters. Treatment of the enamine with one equivalent of an alkylating agent gives an iminium halide. Compare mechanisms of acid catalyzed aldol and enamine Enamines - Alkylation Hydrolysis of the iminium halide gives an alkylated aldehyde or ketone. Overall process is to render the alpha carbonss of ketone nucleophilic enough so that substitution reactions can occur. Enamines – Acylation at a position Enamines undergo acylation when treated with acid chlorides and acid anhydrides. Could this be made via a crossed Claisen followed by decarboxylation. Overall, Acetoacetic Ester Synthesis The acetoacetic ester (AAE) synthesis is useful for the preparation of mono- and disubstituted acetones of the following types: Main points Acidic hydrogen providing a nucleophilic center. Carboxyl to be removed thermally Derived from a halide RX Overall, Malonic Ester Synthesis The strategy of a malonic ester (ME) synthesis is identical to that of an acetoacetic ester synthesis, except that the starting material is a ?-diester rather than a ?-ketoester. Main points Acidic hydrogen providing a nucleophilic center Carboxyl group removed by decarboxylation Introduced from alkyl halide RX Malonic Ester Synthesis Consider the synthesis of this target molecule: Recognize as substituted acetic acid. Malonic Ester Synthesis Malonic Ester Synthesis Steps Treat malonic ester with an alkali metal alkoxide. 2. Alkylate with an alkyl halide. Malonic Ester Synthesis 3. Saponify and acidify. 4. Decarboxylation. Michael Reaction, addition to ?,?-unsaturated carbonyl Michael reaction: the nucleophilic addition of an enolate anion to an ?,?-unsaturated carbonyl compound. Example: Recognition Pattern: Nucleophile – C – C – CO (nitrile or nitro) Michael Reaction Michael Reaction in base Example: Th