Example Carboxylic Acid TM

Diethyl Malonate as a Synthetic Equivalent of Acetic Acid 

Synthesize the following TM from readily available starting materials that contain no more than a four-carbon chain. 

The instructions for this problem point to a disconnection at the nucleophilic alpha carbon, thereby creating a four-carbon electrophile (RX) and a three-carbon nucleophile (enolate). However, the resulting enolate is not stable. Addition of an ester electron-withdrawing group leads to a starting material that can be further simplified. A second disconnection at the alpha carbon results in the familiar diethyl malonate enolate. Recognizing the TM as a derivative of acetic add can help you recognize the double disconnection that is possible. 

The synthesis of this carboxylic acid begins with the deprotonation of diethyl malonate with NaOEt, and alkylation with methyl iodide. A second deprotonation and alkylation with n-butyl bronaide installs the necessary carbon chain. Hydrolysis followed by heat causes the decarboxylation that removes the extra carboxyl group and afford the desired TM. 

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