Total synthesis of wedelolactone

Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.

The reaction between two different carbonyl compounds comprising α hydrogen in the presence of a strong base like lithium diisopropylamide (LDA) to form a crossed aldol product is known as a directed aldol reaction. The directed aldol reaction is depicted in Figure 1.

Aldol condensation is an important route in synthetic organic chemistry used to generate a new carbon–carbon bond under basic or acidic conditions. The aldol condensation reaction presented in Figure 1 constitutes an aldol addition reaction followed by the dehydration process.

Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated β-keto acid.

Overview
Ethers can be prepared from organic compounds by various methods. Some of them are discussed below,
Preparation of Ethers by Alcohol Dehydration
In this method, in the presence of protic acids, alcohol dehydrates to produce alkenes and ethers under different conditions. For example, in the presence of sulphuric acid, dehydration of ethanol at 413 K yields ethoxyethane, whereas it yields ethene at 443 K.

As shown in Figure 1, under acidic conditions, the β-hydroxy ketone undergoes dehydration via an E1 elimination reaction to form an enone.