Acidity-directed synthesis of substituted gamma-butyrolactones from aliphatic aldehydes

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

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.

Baeyer–Villiger oxidation converts aldehydes to carboxylic acids and ketones to esters. The reaction uses peroxy acids or peracids and is often catalyzed by acid. The reaction is named after its pioneers, Adolf von Baeyer and Victor Villiger. The reaction is achieved by a wide range of peracids such as m-chloroperoxybenzoic acid (mCPBA), perbenzoic acid (C6H5COOOH), peracetic acid (CH3COOOH), hydrogen peroxide (H2O2), and tert-butyl hydroperoxide (t-BuOOH).
The carbonyl center is activated by...

The aldol reaction of a ketone under acidic conditions successfully forms an unsaturated carbonyl as the final product instead of an aldol. The acid-catalyzed aldol reaction is depicted in Figure 1.

Although it is possible to reduce a carboxylic acid to an aldehyde, strong reducing agents, like lithium aluminum hydride (LAH), prohibit a controlled reduction, instead causing the generated aldehyde to instantly over-reduce to a primary alcohol.
Reducing carboxylic acid derivatives like acyl chlorides (RCOCl), esters (RCO2R′), and nitriles (RCN) using milder aluminum hydride agents like lithium tri-tert-butoxyaluminum hydride [LiAlH(O-t-Bu)3] and diisobutylaluminum hydride [DIBAL-H] allows...

Aldehydes are more reactive than carboxylic acids and hence, can get over-reduced to alcohol in the presence of strong reducing agents. Therefore, carboxylic acids are inefficient in preparing aldehydes using LAH.
Carboxylic acid derivatives like acid chlorides and esters are more easily reducible than the corresponding acids. The derivatives reduce in the presence of mild reducing agents to give aldehydes. Aldehydes can also be prepared by Rosenmund reduction, that is, the reduction of acid...