Overview

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 the easy conversion of the derivative to the corresponding aldehyde. This is because alkylaluminum hydrides are less reactive than LAH, as the former is more sterically hindered.

According to recent studies, a reductant like diphenylsilane in combination with an air-stable Ni precatalyst and dimethyl dicarbonate as an activator converts most of the carboxylic acid to the aldehyde without causing any over-reduction.

In other studies, a hydrosilane through visible light photoredox catalysis efficiently reduces carboxylic acids to aldehydes.

Ketones, unlike aldehydes, can be directly prepared from carboxylic acids using organolithium reagents. The acid rapidly reacts with two equivalents of an organolithium reagent to form a dianion. This dianion gets protonated to form the corresponding hydrate, which loses a water molecule to give a ketone.

Both aldehydes and ketones can be prepared from nitriles using suitable reducing agents. Aldehydes are formed by the partial reduction of nitriles in the presence of DIBAL-H. The nitrile first forms an aluminum complex, which later, on hydrolysis, yields the corresponding aldehyde. Nitriles can be reduced to ketones via imine intermediates using Grignard or organolithium reagents.

Procedure

Treating a carboxylic acid with lithium aluminum hydride yields an aldehyde, which instantly reduces to a primary alcohol.

This over-reduction occurs because LAH is a strong reductant and aldehydes are more easily reduced than acids.

For successfully preparing aldehydes, easily reducible carboxylic acid derivatives are treated with milder aluminum hydride reducing agents.

Aluminum hydride derivatives are less reactive than lithium aluminum hydride due to their increased steric bulk.

Unlike aldehydes, ketones are formed directly from carboxylic acids by reduction using organolithium reagents.

The acid reacts rapidly with two equivalents of the organolithium reagent to form a dianion. Subsequent protonation yields a hydrate, which on loss of water, gives a ketone.

Both aldehydes and ketones can be prepared from nitriles using suitable reducing agents.

Reducing a nitrile using DIBAL-H forms an aluminum complex, which, following hydrolysis, yields an aldehyde.

Similarly, reducing nitriles with Grignard or organolithium reagents forms an imine intermediate that undergoes acid hydrolysis to give the corresponding ketones.