14.20:
Esters to Alcohols: Hydride Reductions
The reduction of esters with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form primary alcohols.
Notably, two alcohols are formed from an ester, one derived from the acyl group and the other from the alkoxy group. Therefore, the reaction requires two equivalents of the reducing agent, which acts as a source of hydride ions.
The mechanism begins with a nucleophilic attack by the hydride ion at the carbonyl carbon, forming a tetrahedral intermediate.
Next, the carbonyl group is reconstructed with the departure of the alkoxide ion, giving an aldehyde.
Subsequently, a second equivalent of the hydride ion attacks the aldehyde, generating an alkoxide intermediate.
Lastly, protonation of the alkoxide gives a primary alcohol as the final product.
A milder reducing agent like lithium tri(tert-butoxy) aluminum hydride selectively reduces esters to aldehydes.
This reaction is performed at a low temperature, about −78 °C, to prevent further reduction to alcohol.
14.20:
Esters to Alcohols: Hydride Reductions
Esters are reduced to primary alcohols when treated with a strong reducing agent like lithium aluminum hydride. The reaction requires two equivalents of the reducing agent and proceeds via an aldehyde intermediate.
Lithium aluminum hydride is a source of hydride ions and functions as a nucleophile. The mechanism proceeds in three steps. Firstly, the nucleophilic hydride ion attacks the carbonyl carbon of the ester to form a tetrahedral intermediate. Subsequently, the carbonyl group re-forms, and the alkoxide ion departs as the leaving group, generating an aldehyde. Lastly, a second nucleophilic attack by the hydride ion at the carbonyl carbon of the aldehyde yields an alkoxide ion, which gives a primary alcohol as the final product upon protonation.
However, in case the desired product is an aldehyde, it is possible to stop the reaction at the aldehyde intermediate by using a milder reducing agent like diisobutylaluminum hydride or lithium tri(t-butoxy) aluminum hydride, at a lower temperature.