14.21 : Esters to Alcohols: Grignard Reaction

The reaction of an ester with a Grignard reagent, followed by hydrolysis of the magnesium alkoxide salt in aqueous acid, yields a tertiary alcohol. In the case of formate esters, secondary alcohols are formed.

The reaction requires two equivalents of the Grignard reagent and introduces two identical alkyl groups, derived from the Grignard reagent, bonded to the hydroxyl-bearing carbon of the alcohol.

The reaction follows the typical nucleophilic acyl substitution mechanism. The Grignard reagent, a source of carbanions, functions as a nucleophile and attacks the carbonyl carbon of the ester to form a tetrahedral intermediate. Next, the carbonyl group is reconstructed with the departure of the alkoxide ion as a leaving group. The product of the reaction is a ketone intermediate. The reaction does not stop at this stage because ketones are more reactive than esters toward nucleophilic attack. Therefore, an attack from a second equivalent of the carbanion generates a tertiary alkoxide ion, which gives tertiary alcohol as the final product upon protonation.