Chapter 20: Carboxylic Acid Derivatives. NucleophilicAcyl Substitution

Reduction of Esters
(review of Chapter 15)

Reactions usually in Et₂O or THF followed by H₃O⁺work-ups

Summary

• Carboxylic esters are reduced give 2 alcohols, one from the alcohol portion of the ester and a 1^o alcohol from the reduction of the carboxylate portion.
• Esters are less reactive towards Nu than aldehydes or ketones.
• They can only be reduced by LiAlH₄ but NOT by the less reactive NaBH₄
• The reaction requires that 2 hydrides (H^-) be added to the carbonyl group of the ester
• The mechanism is an example of the reactive system type.
• The reaction proceeds via a aldehyde intermediate which then reacts with the second equivalent of the hydride reagent (review)
• Since the aldehyde is more reactive than the ester, the reaction is not normally used as a preparation of aldehydes .

MECHANISM OF THE REACTION OF LiAlH4 WITH AN ESTER
Step 1: The nucleophilic H from the hydride reagent adds to the electrophilic C in the polar carbonyl group of the ester. Electrons from the C=O move to the electronegative O creating the tetrahedral intermediate a metal alkoxide complex.
Step 2: The tetrahedral intermediate collapses and displaces the alcohol portion of the ester as a leaving group, in the form of the alkoxide, RO-. This produces an aldehyde as an intermediate.
Step 3:  Now we are reducing an aldehyde (which we have already seen) The nucleophilic H from the hydride reagent adds to the electrophilic C in the polar carbonyl group of the aldehyde. Electrons from the C=O move to the electronegative O creating an intermediate metal alkoxide complex.
Step 4: This is the work-up step, a simple acid/base reaction. Protonation of the alkoxide oxygen creates the primary alcohol product from the intermediate complex.

© Dr. Ian Hunt, Department of Chemistry