Chapter 20: Carboxylic Acid Derivatives. Nucleophilic Acyl Substitution

Reactions of RLi and RMgX with Esters
(review of Chapter 14)

Reaction usually in Et₂O followed by H₃O⁺ work-up

Reaction type:  Nucleophilic Acyl Substitution then NucleophilicAddition

Summary

• Carboxylic esters, R'CO₂R'', react with 2 equivalents of organolithium or Grignard reagents to give tertiary alcohols.
• The tertiary alcohol that results contains 2 identical alkyl groups (from R in the scheme)
• The reaction proceeds via a ketone intermediate which then reacts with the second equivalent of the organometallic reagent (review)
• Since the ketone is more reactive than the ester, the reaction cannot be used as a preparation of ketones.
• The mechanism is an example of the reactive system type.

MECHANISM OF THE REACTION OF RMgX WITH AN ESTER
Step 1: The nucleophilic C in the organometallic reagent adds to theelectrophilic C in the polar carbonyl group of the ester. Electrons from the C=O move to the electronegative O creating thetetrahderal 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 a ketone as an intermediate.
Step 3: The nucleophilic C in the organometallic reagent adds to the electrophilic C in the polar carbonyl group of the ketone. 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. Protonationof the alkoxide oxygen creates the alcohol product from the intermediate complex.

© Dr. Ian Hunt, Department of Chemistry