Carboxylic Acids and Their Derivatives

Grignard Reaction of Lactones

We have seen earlier that esters react with two equivalents of Grignard reagent to form tertiary alcohols after acidic workup. The reaction occurs through two successive nucleophilic additions: the first addition forms a tetrahedral intermediate that collapses by expelling the alkoxy group, producing a ketone intermediate, which is then attacked by a second equivalent of the Grignard reagent to give the tertiary alcohol.

 

 

Grignard reagents react with lactones by nucleophilic attack on the carbonyl carbon, opening the ring to form a magnesium alkoxide intermediate. Because the ring-opening yields a ketone intermediate, a second equivalent of the Grignard reagent is usually added, ultimately producing a tertiary alcohol after acidic workup.

 

 

This double addition significantly expands the carbon framework of the molecule, adding two new carbon-carbon bonds. Grignard reactions with lactones are therefore powerful methods for generating tertiary alcohols with predictable carbon extension, provided the reaction is carried out under strictly anhydrous conditions to prevent the reagent from being quenched.

Although quite similar, I will also add the reaction of lactones with organolithiums:

 

 

We have a dedicated post on the reactions of Lactones and Lactams with lots of practice problems here.

 

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