Question

Question: Draw a stepwise mechanism for the conversion of lactone C to carboxylic acid D. C is a key intermediate in the synthesis of prostaglandins (Section 19.6) by Nobel Laureate E. J. Corey and co-workers at Harvard University.

Short answer

Answer

Mechanism for the conversion of C to D

Step-by-step solution

Step-by-Step Solution Step 1: Reactivity of lactones

Six-membered lactones are more stable than five-membered lactones and are easily formed.

Lesser lactones with three-membered rings are highly unstable and cannot be isolated.

The reactions of stable lactones are similar to corresponding esters. They undergo hydrolysis, ammonolysis, and polymerization reactions.

Lactones also undergo hydrolysis to their parent compounds.

Reaction of lactones with bases

Lactones are converted to their corresponding carboxylic acid in the presence of bases.

It is a hydrolysis reaction giving the parent compound as the product.

The hydrolysis reaction is reversible. Being a nucleophile, the base attacks the carbonyl carbon directly, thus opening the lactone ring.

Mechanism of base hydrolysis

The reaction is initiated by the attack of hydroxide ion on the carbonyl carbon, which causes the opening of the lactone ring.

The anion thus formed is stabilized by an internal proton transfer.

This is followed by the abstraction of a proton from a water molecule, forming the carboxylic acid product.

Mechanism for the base hydrolysis of lactone