Q7(b). Borane: acid reduced, ester kept; δ-lactone

Introduction. The two ends of the half-ester differ: one is a CO₂H, the other a CO₂Et. The lactone (4-methyltetrahydropyran-2-one) keeps the ester carbon as its C=O and needs the CO₂H end reduced to CH₂OH. The reagent that reduces a carboxylic acid in the presence of an ester is diborane (B₂H₆, or BH₃*THF), followed by acid (lactonisation).

Scheme: Borane reduces CO₂H to CH₂OH; the alcohol then closes the six-membered lactone on the ester.

1. Acyloxyborane formation. Borane is an electrophilic (Lewis-acidic) hydride. The acidic O–H reacts first: RCO₂H + BH₃ → RCO₂BH₂ + H₂. Three such steps give a triacyloxyborane.
2. Activation. In the acyloxyborane the C=O oxygen is bonded through boron, which lowers the electron density on the carbonyl carbon (the carboxylate resonance is lost). The carbonyl oxygen also coordinates further BH₃.
3. Hydride transfer. B–H delivers hydride to the activated C=O (intramolecularly and from added BH₃): the acid is reduced through the aldehyde oxidation level to an alkoxyborane, RCH₂O-B.
4. Ester untouched. The ester carbonyl oxygen is a poor Lewis base and does not bind borane well, so CO₂Et reacts only slowly: this is the chemoselectivity (regioselectivity between the two ends).
5. Work-up and ring closure. Hydrolysis (H₃O⁺) releases the primary alcohol, ethyl 5-hydroxy-3-methylpentanoate. In acid the OH attacks the ester C=O (intramolecular transesterification) and EtOH is lost, closing the unstrained six-membered δ-lactone.

Stereochemistry. No bond to the stereocentre (C-3) is broken, so the configuration is kept; the (S)-half-ester gives the (S)-lactone that is printed. LiBH₄ would do the opposite: it leaves the carboxylate untouched and reduces the ester; the hydroxy acid would close to the enantiomeric lactone. (LiAlH₄ reduces both ends to the diol.)

Conclusion. Reagent: diborane, B₂H₆ (BH₃*THF), then H₃O⁺. Borane reduces the CO₂H through an acyloxyborane to CH₂OH and leaves the ester; the 5-hydroxy ester lactonises to (S)-4-methyltetrahydropyran-2-one with retention of configuration.

Application. Chemoselective borane reduction of acids in the presence of esters is used to make chiral lactones and hydroxy esters from desymmetrised glutaric acid half-esters, building blocks for statins and pheromones.