Ketoreduction

Ketoreduction is the chemical reduction of a ketone to a secondary alcohol. It is a common transformation in organic synthesis. The most widely used reducing agents are sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4). NaBH4 is mild and commonly selective for aldehydes and ketones, furnishing secondary alcohols in solvents such as methanol, ethanol, or THF at 0–25 °C. LiAlH4 is more reactive, reducing a broader range of carbonyls but requiring strictly anhydrous conditions and typically dry ether or THF; workup is exothermic and must be careful.

Mechanistically, these reagents deliver hydride to the carbonyl carbon, forming an alkoxide that is protonated on workup to give the alcohol. Reduction of disubstituted ketones is generally not stereoselective, so prochiral ketones yield racemic secondary alcohols unless a chiral inducer is used.

Enantioselective ketoreductions employ chiral catalysts or auxiliaries. The CBS (Corey–Bakshi–Shibata) reduction uses a chiral oxazaborolidine catalyst with borane to provide enantioenriched secondary alcohols. Other approaches include asymmetric hydrogenation and transfer hydrogenation with chiral ligands.

Applications include the synthesis of pharmaceuticals, natural products, and flavors. Chemoselectivity varies with reagent: NaBH4 reduces aldehydes and many ketones but typically does not reduce esters, while LiAlH4 reduces esters and carboxylic acids. Practical considerations include solvent choice, temperature, and strict moisture control for LiAlH4.