Hydride reagents are not interchangeable. Their selectivity follows from two things: how nucleophilic the hydride is, and whether the reagent is Lewis acidic enough to activate the carbonyl itself.
The nucleophilic hydrides
is reactive because Al–H is weaker and more polarised than B–H, and Li⁺ coordinates the carbonyl oxygen. It reduces nearly every carbonyl: aldehydes, ketones, esters, acids (after deprotonation), amides (to amines) and nitriles (to amines).
is milder and works in alcohols or water. It reduces aldehydes and ketones but leaves esters, acids and amides essentially alone:
Stopping at the aldehyde
is a neutral, Lewis-acidic aluminium hydride. At −78 °C it adds once to an ester. The resulting aluminium hemiacetal survives until work-up, which releases the aldehyde:
Use one equivalent and keep the reaction cold. Warmer conditions or excess reagent go on to the alcohol.
Electrophilic borane
works the other way round. It is electron-poor, so it seeks electron-rich carbonyl oxygens. Carboxylic acids react fastest, via an acyloxyborane, and amides are reduced to amines. Esters are slow. This makes BH₃ the reagent for reducing an acid next to an ester, the reverse of what NaBH₄ would do.
| Reagent | Aldehyde / ketone | Ester | Acid | Amide |
|---|---|---|---|---|
| NaBH₄ | alcohol | slow / none | none | none |
| LiAlH₄ | alcohol | 1° alcohol | 1° alcohol | amine |
| DIBAL-H, −78 °C | alcohol | aldehyde | — | — |
| BH₃·THF | alcohol | slow | 1° alcohol | amine |
Tuned reagents
- is stable at pH 6–7. At that pH it reduces protonated iminium ions much faster than ketones, which is why it is used for reductive amination.
- is very bulky. On substituted cyclohexanones it attacks from the less hindered equatorial direction, giving the axial alcohol.