10.6 : カルボニル化合物からのアルコール: 還元

Alcohols can be prepared from carbonyl compounds by adding two hydrogen atoms across the double bond.

This reduction is important in the synthesis of essential molecules like the perfume ingredient muscone and the antidepressant drug Prozac.

While aldehydes, carboxylic acids, and esters are reduced to primary alcohols, ketones are reduced to secondary alcohols.

The classical method involves catalytic hydrogenation using hydrogen and transition-metal catalysts. However, this requires high temperature and pressure and also reduces any carbon–carbon multiple bonds present in the molecule.

The laboratory method involves the stepwise addition of nucleophilic hydride ions from sodium borohydride, lithium aluminum hydride, and their derivatives, in an irreversible reaction, followed by protonation with solvent or acid. This method selectively reduces the carbonyl group in comparison to hydrogenation.

In unsymmetrical ketones, the planar carbonyl group can undergo a nucleophilic hydride attack from either face with equal probability. This generates a chiral tetrahedral intermediate, giving a pair of enantiomeric products. 

Reduction by sodium borohydride is carried out in polar protic solvents. Lithium aluminum hydride, on the other hand, needs dry, aprotic solvents to avoid its violent reaction with proton donors.

Lithium aluminum hydride is a stronger reducing agent—and hence, more reactive—than sodium borohydride due to the greater polarity of the aluminum–hydrogen bond compared to the boron–hydrogen bond.

This reactivity difference is reflected in the ease with which different carbonyl groups undergo selective reduction by the two hydride reagents.

To illustrate, sodium borohydride can selectively reduce a ketone in the presence of an ester, unlike lithium aluminum hydride that does not allow for selective reduction of the ketone group.

Lithium borohydride and borane are useful reagents with opposite chemoselectivity in reducing esters and acids, respectively.