Borohydride Reduction

Reduction of Aldehydes and Ketones

In the enzyme catalyzed reduction of glucose, a proton along with 2 electrons adds to the carbonyl carbon and a proton adds to the carbonyl oxygen. A proton with 2 electrons, or H-, is called a hydride.

Aldehyde reduction: RCHO + H- + H+ RCH2OH

NADPH is one source of H- in biological systems. We use smaller (and much cheaper) hydride sources for reduction reactions in the laboratory. One of the most common hydride reagents is sodium borohydride, [Na][BH4].

In the first reaction above H- is transferred from the nucleophilic borohydride reagent to the electrophilic carbonyl carbon. This forms an alkoxide salt and BH3. The second step is the protonation of the basic alkoxide with a acid to form the alcohol.

The reaction between a ketone and sodium borohydride is analogous.

Reduction of Carboxylic Acids

The carbonyl carbon of a carboxylic acid is even more electrophilic than the carbonyl carbon in an aldehyde or ketone. However, there is also an acid proton from the carboxylic acid that can react with hydride reagents. For this reason, sodium borohydride does not reduce a carboxylic acid.

A carboxylic acid can react with an alcohol, in the presence of a small amount of an acid, to form a carboxylic acid ester. Then the ester can be reduced.

The reaction of the methyl ester with sodium borohydride is below.

The addition of the hydride to the carbonyl carbon is followed by a second step that eliminates the CH3O- group and reforms the C-O double bond. Overall, this is a substitution of CH3O- for H- at the carbonyl carbon but it proceeds through an intermediate in which the "carbonyl carbon" is bonded to 4 groups and has tetrahedral geometry.

The initially formed aldehyde can react with additional borohydride reagent.

Professor Patricia Shapley, University of Illinois, 2012