Carbonyl reduction

In organic chemistry, carbonyl reduction is the organic reduction of any carbonyl group by a reducing agent.The reaction mechanism for metal hydride reduction is based on nucleophilic addition of hydride to the carbonyl carbon. In some cases, the alkali metal cation, especially Li+, activates the carbonyl group by coordinating to the carbonyl oxygen, thereby enhancing the electrophilicity of the carbonyl.Forming aldehydes from carboxylic acid derivatives is often a challenge, because weaker reducing agents (NaBH4) are incapable of reducing esters and carboxylic acids, which are relatively stable, and stronger reducing agents (LiAlH4) immediately reduce the formed aldehyde to an alcohol.Aldehydes and ketones can be reduced not only to alcohols but also to alkanes. Some reactions for this transformation include the Clemmensen reduction (in strongly acidic conditions) and the Wolff-Kishner reduction (in strongly basic conditions), as well as the various modifications of the Wolff-Kishner reaction. The Caglioti modification, for instance, uses tosylhydrazone with a hydride donor in milder conditions with no base; the Myers modification substitutes hydrazine with bis(tert-butyldimethylsilyl)-hydrazine, uses milder conditions at room temperature, and is rapid and efficient.In α,β-reduction (also called conjugate reduction), the substrate is an α,β-unsaturated carbonyl, an enone or enal.In the reduction of cyclohexanones, the hydride source can attack axially to produce an equatorial alcohol, or equatorially to produce an axial alcohol. In axial attack (shown in red), the hydride encounters 1,3-diaxial strain. In equatorial attack (shown in blue), the hydride avoids the 1,3-diaxial interaction, but the substrate undergoes unfavorable torsional strain when the newly formed alcohol and added hydrogen atom eclipse each other in the reaction intermediate (as shown in the Newman projection for the axial alcohol).