Reductive amination (also known as reductive alkylation) is a form of amination that converts a carbonyl group to an amine via an intermediate imine. The carbonyl group is most commonly a ketone or an aldehyde. It is a common method to make amines and is widely used in green chemistry since it can be done catalytically in one-pot under mild conditions. In biochemistry, dehydrogenase enzymes use reductive amination to produce the amino acid glutamate. Additionally, there is ongoing research on alternative synthesis mechanisms with various metal catalysts which allow the reaction to be less energy taxing, and require milder reaction conditions. Investigation into biocatalysts, such as imine reductases, have allowed for higher selectivity in the reduction of chiral amines which is an important factor in pharmaceutical synthesis.

Reductive amination occurs between a carbonyl such as an aldehyde or ketone and an amine in the presence of a reducing agent. The reaction conditions are neutral or weakly acidic.

There are two ways to conduct a reductive amination reaction: direct and indirect.

In a direct reaction, the carbonyl and amine starting materials and the reducing agent are combined and the reductions are done sequentially. These are often one-pot reactions since the imine intermediate is not isolated before the final reduction to the product. Instead, as the reaction proceeds, the imine becomes favoured for reduction over the carbonyl starting material. The two most common methods for direct reductive amination are hydrogenation with catalytic platinum, palladium, or nickel catalysts and the use of hydride reducing agents like cyanoborohydride (NaBH₃CN).

Indirect reductive amination, also called a stepwise reduction, isolates the imine intermediate. In a separate step, the isolated imine intermediate is reduced to form the amine product.

There are many considerations to be made when designing a reductive amination reaction.

To solve the last issue, asymmetric reductive amination reactions can be used to synthesize an enantiopure product of chiral amines. In asymmetric reductive amination, a carbonyl that can be converted from achiral to chiral is used. The carbonyl undergoes condensation with an amine in the presence of H₂ and a chiral catalyst to form the imine intermediate, which is then reduced to form the amine. However, this method is still limiting to synthesize primary amines which are non-selective and prone to overalkylation.

Palladium hydride (H₂/Pd) is a versatile reducing agent commonly used in reductive amination reactions. Its catalytic efficiency stems from the ability of palladium to adsorb hydrogen gas, forming active hydride species. These hydrides facilitate the reduction of imines or iminium ions—key intermediates in reductive amination—into secondary or tertiary amines. This reaction typically occurs under mild conditions with excellent selectivity, which often makes H₂/Pd the first choice for synthesizing amines in pharmaceuticals and fine chemicals. Additionally, H₂/Pd is compatible with a wide range of functional groups, further enhancing its utility in complex organic synthesis.