Reductive amination

Reductive amination is a chemical reaction which involves the conversion of a aldehyde.

Reaction mechanism

In organic synthesis

In this sodium borohydride). This is indirect reductive amination.

However, it is also possible to carry out the same reaction all in one pot, with the imine formation and reduction occurring concurrently. This is known as direct reductive amination and is carried out with reducing agents that are more reactive toward imines than ketones, such as sodium cyanoborohydride (NaBH₃CN) or sodium triacetoxyborohydride (NaBH(OCOCH₃)₃).

This reaction is related to the Petasis reaction.

Scope

In industry tertiary amines such as hydrogen and a suitable catalyst .

The reaction depicted below is an example of an aniline.^[1]^[2]

The formation of only one enantiomer from the racemic reactant is attributed to dynamic kinetic resolution because both enantiomers in the racemic imine intermediate interconvert through their common enamine.

Biochemistry

A step in the biosynthesis of many α-glutamate. The initial step entails formation of an imine, but the hydride equivalents are supplied by a reduced pyridine to give an aldimine, which hydrolyzes to the amine.^[3] The sequence from keto-acid to amino acid can be summarized as follows:

HO₂CC(O)R → HO₂CC(=NCH-X)R → HO₂CCH(N=CH-X)R → HO₂CCH(NH₂)R

References

^ Catalytic Asymmetric Reductive Amination of Aldehydes via Dynamic Kinetic Resolution Sebastian Hoffmann, Marcello Nicoletti, and Benjamin List J. Am. Chem. Soc. 2006, 128(40), 13074 - 13075. (doi:10.1021/ja065404r)
^ In this reaction the BINAP family. Molecular sieves remove formed water. The enantiomeric ratio is 99:1.
^ Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISNB 1-57259-153-6.