Abstract |
The nitro-Mannich (aza-Henry) reaction, in which a nitroalkane and an imine react to
form a b-nitroamine, is a versatile tool for target-oriented synthesis. Although the first
stereoselective reaction was developed only 20 years ago, and enantioselective and
diastereoselective versions for the synthesis of non-racemic compounds soon after,
there are nowadays a variety of reliable methods which can be used for the synthesis of
APIs and other biologically active substances. Hence many anticancer drugs, antivirals,
antimicrobials, enzyme inhibitors and many more substances, containing C–N bonds,
have been synthesized using this reaction. Several transition metal complexes and
organocatalysts were shown to be compatible with the presence of a wide range of
functional groups in these molecules, and very high levels of asymmetric induction
have been achieved in some cases. The reaction has also been applied in cascade
processes. The structural diversity of the products, ranging from simple heterocycles
or azabicycles to complex alkaloids, iminosugars, amino acids or diamino acids and
phosphonates, shows the versatility of the nitro-Mannich reaction and its potential for
future developments. |