Organocatalyzed Asymmetric Mannich Reaction: An Update

The Mannich reaction is a multicomponent reaction resulting in aminoalkylation of an acidic proton placed next to a carbonyl functional group. It involves an appropriate carbonyl compound, such as formaldehyde and a primary or secondary amine or ammonia. The final product is a beta-amino-carbonyl compound known as a Mannich base. Reactions between aldimines and alpha-methylene carbonyls are also considered as Mannich reaction since these imines are generated from the reaction of amines and aldehydes. It comprises the reaction of primary or secondary amines or ammonia, formaldehyde and appropriate alpha-CH-acidic compounds (nucleophiles) such as carbonyl compounds having alpha-CH-acidic, nitriles, acetylenes, aliphatic nitro compounds, alpha-alkyl-pyridines or imines. Owing to the development of asymmetric organocatalysis, reports on asymmetric Mannich reaction have been drastically increased. The asymmetric Mannich reaction offers access to enantioenriched beta-amino ketones or beta-amino aldehydes, which are present as a scaffold in several natural products. Organocatalysts have been developed not only as a supplement to metal-catalyzed reactions or to biocatalysis, but nowadays, they are extensively used for the synthesis of various optically pure compounds that could not be achieved via metal- or biocatalyzed reactions. In this review, we try to update the advances in organocatalyzed asymmetric Mannich reactions, covering the recent advances of the subject from 2008 to date.