Mannich Reaction

This multi-component condensation of a nonenolizable aldehyde, a primary or secondary amine and an enolizable carbonyl compound affords aminomethylated products. The iminium derivative of the aldehyde is the acceptor in the reaction.

The involvement of the Mannich Reaction has been proposed in many biosynthetic pathways, especially for alkaloids.

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Mechanism

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Recent Literature

Ag-Catalyzed Asymmetric Mannich Reactions of Enol Ethers with Aryl, Alkyl, Alkenyl, and Alkynyl Imines
N. S. Josephsohn, M. L. Snapper, A. H. Hoveyda, J. Am. Chem. Soc., 2004, 126, 3734-3735.

Aminoboranes are highly efficient and mild iminium ion generators in the Mannich-type aminative coupling of aldehydes with silyl ketene acetals. The use of diisopropylaminoboranes enables a three-component Mannich reaction of free secondary amines with aldehydes and silyl ketene acetals.
M. Suginome, L. Uehlin, M. Murakami, J. Am. Chem. Soc., 2004, 126, 13196-13197.

Stereoselective Synthesis of β-Amino Ketones via Direct Mannich-Type Reactions, Catalyzed with ZrOCl₂ · 8 H₂O under Solvent-Free Conditions
B. Eftekhari-Sis, A. Abdollahifar, M. M. Hashemi, M. Zirak, Eur. J. Org. Chem., 2006, 5152-5157.

Oxidative Mannich Reaction of N-Carbobenzyloxy Amines with 1,3-Dicarbonyl Compounds
J-I. Matsuo, Y. Tanaki, H. Ishibashi, Org. Lett., 2006, 8, 4371-4374.

Organocatalytic and Highly Stereoselective Direct Vinylogous Mannich Reaction
T.-Y. Liu, H.-L. Cui, J. Long, B.-J. Li, Y. Wu, L.-S. Ding, Y.-C. Chen, J. Am. Chem. Soc., 2007, 129, 1878-1879.

Asymmetric Mannich Reactions with in Situ Generation of Carbamate-Protected Imines by an Organic Catalyst
J. Song, H.-W. Shih, L. Deng, Org. Lett., 2007, 9, 603-606.

Direct-Type Catalytic Three-Component Mannich Reactions Leading to an Efficient Synthesis of α,β-Diamino Acid Derivatives
M. M. Salter, J. Kobayashi, Y. Shimizu, S. Kobayashi, Org. Lett., 2006, 8, 3533-3536.

The Direct and Enantioselective, One-Pot, Three-Component, Cross-Mannich Reaction of Aldehydes
Y. Hayashi, W. Tsuboi, I. Ashimine, T. Urushima, M. Shoji, K. Sakai, Angew. Chem., 2003, 115, 3805-3808.