Three-component cross-mannich reactions

Scheme 9.7. Enantioselective three-component cross-Mannich reaction of two different aldehydes.

Hayashi Y, Tsuboi W, Ashimine I, Urushima T, Shoji M, Sakai K (2003b) The direct and enantioselective, one-pot, three-component, cross-mannich reaction of aldehydes. Angew Chem Int Ed Engl 42 3677-3680... 

The corresponding /i-amino aldehydes are reduced in situ and the corresponding amino alcohols are isolated in good yield with up to >99 % ee. The Mannich reactions proceed with excellent chemoselectivity and inline formation occurs with the acceptor aldehyde at a faster rate than C-C bond-formation. Moreover, the one-pot three-component direct asymmetric cross-Mannich reaction enables aliphatic aldehydes to serve as acceptors. The absolute stereochemistry of the reaction was determined by synthesis and reveled that L-proline provides syn /i-amino aldehydes with (S) stereochemistry of the amino group. In addition, the proline-catalyzed direct asymmetric Mannich-type reaction has been connected to one-pot tandem cyanation and allylation reaction in THF and aqueous media affording functional a-amino acid derivatives [39, 42]. 

Quite recently, cross-linked dendrimer was also found to be a good support for Sc(III) catalyst [101]. The resultant material could be used in water as a catalyst for three-component Mannich-type reactions and Mukaiyama aldol reactions. A simple immobilization method of Sc species by using montmorillonite as a support has also been reported recently [102]. This method provides a highly active heterogeneous catalyst for Michael reactions under aqueous or solvent-free conditions. 

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