Synfacts 2005(2): 0257-0257  
DOI: 10.1055/s-2005-916111
Bioorganic Chemistry and Organocatalysis
© Georg Thieme Verlag Stuttgart · New York

Direct Catalytic Enantioselective Aza-Diels-Alder Reactions

Contributor(s): Hisashi Yamamoto, Matthew B. Boxer
H. Sundén, I. Ibrahem, L. Eriksson, A. Córdova*
Stockholm University, Sweden
Further Information

Publication History

Publication Date:
25 October 2005 (online)

Significance

While indirect, catalytic, enantioselective aza-Diels-Alder reactions have been reported, this paper describes the first direct, organocatalytic aza-Diels-Alder reaction. Three components, enone, aqueous formaldehyde, and amine, are mixed with the proline catalyst and enantioselectivities greater than 94% are produced in many cases. When the enone was β-substituted, the Mannich adduct was isolable. This indicated a stepwise mechanism where first the proline and enone form a chiral enamine, which reacts with the in situ formed imine (Mannich reaction); the anionic nitrogen then adds intramolecularly in a 1,4-fashion to the iminium ion and hydrolysis leads to the chiral aza-Diels-Alder adduct.