Direct asymmetric Michael addition of cyclic N-sulfonylimines to α,β-unsaturated aldehydes

Article abstract of DOI:10.1002/chem.201002592

As traditional electrophiles, imines have been extensively applied in Mannich-type reactions for the synthesis of amine compounds. On the other hand, owing to the electronwithdrawing character of the imine functionality, the α-protons of imines also show some acidity; thus, imines tend to act as nucleophiles for α-functionalization reactions, although stoichiometric amounts of strong base are usually required. It is expected that the acidity of the a-protons of imines would be greatly increased in compounds that have highly electron-withdrawing substituents on the nitrogen atom; therefore, the direct-type reactions of imines might be realized under mild catalytic conditions. Indeed, in 2008, Kobayashi and co-workers proved this synthetic possibility in the direct Mannich reaction of the N-tosylimine of acetophenone with an activated imine by the catalysis of simple Net₃ ; unfortunately, its applicability is limited due to tautomerization and elimination of the functional groups in the products.As a consequence, the structurally more stable tautomers of imines, enecarbamates and enamides, are generally selected and utilized as the nucleophiles, and have been well explored by Kobayashi and other groups over the past few years, through the catalysis of either metal-based or organic molecules