Possible stereochemical result has been accounted by assuming acyclic transition states A and B . These Michael reactions constituted the first direct catalytic asymmetric reactions of any type s involving aldehyde donors and encouraged the development of aldehyde-based reactions with a range of electrophiles (Scheme 18).
Scheme 18. Mode of Action in Chiral Michael Reaction
The iminium-enamine activation mode can be envisaged to explain the domino oxa-Michael–Michael reaction occurring between 3-methylbut-2-enal and ( E )-2-(2-nitrovinyl)-benzene-1,4-diol upon catalysis with chiral diphenyl prolinol silyl ether, which afford the corresponding enantiopure oxa-Michael–Michael cycloadduct in 76% yield and 99% ee (Scheme 19). The latter can be further implicated in a Michael–aldol sequence through the reaction with crotonaldehyde to afford corresponding hexahydro-6H-benzo-chromene in 74% yield. These two domino reactions have constituted the key steps of the first asymmetric total synthesis of the natural biologically active product (+)-conicol.
Scheme 19. Domino oxa-Michael–Michael Reaction in the Synthesis of (+)-Conicol