Organocatalytic, Asymmetric Eliminative [4+2] Cycloaddition of Allylidene Malononitriles with Enals: Rapid Entry to Cyclohexadiene- Embedding Linear and Angular Polycycles

A direct aminocatalytic synthesis has been developed
for the chemo-, regio-, diastereo-, and enantioselective
construction of densely substituted polycyclic carbaldehydes
containing fused cyclohexadiene rings. The chemistry utilizes,
for the first time, remotely enolizable p-extended allylidenemalononitriles
as electron-rich 1,3-diene precursors in a direct
eliminative [4+2] cycloaddition with both aromatic and
aliphatic a,b-unsaturated aldehydes. The generality of the
process is demonstrated by approaching 6,6-, 5,6-, 7,6-, 6,6,6-,
and 6,5,6-fused ring systems, as well as biorelevant steroid-like
6,6,6,6,5- and 6,6,6,5,6-rings. A stepwise reaction mechanism
for the key [4+2] addition is proposed as a domino bisvinylogous
Michael/Michael/retro-Michael reaction cascade.
The utility of the malononitrile moiety as traceless activating
group of the dicyano nucleophilic substrates is demonstrated.