Exploring the Vinylogous Reactivity of Cyclohexenylidene Malononitriles: Switchable Regioselectivity in the Organocatalytic Asymmetric Addition to Enals Giving Highly Enantioenriched Carbabicyclic Structures

Modulation of the
complex reactivity of cyclohexenylidene malononitriles
using diverse β-aryl-substituted enals and proper organocatalytic
modalities resulted in divergent asymmetric reaction patterns to furnish
angularly fused or bridged carbabicyclic frameworks. In particular,
use of remotely enolizable dicyanodienes 1, under one-pot
sequential amine/NHC catalysis, led to [3 + 2] cycloaddition to afford
ε,δ-bonded spiro[4.5]­decanone structures 5. Alternatively, modifying the standard amine catalysis by adding
a suitable chemical stimulus (p-nitrophenol cocatalyst)
switched the reactivity decidedly toward a domino [4 + 2] cycloaddition
to afford γ′,δ-bonded bicyclo[2.2.2]­octane carbaldehydes 8. Products invariably formed in good yields, with rigorous
chemo-, regio-, diastereo-, and enantiocontrol. Experimental evidence,
including carbon isotope effects measured by 13C NMR, were
indicative of the rate (and stereochemistry) determining step of these
transformations and suggested a stepwise mechanism for the [4 + 2]
cycloadditive pathway.