Bicyclic Guanidine-Catalyzed Asymmetric Cycloaddition Reaction of AnthronesBifunctional Binding Modes and Origin of Stereoselectivity

We report a computational analysis
of the [5,5] bicyclic guanidine-catalyzed
asymmetric cycloaddition reaction of anthrones. Based on extensive
conformational search of key intermediates and transition states on
the potential energy surface and density functional theory calculations,
we studied five plausible binding modes between the guanidine catalyst
and substrates for this reaction. Our results indicate that the most
favorable pathway is a stepwise conjugate addition-Aldol sequence
via the dual hydrogen-bond binding mode. The predicted level of enantioselectivity
is in good agreement with experimental values. Trends in variation
of substrates and catalysts have also been reproduced by our calculations.
Decomposition analysis revealed the significance of aromatic interactions
in stabilizing the key enantioselectivity-determining transition state
structures.