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.
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This research / project is supported by the Institute of Chemical and Engineering Sciences - Project
Grant Reference no. : SC22/17-1A02G4
This research / project is supported by the National University of Singapore - Grant
Grant Reference no. : R-143-000-481-112