An organocatalyzed sulfa-Michael/aldol cascade reaction was developed between mercaptoacetaldehyde and unsaturated pyrrolin-4-ones, which can exist in either E- or Z-configuration. Using a single optimized catalyst, both enantiomers of the formed spirocyclic products are obtainable, depending on the starting configuration of the olefin double bond. While modeling this reaction using density functional theory, we discovered an overlooked effect that the catalyst conformation can have on the enantioselectivity of the transformation. Depending on the orientation of the squaramide group on the catalyst backbone, two different active pseudo-enantiomeric conformations are possible. These conformations are responsible for different organization of the transition states leading to the product, which results in the formation of opposite enantiomers. Our findings can be useful in future method development in order to obtain enantiomeric products using a single enantiomer of the widely used quinine-derived bifunctional squaramide organocatalyst.

DFT study of pseudo-enantiomeric conformations of a quinine-derived bifunctional squaramide organocatalyst

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.