Unusual enantioselectivities in heterogeneous organocatalyzed reactions: Reversal of direction using proline di- versus tri-peptides in the aldol addition

•Asymmetric aldol reactions were studied over supported di- and tri-peptides.•The ee reversed on tripeptide catalyst as compared to the dipeptide.•Quantum chemical calculations showed the conformation of the intermediates.•The stabilities of these intermediates were in agreement with the inversion found.

The heterogeneous asymmetric direct aldol reactions between aldehydes (2-nitrobenzaldehyde, 2-methylpropanal) and ketones (acetone, cyclohexanone) in the presence of polystyrene (PS) resin supported di- and tripeptides were studied under otherwise identical experimental conditions at room temperature in batch reactor. For all three asymmetric aldol reactions reversal of enantiomeric excess was observed on H-Pro-Pro-Glu(OH)-PS catalyst (ee 39–50%) as compared to the H-Pro-Glu(OH)-PS catalyst (ee 52–95%). The determinant role of the conformation of the intermediate adducts held responsible for chiral induction is interpreted by quantum chemical calculations.

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