Exploring “Through‐Bond” Proximity between the Ion Tag and Reaction Site of an Imidazolium‐Proline Catalyst for the Direct Asymmetric Aldol Reaction

Abstract

The incorporation of an imidazolium moiety at the C‐4 position of proline, cis to its COOH group, enabled an interesting study of the effect of through‐bond proximity of the ion tag to the reaction site in an enamine‐mediated direct asymmetric aldol reaction. The new catalyst, having a reduced bond spacer between the imidazolium tag and the amino acid moiety in comparison with conceptually similar predecessors, showed excellent performance in aldol reactions carried out in the presence of water under solvent‐free conditions. High yields and enantioselectivities, along with exceptional diastereoselectivities of the aldol adducts were obtained with just 2 mol‐% loading of the catalyst. The study offers a deeper insight into the role of the ion tag in organocatalysed aldol reactions, which in turn could be a vital pointer for future catalyst design.