Stereoselective Aldol and Conjugate Addition Reactions Mediated by Proline‐Based Catalysts and Its Analogues: A Concise Review

Abstract

The application of amino acids and small peptides as asymmetric organocatalysts in the aldol and conjugate addition reactions is a significant breakthrough in the past decade. The desired stereoselectivity in these reactions can be attained through tunable elements of diversity present in the amino acids/peptides. On this note, the current review highlights the organocatalytic aldol and conjugate addition by proline or its analogous in the form of amide/peptide derivatives. The wide‐ranging works of literature are classified based on the use of single amino acid or peptides as a catalyst. The designing of the aforementioned amide/amino acid/peptide catalyst, including their recent applications, is also detailed. Moreover, the analogous catalysts are also discussed, embedding other hetero‐organic functionalities that mimic the catalytic activity of proline in aldol/conjugate additions.

In Situ Assembly of a Metal‐Templated Catalyst for Asymmetric Aldol Reactions: From the Metal Complexes Equilibria to a Practical System

“…In particular, we have used zinc(II) and pyridine or bipyridine ligands with pendant prolinamide groups to catalyse the asymmetric aldol reaction. [20][21] An auxiliary (bi)pyridine ligand with hydrogen bond donor properties was also necessary to accelerate the reaction, which prompted us to propose a tetrahedral heteromeric zinc complex with the two ligands as the real catalyst for the reaction. [22][23][24][25] The development of those catalytic systems led us to identify some geometric requirements to increase their efficiency: the presence in both bipyridine ligands of two redundant functional groups within the formation of a tetrahedral zinc complex led to a degenerate system with multiple reaction sites.…”

“…Using this approach different combinations of catalytic groups with different structural features can be rapidly tested without the need of long and costly syntheses. In particular, we have used zinc(II) and pyridine or bipyridine ligands with pendant prolinamide groups to catalyse the asymmetric aldol reaction [20–21] . An auxiliary (bi)pyridine ligand with hydrogen bond donor properties was also necessary to accelerate the reaction, which prompted us to propose a tetrahedral heteromeric zinc complex with the two ligands as the real catalyst for the reaction [22–25] .…”

Cooperative assistance of a sulfonamide in a proline-mediated direct asymmetric aldol addition

“…Proline-based catalysts have evidently been at the heart of remarkable advances in the field of asymmetric organocatalysis and have had a particularly profound influence in enamine-mediated transformations such as the direct asymmetric aldol addition. 12 Among the proline-based catalysts, the trans-4-hydroxyproline scaffold represents a major platform upon which a huge number and variety of catalysts have been constructed, particularly toward mediating asymmetric aldol additions with admirable efficiency and stereocontrol. 12d, 13 The influential sulfonamide moiety has not been left out in this regard, and has been incorporated at the 4-position of proline derivatives that have been employed, for instance, in asymmetric Biginelli reactions and Michael additions.…”