Highly Diastereo- and Enantioselective Direct Aldol Reaction Catalyzed by Simple Amphiphilic Proline Derivatives

Abstract

Two novel amphiphilic L-proline derivatives bearing long alkyl chain on the 4-position via ether bonds, 1a and 1b, have been synthesized and evaluated for the asymmetric direct aldol reaction in organic solvents as well as in water. The catalytic activities with 5 mol% of 1a are better than that of 30 mol% of proline itself being used. Especially, high yields (up to 99%), excellent enantioselectivities (up to 99% ee) and anti-diastereoselectivities (up to 99:1) are achieved in the reactions of aromatic aldehydes and cyclic ketones at room temperature with 5 mol% of 1a in water.

The direct catalytic asymmetric aldol reaction

“…As these approaches have been reviewed previously, 10–24 the goal of this review will be to highlight and compare the reactivity, scope and selectivity of a wide range of catalysts, rather than catalogue every example of their use. This review will not focus on design parameters such as catalyst immobilization, 25–35 attaching hydrophobic groups to the catalyst, 30, 36–38 reactions in micelles, 39, 40 host-guest catalytic systems, 41, 42 or the use of ionic liquids 43–54 or surfactants, 55–60 which can be found elsewhere. 12, 13 Instead, this review will highlight what is currently possible synthetically and what challenges remain unmet for enamine-based catalysts.…”

Preparation of Immobilized L‐Prolinamide Via Enzymatic Polymerization of Phenolic L‐Prolinamide and Evaluation of Its Catalytic Performance for Direct Asymmetric Aldol Reaction

“…Among the various catalysts for direct asymmetric aldol reaction, a series of organocatalysts derived from L‐proline are of particular significance. This is why many efforts have been made to modify the structure of L‐proline so as to improve selectivity and reusability, reduce load, and avoid the use of organic solvent . To overcome these drawbacks, researchers also have made attempts to graft organocatalysts with suitable supports .…”

Highly Enantioselective α-aminoxylation Reactions Catalyzed by Isosteviol-proline Conjugates in Buffered Aqueous Media

“…The amphiphilic L-proline derivatives 1a and 1b have the combined catalytic function of L-proline with the hydrophobic effect of the isosteviol subunit, which prompted us to evaluate their catalytic performance for the asymmetric a-aminoxylation reaction in aqueous media in the absence of any additive. To compare the catalytic behavior of different amphiphilic catalysts, the long-alkyl substituted proline derivatives 1c [36] and 1d [37], as well as L-proline 1e, were also examined for the reactions (Fig. 3).…”