Chiral Ionic Liquids Based on l-Cysteine Derivatives for Asymmetric Aldol Reaction

Karolina Zalewska,Małgorzata E Zakrzewska,Luis C Branco

doi:10.3390/catal12010047

Karolina Zalewska, Małgorzata E Zakrzewska + Show 1 more

Open Access

https://doi.org/10.3390/catal12010047

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Abstract

Structure, and consequently properties, of ionic liquids can be easily tailored by changing cation/anion combinations and/or attaching functional groups. By grafting enantiopure moieties to the framework of ionic liquid it is possible to prepare bioinspired chiral molecules that can serve as a reaction medium, additive or even asymmetric catalyst. In this context, new chiral ionic liquids (CILs), based on biomolecules, such as aminoacids (l-Cysteine derivatives), have been synthesised and tested in asymmetric aldol condensation of aldehydes and ketones. The best results were obtained for CILs composed of S-methyl-l-cysteine cation and bis(trifluoromethane)sulfonimide anion, in the reaction of 2- or 4-nitrobenzaldehyde with acetone or cyclohexanone, giving the aldol product in moderate yields 70–76% and high ee values (up to 96%).

Highlights

The major challenge in asymmetric synthesis is the pursuit of novel “green” catalysts exhibiting both high activity and selectivity [1,2,3]
Described as the “third pillar of asymmetric catalysis”, organocatalysis indicates to synthetic chemists an alternative approach towards chiral molecules that does not depend on enzymes nor on transition metals
Since the development of the highly enantioselective amine-catalysed Diels–Alder reaction by MacMillan and co-workers in 2000 [4], continuous improvements and new discoveries have been reported in asymmetric organocatalysis [5,6]

Summary

Introduction

The major challenge in asymmetric synthesis is the pursuit of novel “green” catalysts exhibiting both high activity and selectivity [1,2,3]. Novel chiral RTILs, essentially [S-MeCysNH3][NTf2], 3a, catalysed the asymmetric direct aldol reaction of 2- or 4-nitrobenzaldehyde and acetone or cyclohexanone to give the aldol product in moderate yields (70–79%), with the indicated range of ee values [SMeCysNH3][NTf2], 3a, in the case of 4-hydroxy-3-nitrobenzaldehyde, proved to be a better chiral catalyst than conventional L-proline (Table 2, Entries 5, 6; 76% yield, 95% ee) This can be explained by the fact that electron-withdrawing groups enhance the electrophilicity of carbonyl carbons in aldehydes, which facilitates the reaction, while electron-donating groups reduce the electrophilicity.

Materials and Methods

Findings

Procedure for Catalyst Recovery