Synthesis of C3-Symmetric Cinchona-Based Organocatalysts and Their Applications in Asymmetric Michael and Friedel–Crafts Reactions

Péter Kisszékelyi,Miklós Dékány,Péter Huszthy,Péter Bagi,Zsófia Garádi,Béla Mátravölgyi,József Kupai,Zsuzsanna Fehér,Sándor Nagy,Petra Kozma

doi:10.3390/sym13030521

Abstract

In this work, anchoring of cinchona derivatives to trifunctional cores (hub approach) was demonstrated to obtain size-enlarged organocatalysts. By modifying the cinchona skeleton in different positions, we prepared four C3-symmetric size-enlarged cinchona derivatives (hub-cinchonas), which were tested as organocatalysts and their catalytic activities were compared with the parent cinchona (hydroquinine) catalyst. We showed that in the hydroxyalkylation reaction of indole, hydroquinine provides good enantioselectivities (up to 73% ee), while the four new size-enlarged derivatives resulted in significantly lower values (up to 29% ee) in this reaction. Anchoring cinchonas to trifunctional cores was found to facilitate nanofiltration-supported catalyst recovery using the PolarClean alternative solvent. The C3-symmetric size-enlarged organocatalysts were completely rejected by all the applied membranes, whereas the separation of hydroquinine was found to be insufficient when using organic solvent nanofiltration. Furthermore, the asymmetric catalysis was successfully demonstrated in the case of the Michael reaction of 1,3-diketones and trans-β-nitrostyrene using Hub3-cinchona (up to 96% ee) as a result of the positive effect of the C3-symmetric structure using a bulkier substrate. This equates to an increased selectivity of the catalyst in comparison to hydroquinine in the latter Michael reaction.

Highlights

Over the years, catalysis has been widely explored for the more economical and often more selective production of high-value products [1]
The mono H-bond donor 9-OH has been rereserved in the case of compounds as the cinchona motif was anchored to the served in the case of Type B compounds as the cinchona motif was anchored to the hub, hub, either through the aromatic quinoline (Williamson formation) or through the either through the aromatic quinoline (Williamson etherether formation) or through the quiquinuclidine using copper(I)
Four structurally different C3 -symmetric cinchona organocatalysts were prepared, in which the catalytic units are covalently anchored to a trifunctional central core

Summary

Introduction

Catalysis has been widely explored for the more economical and often more selective production of high-value products [1]. Compounds with rotational symmetry have gained increased attention in asymmetric synthesis because they are believed to be able to improve enantioselectivity by decreasing the number of possible transition states during the reaction [3,4,5]. Due to their beneficial effect on enantioselectivity, C2 - and C3 -symmetric molecules have been the focus of extensive research and, as a result, C3 -symmetric compounds have been successfully applied as catalysts, ligands, molecular receptors, supra- and macromolecular constructs, gelators, metal-organic materials (MOMs), etc. The application of C3 -symmetric trisimidazoline organocatalysts was extended to an enantioand diastereoselective Betti/aza-Michael sequence as well [19]

Methods

Results

Conclusion