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

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 C-3-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 C-3-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-beta-nitrostyrene using Hub(3)-cinchona (up to 96% ee) as a result of the positive effect of the C-3-symmetric structure using a bulkier substrate. This equates to an increased selectivity of the catalyst in comparison to hydroquinine in the latter Michael reaction.

Automated summary

Anchoring cinchona derivatives to trifunctional cores can lead to size-enlarged organocatalysts with varied catalytic activities. The new size-enlarged derivatives showed lower catalytic activities in certain reactions compared to the parent cinchona catalyst, and facilitated catalyst recovery using the PolarClean alternative solvent for nanofiltration-supported applications. Additionally, asymmetric catalysis demonstrated increased selectivity of the catalyst with a bulkier substrate in the Michael reaction.