Asymmetric synthesis with cinchona-decorated CD in a continuous-flow membrane reactor

Over the last two decades organocatalysis has become an attractive synthetic tool in asymmetric catalysis. However, the increasing demand for catalyst recycling and reuse calls for the design of more flexible and sustainable organocatalytic strategies.

Precipitation of the catalyst by salt formation or solvent change, heterogenization of organocatalysts via immobilization on solid support (polymers, silica, magnetic nanoparticles, etc.) are common methods for the recovery of organocatalysts.

Integrated catalysis-separation systems is a rapidly emerging field due to its compact and efficient nature. These recycling methodologies are sustainable with low energy consumption, and their scale-up and implementation in continuous and hybrid processing are relatively straightforward. The efficiency of separation depends mainly on (i) the molecular weight gap between the catalyst and the other components, and (ii) the absolute catalyst retention by the membrane. To meet these requirements, size-enlargement of the catalyst is often required.

Cyclodextrin (CD) anchoring methodology has been proposed to facilitate recovering the enlarged organocatalysts by a recent Journal of Catalysis article. CDs are excellent candidates to provide a platform for the development of size-enlarged organocatalysts, which can be efficiently recycled by membrane filtration.

Cinchona-thiourea and -squaramide organocatalysts were covalently anchored to the inherently large and stable permethyl-β-cyclodextrin. The asymmetric catalysis was successfully demonstrated on the Michael reaction of 1,3-diketones and trans-β-nitrostyrene. For the asymmetric addition both emerging green and conventional solvents were screened (up to 99% ee). Furthermore, quantum chemical modelling revealed that the catalyst anchoring resulted in favorable structural changes, and stronger intermolecular interactions between the catalyst and the reagents.

Continuous organocatalysis was performed in coiled tube flow reactor coupled with a membrane separation unit, which allowed complete recovery of the catalyst and 50% solvent (2-MeTHF) recycling. The 100% conversion, 98% purity, 99% ee, 100% in-line catalyst recovery, and 80 g L-1 h-1 productivity makes it an attractive catalytic platform.

The details of the study can be found here: Kisszekelyi, P; Alammar, A; Kupai, J; Huszthy, P; Barabas, J; Holtzl, T; Szente, L; Bawn, C; Adams, R and Szekely, G; Asymmetric synthesis with cinchona-decorated cyclodextrin in a continuous-flow membrane reactor, J. Catal., 2019, 371:255-261


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