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

Kisszekelyi, Peter, Alammar, Abdulaziz, Kupai, Jozsef, Huszthy, Peter, Barabas, Julia, Holtzl, Tibor, Szente, Lajos, Bawn, Carlo, Adams, Ralph, Szekely, Gyorgy
Journal of catalysis 2019 v.371 pp. 255-261
catalysts, catalytic activity, chemical bonding, chemical reactions, cyclodextrins, enantioselectivity, models, process design, quantum mechanics, solvents
This work presents a cyclodextrin-enhanced organocatalytic method from molecular to process design. Cinchona-thiourea and -squaramide catalysts were covalently anchored to inherently large, stable and well-defined permethyl-β-cyclodextrins. The asymmetric catalysis was successfully demonstrated on the Michael reaction of 1,3-diketones and trans-β-nitrostyrene. Both emerging green and conventional solvents were screened for the asymmetric addition (up to 99% ee), and the Kamlet–Taft solvent parameters were correlated to the enantioselectivity. 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.