Title: Synthesis and Application of Membrane-Grafted and Cyclodextrin Anchored Asymmetric Cinchona-Based Organocatalysts

Abstract:

In this work we continued our research in the field of application of organocatalysts in continuous mode performed in sustainable way.¹ In the first part of this research, we introduce a sustainable membrane-based synthesis–separation platform for enantioselective organocatalysis. An azido derivatized cinchona-squaramide bifunctional catalyst was synthesized and subsequently grafted to the surface of a polybenzimidazole-based nanofiltration membrane. The favorable effect of the covalent grafting—due to the change in geometry and increased secondary interactions—on the catalytic activity due to conformational changes was confirmed by quantum chemical calculations. Asymmetric Michael and aza-Michael reactions of 1,3-dicarbonyl and indole, pyrazole, and triazole derivatives to β-nitrostyrene were performed with as high as 99% enantiomeric excess. This report on the enantioselective aza-Michael reaction of pyrazoles and triazoles opens new frontiers in the application of squaramide-based cinchona catalysts. A catalytic membrane cascade reactor was developed for an integrated synthesis–purification process allowing at least 98% product and substrate recovery, and quantitative in situ solvent recycling. The sustainability of the synthetic methodology was assessed through E-factor and carbon footprint.

In the next part, cinchona-thiourea and -squaramide catalysts were covalently anchored to inherently large, stable and well-defined permethyl-β-cyclodextrins, as well. These catalysts were used in batch and continuous mode with excellent enantioselectivity.

This research was funded by the New National Excellence Program of the Ministry of Human Capacities, grant number ÚNKP-19-4-BME-415, and the Janos Bolyai Research Scholarship of the Hungarian Academy of Science. It was also supported by the National Research, Development and Innovation Office (former OTKA, grant number K128473).

Biography:

Jozsef Kupai works as an assistant professor at Budapest University of Technology and Economics Hungary, he delivers organic chemistry lectures and practices. He is the head of the Organocatalysis Research Group at the Department of Organic Chemistry and Technology. The expertise of the Kupai group (www.kupaigroup.com) members centers on the synthesis, application, and recovery of cinchona based organocatalysts. Dr. Kupai collaborates with Dr. Gyorgy Szekely at the University of Manchester. The Szekely Group is responsible for the process design encompassing flow reactors coupled with membrane purification.