Membrane-Grafted Asymmetric Organocatalyst for an Integrated Synthesis-Separation Platform

Abstract

In this work 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.