Green asymmetric synthesis of tetrahydroquinolines in carbon dioxide medium promoted by lipophilic bifunctional tertiary amine – squaramide organocatalysts

Novel pseudo-enantiomeric bifunctional tertiary amine-squaramides modified with long-chained alkoxy or polyfluoroalkoxy groups, have been synthesized. They catalyzed the asymmetric double-Michael cascade reactions of o-N-tosylaminophenyl α,β-unsaturated ketones with α-nitroolefins in carbon dioxide medium at significantly lower pressure (75 bar) and temperature (35 °C), than known less lipophilic catalysts. Both enantiomers of the pharmacologically valuable methoxy-substituted tetrahydroquinoline derivatives can be prepared in moderate to high yield with promising enantioselectivity (up to 98% ee) under the optimized conditions.