Cinchona-derived squaramide organocatalyzed asymmetric domino aza-Friedel–Crafts/hemiketalization of acenaphthenequinoneimines and naphthols

Abstract

An unprecedented enantioselective aza-Friedel–Crafts/hemiketalization of acenaphthenequinoneimines and naphthols was explored using cinchona-squaramide catalysts. Under the optimized conditions, a range of chiral furanonaphtho–acenaphthene derivatives bearing two vicinal tetra-substituted stereogenic centers were obtained in excellent yields (93–98%) and stereoselectivities (>99 : 1 dr and 90–>99% ee). Five selected products were evaluated for their antiproliferative activities against four types of human cancer cell lines and one human umbilical vein endothelial cell line using the CCK-8 assay. Among them, 6af showed optimal cytotoxicity against the A549 cell line and a good safety profile in normal human cells, which was better than the inhibitory activity of the positive control drug (doxorubicin).