Chiral Brønsted acid-catalyzed asymmetric intermolecular [4 + 2] annulation of ynamides with para-quinone methides

Catalytic asymmetric transformations of ynamides have attracted considerable attention in recent years. However, most of them were limited to intramolecular reactions or required metal catalysts. Herein, a chiral Brønsted acid-catalyzed asymmetric intermolecular [4 + 2] annulation of ynamides with para-quinone methides ( p -QMs) is disclosed, which not only represents the first metal-free protocol for catalytic asymmetric nucleophilic addition of ynamides to electrophiles, but also constitutes the first enantioselective annulation between p -QMs and alkynes. This methodology leads to the practical synthesis of biologically important chiral 4-aryl-3,4-dihydrocoumarins and 4-aryl-coumarins. Preliminary control experiments indicate that the ortho -hydroxyphenyl substituted p -QMs could isomerize into ortho -quinone methides ( o -QMs) in the presence of chiral catalyst, which further react with ynamides via enantioselective [4 + 2] annulation, to generate the chiral product.