Asymmetric Synthesis of 3,4‐Dihydroquinolin‐2‐ones via Organocatalytic [4+2]‐Cyclization of 2‐Amino‐β‐nitrostyrenes with Azlactones

Abstract

Dihydroquinolin‐2‐ones, recognized for their significant bioactive properties, feature a unique six‐membered structure with nitrogen‐containing heterocycles. A breakthrough method has been developed to synthesize enantioenriched 3,4‐dihydroquinoline‐2‐one derivatives. This innovative approach utilizes an asymmetric [4+2]‐cyclization process, combining 2‐amino‐β‐nitrostyrenes with azlactones, and is facilitated by a bifunctional squaramide‐based organocatalyst. This innovative approach has enabled the creation of novel chiral 3,4‐dihydroquinoline‐2‐ones with complex structures, including chiral quaternary centers. The process is remarkably efficient, delivering high yields (up to 91%), excellent enantiomeric excess (up to 97% ee), and superior diastereoselectivity (up to 19:1 dr).