Enantioselective Construction of <i>gem</i>-Difluorinated Tetrahydroindolo[2,1-<i>b</i>]quinazolines via CPA-Catalyzed Asymmetric [4 + 2]-Annulation

Indoloquinazolinones are widely acknowledged as essential scaffolds for the development of diverse biologically active compounds, pharmaceutical agents, and natural products. Given the critical role of fluorine atoms in enhancing the properties of pharmaceuticals and agrochemicals, fluorinated indoloquinazolinones exhibit substantial promise in drug discovery and development. Herein, we developed the CPA-catalyzed asymmetric enantioselective [4 + 2]-annulation reactions between 2-aminophenyl enones and 3,3-difluoro-2-aryl-3<i>H</i>-indoles. This methodology enables the synthesis of various chiral <i>gem</i>-difluorinated tetrahydroindolo[2,1-<i>b</i>]quinazoline derivatives in good to high yields with excellent enantioselectivities.