Enantioselective Synthesis of Complex Fused Heterocycles through Chiral Phosphoric Acid Catalyzed Intramolecular Inverse‐Electron‐Demand Aza‐Diels–Alder Reactions

A stable asymmetric intramolecular Povarov reaction has been established to provide an efficient method to access structurally diverse trans , trans ‐trisubstituted tetrahydrochromeno[4,3‐ b ]quinolines in high stereoselectivities of up to >99:1 diastereomeric ratio and 99 % enantiomeric excess, without any purification step. Additionally, to facilitate large‐scale application of this method, a low catalyst loading protocol was employed, 0.2 mol % chiral phosphoric acid, which provided the cycloadducts without any loss in yield and enantioselectivity. Theoretical studies revealed that the reaction occurred through a sequential Mannich reaction and an intramolecular Friedel–Crafts reaction, wherein the phosphoric acid acted as a bifunctional catalyst to activate the para ‐phenolic dienophile and N ‐2‐hydroxy‐2‐azadiene simultaneously.