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

Lucie Jarrige (1) , Vincent Gandon (2, 3) , Geraldine Masson (1)

1 ICSN - Institut de Chimie des Substances Naturelles
2 ICMMO - Institut de Chimie Moléculaire et des Matériaux d'Orsay
3 LCM - Laboratoire de chimie moléculaire

A stable asymmetric intramolecular Povarov reaction has been established to provide an efficient method to access structurally diverse trans,trans-trisubstituted tetrahydrochromeno[4,3b]quinolines in high stereoselectivities of up to >99:1 dr and 99% ee, without any purification step. Additionally, in order to facilitate largescale application of this method, a low catalyst loading protocol was employed, using 0.2 mol % of chiral phosphoric acid, providing the cycloadducts without any loss in yield and enantioselectivity. The theoretical studies revealed that the reaction occurred through a sequential Mannich reaction and an intramolecular Friedel-Crafts reaction, wherein the phosphoric acid acted as bifunctional catalyst to activate para-phenolic dienophile and N-2-hydroxy-2-azadienes, simultaneously.

Domaines: Chimie organique; Catalyse

Lucie Jarrige, Vincent Gandon, Geraldine Masson. Enantioselective Synthesis of Complex Fused Heterocycles through Chiral Phosphoric Acid Catalyzed Intramolecular Inverse‐Electron‐Demand Aza‐Diels–Alder Reactions. Chemistry - A European Journal, 2020, 26 (6), pp.1406-1413. ⟨10.1002/chem.201904902⟩. ⟨hal-03009627⟩