Chiral Phosphoric Acid-Catalyzed Enantioselective Three-Component Povarov Reaction Using Enecarbamates as Dienophiles: Highly Diastereo- and Enantioselective Synthesis of Substituted 4-Aminotetrahydroquinolines - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of the American Chemical Society Année : 2011

Chiral Phosphoric Acid-Catalyzed Enantioselective Three-Component Povarov Reaction Using Enecarbamates as Dienophiles: Highly Diastereo- and Enantioselective Synthesis of Substituted 4-Aminotetrahydroquinolines

Résumé

Chiral phosphoric acid (5)-catalyzed three-component Povarov reaction of aldehydes 2, anilines 3 , and enecarbamates 4 afforded cis-4-amino-2-aryl (alkyl)-1,2,3,4-tetrahydroquinolines 1 in high yields with excellent diastereoselectivities (>95%) and almost complete enantioselectivities (up to >99%). The reaction was applicable to a wide range of anilines bearing electron-donating (OMe) and electronwithdrawing groups (e.g. Cl, CF 3 , NO 2) and allowed for the first time, the aliphatic aldehydes to be employed in the enantioselective Povarov reaction. With -substituted acyclic enecarbamates, 2,3,4trisubstituted 1,2,3,4-tetrahydroquinolines with three contiguous stereogenic centers were produced in excellent diastereo-and enantioselectivities (87->99% ee). A detailed study about the active catalytic species allowed us to reduce the catalyst loading from 10% to 0.5% with no deterioration of enantiomeric excess. In addition, mechanistic studies allowed us to conclude unequivocally that the Povarov reaction involving enecarbamate as dienophile proceeded via a stepwise mechanism. The key role of the free NH function of the enecarbamate to the success of this transformation was demonstrated. NMR experiments indicating the catalyst-substrate interaction as well as a linear correlation between catalyst and product ees were also documented.
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hal-04047674 , version 1 (27-03-2023)

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Guillaume Dagousset, Jieping Zhu, Géraldine Masson. Chiral Phosphoric Acid-Catalyzed Enantioselective Three-Component Povarov Reaction Using Enecarbamates as Dienophiles: Highly Diastereo- and Enantioselective Synthesis of Substituted 4-Aminotetrahydroquinolines. Journal of the American Chemical Society, 2011, 133 (37), pp.14804-14813. ⟨10.1021/ja205891m⟩. ⟨hal-04047674⟩
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