title: Chiral phosphoric acid-catalyzed enantioselective three-component Povarov reaction using enecarbamates as dienophiles: highly diastereo- and enantioselective synthesis of substituted 4-aminotetrahydroquinolines.
abstract: A 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% ee). The reaction was applicable to a wide range of anilines bearing electron-donating (OMe) and electron-withdrawing groups (e.g., Cl, CF(3), NO(2)) and allowed, for the first time, aliphatic aldehydes to be employed in the enantioselective Povarov reaction. With β-substituted acyclic enecarbamates, 2,3,4-trisubstituted 1,2,3,4-tetrahydroquinolines with three contiguous stereogenic centers were produced in excellent diastereo- and enantioselectivities (87 to >99% ee). A detailed study of 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 in the success of this transformation was demonstrated. NMR experiments indicating the catalyst-substrate interaction as well as a linear correlation between catalyst and product ee's were also documented.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Dagousset
authors.forename: Jieping
authors.initials: J
authors.lastname: Zhu
authors.forename: Géraldine
authors.initials: G
authors.lastname: Masson
mesh_terms: D002219:Carbamates / Q000737:chemistry*; D002384:Catalysis; D010756:Phosphoric Acids / Q000737:chemistry*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D002219:Carbamates; D010756:Phosphoric Acids; D011804:Quinolines; C542964:1,2,3,4-tetrahydroquinoline; C030242:phosphoric acid