title: The Brønsted Acid-Catalyzed, Enantioselective Aza-Diels-Alder Reaction for the Direct Synthesis of Chiral Piperidones.
abstract: We disclose herein the first enantioselective aza-Diels-Alder reaction of β-alkyl-substituted vinylketene silyl-O,O-acetals and imines furnishing a broad range of optically highly enriched 4-alkyl-substituted 2-piperidones. As a catalyst for this one-pot reaction we employed a chiral phosphoric acid which effects a vinylogous Mannich reaction directly followed by ring-closure to the lactam. Subsequent fully diastereoselective transformations including hydrogenation, enolate alkylation, and lactam alkylation/reduction processes converted the cycloadducts into various highly substituted piperidines of great utility for the synthesis of natural products and medicinally active compounds.
authors.affiliation: Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103, Leipzig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Weilbeer
authors.affiliation: Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103, Leipzig, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Sickert
authors.affiliation: Leibniz-Institut für Oberflächenmodifizierung, Permoserstr. 15, 04318, Leipzig, Germany.
authors.forename: Sergei
authors.initials: S
authors.lastname: Naumov
authors.affiliation: Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103, Leipzig, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schneider
mesh_terms: D000478:Alkylation; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D061565:Cycloaddition Reaction; D006865:Hydrogenation; D008968:Molecular Conformation; D010756:Phosphoric Acids / Q000737:chemistry; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001372:Aza Compounds; D001688:Biological Products; D010756:Phosphoric Acids; D010881:Piperidones; C030242:phosphoric acid
keywords: asymmetric synthesis; aza-Diels-Alder reaction; organocatalysis; piperidones; silylketene acetals