title: Enhancement of 5-aminopenta-2,4-dienals electrophilicity via activation by O,N-bistrifluoroacetylation. application to an N-acyl Pictet-Spengler reaction.
abstract: Aminopentadienals resulting from the condensation of tryptamine or homoveratrylamine with glutaconaldehydes were treated with trifluoroacetic anhydride, allowing the formation of tetrahydro-beta-carbolines and tetrahydroisoquinolines bearing an enal function. In this N-acyl Pictet-Spengler reaction the electrophilicity of the aminopentadienals was dramatically increased by O,N-bistrifluoroacetylation. Recovery of the nitrogen nucleophilicity was achieved using a reductive process, and the heterocyclic amines were converted into aminonitriles by a Strecker reaction in the presence of butanal. Cyclization, by intramolecular Michael addition of the in situ generated enamines onto the enal moiety, was achieved in the presence of zinc triflate and involved cyanide ion trapping. In this manner, compounds related to protoemetine and dihydrocorynantheal were obtained, and a reduction step led to a short synthesis of (+/-)-protoemetinol.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. pnuhant@scripps.edu
authors.forename: Philippe
authors.initials: P
authors.lastname: Nuhant
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Raikar
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Wypych
authors.forename: Bernard
authors.initials: B
authors.lastname: Delpech
authors.forename: Christian
authors.initials: C
authors.lastname: Marazano
mesh_terms: D000089:Acetic Anhydrides; D000107:Acetylation; D000447:Aldehydes / Q000737:chemistry*; D000466:Alkadienes / Q000737:chemistry*; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000586:Amination; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry; D003486:Cyanides / Q000737:chemistry; D003500:Cyclization; D005463:Fluoroacetates; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D007477:Ions; D009682:Magnetic Resonance Spectroscopy; D008698:Mesylates / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D014269:Trifluoroacetic Acid / Q000737:chemistry; D014363:Tryptamines / Q000737:chemistry
chemical_list: D000089:Acetic Anhydrides; D000447:Aldehydes; D000466:Alkadienes; D000470:Alkaloids; D002243:Carbolines; D003486:Cyanides; D005463:Fluoroacetates; D006841:Hydrocarbons, Aromatic; D007211:Indoles; D007477:Ions; D008698:Mesylates; D009570:Nitriles; D044005:Tetrahydroisoquinolines; D014363:Tryptamines; C017958:trifluoroacetic anhydride; C030374:indole; D014269:Trifluoroacetic Acid; C012077:trifluoromethanesulfonic acid