Enhancement of 5-aminopenta-2,4-dienals electrophilicity via activation by O,N-bistrifluoroacetylation. application to an N-acyl Pictet-Spengler reaction.
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.
Nuhant
Philippe
P
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
Raikar
Sanjay B
SB
Wypych
Jean-Charles
JC
Delpech
Bernard
B
Marazano
Christian
C
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
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