Enhancement of 5-aminopenta-2,4-dienals electrophilicity via activation by O,N-bistrifluoroacetylation. Application to an N-acyl Pictet-Spengler reaction

Abstract

(Chemical Equation Presented) Aminopentadienals resulting from the condensation of tryptamine or homoveratrylamine with glutaconaldehydes were treated with trifluoroacetic anhydride, allowing the formation of tetrahydro-β-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. © 2009 American Chemical Society.