Synthesis of Tetrazole-Derived Organocatalysts via Azido-Ugi Reaction with Cyclic Ketimines

A new route to tetrazole-derived cyclic amines based on the TMSN₃-modified Ugi reaction with 2-substituted cyclic imines was elaborated. The reaction allows the direct preparation of five-, six-, and seven-membered cyclic amines substituted with a tetrazole ring, which are important types of organocatalysts. The scope and limitations of this method are discussed. In the case of the Ugi reaction with benzyl isocyanide, the N-substituted tetrazoles can be easily debenzylated under catalytic hydrogenation conditions to form NH-tetrazoles in quantitative yields. It was demonstrated that both enantiomers of tetrazole-derived cyclic amines can be prepared by resolution with tartaric acid, thereby initiating a simple route to chiral derivatives. One of the obtained chiral tetrazoles was efficiently used as an organocatalyst in the amination reaction

From Cyclic CF₃‑ketimines to a Family of Trifluoromethylated Nazlinine and Trypargine Analogues

An efficient (one- and two-step) synthesis of trifluoromethylated derivatives of the natural alkaloids nazlinine, trypargine, and homotrypargine was elaborated. Trifluoromethyl-substituted 5–7-membered cyclic imines were used as a masked carbonyl component in the Pictet–Spengler reaction with various tryptamines. As a result, this approach opens access to a family of alkaloid-like compounds bearing a CF₃ group at position 1 of tetrahydro-β-carboline