Synthesis of Isoquinoline/Quinoline/Carboline-Substituted Methylamine Derivatives by an Interrupted Ugi Three-Component Reaction

A hexafluoroisopropanol (HFIP)-promoted Ugi three-component reaction of electron rich aryl, alkenyl or heteroaryl group-tethered isocyanides, aldehydes and amines was developed for the rapid and general synthesis of a wide range of isoquino-line/quinoline/carboline-substituted methylamine and α-amino acid derivatives. In this reaction, the in situ formed nitrilium was intramolecularly trapped by the nucleophiles tethered at isocyanides to form the corresponding heterocyclic framework, wherein an obviously <i>gem</i>-disubstituent (Thorpe-Ingold) effect was observed.