Atom-Economical Synthesis of <i>N</i>-Heterocycles via Cascade Inter-/Intramolecular C−N Bond-Forming Reactions Catalyzed by Ti Amides

Direct and efficient catalytic reactions with excellent regioselectivity for the preparation of a series of substituted isoindoles, isoquinolines, and imidazoles are reported. Reaction of C6H4(2-CN)CC-R with an array of amines, catalyzed by 10 mol % of [σ:η1:η5-(OCH2)(Me2NCH2)C2B9H9]Ti(NMe2) (1), gives a series of substituted isoindoles in very high yields. In a similar manner, interaction of C6H4(2-CH2CN)CC-Ph with various kinds of amines affords a wide range of substituted isoquinolines. On the other hand, treatment of propargylamines (R′CCCH2NHR′′) with nitriles in the presence of 10 mol % of 1 produces a class of substituted imidazoles in high yields. A possible reaction mechanism is proposed, involving sequential inter- and intramolecular C−N bond formation via hydroamination/cyclization reaction of cyanoalkynes with amines or nitriles with propargylamines catalyzed by titanium amides.