Atom-Economical Synthesis of N-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 [sigma:eta(1):eta(5)-(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.