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 C(6)H(4)(2-CN)C[triple bond]C-R with an array of amines, catalyzed by 10 mol % of [sigma:eta(1):eta(5)-(OCH(2))(Me(2)NCH(2))C(2)B(9)H(9)]Ti(NMe(2)) (1), gives a series of substituted isoindoles in very high yields. In a similar manner, interaction of C(6)H(4)(2-CH(2)CN)C[triple bond]C-Ph with various kinds of amines affords a wide range of substituted isoquinolines. On the other hand, treatment of propargylamines (R'C[triple bond]CCH(2)NHR'') 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.