Cobalt-Catalyzed ortho-C-H Functionalization/Alkyne Annulation of Benzylamine Derivatives: Access to Dihydroisoquinolines

A practical picolinamide-directed C-H functionalization/alkyne annulation of benzylamine derivatives enabling access to the previously elusive 1,4-dihydroisoquinoline skeleton was developed using molecular O-2 as the sole oxidant and Co(OAc)(2) as precatalyst. The method is compatible with both internal and terminal alkynes and shows high versatility and functional-group tolerance. Furthermore, full preservation of enantiopurity is observed when using non-racemic alpha-substituted benzylamine derivatives. Kinetic analysis of the reagents and catalyst, labeling experiments, and the isolation and identification of catalytically competent Co-complexes revealed important insights about the mechanism.