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

• Published in: Chemistry : a European journal 2017-08, Vol.23 (48), p.11669-11676
• Main Authors: Martínez, Ángel Manu, Rodríguez, Nuria, Gómez‐Arrayás, Ramón, Carretero, Juan C.
• Format: Article
• Language: English
• Subjects: alkyne; Alkynes; annulation; Catalysts; Chemical reactions; Chemistry; Cobalt; Derivatives; dihydroisoquinoline; Organic chemistry; picolinamide; Preservation; Reagents
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201702283

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 O2 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 α‐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. Molecular O2 as the sole oxidant and simple Co(OAc)2 as precatalyst are key features of a practical procedure for the C−H alkenylation/annulation of benzylamine derivatives with both internal and terminal alkynes, thereby enabling the access to dihydroisoquinolines, including chiral, non‐racemic derivatives. Valuable insights about the reaction mechanism and presumed Co‐species involved in the catalytic cycle are provided.