Rhodium(III)-Catalyzed [4+2] Annulation of N-Arylbenzamidines with Propargyl Alcohols: Highly Regioselective Synthesis of 1-Aminoisoquinolines Controlled by Noncovalent Interaction

A highly regioselective synthesis of 1-aminoisoquinolines has been explored via rhodium(III)-catalyzed C-H bond activation/annulation reactions of propargyl alcohols with N-arylbenzamidines. The imidamide was used as the directing group and the nitrogen source of the heterocycle and for regulating the regioselective migratory insertion of propargyl alcohol through a hydrogen bond. In this transformation, a specific isomer was obtained that would provide a new strategy for the synthesis of 1-aminoisoquinolines with biological activity.

Automated summary

A highly regioselective synthesis of 1-aminoisoquinolines was achieved through Rh(III)-catalyzed reactions, using imidamide as the directing group to achieve high selectivity. This strategy provides a new approach for the synthesis of biologically active 1-aminoisoquinolines.