Construction of Pyranoisoquinolines via Ru(II)-Catalyzed Unsymmetrical Double Annulation of <i>N</i>-Methoxybenzamides with Unactivated Alkynes

Abstract

A ruthenium (Ru)-catalyzed double annulation of easily accessible <i>N</i>-methoxybenzamide derivatives with unactivated alkynes for the synthesis of unusual 6,6-fused pyranoisoquinolines is described. Both <i>ortho</i>-C-H bonds of arenes and the N- and O-moieties of <i>N</i>-methoxybenzamides are involved in the construction of four [(C-C)-(C-N) and (C-C)-(C-O)] bonds in one step under single catalytic conditions. The unsymmetrical annulation of <i>N</i>-methoxybenzamides with two distinct alkynes is also demonstrated. The oxidizable directing group <i>N</i>-methoxyamine (NHOMe) assists the unsymmetrical double annulations of arenes [that use both N- and O-heteroatoms] in a single operation. This synthetic method features excellent substrate scope and tolerates a wide range of functional groups. Peripheral modification of pyranoisoquinolines for the construction of complex heterocyclic compounds is also demonstrated.