Construction of Pyranoisoquinolines via Ru(II)-Catalyzed Unsymmetrical Double Annulation of -Methoxybenzamides with Unactivated Alkynes.

A ruthenium (Ru)-catalyzed double annulation of easily accessible -methoxybenzamide derivatives with unactivated alkynes for the synthesis of unusual 6,6-fused pyranoisoquinolines is described. Both -C-H bonds of arenes and the N- and O-moieties of -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 -methoxybenzamides with two distinct alkynes is also demonstrated. The oxidizable directing group -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.