Synthesis of 4-Aryl Isoquinolinedione Derivatives by a Palladium-Catalyzed Coupling Reaction of Aryl Halides with Isoquinoline-1,3(2 H,4 H)-diones.

The palladium-catalyzed cross-coupling reaction of aryl halides with isoquinoline-1,3(2 H,4 H)-diones for the synthesis of 4-aryl isoquinoline-1,3(2 H,4 H)-diones was developed. The reaction conditions exhibit remarkable compatibility with various aryl halides and isoquinoline-1,3(2 H,4 H)-diones, and the product could be conveniently transformed to 4-aryl tetrahydroisoquinolines. (±) Dichlorofensine was synthesized using this protocol in two steps with an overall yield of 71%.