Synthesis of isoquinolines and pyridines by the palladium- and copper-catalyzed coupling and cyclization of terminal acetylenes

[GRAPHICS] 3-Substituted isoquinolines have been synthesized by the coupling of aryl a nd alkenyl-substituted terminal acetylenes with the tert-butylimine of o-io dobenzaldehyde in the presence of a palladium catalyst. Alkyl-substituted a cetylenes fail to undergo this annulation process. However, the intermediat e iminoalkynes containing aryl, alkenyl, and alkyl substituents produced fr om these palladium-catalyzed reactions undergo copper-catalyzed cyclization in excellent yields and short reaction times. Isoquinolines and pyridines have thus been prepared in a one-pot synthesis via coupling of aryl-, alken yl-, and alkyl-substituted terminal acetylenes with the tert-butylimines of o-iodobenzaldehydes or 3-halo-5-alkenals in the presence of a palladium ca talyst and subsequent copper-catalyzed cyclization of the resulting iminoal kynes. The total synthesis of the isoquinoline natural product decumbenine B has been accomplished in seven steps and 20% overall yield by employing t his palladium-catalyzed coupling/cyclization methodology.