Synthesis of Isoquinolines and Pyridines by the Palladium- and Copper-Catalyzed Coupling and Cyclization of Terminal Acetylenes

Abstract

3-Substituted isoquinolines have been synthesized by the coupling of aryl- and alkenyl-substituted terminal acetylenes with the tert-butylimine of o-iodobenzaldehyde in the presence of a palladium catalyst. Alkyl-substituted acetylenes fail to undergo this annulation process. However, the intermediate iminoalkynes containing aryl, alkenyl, and alkyl substituents produced from 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-, alkenyl-, and alkyl-substituted terminal acetylenes with the tert-butylimines of o-iodobenzaldehydes or 3-halo-2-alkenals in the presence of a palladium catalyst and subsequent copper-catalyzed cyclization of the resulting iminoalkynes. The total synthesis of the isoquinoline natural product decumbenine B has been accomplished in seven steps and 20% overall yield by employing this palladium-catalyzed coupling/cyclization...