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Synthesis of Isoquinolines and Pyridines by the Palladium/Copper-Catalyzed Coupling and Cyclization of Terminal Acetylenes and Unsaturated Imines: The Total Synthesis of Decumbenine B
journal contribution
posted on 2001-12-12, 00:00 authored by Kevin R. Roesch, Richard C. LarockMonosubstituted isoquinolines and pyridines have been prepared in good to excellent yields via
coupling of terminal acetylenes with the tert-butylimines of o-iodobenzaldehydes and 3-halo-2-alkenals in the presence of a palladium catalyst and subsequent copper-catalyzed cyclization of
the intermediate iminoalkynes. In addition, isoquinoline heterocycles have been prepared in
excellent yields via copper-catalyzed cyclization of iminoalkynes. The choice of cyclization conditions
is dependent upon the nature of the terminal acetylene that is employed, as only aryl and alkenyl
acetylenes cyclize under the palladium-catalyzed reaction conditions that have been developed.
However, aryl-, vinylic-, and alkyl-substituted acetylenes undergo palladium-catalyzed coupling
and subsequent copper-catalyzed cyclization in excellent yields. 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 and cyclization methodology.