Subscribe to RSS
Synthesis of Isoquinolines by I2-Mediated Electrophilic Heteroannulation
D. Fischer, H. Tomeba, N. K. Pahadi, N. T. Patil, Z. Huo, Y. Yamamoto*
Tohoku University, Sendai, Japan
22 January 2009 (online)
Reported here is the synthesis of highly substituted isoquinolines 2 via the iodine-mediated electrophilic cyclization of 2-alkynyl-1-methylene azido arenes 1. Several sets of conditions were identified using different iodonium sources, depending on the reactivity of the substrate. Both electron-donating and -withdrawing groups are equally tolerated on the aromatic ring, although electron-neutral and -donating groups are clearly favored at the alkyne terminus. The reaction was extended to include heterocyclic substrates including pyridines, pyrroles, furans and thiophenes 3, to give the corresponding isoquinolines in poor to excellent yield. The utility of this methodology was further demonstrated by the short synthesis of the potent antitumor agent norchelerythrine. A plausible mechanism involving formation of an iodonium species that is intercepted by the azido group, followed by aromatization on loss of N2 is suggested.