The Aryne aza-Diels-Alder Reaction: Flexible Syntheses of Isoquinolines

Two cascade reactions have been developed for the time-efficient preparation of a variety of functionalized aromatic heterocyclic products exhibiting an isoquinoline core. The approach is based on the normal electron-demand [4 + 2] aza-DielsAlder cycloaddition of electron-rich N-aryl imines with arynes. Using this strategy, an expeditious total synthesis of the naturally occurring benzo[c]phenanthridine alkaloid nornitidine was achieved.