A total synthesis of the illudalane sesquiterpene illudinine was realized in eight steps and 14% overall yield from commercially available dimedone. The approach features tandem fragmentation/Knoevenagel-type condensation and microwave-assisted oxidative cycloisomerization to establish the isoquinoline core. Completion of the synthesis involves a recently reported cascade SNAr/Lossen rearrangement on a densely functionalized aryl bromide and an optimized procedure for O-methylation of 8-hydroxyisoquinolines. The oxidative cycloisomerization proceeds by way of a novel inverse-demand intramolecular dehydro-Diels-Alder cycloaddition, which has a potentially broader appeal for preparing substituted isoquinolines.