Two approaches to the synthesis of isoschizogamine were reported. Both routes utilized an efficientaza-Claisen rearrangement to establish the absolute stereochemistry of the all-carbon quaternary centerin the natural product. In the first approach, a highly diastereoselective (10:1) hetero-Diels−Alder reactionwas utilized to reach a densely functionalized tetrahydroquinoline derivative as an advanced intermediateto the targeted alkaloid. An acylamidine intermediate was prepared and studied in the intramolecularcyclization reaction under acidic conditions in our second approach.