A chiral vinyl sulfoxide has been developed that undergoes highly diastereoselective Diels−Alder cycloadditions with various substituted furans in excellent yield. The cycloadducts can be stereoselectively transformed into tetrasubstituted tetrahydrofurans via ring-opening metathesis/cross-metathesis or oxidative cleavage and refunctionalization. A partial synthesis of the bioactive diketopiperazine containing natural product gliocladin C was achieved in nine steps, and 13.4% overall yield. The synthesis featured several novel transformations including the construction of the core structure by an elimination and nucleophilic addition sequence, followed by a Lewis acid promoted coupling with indole giving the key quaternary oxindole intermediate. A new protocol for intramolecular reductive coupling of the oxoindole and bis-unsaturated diketopiperazine led to successful construction of the hexacyclic skeleton.