The antiaromatic diene cyclobutadiene participates in cycloadditions which provide access to rigid polycyclic systems with high strain energy and unusual molecular geometries. Manipulation of these systems allows entry into unexplored chemical space and facile access to medium-ring natural products. A tricarbonylcyclobutadiene iron complex on solid support makes these cycloadditions amenable to diversity oriented synthesis. The regioselectivity observed in generation of a pilot library of substituted bicyclo[2.2.0]hexenes is examined using DFT calculations. Torilin, a guaiane sesquiterpene isolated from the fruits of Torilis japonica, exhibits biological activities including testosterone 5a-reductase inhibition, hKv1.5 channel blocking, hepatoprotective, anti-inflammatory and anti-cancer effects. These apparently disparate activities are reviewed and possible targets discussed. Tandem oxidation and acid catalyzed rearrangement of a tetracyclo[188.8.131.52.0]decane precursor in the presence of TPAP provides the bicyclo[5.3.0]decane core of this natural product with control of relevant stereochemistry. Preliminary synthetic studies toward torilin are reported.