A Second-Generation Approach Toward the Total Synthesis of Dodecahedrane Using a Photochemical Stereoisomerization

We describe our second-generation approach toward the synthesis of dodecahedrane, exploiting dodecahedrane's unique symmetry to guide our retrosynthetic analysis. We describe a photochemical bis-epimerization for the synthesis of monomer fragments, as well as dimerization studies. Ultimately, several intermediates bearing 18 of the 20 carbons present in dodecahedrane were accessed. Although initial efforts to execute an olefin metathesis rearrangement to form key carbon–carbon bonds have been challenging, our studies highlight the potential of symmetry-based disconnections for complex molecule synthesis.