Silver(I)-Catalyzed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres

Bridged or caged polycyclic hydrocarbons have rigid structures that project substituents into precise regions of 3D space, making them attractive as linking groups in materials science and as building blocks for medicinal chemistry. The efficient synthesis of new or underexplored classes of such compounds is therefore an important objective. Herein, we describe the silver(I)-catalyzed rearrangement of 1,4-disubstituted cubanes to cuneanes, which are strained hydrocarbons that have not received much attention from the synthetic community. The synthesis of 2,6-disubstitued or 1,3-disubstituted cuneanes can be achieved with high regioselectivities, with the regioselectivity being dependent on the electronic character of the cubane substituents. A preliminary assessment of cuneanes as scaffolds for medicinal chemistry was also performed, which suggests cuneanes could serve as isosteric replacements of trans-1,4-disubstituted cyclohexanes and 1,3-disubstituted benzenes.