The synthesis of cubane is possible despite its thermodynamic instability. Its strain energy content has been estimated variously to be 166 kcal-mol-1 and 181 kcal-mol-1. Thus, in order to be successful, any attempt to synthesize cubane must necessarily rely upon kinetically accessible pathways; thermodynamic control must be avoided at all costs!

Eaton and Cole's successful early synthesis of cubane-1,4-dicarboxylic acid, as shown the scheme is a marvel of economy and simplicity. With only minor modification, this procedure remains to this day the best available method for large-scale synthesis of 2. Key steps in the kinetically controlled synthesis involve: (i) stereospecific in situ [4 + 2] (Diels-Alder) cyclodimerization of 2-bromocyclo-pentadienone followed by (ii) intramolecular [2 + 2] photocyclization of the resulting endo Diels-Alder cycloadduct, and (iii) semibenzilic acid rearrangement performed on 5,9-dibromo- pentacyclo- [5.3.0.0(2,5).0(3,9).0(4,8)]decane-6,10-dione , 4. A recent improvement in the method for bis-decarboxylation to cubane which utilizes the Barton decarboxylation procedure has been published by Eaton and co-workers.