Two-Step Synthesis of Heptacyclo[6.6.0.02,6 .03,13 .04,11 .05,9 .010,14 ] tetradecane from Norbornadiene: Mechanism of the Cage Assembly and Post-synthetic Functionalization.

A selective and scalable two-step approach to the dimerization of norbornadiene (NBD) into its thermodynamically most stable dimer, heptacyclo[6.6.0.02,6 .03,13 .04,11 .05,9 .010,14 ] tetradecane, (HCTD) is reported. Calculations indicate that the reaction starts with the Rh-catalyzed stepwise homo Diels-Alder cyclisation of NBD into its exo-cis-endo dimer. Treatment of this compound with acid promotes its evolution to HCTD via a [1,2]-sigmatropic rearrangement. The assemblies of 7,12-disubstituted cages from 7-(alkyl/aryl) NBDs, as well as the selective post-synthetic C-H functionalization of the core HCTD scaffold at position C1, or positions C1 and C4 are described.