Synthesis, Chiral Resolution, and Absolute Configuration of Dissymmetric 4,15-Difunctionalized [2.2]Paracyclophanes

Despite the fact that functionalized
planar chiral [2.2]­paracyclophanes
have received a lot of attention, the chemistry of pseudo-meta 4,15-distubstituted [2.2]­paracyclophanes is largely
unexplored. This is mainly due to the fact that the 4,5-dibromo-functionalized
[2.2]­paracyclophane is much less prone to halogen-metal exchange reactions
than its constitutional pseudo-ortho or pseudo-para isomers. Here, we give an account of an efficient protocol
to achieve this, which allows the synthesis of a broad variety of
4,15-disubstituted [2.2]­paracyclophanes. Furthermore, we were able
to resolve several of the racemic compounds via chiral HPLC and assign
the absolute configurations of the isolated enantiomers by X-ray diffraction
and/or by the comparison of calculated and measured CD-spectra.