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

Abstract

Despite the fact that functionalized planar chiral [2.2]­paracyclophanes have received a lot of attention, the chemistry of pseudo-<i>meta</i> 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-<i>ortho</i> or pseudo-<i>para</i> 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