Chiroptical Properties of Nona- and Dodecamethoxy Cryptophanes

Enantiopure cryptophane derivatives bearing nine (<b>2</b>, <b>3</b>) and 12 (<b>4</b>) methoxy substituents attached on the six aromatic rings were separated by HPLC using chiral stationary phases. The chiroptical properties of compounds <b>2</b>–<b>4</b> were determined from polarimetry, electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) experiments and were compared to those of cryptophane-A (<b>1</b>) derivative. ECD spectra of <b>1</b> and <b>4</b> were calculated by time-dependent density functional theory (TDDFT) to determine the absolute configuration (AC) of cryptophane derivatives. The (+)-<i>PP</i> absolute configuration was thus established for the <i>anti</i>-cryptophane-A (<b>1</b>) and its congeners <b>2</b> and <b>4</b>. VCD experiments associated with DFT calculations confirmed the (+)-<i>PP</i> configuration of <i>anti</i>-compounds <b>2</b> and <b>4</b> and established the (+)-<i>PM</i> configuration of the <i>syn</i>-<b>3</b> compound as well. This study revealed the preferential all-<i>trans</i> (<i>TTT</i>) conformation of the three ethylenedioxy linkers for the CHCl₃@<b>1</b>, CHCl₃@<b>3</b>, and CHCl₃@<b>4</b> complexes, whereas the <i>GTT</i> conformation was found the most favorable for the CHCl₃@<b>2</b> complex