Importance of Molecular Symmetry for Enantiomeric Excess Recognition by NMR


Recently prochiral solvating agents (pro-CSA) became a spotlight for the detection of enantiopurity by NMR. Chemical shift non-equivalency in achiral hosts introduced by the presence of chiral guest yields observable resonance signal splitting correlating to the enantiomeric excess (e.e.). In this work, symmetry is our lens to explain porphyrin-based supramolecular receptors’ activity in a chiral environment. Based on extensive NMR analyses of the atropisomeric receptors, host symmetry is shown to be affected by porphyrin nonplanarity and further desymmetrized in the presence of a chiral guest. We have formulated a simple, symmetry-based protocol that can be used to identify pro-CSA candidates. As such, the exposed porphyrin inner core (N–H), with its strong hydrogen bond abilities, for the first time, has been exploited in enantiomeric composition analysis. Our approach in e.e. detection by N–H signals appearing in a previously underutilized region of the spectrum (below 0 ppm.), shows chemical shifts (the e.e. dependent splitting) three times more sensitive to enantiomeric compositions than previously reported systems. The findings are complemented by extensive 2D NMR studies, including the first reporting of e.e. dependent  in non-hydrogen NMR, and supporting by density functional theory (DFT) calculations.