The construction of C1-symmetric architectures is of paramount importance, as their complete lack of symmetry creates a uniquely asymmetric confined environment, which is highly desirable for applications such as enantioselective recognition and catalysis. While numerous C1-symmetric architectures have been successfully constructed via covalent synthesis, the assembly of such inherently chiral, fully asymmetric topologies through noncovalent interactions remains largely unexplored and represents a formidable challenge in supramolecular chemistry. We report herein the first enantioselective synthesis of inherently chiral C1-symmetric supramolecular structures through a rational stepwise symmetry-breaking strategy. Starting from a D4h-symmetric Pd2L4 coordination cage, the symmetry was systematically reduced to D2h, C2v, Cs, and final C1 via the sequential introduction of an exohedral and two endohedral symmetry-breaking groups (SBG). The endohedral SBGs bear a central chirality center, enabling effective chirality transfer to the cage framework and facilitating the enantioselective assembly. The resulting C1-symmetric cages were thoroughly characterized by 1H/2D NMR, high-resolution mass spectroscopy, and CD spectroscopy. DFT calculations and variable-temperature NMR spectroscopy provide mechanistic insight into the chiral induction process. The generality of this strategy was demonstrated by constructing inherently chiral nanocavities with varying endohedral SBGs and internal functional groups. Preliminary host-guest studies confirmed the binding capability of these chiral cavities toward both neutral and anionic guest molecules. The inherent asymmetry of the cavity facilitates enantiomer discrimination, and its enantioselectivity can be modulated through cavity editing by introducing small internal functional groups. Our study establishes a versatile approach to construct highly asymmetric confined nanoenvironment, offering new opportunities for asymmetric catalysis and molecular recognition.
Yu et al. (Wed,) studied this question.