Large-Scale Synthesis of Enantiopure Molecular Cages: Chiroptical and Recognition Properties

A convenient and efficient gram-scale synthesis for enantiopure hemicryptophane-tren (tren=tris(2-aminoethyl)amine) derivatives has been developed. The four-step synthesis is based on the optical resolution of a key intermediate, cyclotriveratrylene, for which the energy barrier for racemization has been measured to ensure that no racemization occurs during the two last steps of the synthetic pathway. The assignments of the absolute configurations have been performed by electronic circular dichroism and the enantiopurity was determined by NMR spectroscopy in the presence of enantiopure camphor sulfonic acid. To highlight the interest of such compounds, the recognition of norephedrine neurotransmitter was investigated and showed a remarkable enantioselectivity towards the C₃ symmetrical hosts. Finally, this highly modular synthetic pathway was used to provide eight enantiopure hemicryptophanes with different sizes, shapes, and functionalities. These results underline the high potential of this approach, which could lead to many applications in chiral recognition or asymmetric supramolecular catalysis. Separated at birth: Easy and large-scale access to enantiopure molecular cages of different shapes and sizes is described. Assignments of the absolute configurations and recognition properties of these cage compounds are also presented (see figure).