Catalytic Enantioselective De Novo Synthesis of C 1-Symmetric Inherently Chiral Cages

Abstract We report herein a catalytic asymmetric de novo synthesis of inherently chiral molecular cages featuring C1 symmetry. The construction begins with the preparation of a Cs-symmetric ABAC-type oxahomocalix[2]arene[2]triazine macrocyclic precursor through a “3+1” cyclization, which is subsequently converted to the target cages by double aromatic nucleophilic substitution (SNAr) with linear bis(benzyl alcohol) linkers. The key cage-forming step proceeds with enantioselectivities up to 98% ee under the catalysis of a chiral cinchona-derived phase transfer catalyst. Moreover, we demonstrate the utility of the cages as chiral catalysts for the stereoselective deprotonation of chiral primary ammonium salts. This study provides an approach for the bottom-up construction and application of inherently chiral functional molecules with sophisticated topological architectures.