Inherently Chiral Bambus[4]urils

Abstract

A new class of bambus[4]urils (BU[4]s) composed of asymmetric N,N'-disubstituted glycoluril subunits with different alkyl groups were designed, synthesized, and fully characterized by NMR techniques and X-ray crystallography. Structural studies showed that four macrocyclic diastereoisomers are possible: two S_n symmetric achiral macrocycles and two macrocycles that are "inherently" chiral. The relative "head-to-tail" arrangement of the N-substituents in Bn₄Me₄BU[4], 5a, clearly observed by X-ray spectroscopy analysis, determines the overall symmetry of the bambusuril structure. Chiral Pr₄Me₄BU[4], 4b, was resolved by chiral high-performance liquid chromatography (HPLC) into its enantiomers, and all four inherently chiral bambusuril pairs (two Pr₄Me₄BU[4] and two Bn₄Me₄BU[4] stereoisomers, 4b, 4d, 5b, and 5d) were clearly observed by ¹H NMR spectroscopy with the aid of (R)-BINOL as a chiral solvating agent. This latter methodology provides a rapid and powerful approach for investigating the enantiopurity of inherently chiral cavitands, which complements and augments the conventional chromatographic approaches.