Synthesis of a cross-chain bridging cryptand

Abstract

We present two methodologies for synthesizing cross–chain bridging cryptand 1 that incorporates tri- and tetra(ethylene glycol) linkers (methods B and C). Method B involves the synthesis through the intramolecular cross-linking of C2-symmetric crown ether 3. While this method does not substantially reduce the lengthy reaction steps compared to the previous approach, it improves the overall yield of cryptand 1a containing three tri(ethylene glycol) linkers and allows for the creation of a new form of a cross–chain bridging cryptand 1c with one distinct and two identical linkers. However, method C entails a synthesis accomplished through a triple-linking reaction in a single step. This method offered a streamlined synthesis of cryptand 1. The crucial triple linking reaction produced cross–chain bridging cryptand 1 as the major isomer and the corresponding linear regioisomer 6 as the minor isomer. Moreover, we observed the interconversion of enantiomers of cryptand 1c, which contains a 28-membered macrocycle, under chiral high-performance liquid chromatographic (HPLC) analytical conditions (with a half-life of 20.7 min at room temperature). Finally, X-ray crystallography confirmed the cross–chain bridging structure in the two chemically equivalent chains in the solid state of cryptand 1a.