A facile route to old and new cyclophanes via self-assembly and capture

Abstract

Cyclophanes are a venerable class of macrocyclic and/or cage compounds that often feature high strain, unusual conformations and quite surprising properties, many of which are legendary in physical organic chemistry. However, the discovery of new, diverse cyclophanes and derivatives has been hindered by syntheses that are traditionally low-yielding, requiring long reaction times, laborious purification steps and often extreme conditions. Herein, we demonstrate a new self-assembly route to a variety of discrete cyclic and caged disulfide structures, which can then be kinetically captured upon sulfur extrusion at room temperature to give a diversity of new thioether (hetera)cyclophanes in high yield. In addition to the synthesis of novel macrocycles (dimers through hexamers), this process provides an improved route to a known macrobicyclic trithiacyclophane. This technique also enables the facile isolation of a tetrahedral macrotricyclic tetrathiacyclophane in two steps at an ambient temperature.

Self‐Assembly of a Trithioorthoformate‐Capped Cyclophane and Its Endohedral Inclusion of a Methine Group

“…However, the incorporation of a trithioorthoformate moiety as part of an in ‐cyclophane–where a methine hydrogen is projected directly into the ring system–has not been observed as a product of supramolecular self‐assembly . We previously described an unusual pnictogen‐enhanced iodine oxidation method for the self‐assembly of disulfide‐based cyclophanes . The directing behavior of the pnictogen leads to remarkable resistance to the formation of insoluble, kinetic polymers, enabling rapid and selective syntheses of many discrete disulfide macrocycles and cages for an assortment of different ligand systems.…”

“…By using a three‐fold ligand, H 3 L , the products were, by design, hypothesized to be the tetrahedral spheriphane 1 , and the dimer 3 . The oxidation of 1,3,5‐tris(mercaptomethyl)benzene (H 3 L ) was executed by treating the free trithiol ligand with iodine and antimony trichloride in a solution of chloroform, resulting in the self‐assembly of these primary products: tetrahedron ( 1 ) and dimer ( 3 ) (Scheme ) . However, we did not expect to isolate a third species of intermediate size, cage 2 , upon purification by gel permeation chromatography.…”

Desymmetrized Leaning Pillar[6]arene

“…In the past five decades, several important categories of supramolecular macrocycles, that is, crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillararenes, have provided a wide range of functions as high‐performance supramolecular hosts . More recently, a large number of new synthetic macrocyclic containers with novel structures and excellent host‐guest properties were reported, including calix[4]imidazolium, “Texas‐sized” box, Ex‐box, bambus[6]uril, cyanostar, molecular triangular prisms, oxatub[4]arene, thioether cyclophanes, corona[5]arenes, janusarene, and others…”

On the Stability of Cyclophane Derivates Using a Molecular Fragmentation Method

“…The stability of cyclophane molecules is also strongly influenced by intramolecular interactions. The interactions of π‐stacked aromatic rings are of importance in organic electronics and photovoltaics and single‐molecule electronics . Such systems have also been the topic of discussion regarding the importance of electron correlation effects contributing to the π‐stacking interaction .…”