Formation of a Hydrogen-Bonded Barbiturate [2]-Rotaxane

Abstract

Interlocked structures containing the classic Hamilton barbiturate binding motif comprising two 2,6-diamidopyridine units are reported for the first time. Stable [2]-rotaxanes can be accessed either through hydrogen-bonded preorganization by a barbiturate thread followed by a Cu(+)-catalyzed "click" stoppering reaction or by a Cu(2+)-mediated Glaser homocoupling reaction.

Recent Advances in the Synthesis and Application of Hydrogen Bond Templated Rotaxanes and Catenanes

“…While the vast majority of hydrogen bond templated interlocked molecules possess a bis‐isophthalamide macrocycle, examples without such a component are known. For example, Tucker and McClenaghan prepared [2]rotaxane 86 by stoppering a pseudorotaxane consisting of macrocycle 83 and bis‐azide functionalized barbiturate 84 , with bulky terphenyl alkyne stopper 85 , relying on the complementarity of the bis‐2,6‐diaminopyridyl motif for the barbiturate functionality (Figure ) . The yield was modest at 22 %, but the researchers did only use 1.1 equivalents of 83 and 2.1 equivalents of 85 (with respect to the barbiturate 84 ).…”

Supramolecular Architectures Incorporating Hydrogen‐Bonding Barbiturate Receptors

“…This structural disposition was predicted by Anslyn and Dougherty to be conducive to, for example, rotaxane formation 25. Recently this structural organisation was exploited using a cyclic receptor ( 5 ) along with a barbiturate with short azide‐terminated arms ( 15 , Scheme ) which, unlike longer arm variants, was demonstrated to engage in effective threading ( K ass =23 500 M −1 ) 3. Covalent capture of the assembly (Scheme ) was achieved under mild reaction conditions.…”

“…Top: Barbiturate‐templated Cu + ‐catalysed “click” stoppering reaction. Bottom: A Cu 2+ ‐mediated Glaser homocoupling reaction 3…”

“…One should note that whereas the representations in Scheme imply a fully planar host–guest complex, single‐crystal X‐ray structures that were obtained of the 1:1 complex between the Hamilton receptor and barbital indicate that the guest is not perfectly coplanar with the pyridine units, but tilted at an acute angle, with the central barbiturate 5 position being the most distant from the receptor plane, and also that all six potential hydrogen bonds are formed 2b. A recent, representative host–guest crystal structure of 1 ⊂ 5 is shown in Figure 1 3…”

“… Single‐crystal X‐ray structure of a 1:1 host–guest molecular complex of cyclic receptor 5 with barbital ( 1 ) along with structural formulas 3…”